Evaluation of Salivary Flow Rate in Patients undergoing Chemotherapy for Solid Tumors / Avaliação de Fluxo Salivar em Pacientes Submetidos à Quimioterapia para Tumores Sólidos

Chemotherapy for cancer treatment offers the possibility of eradicating neoplastic cells, however, its use can result in systemic and oral adverse effects, with emphasis on the qualitative-quantitative modification of saliva. To evaluate the stimulated salivary flow rate (SFR) in patients undergoing chemotherapy for treatment of solid malignancies. This was a cross-sectional study with twenty patients diagnosed with solid tumors undergoing chemotherapy with cytotoxic drugs. Subjects were submitted to stimulated sialometry in the 1st cycle of chemotherapy (baseline, 7th day and 14th day). Additionally, sociodemographic data regarding these patients were collected in a standardized questionnaire. Descriptive and inferential statistical analysis were performed, with a significance level of p<0.05. There was a predominance of women (75%) aged over 40 years old (90%). The most prevalent tumor location was breast (55%), followed by ovaries (15%), and the most used drug was cyclophosphamide (50%). In the sample, no statistically significant result was observed with regard to SFR (p>0.05) in the studied periods. The data suggest that the 1st cycle of chemotherapy was not able to induce significant changes in the SFR. New studies need to be performed for the prospective identification of potential changes in salivary parameters.(AU)

A quimioterapia para tratamento do câncer oferece possibilidade de erradicação das células neoplásicas, todavia, seu emprego pode resultar em efeitos adversos sistêmicos e em cavidade oral, com destaque para modificação quali-quantitativa da saliva. Avaliar a velocidade de fluxo salivar (VFS) estimulado em pacientes sob quimioterapia para tratamento de neoplasias malignas sólidas. Tratou-se de um estudo transversal, no qual vinte pacientes com tumores sólidos sob regime quimioterápico com drogas sabidamente citotóxicas, foram submetidos à sialometria estimulada no 1º ciclo de quimioterapia (baseline, 7º dia e 14º dia). Adicionalmente, foram coletados dados referentes às características sociodemográficas desses pacientes. Foi realizada análise estatística descritiva e inferencial, com nível de significância p<0,05. Observou-se predominância de mulheres (75%) em idade acima dos 40 anos (90%). A localização do tumor mais prevalente foi a mama (55%), seguida de ovários (15%) e a droga mais utilizada foi a ciclofosfamida (50%). Na amostra não foi observado resultado estatisticamente significativo no que diz respeito à variável VFS (p>0,05) nos períodos estudados. Os dados sugerem que o 1° ciclo de quimioterapia não foi capaz de induzir alterações significativas na VFS. Novos estudos precisam ser realizados para a identificação prospectiva de potenciais alterações nos parâmetros salivares.(AU)

Heart protective effects of cardioactive drugs associated with antineoplastic treatment against breast cancer.

The prevalence of breast cancer in women is a fundamental problem in public health worldwide. There is consensual evidence that many chemotherapeutic agents might have harmful effects on the cardiovascular system of patients. The cardiotoxicity of chemotherapeutic drugs might lead to ventricular systolic dysfunction and heart failure, and consequently cardioactive drugs, such as antihypertensive, might mitigate those cardiac dysfunctions. Thus, this study carried out an integrative literature review on the potential benefits of cardioactive drugs in cardiovascular repercussions resulting from chemotherapy (CT), especially in women with breast cancer. The research involved articles available on the PubMed, LILACS, and MedLine databases, using as descriptors "breast cancer", "chemotherapy", "cardiotoxicity", and "antihypertensive"; 11 articles were selected. The data corroborate an association between the use of antineoplastic drugs (anthracyclines, fluorouracil, and anti-HER2 monoclonal antibody, trastuzumab) and cardiotoxic effects, and anthracyclines are the most studied CT drugs in relation to cardiac dysfunction. The cardioprotective effect of cardioactive drugs, including non-selective and selective beta-blockers classes, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, could be observed in clinical outcomes. Nonetheless, the drugs have different cardioprotective effects on breast cancer patients and left ventricular ejection fraction; the serum concentrations of troponins and brain natriuretic peptide were the most frequent parameters analysed in selected articles. In summary, cardiovascular parameters should be followed-up in patients undergoing oncology treatment in all stages, regardless of the therapeutic scheme carried out, given the risk of developing and worsening such heart conditions.

