Adipokines from adipose tissue and common variable immunodeficiency: Is there any association?

Adiponectin and leptin are adipokines, secreted by white adipose tissue (WAT), which play an important role in energy homeostasis. Some evidence has shown that adipokine-producing adipose cells present in the bone marrow (BM) appear to exert an influence on hematopoiesis and B cell development. Common variable immunodeficiency (CVID) is one of the most common inborn errors of immunity in humans. In CVID, numerical and/or functional defects of B cells and their precursors result in hypogammaglobulinemia, usually Immunoglobulin (Ig) A and IgG. Manifestations of CVID include immunodeficiency, autoimmunity, inflammation and lymphoproliferation, resulting in a wide range of phenotypes. How adipokines interact and influence the pathophysiology of CVID is still unclear. In this review, we seek to summarize the aspects known so far concerning the interface between adipokines, B cells and CVID. More research is needed to fully understand these interactions; this knowledge is a potential avenue for the discovery of useful biomarkers and may provide new therapeutic targets for the treatment of patients with CVID and related diseases.

Photobiomodulation for the management of xerostomia and oral mucositis in patients with cancer: a randomized clinical trial.

To evaluate the applicability of photobiomodulation therapy (PBM-T) in the management of xerostomia and OM. Fifty-three patients with head and neck squamous cell carcinoma were randomized into two groups: Sham and PBM-T. The Sham group received artificial saliva and laser simulation, while the PBM-T group received artificial saliva and PBM-T. Xerostomia-related quality of life (QoL), the presence or absence of OM lesions, the decayed-missing-filled teeth (DMFT) index, and periodontal charts were evaluated. The results of the QoL questionnaire, DMFT index, and periodontal chart were analyzed with the Kruskal-Wallis test, followed by the Student-Newman-Keuls test, while OM findings were compared using the Mann-Whitney test. QoL scores significantly increased in the Sham group (p < 0.0001), denoting more severe xerostomia symptoms (p = 0.0074), and decreased in the PBM-T group, indicating no or very mild xerostomia. Higher grades of OM were found in the Sham group than the PBM-T group (p = 0.0001). There was no significant difference in DMFT index or periodontal charts between the groups (p > 0.05). PBM-T improved QoL in patients with head and neck cancer treated with radiotherapy, whether as radiation alone or as an adjunct to chemotherapy and surgery.

In vitro evaluation of EDTA combined with photodynamic therapy to reduce Streptococcus mutans in carious dentin.

BACKGROUND: This in vitro study aimed to evaluate the use of EDTA combined with photodynamic therapy to reduce Streptococcus mutans in carious dentin. METHODS: Sixty third molars were sectioned to obtain flat dentin surfaces. All specimens were waterproofed, except for the coronal dentin, and subjected to cariogenic challenge in brain-heart infusion (BHI) broth supplemented with 0.5% yeast extract, 1% glucose, 1% sucrose, and standard strain of S. mutans (ATCC 25175). The specimens were divided into 6 groups (n = 10 each): (1) control - caries collection; (2) EDTA - 17% EDTA was actively applied with a microbrush for 1 min; (3) aPDT - antimicrobial photodynamic therapy with 0.01% methylene blue photosensitizer (wavelength of 660 nm, energy of 4 J, power of 100 mW, spot size of 0.028 cm2, energy density of 142 J/cm2 for 40 s); (4) EDTA+aPDT - 17% EDTA actively applied for 1 min plus aPDT; (5) (EDTA+PT) + L - application of EDTA compounded with photosensitizer plus laser irradiation; and (6) PT - photosensitizer alone. Collection of caries was performed after the different cavity disinfection protocols. Aliquots from each dilution were seeded for colony-forming unit (CFU) counts. The results were log10-transformed and analyzed by the Kruskal-Wallis test (Student-Newman-Keuls). RESULTS: There was a significant reduction in S. mutans after aPDT (p<0.05), EDTA+aPDT (p<0.001), and (EDTA+PT) + L (p<0.001). The percentage of microbial reduction in ascending order was as follows: EDTA: 1.65%; PT: 15.51%; aPDT: 38.28%; EDTA+aPDT: 75.24%; and (EDTA+PT) + L: 97.35%. CONCLUSION: Application of 17% EDTA prior to photosensitization or compounded with a photosensitizer increased the antimicrobial effect of aPDT on S. mutans in carious dentin.

Effect of cetrimide 2% with and without photodynamic therapy to reduce Streptococcus mutans burden in dentinal carious lesions.

