THAYS NICOLLI FRAGOSO DA SILVA
Índice h a partir de 2011
4
Projetos de Pesquisa
Unidades Organizacionais
LIM/50 - Laboratório de Patologia das Moléstias Infecciosas, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- Analysis of iron superoxide dismutase-encoding DNA vaccine on the evolution of the Leishmania amazonensis experimental infection(2015) CAMPOS, B. L. S.; SILVA, T. N.; RIBEIRO, S. P.; CARVALHO, K. I. L.; KALLAS, E. G.; LAURENTI, M. D.; PASSERO, L. F. D.The present work aimed to evaluate the immunogenicity of Leishmania amazonensis iron superoxide dismutase (SOD) -encoding DNA experimental vaccine and the protective properties of this DNA vaccine during infection. The SOD gene was subcloned into the pVAX1 plasmid, and it was used to immunize BALB/c mice. Twenty-one days after the last immunization, mice were sacrificed (immunogenicity studies) or subcutaneously challenged with L. amazonensis (studies of protection), and alterations in cellular and humoral immune responses were evaluated, as well as the course of infection. Mice only immunized with pVAX1-SOD presented increased frequencies of CD4(+) IFN-gamma(+), CD8(+) IFN- gamma(+) and CD8(+) IL-4(+) lymphocytes; moreover, high levels of IgG2a were detected. After challenge, mice that were immunized with pVAX1-SOD had increased frequencies of the CD4(+) IL- 4(+), CD8(+) IFN-gamma(+) and CD8(+) IL-4(+) T lymphocytes. In addition, the lymph node cells produced high amounts of IFN-gamma and IL-4 cytokines. Increased IgG2a was also detected. The pattern of immunity induced by pVAX1-SOD partially protected the BALB/c mice from a challenge with L. amazonensis, as the animals presented reduced parasitism and lesion size when compared to controls. Taken together, these results indicate that leishmanial SOD modulates the lymphocyte response, and that the elevation in IFN-gamma possibly accounted for the decreased skin parasitism observed in immunized animals.
- Nanostructured Lipid Carriers as Robust Systems for Lupeol Delivery in the Treatment of Experimental Visceral Leishmaniasis(2023) JESUS, Jessica Adriana; SILVA, Thays Nicolli Fragoso da; SOUSA, Ilza Maria Oliveira; FERREIRA, Aurea Favero; LAURENTI, Marcia Dalastra; COSTA, Paulo Cardoso da; FERREIRA, Domingos de Carvalho de; PASSERO, Luiz Felipe DominguesLeishmaniasis is a neglected tropical disease that affects millions of people around the world. Available therapy causes severe side effects, has unacceptable prices for some specific formulations, and the existence of drug-resistant parasites limits the use of the currently available arsenal of antiparasitic drugs. Therefore, natural products serve as one of the main sources to develop new and effective alternative drugs against leishmaniasis. In this sense, the present study evaluated the potential of the triterpene Lupeol (Lu) entrapped in nanostructured lipid carriers (NLCs) for the treatment of experimental visceral leishmaniasis. The therapeutic efficacy of Lu or Lu entrapped in NLC (Lu-NLC) was investigated in golden hamsters infected with Leishmania (Leishmania) infantum. Lu-NLC presented a mean particle size of 265.3 +/- 4.6 nm, a polydispersity index of <0.25 and a zeta potential of -37.2 +/- 0.84 mV; the efficacy of encapsulation was 84.04 +/- 0.57%. Studies on hamsters showed that Lu-NLC (5 mg/kg) administered intraperitoneally for 10 consecutive days caused a reduction of 99.9% in the number of parasites in the spleen and liver compared to the untreated infected control. On the contrary, Lu-treated animals (5 mg/kg) had 94.4 and 90.2% less parasites in the spleen and liver, respectively, than the infected group. Additionally, a significant preservation of splenic and hepatic tissues was observed in animals treated with Lu-NLC or Lu. Furthermore, Lu-NLC-treated animals produced high levels of anti-Leishmania IgG2 isotype. These data indicate that NLC potentialized Lu efficacy in experimental visceral leishmaniasis. This work suggests that Lu and nanoformulations carrying this compound may be considered as an important tool to be included in the alternative therapy of leishmaniasis.
- Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis(2020) JESUS, Jessica Adriana; SILVA, Thays Nicolli Fragoso da; YAMAMOTO, Eduardo Seiji; LAGO, Joao Henrique G.; LAURENTI, Marcia Dalastra; PASSERO, Luiz Felipe DominguesUrsolic acid (UA) is a triterpene with a broad array of pharmacological activities. In leishmaniasis, UA killed different species of parasites, and it was active in the experimental model of cutaneous and visceral leishmaniasis. Thus, the objective of this work was to study the therapeutic efficacy of the conventional drugs amphotericin B (AmB) or glucantime (Glu) combined with UA in experimental visceral and cutaneous leishmaniasis, respectively. L. (L.) infantum-infected hamsters were treated with AmB alone or combined with UA. L. (L.) amazonensis-infected BALB/c mice were treated with Glu alone or combined with UA. Animals were treated for 15 consecutive days by intraperitoneal or intralesional routes. Following one week after the last dose, the tissue parasitism and cellular immune responses were analyzed. Hamsters treated with 0.2 and 1.0 mg/kg of AmB plus 1.0 mg/kg of UA showed low hepatic and splenic parasitisms; however, AmB given as monotherapy did not reduce the number of viable parasites in the spleen of treated animals. In cutaneous leishmaniasis, Glu given as monotherapy was inactive at 2.0 mg/kg, showed mild activity at 10.0 mg/kg, and at 50.0 mg/kg was highly active at eliminating parasites in the skin. When animals were treated with Glu plus UA, higher leishmanicidal activity was observed in comparison to all groups treated with monotherapy schemes, and such activity was related to lesion improvement and upregulation of IFN-gamma production. Altogether, data suggest that the association of drugs for the treatment of leishmaniasis can increase the efficiency of the treatment and decrease the toxicity associated to the conventional drugs.
- Differential modulation of macrophage response elicited by glycoinositolphospholipids and lipophosphoglycan from Leishmania (Viannia) shawi(2015) PASSERO, Luiz F. D.; ASSIS, Rafael R.; SILVA, Thays N. F. da; NOGUEIRA, Paula M.; MACEDO, Diego H.; PESSOA, Natalia L.; CAMPOS, Marco A.; LAURENTI, Marcia D.; SOARES, Rodrigo P.In this work, some aspects of the glycobiology of Leishmattia shawl were examined, as it is a causative agent of cutaneous leishmaniasis in the New World. Additionally, the interaction of L. shawl's main glycoconjugates [lipophosphoglycan (LPG) and glycoinositolphospholipids (GIPLs)] with macrophages was evaluated in vitro. L. shawl LPG was devoid of side-chains in its repeat units, whereas monosaccharide analysis showed that GIPLs were suggestive of mannose-rich (type I or hybrid). In order to evaluate the biological roles of those molecules, BALB/c resident peritoneal macrophages were incubated with these glycoconjugates for 24 h, and the levels of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-12p70 and IL-10, were determined. In general, the GIPLs exhibited a greater proinflammatory role than the LPGs did. However, for the first time, the GIPLs from this species were able to trigger the production of IL-10, an anti-inflammatory cytokine. In conclusion, L shawl glycoconjugates were able to interact with the innate immune compartment. These data reinforce the role of parasite glycoconjugates during parasite and host cell interactions.
- Preclinical Assessment of Ursolic Acid Loaded into Nanostructured Lipid Carriers in Experimental Visceral Leishmaniasis(2021) JESUS, Jessica Adriana; SOUSA, Ilza Maria Oliveira; SILVA, Thays Nicolli Fragoso da; FERREIRA, Aurea Favero; LAURENTI, Marcia Dalastra; ANTONANGELO, Leila; FARIA, Caroline Silverio; COSTA, Paulo Cardoso da; FERREIRA, Domingos de Carvalho; PASSERO, Luiz Felipe DominguesUrsolic acid, a triterpene produced by plants, displayed leishmanicidal activity in vitro and in vivo; however, the low solubility of this triterpene limits its efficacy. To increase the activity of ursolic acid (UA), this triterpene was entrapped in nanostructured lipid carriers (UA-NLC), physical-chemical parameters were estimated, the toxicity was assayed in healthy golden hamsters, and the efficacy of UA-NLC was studied in experimental visceral leishmanisis. UA-NLC exhibited a spherical shape with a smooth surface with a size of 266 nm. UA-NLC displayed low polydispersity (PDI = 0.18) and good colloidal stability (-29.26 mV). Hamsters treated with UA-NLC did not present morphological changes in visceral organs, and the levels of AST, ALT, urea and creatinine were normal. Animals infected with Leishmania (Leishmania) infantum and treated with UA-NLC showed lower parasitism than the infected controls, animals treated with UA or Amphotericin B (AmB). The therapeutic activity of UA-NLC was associated with the increase in a protective immune response, and it was associated with a high degree of spleen and liver preservation, and the normalization of hepatic and renal functions. These data indicate that the use of lipid nanoparticles as UA carriers can be an interesting strategy for the treatment of leishmaniasis.