Impact of photobiomodulation for oral mucositis on body weight and BMI of patients with head and neck cancer.

PURPOSE: To evaluate the impact of photobiomodulation for oral mucositis on body weight and body mass index (BMI) in head and neck cancer patients. METHODS: Patients were separated into two groups: photobiomodulation (PBM) (n = 17) and SHAM (n = 19). Participants assigned to the PBM group received the photobiomodulation therapy on alternate days at 33 different sites of the oral mucosa (1 J for 10 s per application point) using a low-power aluminum gallium arsenide (AsGaAl) laser device with a maximum output power of 86.7 mW and a wavelength of 660 nm (red). The same protocol was performed in patients allocated in the SHAM group but with the device turned off. At the first and twenty-fourth radiotherapy sessions, participants from both groups underwent an intraoral examination to assess the presence or absence of mucositis using the WHO scale, and measurements of weight and height for BMI calculation were undertaken. RESULTS: All patients had significant differences in weight and BMI throughout the study period. Patients in the PBM group lost less weight (p < 0.01) and had a reduced BMI loss (p < 0.01) in comparison to patients in the SHAM group. Although PBM did not prevent oral mucositis, it decreased its severity (p < 0.01). CONCLUSION: Photobiomodulation for oral mucositis reduced weight loss and prevented a reduction in BMI in patients who underwent chemoradiotherapy for head and neck cancer. Retrospectively registered at https://data.mendeley.com//datasets/4kd7s49wk4/1 .

Nutritional supplements in the management of oral mucositis in patients with head and neck cancer: Narrative literary review.

BACKGROUND AND AIMS: Oral mucositis is the most common side effect in response to anticancer therapies in the head and neck region. It has a debilitating potential for the health of affected individuals, negatively interfering with nutritional status and quality of life. Due to the great complexity of its pathogenicity, different forms of interventions for prevention and treatment are being studied, including nutritional supplements with vitamin E, zinc and glutamine. This study aimed to review the literature on the influence of nutrients, in supplement form, for prevention and/or treatment of mucositis in patients with head and neck cancer. METHODS: A survey of studies related to the definition, treatment and prevention of mucositis with nutrients was carried out between January 2018 and July 2019, using the Pubmed, Cochrane Library and Scielo databases. In the end, 61 relevant scientific publications were selected between the years 2004 and 2019. RESULTS: Nutrients such as vitamin E, glutamine and zinc are forms of supplementation that have positive effects on the manifestation and severity of oral mucositis due to their antioxidant and immunomodulatory properties. However, some studies reveal that antioxidant properties may reduce the effectiveness of antineoplastic therapy. CONCLUSIONS: This study suggests the effectiveness of vitamin E, zinc and glutamine in preventing and treating oral mucositis. However, the importance of new clinical researches to clarify possible doubts is highlighted, as well as the creation of a protocol that includes the dose, route and time of administration, for greater safety in use.

Evaluation of preventive laser photobiomodulation in patients with head and neck cancer undergoing radiochemotherapy: Laser in patients with head and neck cancer.

AIMS: This study aimed to evaluate the effect of laser photobiomodulation in the prevention of oral mucositis (OM), salivary hypofunction and referred pain in patients with head and neck cancer. METHODS AND RESULTS: This randomized clinical study divided patients into two groups: the laser group (LG, n = 30) and the control group (CG, n = 24). The LG (InGaAlP, 660 nm, 86.7 mW, 2 J/cm2 ) participated in the preventive protocol, while the CG underwent a simulated procedure without light emission. The degree of OM, salivary flow, and referred pain were evaluated at five different periods of radiotherapy. Both groups showed a significant increase in the degree of OM (P < .01). Regarding OM, salivary flow, and oral pain, there were no significant differences between the groups. CONCLUSIONS: The laser photobiomodulation protocol used in this study was not effective in preventing radiochemotherapy-induced OM, salivary hypofunction, and referred pain in patients with head and neck cancer. Notably, although the development of OM did not differ significantly according to the use of laser therapy, the severity of oral mucositis was reduced in patients who underwent laser therapy compared to that in patients who did not.

