EFAR - Escola de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/451
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O curso de Farmácia em Ouro Preto foi criado em 1839, sendo a mais antiga Escola de Farmácia da América Latina.
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Item Cell immune response in mice skin stimulated with different adjuvants by intradermal route.(2022) Mathias, Fernando Augusto Siqueira; Cardoso, Jamille Mirelle de Oliveira; Reis, Levi Eduardo Soares; Souza, Juliana Vitoriano de; Moreira, Nádia das Dores; Ostolin, Thais Lopes Valentim Di Paschoale; Brito, Rory Cristiane Fortes de; Soares, Rodrigo Dian de Oliveira Aguiar; Vieira, Paula Melo de Abreu; Carneiro, Cláudia Martins; Roatt, Bruno Mendes; Reis, Alexandre BarbosaAdjuvants act in the innate immunity and, when combined to vaccine antigens, can produce a more intense response, improving the antigen presentation, directing the immune system, excellent for new vaccine formulations. This study evaluated the use of the intradermal route and the immune response triggered by a single dose of the adjuvants Aluminum Hydroxide (Al(OH)3 ), Montanide Pet Gel A (MPGA), Glucopyranosyl Lipid A Stable Emulsion (GLA-SE), and Resiquimod (R-848) in the mice skin. As control mice received sterile saline. MPGA and GLA-SE led to cell recruitment when compared with control group, with intense presence of neutrophils in first 12 hours, replaced by macrophages after 168 hours. R-848 and Al(OH)3 showed similar cell recruitment profiles. Regarding cytokine production, groups that received MPGA and GLA-SE produced high levels of IL-6, TNF-α, and IFN-γ. R-848 and Al(OH)3 groups displayed similar profile of cytokine production only at the first hour. Our results suggest that the intradermal route is efficient inducing immune system activation and GLA-SE was promising adjuvants for a type 1 immune response vaccine.Item Kinetics of phenotypic and functional changes in mouse models of sponge implants : rational selection to optimize protocols for specific biomolecules screening purposes.(2020) Lanna, Mariana Ferreira; Resende, Lucilene Aparecida; Soares, Rodrigo Dian de Oliveira Aguiar; Miranda, Marina Barcelos de; Mendonça, Ludmila Zanandreis de; Melo Júnior, Otoni Alves de Oliveira; Mariano, Reysla Maria da Silveira; Leite, Jaqueline Costa; Silveira, Patricia; Oliveira, Rodrigo Corrêa de; Dutra, Walderez Ornelas; Reis, Alexandre Barbosa; Martins Filho, Olindo Assis; Moura, Sandra Aparecida Lima de; Lemos, Denise da Silveira; Giunchetti, Rodolfo CordeiroThe sponge implant has been applied as an important in vivo model for the study of inflammatory processes as it induces the migration, proliferation, and accumulation of inflammatory cells, angiogenesis, and extracellular matrix deposition in its trabeculae. The characterization of immune events in sponge implants would be useful in identifying the immunological events that could support the selection of an appropriate experimental model (mouse strain) and time post-implant analysis in optimized protocols for novel applications of this model such as in biomolecules screening. Here, the changes in histological/morphometric, immunophenotypic and functional features of infiltrating leukocytes (LEU) were assessed in sponge implants for Swiss, BALB/c, and C57BL/6 mice. A gradual increase of fibrovascular stroma and a progressive decrease in LEU infiltration, mainly composed of polymorphonuclear cells with progressive shift toward mononuclear cells at late time-points were observed over time. Usually, Swiss mice presented a more prominent immune response with late mixed pattern (pro-inflammatory/anti-inflammatory: IL-2/IFN-γ/IL-4/IL-10/IL-17) of cytokine production. While BALB/c mice showed an early activation of the innate response with a controlled cytokine profile (low inflammatory potential), C57BL/6 mice presented a typical early pro-inflammatory (IL-6/TNF/IFN-γ) response with persistent neutrophilic involvement. A rational selection of the ideal time-point/mouse-lineage would avoid bias or tendentious results. Criteria such as low number of increased biomarkers, no recruitment of cytotoxic response, minor cytokine production, and lower biomarker connectivity (described as biomarker signature analysis and network analysis) guided the choice of the best time-point for each model (Day5/Swiss; Day7/BALB/c; Day6/C57BL/6) with wide application for screening purposes, such as identification of therapeutic biomolecules, selection of antigens/adjuvants, and follow-up of innate and adaptive immune response to vaccines candidates.Item Effect on cellular recruitment and the innate immune response by combining saponin, monophosphoryl lipid-A and incomplete freund’s adjuvant with Leishmania (Viannia) braziliensis antigens for a vaccine formulation.