AUREA FAVERO FERREIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/50 - Laboratório de Patologia das Moléstias Infecciosas, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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- In situ expression of Th17 immunologic mediators in American cutaneous leishmaniasis caused by Leishmania (V.) braziliensis and Leishmania (L.) amazonensis in the Brazilian Amazon(2023) RODRIGUES, G. F.; ALCâNTARA, L. S.; BARROS, J. P. B.; LIMA, A. C. S. de; CAMPOS, M. B.; MORAES, C.; FERREIRA, A. F.; MATTA, V. L. R.; LAURENTI, M. D.; CORBETT, C. E. P.; SILVEIRA, F. T.; GOMES, C. M. C.American cutaneous leishmaniasis (ACL) presents a wide spectrum of clinical and immunopathological manifestations. In Brazil, Leishmania (L.) amazonensis[La] and Leishmania(V.)braziliensis[Lb] show the highest pathogenic potential for humans causing different clinical forms: localized cutaneous leishmaniasis (LCL : Lb/La), anergic diffuse cutaneous leishmaniasis (ADCL : La) and mucocutaneous leishmaniasis (MCL : Lb). ADCL and MCL are the most severe forms and infection leads to a cellular immune response at the hyposensitivity and hypersensitivity poles. Th17-cells are involved in the ACL pathogenesis, are derived from naïve TCD4+ cells regulated by RORγt, differentiate in presence of IL-6, TGF-β, IL- 1β, IL-23 and express IL-17. Aim of this study was to characterize the cellular immune response mediated by Th17-profile cells through in situ determination of the expression of RORγt, IL-17, IL-6, TGF-β, IL-1β, and IL-23 in the ACL clinical-immunopathological spectrum caused by L.(L.)amazonensis and L.(V.)braziliensis. Biopsies of skin and mucosal lesions from forty patients including ADCL(n=8), LCL[La](n=17), LCL[Lb](n=9) and MCL(n=6), were examined by immunohistochemistry. The immunostained cells density (cells/mm2) was determined in image analysis system using AxionVision 4.8 software (Zeiss). As the disease evolution time (DET) was different among ACL patients, the effect of DET on the expression of immunological markers was evaluated in different clinical forms and histopathological changes, using ANCOVA. Our results showed significantly increased expression of RORγt, IL-17, IL-6, IL-1β and IL-23 in patients with ACL polar forms (ADCL and MCL); higher TGF-β expression was found in ADCL. DET influenced the expression of RORγt and IL-6 in: clinical forms of ACL and in categories of parasitism. DET also affected the production of RORγt, IL-17, IL-6, TGF-β and IL-1β in types of inflammatory infiltrate, evidencing that DET had effect on the expression of Th17 profile cytokines in ACL. Together, the expression of immunological mediators of Th17 profile in the ACL spectrum, as well as the DET effect, demonstrate the participation of this cell lineage in the immunopathogenesis of ACL, mainly in the polar and more severe forms of ACL spectrum. The dubious role played by Th17-cells may favors immune response suppression and parasitic persistence in ADCL, while in MCL it contributes to an exacerbated immune response and parasite scarcity.
- Histopathological characteristics of cutaneous lesions caused by Leishmania Viannia panamensis in Panama(2018) GONZÁLEZ, Kadir; DIAZ, Rosendo; FERREIRA, Aurea F.; GARCÍA, Víctor; PAZ, Héctor; CALZADA, José E.; RUÍZ, Michelle; LAURENTI, Márcia; SALDAñA, AzaelABSTRACT Cutaneous leishmaniasis (CL) is an endemic disease in the Republic of Panama, caused by Leishmania (Viannia) parasites, whose most common clinical manifestation is the presence of ulcerated lesions on the skin. These lesions usually present a chronic inflammatory reaction, sometimes granulomatous, with the presence of lymphocytes, plasma cells and macrophages. This study describes the histopathological characteristics found in the skin lesions of patients with CL caused by Leishmania (V.) panamensis in Panama. We analyzed 49 skin biopsy samples from patients with clinical suspicion of CL, by molecular tests (PCR for subgenus Viannia and HSP-70) and by Hematoxylin-Eosin staining. Samples were characterized at the species level by PCR-HSP-70/RFLP. From the 49 samples studied, 46 (94%) were positive by PCR and were characterized as Leishmania (V.) panamensis. Of these, 48% were positive by Hematoxylin-Eosin staining with alterations being observed both, in the epidermis (85%) and in the dermis (100%) of skin biopsies. The inflammatory infiltrate was characterized according to histopathological patterns: lymphohistiocytic (50%), lymphoplasmacytic (61%) and granulomatous (46%) infiltration, being the combination of these patterns frequently found. The predominant histopathological characteristics observed in CL lesions caused by L. (V.) panamensis in Panama were: an intense inflammatory reaction in the dermis with a combination of lymphohistiocytic, lymphoplasmacytic and granulomatous presentation patterns and the presence of ulcers, acanthosis, exocytosis and spongiosis in the epidermis.