Frequência de comorbidades associadas ao tratamento radioterápico de cabeça e pescoço / Frequency of comorbities associated with radiotherapic head and neck treatment

Introdução: a radioterapia é uma das principais modalidades de tratamento das neoplasias malignas de cabeça e pescoço. Entretanto sua ação não se restringe às células cancerígenas, produzindo efeitos colaterais comumente reportadas pelos pacientes. Objetivo: avaliar a ocorrência de comorbidades de interesse para o Cirurgião-dentista, relacionadas ao tratamento oncológico em pacientes submetidos a radioterapia de cabeça e pescoço (RCP) associada ou não a quimioterapia em um serviço de referência do Sistema Único de Saúde na cidade de Salvador-BA. Metodologia: foram incluídos 35 indivíduos submetidos a RCP associado ou não a quimioterapia. Foi realizada consulta odontológica a cada 48 horas, a fim de identificar queixas de disgeusia, disfagia e xerostomia e a instalação de lesões orais, como candidíase e mucosite oral. Resultados: 82,9% da amostra foi composta de indivíduos do gênero masculino e 17,1% do feminino, com idade média de 58,2 anos. Com relação às comorbidades relativas ao tratamento radioterápico em região de cabeça e pescoço, pode-se observar alta prevalência de mucosite oral (74,28%), disfagia (60%), candidíase (40%) e, em menor número, disgeusia (22,85%) e xerostomia (14,28%). Conclusão: a RCP, embora se apresente como uma eficiente modalidade terapêutica para neoplasias malignas, usualmente se associa a uma série de complicações na região irradiada. Na amostra estudada, a mucosite oral foi a comorbidade mais frequente, seguida de disfagia e candidíase.

Introduction: radiation therapy is one of the main treatment modalities for malignant head and neck neoplasms. However its action is not restricted to cancer cells, producing side effects commonly reported by these patients. Objective: evaluating the occurrence of comorbidities of interest to the dentist related to cancer treatment in patients undergoing head and neck radiotherapy (CPR) associated or not with chemotherapy in a reference service of the Unified Health System in Salvador-BA. Metodology: 35 individuals submitted CPR with or without chemotherapy were included. Dental appointments were performed every 48 hours to identify complaints of dysgeusia, dysphagia and xerostomia and oral lesions development such as candidiasis and oral mucositis. Results: 82.9% of the sample was composed of males and 17.1% females, mean age 58.2 years. It is possible to observe an occurrence of oral mucositis (74.28%), dysphagia (60%), candidiasis (40%) and, in a smaller number, dysgeusia (22.85%) and xerostomia (14.28%) the occurrence of oral mucositis in the head and neck region may be observed. Conclusion: head and neck radiotherapy, although presenting as an efficient therapeutic modality for malignant neoplasms, is usually associated with a series of complications in the irradiated region. In the studied sample, oral mucositis was the most prevalent comorbidity, followed by dysphagia and candidiasis.

Ocorrência de candidíase oral em pacientes portadores de câncer de cabeça e pescoço submetidos aos tratamentos antineoplásicos / Occurrence of Oral Candidiasis in Patients with Head and Neck Cancer submitted to antineoplastic treatments

Objetivo: avaliar a frequência de candidíase oral em pacientes portadores de câncer de cabeça e pescoço submetidos à radio e (ou) quimioterapia em um serviço de referência vinculado ao Sistema Único de Saúde do município de Salvador (BA). Metodologia: trata-se de um estudo seccional, realizado em uma amostra de conveniência e não probabilística de pacientes portadores de câncer de cabeça e pescoço submetidos à radio e (ou) quimioterapia. Foram coletados dados relativos às pessoas com candidíase oral, tais como sexo, idade e o tipo de tratamento a que foram submetidas (quimioterapia, radioterapia ou ambos), bem como a localização e o diagnóstico clínico do tipo de candidíase. Resultados: do total de 36 pacientes que se enquadraram nos critérios de inclusão, 16 apresentaram candidíase (44,4%). Onze indivíduos (68,75%) eram do sexo masculino e 07 (43,75%) possuíam faixa etária situada entre a quinta e a sexta décadas de vida. O tipo de candidíase prevalente foi a pseudomembranosa (87,5%), e o local mais acometido foi o palato duro (50%). Dos 16 pacientes com candidíase oral, 14 (87,5%) realizaram a radioterapia associada à quimioterapia, enquanto que 02 (12,5%) realizaram apenas a radioterapia. Conclusão: a candidíase oral é uma condição clínica muito comum nos pacientes portadores de neoplasias submetidos aos tratamentos antineoplásicos. A presença do cirurgião-dentista na equipe multidisciplinar que acompanha os pacientes oncológicos é relevante, pois poderá auxiliar na prevenção e no tratamento da candidíase e de outras condições clínicas.