(2019) Souza, Juliana Vitoriano de; Mathias, Fernando Augusto Siqueira; Moreira, Nádia das Dores; Soares, Rodrigo Dian de Oliveira Aguiar; Vieira, Paula Melo de Abreu; Carvalho, Andréa Teixeira de; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Brito, Rory Cristiane Fortes de; Fujiwara, Ricardo Toshio; Roatt, Bruno Mendes; Melo, Maria Norma; Reis, Alexandre BarbosaThe poor immunogenicity displayed by some antigens has encouraged the development of strategies to improve the immune response and safety of vaccine candidates, resulting in an intense search for substances that potentiate vaccine response. Adjuvants have these properties helping vaccine candidates to induce a strong, durable, and fast immune response. In this study, we evaluated the specific immune response of adjuvants alone, Saponin (SAP), Incomplete Freund’s Adjuvant (IFA) and Monophosphoryl lipid-A SE (MPL-SE ) and in combination with total antigen of L. braziliensis (LB): LBSAP, LBIFA and LBMPL. The specific immune response induced by these compositions demonstrated that they were powerfully immunogenic, increasing cellular infiltration in the skin. Draining lymph nodes cultures showed that LBIFA and LBMPL have higher ability to increase the capacity of APCs to present antigens, with increased frequency of CD11c+ CD86+ cells. SAP, MPL, LBSAP, LBIFA and LBMPL could activate lymphocytes increasing expression of CD69 and CD25. LBSAP group was an excellent inducer of pro-inflammatory cytokines at 24 h. At 48 h, higher cytokines production was observed in IFA, LBIFA, MPL and LBMPL groups. Our data demonstrate that LBSAP and LBMPL are potential formulations to be tested in other experimental models. Also, the data obtained could expand the knowledge about immune response after sensitization and also contribute to the development of safe, immunogenic and effective vaccines.Item Multicomponent LBSap vaccine displays immunological and parasitological profiles similar to those of Leish-Tec® and Leishmune® vaccines against visceral leishmaniasis.(2016) Mendonça, Ludmila Zanandreis de; Resende, Lucilene Aparecida; Lanna, Mariana Ferreira; Soares, Rodrigo Dian de Oliveira Aguiar; Roatt, Bruno Mendes; Castro, Renata Alves de Oliveira e; Batista, Maurício Azevedo; Lemos, Denise da Silveira; Estanislau, Juliana de Assis Silva Gomes; Fujiwara, Ricardo Toshio; Rezende, Simone Aparecida; Martins Filho, Olindo Assis; Oliveira, Rodrigo Corrêa de; Dutra, Walderez Ornelas; Reis, Alexandre Barbosa; Giunchetti, Rodolfo CordeiroBackground: In past years, many researchers have sought canine visceral leishmaniasis (CVL) prevention through the characterization of Leishmania antigens as vaccine candidates. Despite these efforts, there is still no efficient vaccine for CVL control. Methods: In the present study, we performed a pre-clinical vaccine trial using BALB/c mice to compare the effects of the multicomponent LBSap vaccine with those of Leish-Tec® and Leishmune®. Blood was collected to determine the frequency of peripheral blood cells and to evaluate hematologic and immunophenotypic parameters. Liver and spleen samples were collected for parasitological quantification, and spleen samples were used to access the cytokine profile. Results: When measuring total IgG and IgG1 anti-Leishmania levels after the third vaccination and L. infantum challenge, it was evident that all vaccines were able to induce humoral immune response. Regarding the innate immune response, increased levels of NK CD3-CD49+ cells were the hallmark of all vaccinated groups, whereas only the Leish-Tec® group displayed a high frequency of CD14+ monocytes after L. infantum challenge. Moreover, CD3+CD4+ T cells were the main circulating lymphocytes induced after L. infantum challenge with all evaluated vaccines. Importantly, after L. infantum challenge, splenocytes from the Leishmune® vaccine produced high levels of IL-2, whereas a prominent type 1 immune response was the hallmark of the LBSap vaccine, which presented high levels of IL-2, IL-6, TNF-α, and IFN-γ. The efficacy analysis using real-time polymerase chain reaction demonstrated a reduction in the parasitism in the spleen (Leishmune®: 64 %; LBSap: 42 %; and Leish-Tec®: 36 %) and liver (Leishmune®: 71 %; LBSap: 62 %; and Leish-Tec®: 48 %). Conclusions: The dataset led to the conclusion that the LBSap vaccination was able to induce immune and efficacy profiles comparable with those of commercial vaccines, thus demonstrating its potential as a promising vaccine candidate for visceral leishmaniasis control.Item Immunological profile of resistance and susceptibility innaturally infected dogs by Leishmania infantum.