RESUMO
The majority of therapeutic strategies for mycosis require the protracted administration of antifungals, which can result in significant toxicities and have unacceptable failure rates. Hence, there is an urgent need for the development of improved therapeutic approaches, and monoclonal antibody-based drugs are potentially a powerful alternative to standard antifungals. To develop a broad antibody-like reagent against mycosis, wheat germ agglutinin (WGA) was linked to the effector Fc region of murine IgG2a. The resultant WGA-Fc displayed high affinity to purified chitin and bound efficiently to fungal cell walls, co-localizing with chitin, in patterns ranging from circular (Histoplasma capsulatum) to punctate (Cryptococcus neoformans) to labeling at the bud sites (Candida albicans and Saccharomyces cerevisiae). WGA-Fc directly inhibited fungal growth in standard cultures. WGA-Fc opsonization increased fungal phagocytosis, as well augmented the antifungal functions by macrophages. Prophylactic administration of WGA-Fc fully protected mice against H. capsulatum, correlating with a reduction in lung, spleen and liver fungal burdens. Administration of WGA-Fc also dramatically diminished pulmonary inflammation. Hence, the opsonic activity of WGA-Fc effectively modulates fungal cell recognition and promotes the elimination of fungal pathogens. Therefore, we propose WGA-Fc as a potential "pan-fungal" therapeutic that should be further developed for use against invasive mycoses.
Assuntos
Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Imunoconjugados/farmacologia , Infecções Fúngicas Invasivas/tratamento farmacológico , Proteínas Recombinantes de Fusão/farmacologia , Animais , Antifúngicos/uso terapêutico , Células CHO , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Quitina/metabolismo , Cricetulus , Modelos Animais de Doenças , Fungos/metabolismo , Humanos , Hibridomas , Imunoconjugados/genética , Imunoconjugados/uso terapêutico , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/farmacologia , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Imunoglobulina G/genética , Imunoglobulina G/farmacologia , Imunoglobulina G/uso terapêutico , Infecções Fúngicas Invasivas/microbiologia , Camundongos Endogâmicos C57BL , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/uso terapêutico , Aglutininas do Germe de Trigo/genética , Aglutininas do Germe de Trigo/farmacologia , Aglutininas do Germe de Trigo/uso terapêuticoRESUMO
The purpose of this study was to evaluate the hydrogenionic potential and electrical conductivity of Portland cements and MTA, as well as the amount of arsenic and calcium released from these materials. In Teflon molds, samples of each material were agitated and added to plastic flasks containing distilled water for 3, 24, 72 and 168 h. The results were analyzed with a Kruskal-Wallis non-parametric test for global comparisons and a Dunn-Tukey test for pairwise comparisons. The results revealed no significant differences in the pH of the materials (p > 0.05). The electrical conductivity of the cements were not statistically different (p > 0.05). White non-structural cement and MTA BIO released the largest amount of calcium ions into solution (p < 0.05), while arsenic release was insignificant in all of the materials (p > 0.05). The results indicated that the physico-chemical properties of Portland cements and MTA were similar. Furthermore, all materials produced an alkaline environment and can be considered safe for clinical use because arsenic was not released. The electrical conductivity and the amount of calcium ions released into solution increased over time.
Assuntos
Compostos de Alumínio/química , Arsênio/análise , Compostos de Cálcio/química , Cálcio/análise , Cimentos Dentários/química , Óxidos/química , Materiais Restauradores do Canal Radicular/química , Silicatos/química , Combinação de Medicamentos , Condutividade Elétrica , Concentração de Íons de Hidrogênio , Teste de Materiais , Espectrofotometria , Fatores de TempoRESUMO
The purpose of this study was to evaluate the hydrogenionic potential and electrical conductivity of Portland cements and MTA, as well as the amount of arsenic and calcium released from these materials. In Teflon molds, samples of each material were agitated and added to plastic flasks containing distilled water for 3, 24, 72 and 168 h. The results were analyzed with a Kruskal-Wallis non-parametric test for global comparisons and a Dunn-Tukey test for pairwise comparisons. The results revealed no significant differences in the pH of the materials (p > 0.05). The electrical conductivity of the cements were not statistically different (p > 0.05). White non-structural cement and MTA BIO released the largest amount of calcium ions into solution (p < 0.05), while arsenic release was insignificant in all of the materials (p > 0.05). The results indicated that the physico-chemical properties of Portland cements and MTA were similar. Furthermore, all materials produced an alkaline environment and can be considered safe for clinical use because arsenic was not released. The electrical conductivity and the amount of calcium ions released into solution increased over time.