Objective: to assess the frequency of candidiasis in patients with head and neck cancer submitted to radio and (or) chemotherapy in a referral service linked to the Unified Health System of the city of Salvador, Bahia. Methodology: this is a cross-sectional study consisting of a non-probabilistic sample of patients with oral candidiasis diagnosed in a convenience group. Data were collected on people with oral candidiasis, such as gender, age and type of treatment (chemotherapy, radiotherapy or both), as well as the location and clinical diagnosis of the type of candidiasis. Results: Oo the total of 36 patients that met the inclusion criteria, 16 presented candidiasis (44.4%). Eleven individuals (68.75%) were males and 07 (43.75%) had an age group between the fifth and sixth decades of life. The most prevalent type of candidiasis was pseudomembranous (87.5%) and the most affected site was the hard palate (50%). Of the 16 patients with oral candidiasis, 14 (87.5%) underwent radiotherapy associated with chemotherapy, while 02 (12.5%) only underwent radiotherapy. Conclusion: oral candidiasis is a very common clinical condition in patients with neoplasia submitted to antineoplastic treatments. The presence of the dental surgeon in the multidisciplinary team that follows up oncological patients is relevant, as it may help in the prevention and treatment of candidiasis and other clinical conditions

Estudo epidemiológico e nível de conhecimento de pacientes oncológicos acerca da mucosite oral e laserterapia / Epidemiological study and level of knowledge of oncologic patients about oral mucositis and lasertherapy / Estudio epidemiológico y nivel de conocimiento de pacientes oncológicos acerca de la mucositis y laserterapia

O presente estudo objetivou analisar o perfil epidemiológico e o nível de conhecimento acerca da mucosite oral e laserterapia de uma população que realizou tratamento quimioterápico em um serviço público de saúde (CICANBA) nos anos de 2014 e 2015. Foram analisados 50 prontuários e aplicados questionários semiestruturados a fim de verificar a percepção dos pacientes. Adicionalmente, o exame da cavidade bucal permitiu identificar lesões resultantes dos efeitos adversos da quimioterapia sobre a mucosa oral. Observou-se que a maioria dos pacientes era do sexo feminino (72%) e o tipo de câncer mais prevalente foi o de mama (62.06%). Cerca de 50% dos pacientes possuíam apenas o Ensino Fundamental e 42% tinha renda familiar correspondente a um salário mínimo. Nessa amostra, constataram-se maiores percentuais de tumores graduados como T2 e T4 (72.21%). O exame bucal evidenciou maior frequência de periodontopatias e lesões cariosas (51.72%). Ao avaliar o conhecimento, 78% não souberam conceituar a mucosite e 72% desconheciam o uso do laser como terapia adjuvante. Logo, os dados indicam que a maioria dos usuários do CICAN-BA é de baixa renda e baixo nível de escolaridade, fato este que pode justificar a falta de compreensão acerca do câncer e de suas abordagens terapêuticas. [AU]

This study analyzed the epidemiological profile and the level of knowledge about oral mucositis and laser therapy in a population who performed chemotherapy treatment in a public health service (CICAN-BA) for the years of 2014 and 2015. Fifty handbooks analyzed and questionnaires applied to verify the patient's perception. In addition, examination of the oral cavity has allowed us to identify injuries resulting from side effects of chemotherapy on the oral mucosa. Seventy two per cent of the patients were female and the most prevalent type of cancer was breast cancer (62.06%). About 50% of patients only concluded elementary School and 42% had family income corresponding to the minimum wage. T2 and T4 tumors were more prevalent (72.21%). The oral examination revealed a higher frequency of periodontal disease and carious lesions (51.72%). To assess knowledge, 78% could not conceptualize mucositis and 72% did not use the laser as adjuvant therapy. The data indicate that most users of CICAN-BA are individuals of low income and education level, justifying the lack of understanding about cancer and its therapeutic approaches. [AU]