(2014) Leal, Gleisiane Gomes de Almeida; Roatt, Bruno Mendes; Soares, Rodrigo Dian de Oliveira Aguiar; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Carvalho, Andréa Teixeira de; Martins Filho, Olindo Assis; Francisco, Amanda Fortes; Cardoso, Jamille Mirelle de Oliveira; Mathias, Fernando Augusto Siqueira; Oliveira, Rodrigo Corrêa de; Carneiro, Mariângela; Vital, Wendel Coura; Reis, Alexandre BarbosaVisceral leishmaniasis has a great impact on public health, and dogs are considered the maindomestic reservoir of Leishmania infantum, the causal parasite. In this study, 159 animalsnaturally infected by L. infantum from an endemic area of Brazil were evaluated through ananalysis of cellular responses, using flow cytometry, and of the hematological parameters.The results confirmed that disease progression is associated with anemia and reductionsin eosinophils, monocytes and lymphocytes. The investigation of the immune response,based on the immunophenotypic profile of peripheral blood, showed declines in the abso-lute numbers of T lymphocytes CD5+and their subsets (CD4+and CD8+) and a drop of Blymphocytes in asymptomatic seropositive (AD-II) and symptomatic seropositive (SD) dogs.Neutrophils, when stimulated with soluble antigen of L. infantum, showed higher synthesisof interferon (IFN)- _+in AD-II and SD groups, with decreased production of interleukinItem Cytokine and nitric oxide patterns in dogs immunized with LBSap vaccine, before and after experimental challenge with Leishmania chagasi plus saliva of Lutzomyia longipalpis.(2013) Resende, Lucilene Aparecida; Roatt, Bruno Mendes; Soares, Rodrigo Dian de Oliveira Aguiar; Viana, Kelvinson Fernandes; Mendonça, Ludmila Zanandreis de; Lanna, Mariana Ferreira; Lemos, Denise da Silveira; Oliveira, Rodrigo Corrêa de; Martins Filho, Olindo Assis; Fujiwara, Ricardo Toshio; Carneiro, Cláudia Martins; Reis, Alexandre Barbosa; Giunchetti, Rodolfo CordeiroIn the studies presented here, dogs were vaccinated against Leishmania (Leishmania) cha-gasi challenge infection using a preparation of Leishmania braziliensis promastigote proteinsand saponin as adjuvant (LBSap). Vaccination with LBSap induced a prominent type 1immune response that was characterized by increased levels of interleukin (IL-) 12 andinterferon gamma (IFN- _) production by peripheral blood mononuclear cells (PBMC) uponstimulation with soluble vaccine antigen. Importantly, results showed that this type ofresponsiveness was sustained after challenge infection; at day 90 and 885 after L. chagasichallenge infection, PBMCs from LBSap vaccinated dogs produced more IL-12, IFN- _ andconcomitant nitric oxide (NO) when stimulated with Leishmania antigens as comparedto PBMCs from respective control groups (saponin, LB- treated, or non-treated controldogs). Moreover, transforming growth factor (TGF)- _ decreased in the supernatant of SLcA-stimulated PBMCs in the LBSap group at 90 days. Bone marrow parasitological analysisrevealed decreased frequency of parasitism in the presence of vaccine antigen. It is con-cluded that vaccination of dogs with LBSap vaccine induced a long-lasting type 1 immuneresponse against L. chagasi challenge infection.Item Analysis of the cytokine profile in spleen cells from dogs naturally infected by Leishmania chagasi.(2007) Lage, Ramon Silva; Oliveira, Guilherme Corrêa de; Busek, Solange Cristina Uber; Guerra, Luanda Liboreiro; Giunchetti, Rodolfo Cordeiro; Oliveira, Rodrigo Corrêa de; Reis, Alexandre BarbosaRecent studies suggest that asymptomatic dogs infected with canine visceral leishmaniasis (CVL) develop a Th1 immunological profile whilst oligosymptomatic and symptomatic CVL-infected animals present a Th2 profile. In the present study, an RT-PCR method has been standardised and employed to evaluate the frequency and the semi-quantitative level of expression of the cytokines IL-4, IL-10, IL-12, INF- g and TNF- a in splenocytes of 30 dogs naturally infected with Leishmania chagasiand of 7 non-infected dogs (NID). An increase in the level of expression of IL-12 ( p = 0.059) was detected in all CVL-infected dogs compared with NID. In dogs exhibiting high parasitism, the frequency of expression of IL-10 was higher ( p = 0.011) than in animals presenting low parasitism or