Use of Tc-rCRP as a target for lytic antibody titration after experimental Trypanosoma cruzi infection.

Experimental Chagas disease has been used as a model to identify several host/parasite interaction factors involved in immune responses to Trypanosoma cruzi infection. One of the factors inherent to this parasite is the complement regulatory protein (Tc-CRP), a major epitope that induces production of lytic antibodies during T. cruzi infections. Previous studies have evaluated the function of Tc-CRP as an antigenic marker via ELISAs, which demonstrated high sensitivity and specificity when compared to other methods. Therefore, this study aimed to assess and compare the levels of lytic antibodies induced by this protein following experimental infection using different T. cruzi strains. Our results demonstrated that infections induced by strains isolated from vectors resulted in subpatent parasitaemia and low reactivity, as assessed by Tc-rCRP ELISAs. On the other hand, mice inoculated with T. cruzi strains isolated from patients developed patent parasitaemia, and presented elevated lytic antibodies titres, as measured by Tc-rCRP ELISA. In addition, comparison between different mouse lineages demonstrated that Balb/c mice were more reactive than C57BL/6 mice in almost all types of infections, except those infected by the AQ-4 strain. Parasites from the Hel strain generated the greatest lytic antibody response in all evaluated models. Therefore, application of sensitive techniques for monitoring immune responses would enable us to establish growth curves for lytic antibodies during the course of the infection, and allow us to discriminate between T. cruzi strains that originate from different hosts.

Correlation between the virulence of T. cruzi strains, complement regulatory protein expression levels, and the ability to elicit lytic antibody production.

Trypanosoma cruzi trypomastigotes are able to resist lysis via the complement system, which involves many surface proteins including the complement regulatory protein (CRP). To examine the diversity in CRP recognition among strains of T. cruzi, the expression levels of the translated protein on trypomastigote surfaces were analyzed by flow cytometry, and associations between protein expression and the biological behavior of these strains, especially the ability to induce lytic antibodies in animal models, were assessed. The highly virulent T. cruzi strains Ninoa, INC-5, and Colombiana and the less virulent strains CL-Brener, LGB-231, and JG were used in the experiments. An expression profile analysis showed that the Colombiana and INC-5 strains have higher translated protein levels and induced higher production of antibodies in mice than the other strains. Our results indicated that there are differences in the surface expression of CRP between parasite strains, with a tendency for the most virulent strains to have higher expression levels. Combined, these results contribute to a better understanding of CRP functions and the complexity of host-parasite interactions, considering the large number of virulence factors involved in the process.

The Driving of Immune Response by Th1 Adjuvants in Immunization of Mice with Trypanosoma cruzi marinkellei Elicits a Controversial Infection Control.

In previous studies, we have demonstrated that inoculation with a Trypanosoma cruzi marinkellei (avirulent RM1 strain) was able to reduce parasitemia in mice challenged with T. cruzi, although it was not able to prevent histopathological lesions. Th1 response stimulation by immunization is necessary for T. cruzi infection control, but the resistance is also dependent on immunoregulatory mechanisms, which can be induced by adjuvants. Thus, we evaluated whether inoculation of T. cruzi marinkellei associated with administration of different adjuvants would be capable of inducing different patterns of immune response to maximize the immune response against T. cruzi (virulent Romildo strain) infection. Two hundred eighty nonisogenic mice were divided into 14 groups according to the immunization scheme and the subsequent challenge with virulent Romildo T. cruzi strain. Nonimmunized groups and animals inoculated without adjuvants were also included. Immune protection was not observed with Th2 adjuvants (incomplete Freund's adjuvant [IFA] and Alum) due to high parasitemia. Th1/Th2-polarizing adjuvants also did not induce immune protection because inulin was unable to maintain survival, and immune-stimulating complexes induced intense inflammatory processes. Animals sensitized with RM1 strain without adjuvants were able to reduce parasitemia, increase survival, and protect against severe histological lesions, followed by adequate cytokine stimulation. Finally, our results demonstrate that the early and balanced IFN-γ production becomes critical to promote protection and that Th1 adjuvant elicited a controversial infection control due to increased histopathological damage. Therefore, the host's immunomodulation remains one of the most important challenges in the research for effective protection against T. cruzi infection. Similarly, the identification of protective antigens in the RM1 strain of T. cruzi marinkellei may contribute to further studies on vaccine development against human Chagas disease.