Este estudio tuvo como objetivo analizar el perfil epidemiológico y el nivel de conocimiento sobre la mucositis oral y laserterapia de una población que llevó a cabo el tratamiento de quimioterapia en un servicio de salud pública (CICAN-BA) en los años 2014 y 2015. Se analizaron 50 registros médicos y se aplicaron cuestionarios semiestructurados para verificar la percepción de los pacientes. Además, el examen de la cavidad bucal nos ha permitido identificar las lesiones resultantes de los efectos adversos de la quimioterapia en la mucosa oral. Se observó que la mayoría de los pacientes era del sexo femenino (72%) y el tipo más frecuente de cáncer fue el de mama (62.06%). Un 50% de los pacientes poseían solo estudios primarios y el 42% tenía ingreso familiar correspondiente a un salario mínimo. En esta muestra, se encontró un mayor porcentaje de tumores graduados como T2 y T4 (72.21%). El examen bucal reveló una mayor frecuencia de las enfermedades periodontales y las lesiones cariosas (51.72%). Al evaluar los conocimientos, el 78% no supo conceptualizar la mucositis y el 72% desconocían el uso del láser como terapia adyuvante. Así, los datos indican que la mayoría de los usuarios del CICAN/BA tiene bajos ingresos familiares y nivel de educación, lo que puede justificar la falta de comprensión sobre el cáncer y sus enfoques terapéuticos. [AU]

Immune Checkpoints in Leprosy: Immunotherapy As a Feasible Approach to Control Disease Progression.

Leprosy remains a health problem in several countries. Current management of patients with leprosy is complex and requires multidrug therapy. Nonetheless, antibiotic treatment is insufficient to prevent nerve disabilities and control Mycobacterium leprae. Successful infectious disease treatment demands an understanding of the host immune response against a pathogen. Immune-based therapy is an effective treatment option for malignancies and infectious diseases. A promising therapeutic approach to improve the clinical outcome of malignancies is the blockade of immune checkpoints. Immune checkpoints refer to a wide range of inhibitory or regulatory pathways that are critical for maintaining self-tolerance and modulating the immune response. Programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4, and lymphocyte-activation gene-3 are the most important immune checkpoint molecules. Several pathogens, including M. leprae, are supposed to utilize these mechanisms to evade the host immune response. Regulatory T cells and expression of co-inhibitory molecules on lymphocytes induce specific T-cell anergy/exhaustion, leading to disseminated and progressive disease. From this perspective, we outline how the co-inhibitory molecules PD-1, PD-L1, and Th1/Th17 versus Th2/Treg cells are balanced, how antigen-presenting cell maturation acts at different levels to inhibit T cells and modulate the development of leprosy, and how new interventions interfere with leprosy development.

Immune checkpoints in leprosy: immunotherapy as a feasible approach to control disease progression

Leprosy remains a health problem in several countries. Current management of patients with leprosy is complex and requires multidrug therapy. Nonetheless, antibiotic treatment is insufficient to prevent nerve disabilities and control Mycobacterium leprae. Successful infectious disease treatment demands an understanding of the host immune response against a pathogen. Immune-based therapy is an effective treatment option for malignancies and infectious diseases. A promising therapeutic approach to improve the clinical outcome of malignancies is the blockade of immune checkpoints. Immune checkpoints refer to a wide range of inhibitory or regulatory pathways that are critical for maintaining self-tolerance and modulating the immune response. Programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4, and lymphocyte-activation gene-3 are the most important immune checkpoint molecules. Several pathogens, including M. leprae, are supposed to utilize these mechanisms to evade the host immune response. Regulatory T cells and expression of co-inhibitory molecules on lymphocytes induce specific T-cell anergy/exhaustion, leading to disseminated and progressive disease. From this perspective, we outline how the co-inhibitory molecules PD-1, PD-L1, and Th1/Th17 versus Th2/Treg cells are balanced, how antigen-presenting cell maturation acts at different levels to inhibit T cells and modulate the development of leprosy, and how new interventions interfere with leprosy development.