medium parasitism (MP) and in NID animals, whilst the level of expression of IL-10 was higher (p = 0.0094) than in animals exhibiting MP and in the NID group. Positive correlations between the levels of expression of IL-10 with respect to the progression of the disease (IL-10: r = 0.3510; p = 0.0337) and the levels of expression of IL-10 and INF- g increase in parasitism (IL-10: r = 0.3428; p = 0.0438 and INF- g: r = 0.4690; p = 0.0045) were observed. Such data suggest that CVL is marked by a balanced production of Th1 and Th2 cytokines, with a predominant accumulation of IL-10 as a consequence of an increase in parasitic load and progression of the disease, and INF- g was related with the increase in parasitic load.Item T-cell-derived cytokines, nitric oxide production by peripheral blood monocytes and seric anti- Leishmania (Leishmania) chagasi IgG subclass patterns following immunization against canine visceral leishmaniasis using Leishvaccine and Leishmune ®.(2009) Araújo, Márcio Sobreira Silva; Andrade, Renata Aline de; Avelar, Renato Sathler; Carvalho, Andréa Teixeira de; Andrade, Mariléia Chaves; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Malaquias, Luiz Cosme Cotta; Melo, Maria Norma; Martins Filho, Olindo AssisIt is generally accepted that distinct cytokine expression by the cellular immune response plays a critica role during the outcome of experimental as well as natural canine visceral Leishmaniasis (CVL). Despite the fact that immunoprophylaxis of CVL has become an important control strategy and protective immunity has been reported upon immunization with whole as well as purifiedLeishmaniaantigens, the cytokine profile of T-cells triggered by anti-CVL vaccines still remain to be determined. Herein, we have developed a cross-sectional analysis of German Shepherd dogs submitted to vaccination protocols with Leishvaccine (n = 6) and Leishmune ® (n = 6). Our data identified distinct immunological profiles elicited by Leishvaccine and Leishmune ® , with the Leishvaccine triggering a mixed, IFN- and IL-4, cytokine pattern in addition to high levels of anti- LeishmaniaIgG1, whereas the Leishmune ® induced an immunological pattern char- acterized by enhanced levels of IFN- , NO and anti- Leishmania chagasi IgG2. It was important to notice that despite the distinct immunological patterns triggered by Leishvaccine and Leishmune ® , the ability of both immunobiologicals to activate T-cell-derived IFN- synthesis further suggesting their immunogenic potential against CVL. These findings added support to our hypothesis that both antigenic composition (whole antigen in Leishvaccine versus purified antigen in Leishmune ® ) as well as the adjuvant nature (BGC and saponin) used for the vaccine formulation may count for the distinct activation pattern observed.Item Cytokine and transcription factor profiles in the skin of dogs naturally infected by Leishmania (Leishmania) chagasi presenting distinct cutaneous parasite density and clinical status.(2011) Souza, Daniel Menezes; Oliveira, Rodrigo Corrêa de; Cota, Renata Guerra de Sá; Giunchetti, Rodolfo Cordeiro; Carvalho, Andréa Teixeira de; Martins Filho, Olindo Assis; Oliveira, Guilherme Corrêa de; Reis, Alexandre BarbosaThe immune response in the skin of dogs infected withLeishmania chagasi and its asso-ciation with distinct levels of tissue parasitism and clinical progression of canine visceral leishmaniasis (CVL) are poorly understood and limited studies are available. A detailed analysis of the profiles of cytokines (IFN- , IL-4, IL-5, IL-10, IL-12, IL-13, TGF- 1 and TNF- ) and transcription factors (T-bet, GATA-3 and FOXP3) in the skin of 35 naturally infected dogs was carried out using real-time PCR alongside determinations of skin parasite density and the clinical status of CVL. A mixed cytokine profile with high levels of expression of IFN- , TNF- and IL-13 was determined in asymptomatic dogs. Additionally, the levels of transcription factors GATA-3 and FOXP3 were correlated with the asymptomatic disease. A mixed cytokine profile was also observed during active CVL. Moreover, high levels of IL-10 and TGF- 1, concomitant with the low expression of IL-12, may represent a key condition that allows persistence of parasite replication in the skin. The results obtained indicate that in asymptomatic disease or lower levels of skin parasite density, a mixed inflammatory, regulatory immune response profile may be of major relevance for both the maintenance of the clinical status of the dogs as well as for parasite persistence and replication at low levels.