Análise crítica com TCFC da altura e espessura em sítios maxilares edêntulos potenciais para implantes dentários, usando-se a técnica all-on-four: estudo piloto / A critical CBCT analysis of height and thickness in edentulous maxillary potential implant sites regarding the all-on-four technique: pilot study

A técnica da cirurgia guiada sem retalho representa um grande avanço tecnológico, e é considerada uma realidade na Osseointegração. Sendo assim, a sua execução deve seguir alguns cuidados para o sucesso no tratamento proposto, no que tange alguns aspectos essenciais, a exemplo da disponibilidade óssea mínima para correta instalação dos implantes. Portanto, foi realizado um estudo tomográfico com amostra de 20 maxilas totalmente edêntulas para avaliar a viabilidade da instalação virtual de implantes no software Dental Slice, de acordo com a disponibilidade óssea, seguindo o protocolo all-on-four, além de mensurar nos cortes tomográficos a altura e a espessura dos sítios de instalação dos implantes. Os resultados encontrados de acordo com a análise estatística foram: 5% das maxilas estudadas apresentaram disponibilidade suficiente para a inserção completa dos quatro implantes no osso remanescente; 95% das maxilas apresentaram áreas de fenestrações ou ausência completa de possibilidade de inserção. Nos 80 sítios de instalação de implantes mensurados foram encontradas médias de 8,58 mm (p=0,66) e de 3,52 mm (p=0,85) de altura e de espessura óssea, respectivamente. Os autores concluem que apenas 5% das 20 maxilas estudadas foram consideradas viáveis para a inserção completa de implantes seguindo o protocolo all-on-four...

Guided flapless surgery has proved to be a major breakthrough in the practice of Implantodontics, but certain precautions should be taken in the execution of this technique, particularly with respect to the minimum availability of bone required for the successful implant placement. With this in mind, a tomographic study of 20 completely edentulous maxillae was carried out using Dental Slice software, to measure the bone height and thickness of potential implant insertion sites and evaluate the viability of installing implants following an ‘All-on-four’ protocol. A total of 80 sites were evaluated and a mean height of 8.58mm (p= 0.66) and a mean thickness of 3.52 mm (p= 0.85) were recorded. Statistical analysis of the results showed that only 5% of the maxillae studied had suffi cient remaining bone for the complete insertion of four implants, while 95% either presented areas of fenestration or were completely inadequate for implant placement. It was concluded that complete implant insertion following an ‘All-on-four’ protocol was viable in only 5% of studied cases...

Reabilitação oral com implantes em pacientes com displasia ectodérmica / Oral rehabilitation in patients with ectodermal dysplasia: a case report

A displasia ectodérmica (DE) é uma desordem genética com amplo espectro de manifestações clínicas. A hipodontia ou anodontia é uma característica intrabucal muito frequente. Este achado cria a necessidade de reabilitação, não só com o objetivo de devolver a função mastigatória, mas com o intuito de resgatar a estética e a autoestima destes pacientes. Desde 1988, tem sido relatado na literatura a reabilitação de indivíduos com DE através de implantes osseointegrados, visto que há vantagens em relação à retenção (função), considerando as próteses convencionais. O objetivo deste artigo foi realizar um relato de caso de um paciente, de 21 anos, sexo masculino, diagnosticado com displasia ectodérmica hipohidrótica (DEH) e severa hipodontia, que recebeu quatro implantes dentários entre os forâmenes mentuais.

