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Papers by Claudia Bitencourt

European Journal of Pharmaceutical Sciences, 2009

In the last decades, the incidence of histoplasmosis, a pulmonary fungal disease caused by Histop... more In the last decades, the incidence of histoplasmosis, a pulmonary fungal disease caused by Histoplasma capsulatum, has increased worldwide. In this context, vaccines for the prevention of this infection or therapies are necessary. Cell-free antigens (CFAgs) from H. capsulatum when administered for murine immunization purposes are able to confer protection and control of the infection, since they activate cellular immunity. However, the most of vaccination procedures need several antigens administrations and immunoadjuvants, which are not approved for use in humans. The aim of this study was to develop and characterize a vaccination approach using biodegradable PLGA microspheres (MS) that could allow the controlled and/or sustained release of the encapsulated antigens from H. capsulatum. CFAgs-loaded MS presented a size less than 10 m, were marked engulfed by bone marrow-derived macrophages (BMDM) and induced the nitric oxide (NO) and tumor necrosis factor-␣ (TNF-␣) production by these cells. Our data show that CFAgs-loaded MS induce cell activation, suggesting an immunostimulant effect to be further investigated during immunization procedures. CFAgsloaded MS present potential to be used as vaccine in order to confer protection against H. capsulatum infection.

European Journal of Pharmaceutical Sciences

Because of the potential protective role of leukotrienes (LTs) in histoplasmosis and the therapeu... more Because of the potential protective role of leukotrienes (LTs) in histoplasmosis and the therapeutic and prophylactic effects of cell-free antigens from Histoplasma capsulatum (CFAgs), the aim of this study was to develop and characterise biodegradable LTB 4 /CFAgs-loaded microspheres (MS) that could promote cellular activation for future immunisation purposes. LTB 4 /CFAgs-loaded MS that were developed through a double emulsion/extraction process were characterised according to their size, zeta potential, morphology, entrapment efficiency and in vitro release kinetics. We evaluated the uptake of LTB 4 /CFAgsloaded MS by bone marrow derived-macrophages (BMDM). The TNF-a and chemokines, and nitrite production, in the supernatant of BMDM cultures were analysed by enzyme-linked immunosorbent assay (ELISA) and Griess reaction, respectively. We found an instantaneous release of CFAgs and a prolonged release of LTB 4 from the poly-(D,L-lactide-co-glycolide) (PLGA) MS. The microencapsulation process did not alter the zeta potential nor the spherical morphology of the MS. The appropriate size of the LTB 4 / CFAgs-loaded MS (smaller than 10 lm) enabled the efficient uptake by BMDM and also induced TNFa, CXCL1/KC, CCL2/MCP-1, CCL5/RANTES and nitrite oxide release by these cells. In conclusion, the biodegradable LTB 4 /CFAgs-loaded MS were able to efficiently activate murine BMDM and thereby have the potential to be used in an effective vaccine against H. capsulatum infection.

Clinical Immunology, 2010

Ischemic heart disease, and the development of secondary myocardial events such as myocardial inf... more Ischemic heart disease, and the development of secondary myocardial events such as myocardial infarction, remains the world's leading cause of death. The present study aimed to investigate the potential cooperative cardioprotective effect of leukotriene B4 (LTB4) and platelet-activating factor (PAF) receptors blockade in a model of transient myocardial ischemia in mice. To this aim, C57BL/6 mice were pretreated orally 2 hours before left anterior descending coronary artery ligation (LAD) with either vehicle (water), SR27,417 (0.3 mg/kg), BIIL284 (0.01 mg/kg) or a combined administration of SR27,417 and BIIL284 (n = 5-7). Ligation was made 1 mm above the origin of the second and third branch of the LAD to induce regional myocardial ischemia for a period of 30 minutes followed by 48 hours of reperfusion. Prior to sacrifice, LAD was reoccluded and 5% Evans blue dye was perfused retrogradly to delineate the area-at-risk (AAR). The total left ventricle (LV) area, AAR and infarct area (IA) were determined following 1% triphenyltetrazolium chloride staining. Our results show that a transient myocardial ischemia elicited a 31 ± 1% infarct area (IA/LV). Whereas SR, administered alone, did not exert any significant cardioprotective effect (35 ± 2%), BIIL significantly reduced LV infarct area by 55% (P b 0.01). A cooperative effect of combined drug administration was observed, inasmuch as the IA/LV was reduced by 81% (P b 0.01) by pretreating mice with SR and BIIL. Our results support the potential application of combined LTB4 and PAF receptor antagonists against myocardial injury elicited following transient myocardial ischemia.