Análise do envolvimento de células T reguladoras na hanseníase / Analysis of the involvement of regulatory T cells in leprosy

A hanseníase é uma doença crônica causada por Mycobacterium leprae e apresenta diversas formas clínicas. O entendimento da interação parasita-hospedeiro na hanseníase evidenciou que ocorre a persistência assintomática do patógeno, caracterizando um estado de latência. Os fatores mais importantes relacionados com a permanência do patógeno são: a patogenicidade do agente infeccioso e o perfil da resposta imune, no qual os eventos de migração celular, produção de citocinas, as células efetoras e reguladoras são extremamente relevantes. As células T reguladoras (Treg) desempenham papel central na regulação da resposta imune em infecções crônicas o que favorece a persistência do patógeno. A importância de células T reguladores na hanseníase ainda é pouco conhecida. Neste trabalho investigou-se a presença de células T reguladoras em lesões e sangue periférico de indivíduos com hanseníase. Inicialmente avaliou-se a proliferação e a produção de citocinas por células mononucleares do sangue periférico (PBMC) de pacientes com hanseníase. Os resultados evidenciaram que não há diferenças quanto à proliferação de células T e produção de IFN-γ e TNF-α por células desses pacientes, mas a produção de IL-4 e IL-5 foi detectada apenas entre os pacientes com hanseníase virchoviana. Em relação à presença de células T reguladoras, os resultados evidenciaram aumento no número de linfócitos T CD4+CD25+FoxP3+ no sangue periférico de pacientes com hanseníase virchoviana. As células T reguladoras dos pacientes com hanseníase apresentaram elevada expressão de moléculas co-inibitórias PD-1, CTLA-4, GITR e ICOS. De modo relevante, as células T CD4+CD25+ isolados de pacientes com hanseníase virchoviana apresentaram maior atividade supressora quando comparado às células isoladas de pacientes com hanseníase tuberculóide. As células T CD4+CD25+ de pacientes com hanseníase virchoviana inibiram a proliferação de PBMC alogênico e a produção de IFN-γ e TNF-α...

Leprosy is caused by Mycobacterium leprae and its clinical features depend on the host immune background. The understanding of parasite-host interactions in leprosy have highlighted asymptomatic persistence of the pathogen, which indicates that this infection becomes latent. The most important factors related to the permanence of pathogens are: the pathogenicity of the infectious agents; the profile of the immune response developed by the host whose events of cellular migration, cytokines production, and the effector and regulatory cells are extremely relevant. The regulatory T cells (Treg) seem to play a central role in the regulation of the immune response in chronic infections, which favors the persistence of the pathogen. Herein, we analyzed the relation between tuberculoid and lepromatous leprosy with the presence and function of T regulatory cells from peripheral blood mononuclear cells (PBMC) and skin lesions from these patients. First, the proliferation and cytokine production of PBMC isolated from leprosy patients were analyzed. We did not observe any difference in the proliferation ability or IFN-γ and TNF-α release; however, the production of IL-4 and IL-5 was detected only in patients with lepromatous leprosy. Furthermore, T CD4+CD25+FoxP3+ cells were detected in the PBMC of patients with leprosy and these cells from lepromatous patients showed high expression of co-inhibitory molecules such as PD-1, GITR, CTLA-4 and ICOS. T CD4+CD25+cells isolated from patients with lepromatous leprosy were significantly more suppressive than the cells obtained from tuberculoid patients. In addition, TCD4+CD25+ cells isolated from patients with lepromatous leprosy inhibited allogeneic PBMC proliferation and their production of IFN-γ and TNF-α. The results also demonstrated that IL- 10 and TGF-ß were co-expressed with CD25+ cells at the inflammatory infiltrate of skin lesions from lepromatous patients, but similar results were not detected among tuberculoid...

The essential role of toll like receptor-4 in the control of Aggregatibacter actinomycetemcomitans infection in mice.