The ectodermal dysplasia (ED) is a genetic disorder with ample spectrum of clinical manifestations. Also, hypodontia or anodontia is a very frequent intra-oral finding. In this way, not only masticatory function must be developed, but also esthetics and patient self-esteem. Since 1988, rehabilitation of ED individuals with osseointegrated implants has been proposed due to their inherent advantages when compared to the conventional complete dentures. The aim of this paper is to report a 20 years-old male patient diagnosed with hypohidrotic ectodermal dysplasia (HED) and severe hypodontia receiving four dental implants in between the mental foramina.

Avaliação dos tecidos peri-implantares em pacientes reabilitados com próteses totais fixas implantossuportadas / Evaluation of peri-implant tissues in patients rehabilitated with total fixed prostheses

Este estudo propõe uma avaliação das condições dos tecidos peri-omplantares em pacientes reabilitados com próteses totais fixas sobre implantes em maxilas e/ou mandíbulas, atendidos no Curso de especialização em Implantodontia da Universidade federal da Bahia (UFBA). A amostra constituiu-se de oito pacientes, e foram analisados mobilidade, dor, profundidade de sonfagem, índice de placa, índice de sangramento, supuração e faixa de tecido ceratinizado. De um total de 49 implantes avaliados, apenas um (2,04%) apresentou peri-implantite (com supuração e profundidade de sondagem de 6mm). Os resultados confirmam a necessidade de se estabelecer um programa de terapia de suporte para o paciente com implantes osseointegrados.

The aim of this study was to evaluate the peri-implants tissues conditions in the patients whose maxillae and/ or mandibles were rehabilitated using implant supported total fixed prostheses in the Specialist Implantodontology Program at the Federal University of Bahia (UFBA). The sample comprised of eight patients and the following factors were analyzed: mobility, pain, probing depth, the amount of plaque present, the amount of bleeding, suppuration and the keratinized tissue. Of a total of 49 implants evaluated, only one presented periimplantitis (with suppuration and a probing depth of 6mm). The results confirmed the necessity of establishing a therapeutic support program for patients with osseointegrated implants.

Immunization of mice with a Trypanosoma cruzi-like strain isolated from a bat: predictive factors for involvement of eosinophiles in tissue damage.

The granules of eosinophiles are cytotoxic to Trypanosoma cruzi trypomastigote and amastigote forms and to several cell types of the host, revealing their role in either parasite elimination or the production of tissue lesions. In this study, we evaluated the biological characteristics of T. cruzi infection that are responsible for the increase in tissue eosinophile levels in mice previously immunized with a bat isolated T. cruzi-like strain that does not infect mice. Nonisogeneic mice were divided into 24 groups that received from zero to three inoculations of T. cruzi-like RM1 strain, with or without adjuvant, followed by challenge with T. cruzi VIC or JG strains. Uni- and multivariate comparisons were performed comparing the tissue eosinophile levels with the parasitemia peak, severity of myositis in skeletal muscle, phase of infection, and the immunization strategies induced by the T. cruzi-like strain (adjuvant, number of reinoculations, and parasites). Although the severity of inflammation was higher in the acute phase, the score of tissue eosinophiles was similar in the acute and chronic phases of infection. In addition, there was a positive correlation among eosinophile levels and parasitemia peak. In the chronic phase, a greater eosinophile count was accompanied by an augmentation of myositis. Regardless of the phase of infection, we observed a positive correlation between the intensity of eosinophile infiltration and the number of sensitizations with T. cruzi-like strain. The multivariate analysis showed that the peak of parasitemia, number of inoculations with the T. cruzi-like strain, and severity of myositis were associated with greater tissue eosinophilia, in comparison with adjuvant, T. cruzi strains used in the challenge or tissue parasitism. Therefore, tissue eosinophile levels proved to be an important parameter in the pathogenesis of experimental Chagas disease in the acute and chronic phases of infection and might be related to reinfections, parasite multiplication ability, and severity of inflammatory process.

Absence of experimental cross-protection induced by a Trypanosoma cruzi-like strain isolated from bats.