- 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.
- Therapeutic effect of ursolic acid in experimental visceral leishmaniasis(2017) JESUS, Jessica A.; FRAGOSO, Thais N.; YAMAMOTO, Eduardo S.; LAURENTI, Marcia D.; SILVA, Marcelo S.; FERREIRA, Aurea F.; LAGO, Joao Henrique G.; GOMES, Gabriela S.; PASSERO, Luiz Felipe D.Leishmaniasis is an important neglected tropical disease, affecting more than 12 million people worldwide. The available treatments are not well tolerated and present diverse side effects in patients, justifying the search for new therapeutic compounds. In the present study, the therapeutic potential and toxicity of ursolic acid (UA), isolated from the leaves of Baccharis uncinella C. DC. (Asteraceae), were evaluated in experimental visceral leishmaniasis. To evaluate the therapeutic potential of UA, hamsters infected with L. (L.) infantum were treated daily during 15 days with 1.0 or 2.0 mg UA/kg body weight, or with 5.0 mg amphotericin B/kg body weight by intraperitoneal route. Fifteen days after the last dose, the parasitism of the spleen and liver was stimated and the main histopathological alterations were recorded. The proliferation of splenic mononuclear cells was evaluated and IFN-gamma, IL-4, and IL-10 gene expressions were analyzed in spleen fragments. The toxicity of UA and amphotericin B were evaluated in healthy golden hamsters by histological analysis and biochemical parameters. Animals treated with UA had less parasites in the spleen and liver when compared with the infected control group, and they also showed preservation of white and red pulps, which correlate with a high rate of proliferation of splenic mononuclear cells, IFN-g mRNA and iNOS production. Moreover, animals treated with UA did not present alterations in the levels of AST, ALT, creatinine and urea. Taken together, these findings indicate that UA is an interesting natural compound that should be considered for the development of prototype drugs against visceral leishmaniasis. (C) 2016 The Authors.
- Histopathological features of skin lesions in patients affected by non-ulcerated or atypical cutaneous leishmaniasis in Honduras, Central America(2018) PACHECO, Carmen Maria Sandoval; FLORES, Gabriela Venicia Araujo; FERREIRA, Aurea Favero; OCHOA, Wilfredo Sosa; MATTA, Vania Lucia Ribeiro da; VALERIANO, Concepcion Zuniga; CORBETT, Carlos Eduardo Pereira; LAURENTI, Marcia DalastraIn Honduras visceral leishmaniasis and non-ulcerated or atypical cutaneous leishmaniasis (NUCL) are caused by the species Leishmania (L.) infantum chagasi. NUCL is the most common clinical form in the southern regions of the country, mainly affecting the young. In view of the lack of knowledge about the pathogenesis of the disease pattern caused by L. (L) infantum chagasi in individuals affected by NUCL, the aim of the present study was to describe in detail the histopathological features of the skin lesion caused by the parasite. Biopsies from human NUCL lesions with a positive parasitological diagnosis were collected and processed using standard histological techniques. Paraffin sections stained by haematoxylin and eosin were used to examine the histopathological alterations seen in the skin. The lesions varied between 3 and 5 mm, and the majority of the patients (60%) had a single lesion. Lesions were more frequently seen in females (65%), with an average age of 33.4 years. Microscopically, the skin lesions were characterized by mononuclear inflammatory infiltrate in the dermis composed of lymphocytes, macrophages and a few plasma cells. The intensity of the infiltration varied from discrete to intense. In both cases, the parasitic infection was discrete. Granulomas were present in 60% of cases and were associated with intense inflammation. The data revealed by the histopathological alterations in the skin of individuals affected by NUCL suggest activation of a cellular immune response that potentially controls parasite spreading.