OBJECTIVE: Aggregatibacter actinomycetemcomitans is an oral Gram-negative bacterium that contributes to periodontitis progression. Isolated antigens from A. actinomycetemcomitans could be activating innate immune cells through Toll-like receptors (TLRs). In this study, we evaluated the role of TLR4 in the control of A. actinomycetemcomitans infection. MATERIAL AND METHODS: We examined the mechanisms that modulate the outcome of A. actinomycetemcomitans-induced periodontal disease in TLR4(-/-) mice. The production of cytokines was evaluated by ELISA. The bacterial load was determined by counting the number of colony-forming units per gram of tissue. RESULTS: The results showed that TLR4-deficient mice developed less severe periodontitis after A. actinomycetemcomitans infection, characterized by significantly lower bone loss and inflammatory cell migration to periodontal tissues. However, the absence of TLR4 facilitated the A. actinomycetemcomitans dissemination. Myeloperoxidase activity was diminished in the periodontal tissue of TLR4(-/-) mice. We observed a significant reduction in the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta in the periodontal tissue of TLR4(-/-) mice. CONCLUSION: The results of this study highlighted the role of TLR4 in controlling A. actinomycetemcomitans infection.

Absence of TLR2 influences survival of neutrophils after infection with Candida albicans.

Candida albicans is an opportunistic pathogen, which causes local and/or disseminated diseases in immunosuppressed humans. Phagocytic cells play a critical role in the immune response against C. albicans. Toll like receptors (TLR) are important in the identification of invading microorganisms and in the regulation of neutrophil survival. TLR2 has been shown to participate in the response against pathogenic yeasts and to increase the functional life span of neutrophils. In view of these observations, we studied the involvement of TLR2 in neutrophil function after C. albicans infection. The absence of TLR2 resulted in lower chemotaxis of neutrophils to the site of infection. This in turn was associated with lower levels of chemokines from neutrophils, facilitating the dissemination of the pathogen to the lymph nodes and spleen. A high frequency of apoptotic neutrophils and macrophages in the inflammatory exudates from TLR2(-/-) mice was found. In addition, the phagocytic activity of neutrophils and macrophages, nitric oxide production and myeloperoxidase activity were diminished in cells from TLR2(-/-) mice. Together, these data demonstrate the importance of TLR2 signals for neutrophils activation and survival after C. albicans infection.

The role of toll-like receptor 2 in the recognition of Aggregatibacter actinomycetemcomitans.

BACKGROUND: Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) is a Gram-negative bacterium present in the oral cavity and is usually associated with localized aggressive periodontitis. Isolated antigens from A. actinomycetemcomitans can activate innate immune cells through Toll-like receptors (TLRs), which are molecules that recognize structural components conserved among microorganisms. In this study, we evaluate the role of TLR2 in the recognition of A. actinomycetemcomitans. METHODS: Macrophages and neutrophils from knockout mice with targeted disruption of TLR2 (TLR2(-/-) mice) and wild-type mice were collected and used for the subsequent assays. The production of cytokines and chemokines was evaluated by enzyme-linked immunosorbent assay (ELISA), and the presence of apoptotic cells was determined by flow cytometry. In addition, the mechanisms that modulate the outcome of A. actinomycetemcomitans-induced periodontal disease in TLR2(-/-) mice were examined. RESULTS: The results show that TLR2-deficient mice developed more severe periodontitis after A. actinomycetemcomitans infection, characterized by significantly higher bone loss and inflammatory cell migration to periodontal tissues. The inflammatory cell influx into the peritoneal cavities of TLR2(-/-) mice was three-fold lower than that observed for the littermate controls. A significantly diminished production of the cytokines tumor necrosis factor-alpha and interleukin-1beta as well as the chemokine CC-ligand-5 in the peritoneal cavities of TLR2(-/-) mice was observed. In addition, a high frequency of apoptotic cells in the inflammatory exudates from TLR2(-/-) mice was observed. Phagocytosis and nitric oxide production was diminished in cells from TLR2(-/-) mice, facilitating the dissemination of the pathogen to the spleen. CONCLUSION: The results of this study highlight the involvement of TLR2 in recognizing A. actinomycetemcomitans and its essential role in controlling A. actinomycetemcomitans infection.