To evaluate the use of cetrimide alone and combined with photodynamic therapy to reduce S. mutans burden in carious lesions. Sixty permanent third molars were sectioned and the coronal dentin exposed. A cariogenic challenge was performed using brain-heart infusion (BHI) medium supplemented and S. mutans ATCC 25175. Specimens were incubated in anaerobic jars at 37 °C for 15 days, with BHI renewed every 24 h. After 15 days, specimens were randomly divided into six groups (n = 10): C, control (no treatment); CHX, application of chlorhexidine 2%; CT, application of cetrimide 2%; CT+aPDT, application of cetrimide 2% followed by methylene blue dye and aPDT (antimicrobial photodynamic therapy: wavelength 660 nm, energy 4J, power 100 mW, spot size 0.0028 cm2, energy density 142 J/cm2 for 40 s); ES+aPDT, application of experimental solution (methylene blue dye with cetrimide) and aPDT; and aPDT alone. Carious tissue from each specimen was collected before and after the applications. Five decimal dilutions were performed, and the resulting solution was seeded in mitis-salivarius-bacitracin agar. Plates were incubated in anaerobic jars at 37 °C for 48 h. Analysis of variance (ANOVA) with post hoc Tukey's test was used to compare total S. mutans counts. Significant reductions in S. mutans were observed after application of CT+aPDT (0.30 (0.97), p < 0.0001) and ES+aPDT (0.52 (1.13), p < 0.0001). Cetrimide 2% with methylene blue dye, applied consecutively or as a mixture, can be used as a photosensitizing agent for aPDT to reduce S. mutans burden in dentinal caries.

Autoimmunity and periodontal disease: Arguing a possible correlation.

Currently, there is a growing interest in studying systemic conditions associated with periodontal disease such as autoimmune disorders. Periodontal disease is a destructive inflammatory disease of the dental supporting tissues. The microorganisms associated with periodontal disease constitute diverse species that can colonize the oral cavity and influence the emergence or evolution of autoimmunity, characterized by a breakdown in the mechanisms of tolerance to self-antigens. Here, we reviewed and discussed a possible correlation between periodontal disease and autoimmunity, placing periodontal-pathogenic microorganisms as orchestrators of these pathological conditions.

Deciphering targets of Th17 cells fate: From metabolism to nuclear receptors.

Evidence indicates that reprogramming of metabolism is critically important for the differentiation of CD4 + T lymphocytes, and the manipulation of metabolic pathways in these cells may shape their fate and function. Distinct subgroups from T lymphocytes, such as Th17, adopt specific metabolic programmes to support their needs. Some important metabolic reactions, such as glycolysis, oxidative phosphorylation, are considered important for the differentiation of these lymphocytes. Since their discovery nearly a decade ago, Th17 lymphocytes have received significant attention because of their role in the pathology of several immune-mediated inflammatory diseases such as multiple sclerosis. In this review, it will be discussed as the involvement of T cell metabolism and as metabolic reprogramming in activated T cells dictates fate decisions to Th17. The involvement of nuclear receptors such as RORyt e PPARs in the induction of Th17 cells was also discussed. Understanding the metabolic pathways involved in the differentiation of the distinct subgroups of T lymphocytes helps in the design of promising therapeutic proposals.

Imunoterapia com células t-car: bioengenharia contra a leucemia linfoblástica aguda car-t cells / Immunotherapy: bioengineering against acute lymphoblastic leukemia

Introdução: Uma atual abordagem da imunoterapia do câncer baseia-se na modifi cação genética de linfócitos T, através da expressão deuma molécula de superfície capaz de atuar como um receptor específi co. Tal molécula foi intitulada Receptor Antigênico Quimérico (CAR)e tem a função de reconhecer antígenos presentes em células tumorais para redirecionar o ataque linfocitário. Desenvolvido como umtratamento para a Leucemia Linfoblástica Aguda (LLA) do tipo B, o receptor CAR expresso pela célula modifi cada atua especifi camente noreconhecimento do CD19, principal cluster de diferenciação da linhagem linfoide B. Ao reconhecer o antígeno, o sítio interno da moléculatransmite um sinal de ativação do ataque citolítico, o qual atinge apenas a célula-alvo e promove sua eliminação com baixa toxicidade.Objetivo: Descrever a manipulação e funcionamento da imunoterapia com Células T-CAR no tratamento da LLA do tipo B e destacar osbenefícios desta técnica para os pacientes. Método: Estudo de revisão bibliográfi ca a partir de artigos de bases de dados online PubMede do Portal Capes, no período de 2011 a 2017 e livros acadêmicos correlacionados. Conclusão: Com as técnicas de engenharia genética,a imunoterapia com Células T-CAR proporcionou melhora signifi cativa na qualidade de vida dos pacientes de ensaios clínicos devido àbaixa agressividade do tratamento e alta especifi cidade contra a célula tumoral, atingindo taxas próximas de 95% de remissão completada doença. Os resultados indicam novas oportunidades de avanço no tratamento da LLA e outras neoplasias.

