RESUMO
A mouse model of cutaneous leishmaniasis (CL) by Leishmania (Viannia) panamensis (L(V)p) that reproduces the characteristics of the human disease remains elusive. Here we report the development of a CL model that uses a mouse-adapted L(V)p isolate to reproducibly induce a dermal disease with a remarkable similarity to human CL. BALB/c mice infected intradermally in the ear with 105 stationary UA-946 L(V)p promastigotes develop a progressive cutaneous disease that exhibits the typical ulcerated lesions with indurated borders observed in CL patients. Although most of parasites in the inoculum die within the first week of infection, the survivors vigorously multiply at the infection site during the following weeks, paralleling disease appearance and aggravation. Regional lymphadenopathy as well as lymphatic dissemination of parasites to draining lymph nodes (dLN) was evidenced early after infection. Viable parasites were also isolated from spleen at later timepoints indicating systemic parasitic dissemination, but, strikingly, no signs of systemic disease were observed. Increasing numbers of myeloid cells and T lymphocytes producing IFNγ and IL-4 were observed in the dLN as disease progressed. A mixed adaptive L(V)p-specific T cell-mediated response was induced, since ex vivo recall experiments using dLN cells and splenocytes revealed the production of type 1 (IFNγ, IL-2), type 2 (IL-4, IL-13), regulatory (IL-10), and inflammatory (GM-CSF, IL-3) cytokines. Humoral adaptive response was characterized by early production of IgG1- followed by IgG2a-type of L(V)p-specific antibodies. IFNγ/IL-4 and IgG2a/IgG1 ratios indicated that the initial non-protective Th2 response was redirected toward a protective Th1 response. In situ studies revealed a profuse recruitment of myeloid cells and of IFNγ- and IL-4-producing T lymphocytes to the site of infection, and the typical histopathological changes induced by dermotropic Leishmania species. Evidence that this model is suitable to investigate pharmacological and immunomodulatory interventions, as well as for antigen discovery and vaccine development, is also presented. Altogether, these results support the validity and utility of this novel mouse model to study the pathogenesis, immunity, and therapeutics of L(V)p infections.
RESUMO
Insulin-expressing islet-like cell clusters derived from precursor cells have significant potential in the treatment of type-I diabetes. Given that cluster size and uniformity are known to influence islet cell behavior, the ability to effectively control these parameters could find applications in the development of anti-diabetic therapies. In this work, we combined micro and nanofabrication techniques to build a biodegradable platform capable of supporting the formation of islet-like structures from pancreatic precursors. Soft lithography and electrospinning were used to create arrays of microwells (150-500 µm diameter) structurally interfaced with a porous sheet of micro/nanoscale polyblend fibers (~0.5-10 µm in cross-sectional size), upon which human pancreatic ductal epithelial cells anchored and assembled into insulin-expressing 3D clusters. The microwells effectively regulated the spatial distribution of the cells on the platform, as well as cluster size, shape and homogeneity. Average cluster cross-sectional area (~14000-17500 µm(2)) varied in proportion to the microwell dimensions, and mean circularity values remained above 0.7 for all microwell sizes. In comparison, clustering on control surfaces (fibers without microwells or tissue culture plastic) resulted in irregularly shaped/sized cell aggregates. Immunoreactivity for insulin, C-peptide and glucagon was detected on both the platform and control surfaces; however, intracellular levels of C-peptide/cell were ~60 % higher on the platform.
Assuntos
Técnicas de Cultura de Células/instrumentação , Regulação da Expressão Gênica , Insulina/metabolismo , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Microtecnologia/instrumentação , Nanotecnologia/instrumentação , HumanosRESUMO
La periodontitis es una enfermedad infec-ciosa caracterizada por un conjunto de alte-raciones que afectan los tejidos soporte de las piezas dentales. Su etiología por muchos años ha sido considerada básicamente bac-teriana. Estudios recientes han analizado la presencia de algunos miembros de la fami-lia de los virus de la familia herpesviridae en el periodonto y el posible efecto que su infección podría ocasionar en él. Esta presentación de un caso clínico contribuye a la evidencia que vincula a algunos de los herpes virus en la etiopatogénesis de la enfermedad periodontal...(AU)
Periodontitis is an infectious disease cha-racterized by a variety of alterations, affec-ting tooth supporting tissues. For many years, its aetiology has been considered basically of bacterial origin. Recent studies have analyzed the occurrence of herpes vi-ruses in the periodontum and their possible effects to cause periodontitis. This case report provides evidence that link herpes viruses to the development of certain types of periodontitis...(AU)
Assuntos
Humanos , Doenças Periodontais , Periodontia , Simplexvirus , Medicina Bucal , Periodontia/classificação , Odontologia , Periodontite Crônica , Herpes ZosterRESUMO
Introducción. La leishmaniaisis es una enfermedad encontrada en focos naturales de infección donde están presentes insectos vectores y mamíferos reservorios de Leishmania. Objetivo. Registrar por primera vez la presencia de Leishmania (Leishmania) mexicana Biagi, 1953, en el corregimiento de San Matías, municipio de Gómez Plata, departamento de Antioquia. Materiales y métodos. La especie fue aislada de un paciente con leishmaniasis cutánea localizada e identificada por la técnica de Inmunofluorescencia utilizando anticuerpos monoclonales específicos de especie y electroforesis de enzimas . Resultados y conclusión. Su perfil isoenzimático similar al de las cepas de referencia L. (L.) mexicana (MNCY/BZ/62/M379) y L. (L.) mexicana MHOM/BE/82/BEL21), permitió concluír que la especie aislada del paciente es L. (L.) mexicana.
Introduction. Leishmaniasis is found in natural foci of infection where both sand fly vectors and mammalian reservoirs of Leishmania are present. Objective. To report for the first time the presence of Leishmania (Leishmania) mexicana Biagi, 1953, in the village of San Matías, municipality of Gomez Plata, Department of Antioquia. Materials and methods. The parasite was isolated from a patient with localized cutaneous leishmaniasis and was identified by the immunofluorescence technique using specific monoclonal antibodies against L. mexicana species and isoenzyme electrophoresis. Results and conclusion. The isoenzymatic profiles of the reference strains L. (L.) mexicana (MNCY/BZ/62/M379) and L. (L.) mexicana (MHOM/BE/82/BEL21) were similar to that of the isolate recovered from the patient, allowing us to classify it as L. (L.) mexicana.
Assuntos
Leishmania , Leishmaniose , ColômbiaRESUMO
INTRODUCTION: Leishmaniasis is found in natural foci of infection where both sand fly vectors and mammalian reservoirs of Leishmania are present. OBJECTIVE: To report for the first time the presence of Leishmania (Leishmania) mexicana Biagi, 1953, in the village of San Matías, municipality of Gomez Plata, Department of Antioquia. MATERIALS AND METHODS: The parasite was isolated from a patient with localized cutaneous leishmaniasis and was identified by the immunofluorescence technique using specific monoclonal antibodies against L. mexicana species and isoenzyme electrophoresis. RESULTS AND CONCLUSION: The isoenzymatic profiles of the reference strains L. (L.) mexicana (MNCY/BZ/62/M379) and L. (L.) mexicana (MHOM/BE/82/BEL21) were similar to that of the isolate recovered from the patient, allowing us to classify it as L. (L.) mexicana.