Caracterização do papel do receptor do tipo Toll 4 (TLR4) em infecção por Aggregatibacter actinomycetemcomitans / The role of TLR4 (Toll like receptor 4) in the recognition of Aggregatibacter actinomycetemcomitans

Os tecidos periodontais estão em confronto continuo com microorganismos capazes de disparar mecanismos da resposta imune inata, dando origem ao infiltrado inflamatório. Estudos recentes mostraram a importancia dos receptores do tipo Toll (TLRs) na fase inicial de reconhecimento de diferentes patogenos. A participação de receptores tipo Toll (TLRs) na resposta de neutrófilos e macrófagos frente a periodontopatógenos precisa ser determinada. Nesse estudo procuramos caracterizar o infiltrado inflamatório presente no peritônio de animais deficientes de TLR4^-/-, avaliar a atividade fagocítica, bem como a produção de óxido nítrico (NO) e a atividade de mieloperoxidase (MPO) no curso da infecção por Aggregatibacter actinomycetemcomitans. A ausência de TLR4 não influenciou a quimiotaxia de neutrófilos e macrófagos para o local da infecção, a produção de óxido nítrico, a atividade de MPO e a viabilidade celular. No entanto, neutrófilos e macrófagos de animais TLR4^-/- apresentaram menor atividade fagocítica quando comparado ao grupo controle (camundongos WT). Em relação a doença periodontal induzida experimentalmente com Aggregatibacter actinomycetemcomitans em camundongos deficientes de TLR4, os resultados mostraram que 100% dos animais deficientes de TLR4 sobreviveram a infecção durante o período de observação. Em relação a análise de perda óssea, os dados revelaram uma menor perda progressiva de osso alveolar na região dos molares de animais deficientes de TLR4. A ausência do receptor interferiu na disseminação da bactéria, uma vez que se observou um grande número de bacilos no linfonodo e baco dos animais que não expressaram TLR4, diferente do observado para os animais selvagens (WT). Os resultados indicam a importância da sinalização via TLR4 durante a resposta imune contra Aggregatibacter actinomycetemcomitans (AU).

Aggregatibacter actinomycetemcomitans is an oral gram negative bacteria that contributes to periodontitis progression. Isolated antigens from A. actinomycetemcomitans could be activating innate immune cells through Toll-like receptors (TLRs), molecules that recognize structural components conserved among microorganisms. In this study, we evaluated the role of TLR4 in the recognition of Aggregatibacter actinomycetemcomitans. Neutrophils and macrophage from TLR4 deficient mice and WT mice were collected and used for the subsequent assays. The phagocytosis of leukocytes against A. actinomycetemcomitans and the presence of apoptotic cells were determined by flow cytometry. The in vivo and in vitro production of NO and MPO was evaluated 24h after A. actinomycetemcomitans challenge. In addition, we examined the mechanisms that modulate the outcome of A. actinomycetemcomitans-induced periodontal disease in TLR4^-/- mice. The results show that inflammatory cells influx in peritoneal cavity of TLR4^-/- mice was similar to that observed into their littermate controls. The phagocytic activity was diminished by cells from TLR4^-/- mice. In addition, we did not observe difference in NO and MPO production and the frequency of apoptotic cells between cells from TLR4^-/- and WT mice. The results showed that TLR4-deficient mice developed less severe periodontitis after A. actinomycetemcomitans infection, characterized by significantly lower bone loss and inflammatory cell migration to periodontal tissues. Together, these data demonstrate the role TLR4 signals for neutrophils activation afterA. actinomycetemcomitans infection and development of periodontal disease.

Resistência à fratura de intermediários cerâmicos experimentais: estudo in vitro / Fracture resistance of experimental ceramic abutments: study in vitro

O sistema In-Ceram Zircônia (Vita Zahnfabrik) foi criado para confecção de infra-estruturas cerâmicas. A partir deste sistema, através de uma metodologia própria, conseguiu-se confeccionar intermediários cerâmicos para implantes. A proposta deste trabalho foi avaliar in vitro a resistência à fratura de intermediários experimentais para implantes construídos em In-Ceram Zircônia e restaurado com coroa de In-Ceram Alumina. Simulou-se um incisivo central superior instalado com 135° de angulação (inclinação entre os incisivos centrais superiores e inferiores) em uma máquina de ensaio que imprimiu carga na região de cíngulo até que se desse a ruptura de algum componente. Dos sete corpos de prova, cinco fraturaram o implante e dois fraturaram a base do intermediário de cerâmica. A média encontrada para as forças de compressão foi de 305,6 N. Constatou-se, ao ser aplicado o teste de Kolmogorov-Simirnov, ser a amostra normal e usando o teste “t”- Student verificou-se que a força alcançada para fratura das amostras foi estatisticamente superior (p = 0,0191) quando comparada à carga mastigatóriafisiológica (aproximadamente 235 N.