- Therapeutic effect of ursolic acid in experimental visceral leishmaniasis (vol 7, pg 1, 2017)(2017) JESUS, Jessica A.; FRAGOSO, Thais N.; YAMAMOTO, Eduardo S.; LAURENTI, Marcia D.; SILVA, Marcelo S.; FERREIRA, Aurea F.; LAGO, Joao Henrique G.; SANTOS-GOMES, Gabriela; PASSERO, Luiz Felipe D.
- Role of antigen-presenting cells in non-ulcerated skin lesions caused by Leishmania (Leishmania) infantum chagasi(2023) PACHECO, Carmen M. Sandoval M.; FLORES, Gabriela V. Araujo V.; FERREIRA, Aurea F. F.; MATTA, Vania L. R. da; GOMES, Claudia M. de Castro M.; SOSA-OCHOA, Wilfredo H. H.; ZUNIGA, Concepcion; SILVEIRA, Fernando T. T.; CORBETT, Carlos E. P.; LAURENTI, Marcia D.In Central America, infection by Leishmania (Leishmania) infantum chagasi causes visceral leishmaniasis and non-ulcerated cutaneous leishmaniasis (NUCL). This work aimed to evaluate the participation of subpopulations of antigen-presenting cells in skin lesions of patients affected by NUCL through double-staining immunohistochemistry using cellular and intracellular markers. Twenty-three skin biopsies from patients affected by NUCL were used. Histological sections stained by HE were used for histopathological study. Immunohistochemical studies were performed using primary antibodies against Langerhans cells, dermal dendritic cells, T lymphocytes, and the cytokines IL-12, IFN-gamma, TNF-alpha, iNOS, and IL-10. The histopathological lesions were characterized by an inflammatory infiltrate, predominantly lymphohistiocytic, of variable intensity, with a diffuse arrangement associated with epithelioid granulomas and discreet parasitism. Double-staining immunohistochemistry showed higher participation of dendritic cells producing the proinflammatory cytokine IL-12 in relation to the other evaluated cytokines. Activation of the cellular immune response was marked by a higher density of CD8 Tc1-lymphocytes followed by CD4 Th1-lymphocytes producing mainly IFN-gamma. The data obtained in the present study suggest that antigen-presenting cells play an important role in the in situ immune response through the production of proinflammatory cytokines, directing the cellular immune response preferentially to the Th1 and Tc1 types in NUCL caused by L. (L.) infantum chagasi.
- Leishmania (L.) infantum chagasi isolated from skin lesions of patients affected by non-ulcerated cutaneous leishmaniasis lead to visceral lesion in hamsters(2023) FLORES, Gabriela V. Araujo; PACHECO, Carmen M. Sandoval; FERREIRA, Aurea F.; TOMOKANE, Thaise Yumie; NUNES, Juliana B.; COLOMBO, Fabio A.; SOSA-OCHOA, Wilfredo H.; ZUNIGA, Concepcion; SILVEIRA, Fernando T.; CORBETT, Carlos E. P.; LAURENTI, Marcia D.In Central America, Leishmania (L.) infantum chagasi infection causes visceral leishmaniasis (VL) and non -ulcerated cutaneous leishmaniasis (NUCL). The aim of the present study was to evaluate the course of an experimental infection in hamsters caused by L. (L.) infantum chagasi isolated from patients affected by NUCL compared with a strain isolated from a patient with VL. Stationary phase parasites in culture were inoculated through subcutaneous and intraperitoneal routes in hamsters. Following the post-infection times, a histopath-ological study, parasite load and cytokine determination in skin from the cutaneous inoculation site and viscera were performed. Animals subcutaneously infected with the different strains did not develop macroscopic lesions at the inoculation site, and the histopathological changes in the dermis were very slight. Regarding the histo-pathological study of the viscera, we observed the portal mononuclear inflammatory infiltrate, the presence of nodules in the hepatic parenchyma and the proliferation of macrophages in the spleen, which increased over the infection course. Overall, the parasite load in the liver and spleen and in the total IgG titres in the sera of infected hamster showed an increase with the time of infection, regardless of the route of inoculation. Regarding cellular immunity, we did not observe an increase or decrease in pro-and anti-inflammatory cytokines compared to the healthy control, except for IL-10, which was evident in the infected animals. The data showed that strains iso-lated from NUCL cause visceral lesions in the hamsters regardless of the route of inoculation, and they were similar to parasites isolated from VL humans.
- 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.