Fibrogenesis & Tissue Repair, 2011

Hyaluronidases (HYALs) comprise a group of enzymes that degrade hyaluronic acid (HA). In this rep... more Hyaluronidases (HYALs) comprise a group of enzymes that degrade hyaluronic acid (HA). In this report, we reveal that a single intranasal inoculation of HYAL induces an increase in mononuclear cells within the bronchoalveolar space demonstrating a mesenchymal-like phenotype, expressing stem cell antigen-1 (SCA-1), CD44 and CD73 but not CD34, CD45, CD3, CD4, CD8 or CD19. This influx of mesenchymal stem cell (MSC)-like cells was dependent on leukotriene production within the lung parenchyma. These findings prompted experiments demonstrating that HYAL treatment potently blocked bleomycin-induced lung injury and fibrosis while decreasing transforming growth factor (TGF)-β production and collagen deposition. These data suggest that HYAL is a novel and promising tool to use autologous MSC-like cells in the treatment of pulmonary fibrosis.

Toxicon, 2011

Scorpion envenomation induces a systemic immune response, and neurotoxins of venom act on specifi... more Scorpion envenomation induces a systemic immune response, and neurotoxins of venom act on specific ion channels, modulating neurotransmitter release or activity. However, little is known about the immunomodulatory effects of crude venom from scorpion Tityus serrulatus (TsV) or its toxins (Ts1, Ts2 and Ts6) in combination with lipopolysaccharide (LPS). To investigate the immunomodulatory effects of TsV and its toxins (Ts1, Ts2 and Ts6), J774.1 cells were stimulated with different concentrations (25, 50 and 100 mg/mL) of venom or toxins pre-stimulated or not with LPS (0.5 mg/mL). Macrophage cytotoxicity was assessed, and nitric oxide (NO) and cytokine production were analyzed utilizing the culture supernatants. TsV and its toxins did not produce cytotoxic effects. Depending on the concentrations used, TsV, Ts1 and Ts6 stimulated the production of NO, interleukin (IL)-6 and tumor necrosis factor (TNF)-a in J774.1 cells, which were enhanced under LPS co-stimulation. However, LPS þ Ts2 inhibited NO, IL-6 and TNF-a production, and Ts2 alone stimulated the production of IL-10, suggesting an anti-inflammatory activity for this toxin. Our findings are important for the basic understanding of the mechanisms involved in macrophage activation following envenomation; additionally, these findings may contribute to the discovery of new therapeutic compounds to treat immune-mediated diseases.

Com este artigo, busca-se analisar o desenvolvimento de competências organizacionais nos diferent... more Com este artigo, busca-se analisar o desenvolvimento de competências organizacionais nos diferentes negócios de uma empresa do setor calçadista do RS e a sua articulação com as práticas de gestão, com base na sua história. Entende-se que as competências devem ser compreendidas sob uma perspectiva dinâmica, pois as mudanças são constantes no mercado. Nesse contexto, a trajetória de uma organização pode ser considerada como um dos pontos fundamentais para o entendimento da dinâmica organizacional, pois a análise de sua história gera informações que explicam as mudanças realizadas e as estratégias planejadas ao longo do tempo. Trata-se de uma pesquisa qualitativa, de natureza exploratória e descritiva, desenvolvida mediante o método de estudo de caso no Grupo Paquetá. Os dados foram coletados por meio de entrevistas semiestruturadas com diretores e gerentes (22 depoimentos) e de análise documental. Os principais resultados encontrados revelam que o Grupo Paquetá possui as competências distintivas que se referem às capacidades de gestão e técnica. Essas competências distintivas originaram as competências intermediárias/funcionais que têm como base os três elementos da competência organizacional do Grupo: inovação e tecnologia, pessoas, estrutura e processos consolidados ao longo da trajetória da empresa.

SSRN Electronic Journal, 2001