This study evaluated the possibility of inoculation and reinoculation with a trypanosomatid isolated from bats that is morphologically, biologically and molecularly similar to Trypanosoma cruzi, to protect against infection by virulent strains. Non-isogenic mice were divided into 24 groups that received from zero to three inoculations of Trypanosoma cruzi-like strain RM1, in the presence or absence of Freunds adjuvant, and were challenged with the VIC or JG strains of Trypanosoma cruzi. Parasitemia and survival were monitored and animals were sacrificed for histopathological analysis. Animals immunized with Trypanosoma cruzi-like strain RM1 presented decreased parasitemia, independently of the number of inoculations or the presence of adjuvant. In spite of this reduction, these animals did not present any protection against histopathological lesions. Severe eosinophilic infiltrate was observed and was correlated with the number of inoculations of Trypanosoma cruzi-like strain RM1. These findings suggest that prior inoculation with this strain did not protect against infection but, rather, aggravated the tissue inflammatory process.

Absence of experimental cross-protection induced by a Trypanosoma cruzi-like strain isolated from bats / Ausência de proteção cruzada experimental induzida por uma cepa Trypanosoma cruzi-like isolada de morcego

This study evaluated the possibility of inoculation and reinoculation with a trypanosomatid isolated from bats that is morphologically, biologically and molecularly similar to Trypanosoma cruzi, to protect against infection by virulent strains. Non-isogenic mice were divided into 24 groups that received from zero to three inoculations of Trypanosoma cruzi-like strain RM1, in the presence or absence of Freund’s adjuvant, and were challenged with the VIC or JG strains of Trypanosoma cruzi. Parasitemia and survival were monitored and animals were sacrificed for histopathological analysis. Animals immunized with Trypanosoma cruzi-like strain RM1 presented decreased parasitemia, independently of the number of inoculations or the presence of adjuvant. In spite of this reduction, these animals did not present any protection against histopathological lesions. Severe eosinophilic infiltrate was observed and was correlated with the number of inoculations of Trypanosoma cruzi-like strain RM1. These findings suggest that prior inoculation with this strain did not protect against infection but, rather, aggravated the tissue inflammatory process.

Este trabalho avaliou a possibilidade da inoculação e reinoculação de um tripanossomatídeo isolado de morcego, morfológica, biológica e molecularmente semelhante ao Trypanosoma cruzi, na proteção contra a infecção por cepas virulentas. Camundongos não-isogênicos foram divididos em 24 grupos, que receberam de zero a três inóculos da cepa RM1 de Trypanosoma cruzi-like, na presença ou ausência de adjuvante de Freund e desafiados com as cepas de Trypanosoma cruzi VIC ou JG. Acompanhou-se a parasitemia e a sobrevida e os camundongos foram sacrificados para análise histopatológica. Os animais imunizados com a cepa RM1 de Trypanosoma cruzi-like apresentaram redução da parasitemia, independente do número de inóculos ou presença de adjuvante. Apesar dessa redução, os animais não apresentaram proteção contra lesões histopatológicas e observaram-se intensos infiltrados eosinofílicos que foram correlacionados com o número de inóculos da cepa RM1 de Trypanosoma cruzi-like. Sugere-se que a inoculação prévia dessa cepa, ao invés de proteger contra a infecção, agravou o processo inflamatório tecidual.

Prototipagem aplicada ao planejamento reverso das fixações zigomáticas / Bio-modelling applied to the reverse planning of zygomatic fixtures

A prototipagem rápida tornou-se um importante exame auxiliar para o diagnóstico e tratamento, com fixações zigomáticas (FZ), de maxilas severamente reabsorvidas. Nestas situações, a necessidade de construção de um planejamento fidedigno que minimize variáveis cirúrgicas e protéticas é determinante para o sucesso clínico. Portanto, a utilização de biomodelos no planejamento reverso das FZs tem-se tornado uma rotina, pois reduz o custo global do tratamento, possibilita simulações cirúrgicas prévias, elimina erros potenciais e conduz a resultados mais previsíveis. Assim sendo, a partir de uma revista da literatura e da apresentação de casos clínicos, este artigo se propõe apresentar a prototipagem rápida como recurso auxiliar no planejamento reverso das FZs