Introduction: A current approach to cancer immunotherapy is based on the genetic modifi cation of T-lymphocytes by the expression ofa cell surface molecule able to act as a specifi c receptor. Such molecule has been called Chimeric Antigen Receptor (CAR) and has thefunction of recognizing antigens in tumor cells to redirect the lymphocyte attack. Developed as a treatment for Acute LymphoblasticLeukemia (ALL) type B, the CAR-receptor expressed by the modifi ed cell acts specifi cally on the recognition of CD19, the majordifferentiation cluster of lymphoid B lineage. After antigen recognition, the molecule internal site transmits a signal of cytolytic attackactivation, which reaches only the target cell, therefore promoting its elimination with low toxicity. Objective: To describe manipulationand functioning of immunotherapy with CAR-T cells on the treatment of type B ALL and to highlight the benefi ts of this technique forthe patients. Method: Bibliographic review study based on articles from online databases PubMed and Capes Portal from 2011 through2017 and correlated academic books. Conclusion: With genetic engineering techniques, CAR-T Cells immunotherapy provided signifi cantimprovement in life quality of clinical trials patients, due to low treatment aggressiveness, as well as high specifi city against tumor cells,with disease complete remission rates near to 95%. The results point out new opportunities for advancement in the treatment of ALLand other neoplasms.

Introducción: Actualmente, uno de los enfoques en inmunoterapia para cáncer es la modifi cación genética de linfocitos T a través dela expresión de moléculas de superfi cie capaces de actuar como receptor específi co. Estas moléculas se llaman Receptor AntigénicoQuimérico (CAR) y su función es reconocer antígenos presentes en las células tumorales direccionando el ataque linfocitario. El receptorCAR fue desarrollado para el tratamiento de Leucemia Linfoblástica Aguda (LLA) tipo B y se expresa en la célula modifi cada para actúarespecífi camente en el reconocimiento de CD19, principal marcador de diferenciación del linaje de linfocitos B. Cuando es reconocido elantígeno, el sitio interno de la molécula trasmite una señal de activación para iniciar el ataque citolítico, atacando de forma específi ca alas células cancerígenas y promoviendo la eliminación de éstas con baja toxicidad. Objetivo: Describir la manipulación y funcionamientode la inmunoterapia con células T-CAR en el tratamiento de LLA tipo B y mostrar los benefi cios de la técnica en los pacientes. Método:Estudio de revisión bibliográfi ca de artículos científi cos de los años 2011-2017 en bases de datos on-line y libros académicos relacionados.Conclusión: Gracias a las técnicas de ingeniería genética, la inmunoterapia con células T-CAR proporcionó una mejora signifi cativa en lacalidad de vida de los pacientes participantes de ensayos clínicos, debido a la baja agresividad del tratamiento y a la alta especifi cad delmismo contra las células tumorales. Siendo la tasa de remisión completa de la enfermedad de aproximadamente un 95%. Los resultadosmuestran nuevas oportunidades de avances en el tratamiento de la LLA y en otras neoplasias.

Efeito da fluoretação da água na concentração de fluoreto salivar / Water fluoridation effect in the fluoride concentration of saliva

O fluoreto é considerado um micronutriente essencial na formação de ossos e dentes. A diminuição da cárie dentária nos últimos anos, tem sido atribuída à presença de flúor no meio bucal, prevenido a desmineralização do esmalte dentário e inibindo a atividade bacteriana local. O consumo de água fluoretada, na concentração de 0,6 a 0,8 mg/L, tem sido considerada a forma mais abrangente e menos dispendiosa do íon fluoreto ao organismo. O objetivo deste trabalho foi verificar a influência do consumo de água fluoretada no nível de fluoreto salivar. Os resultados demonstraram que a maior parte da população de 0,01 a 0,05 mg de fluoreto por litro de saliva independente da ingestão de água com fluoreto na concentração recomendada para manutenção da saúde bucal