Topical anti-inflammatory activity of yacon leaf extracts

Smallanthus sonchifolius (Poepp.) H. Rob. , Asteraceae, known as yacon, is an herb that is traditionally used for the treatment of diabetes in folk medicine. However, recent studies have demonstrated that this plant has other interesting properties such as anti-microbial and anti-inflammatory actions. Thus, the purpose of this study was to evaluate the topical anti-inflammatory property of different extracts prepared from yacon leaves and analyze the role of different chemical classes in this activity. Three yacon leaf extracts were obtained: aqueous extract, where chlorogenic acid derivatives and sesquiterpene lactones were detected; leaf rinse extract, rich in sesquiterpene lactones; and polar extract, rich in chlorogenic acid derivatives. All the extracts exhibited anti-edematogenic activity in vivo (aqueous extract: 25.9% edema inhibition at 0.50 mg/ear; polar extract: 42.7% inhibition at 0.25 mg/ear; and leaf rinse extract: 44.1% inhibition at 0.25 mg/ear). The leaf rinse extract furnished the best results regarding neutrophil migration inhibition, and NO, TNF-? and PGE2 inhibition. These data indicate that both sesquiterpene lactones and chlorogenic acid derivatives contribute to the anti-inflammatory action, although sesquiterpene lactones seem to have more pronounced effects. In conclusion, yacon leaf extracts, particularly the sesquiterpene lactone-rich extract, has potential use as topical anti-inflammatory agent.FAPESP #2007/00844-3CAPES #314/0

Dose-Response Met-RANTES Treatment of Experimental Periodontitis: A Narrow Edge between the Disease Severity Attenuation and Infection Control

Chemokines and chemokine receptors have been implicated in the selective migration of leukocyte subsets to periodontal tissues, which consequently influences the disease outcome. Among these chemoattractants, the chemokines CCL3, CCL4 and CCL5 and its receptors, CCR1 and CCR5, have been associated with increased disease severity in mice and humans. Therefore, in this study we investigated the modulation of experimental periodontitis outcome by the treatment with a specific antagonist of CCR1 and 5 receptors, called met-RANTES. C57Bl/6 mice was orally infected with Aggregatibacter actinomycetemcomitans and treated with 0.05, 0.1, 0.5, 1.5 and 5 mg doses of met-RANTES on alternate days, and evaluated by morphometric, cellular, enzymatic and molecular methods. At 0.5 mg up to 5 mg doses, a strong reduction in the alveolar bone loss and inflammatory cell migration were observed. Interestingly, 5 mg dose treatment resulted in the maximum inhibition of inflammatory cell migration, but resulted in a similar inhibition of bone loss when compared with the lower doses, and also resulted in increased bacterial load and CRP response. When 0.5 and 5 mg therapy regimens were compared it was observed that both therapeutic protocols were able to downregulate the levels of pro-inflammatory, Th1-type and osteoclastogenic cytokines, and CD3+ and F4/80+ cells migration to periodontal tissues, but the high dose modulates host response in a more pronounced and unspecific and excessive way, interfering also with the production of antimicrobial mediators such as MPO, iNOS and IgG, and with GR1+ and CD19+ cells migration. Our results demonstrate a thin line between beneficial immunoregulation and impaired host defense during experimental periodontitis, and the determination of the exact equilibrium point is mandatory for the improvement of immune-targeted therapy of periodontitis

Efficacy of Papacarie¯ in reduction of residual bacteria in deciduous teeth: a randomized, controlled clinical trial

OBJECTIVES: The aim of the present study was to analyze the efficacy of Papacarie¯ gel compared with the traditional method (low-speed bur) in reducing the counts of total bacteria, Lactobacillus, total Streptococcus and Streptococcus mutans group. METHODS: A randomized, controlled clinical trial with a split-mouth design was performed. The sample comprised 40 deciduous teeth in 20 children (10 males and 10 females) aged four to seven years. The teeth were randomly allocated to two groups: G1, or chemomechanical caries removal with Papacarie Duo¯, and G2, or the removal of carious dentin tissue with a low-speed bur. Infected dentin was collected prior to the procedure, and the remaining dentin was collected immediately following the removal of the carious tissue. Initial and final counts of bacterial colonies were performed to determine whether there was a reduction in the number of colony-forming units (CFUs) of each microorganism studied. ClinicalTrials.gov: NCT01811420. RESULTS: Reductions were found in the numbers of total bacteria, total Streptococcus and Streptococcus mutans group following either of the caries removal methods (p;0.05). CONCLUSION: Papacarie¯ is an excellent option for the minimally invasive removal of carious tissue, achieving significant reductions in total bacteria, total Streptococcus and S. mutans with the same effectiveness as the traditional caries removal method

Fcγ receptors on aging neutrophils

Objective: Neutrophils are key effector cells of the innate immune system. They recognize antigens through membrane receptors, which are expressed during their maturation and activation. Neutrophils express FcγRII (CD32), FcγRIII (CD16), and FcγRI (CD64) after being activated by different factors such as cytokines and bacterial products. These receptors are involved with phagocytosis of IgG-opsonized microbes and enhance defense mechanisms. Based on that, our study seeks to compare the expression of FcγRII, FcγRIII, FcγRI, and CD11b on neutrophils from elderly and young subjects and their expression after in vitro activation with cytokines and LPS. Methodology: Neutrophils were isolated from human peripheral blood and from mice bone marrow by density gradient. After isolation, FCγRs expression was immediately analyzed by flow cytometry or after in vitro stimulation. Results: In freshly isolated cells, the percentage of FcγRIIIb+ and CD11b+ neutrophils were higher in samples from young individuals; FcγRIIIa expression was more prominent on aged neutrophils; FcγRIA expression was similar in all samples analyzed. Exposure to CXCL8 and LPS resulted in a higher percentage of FcγRIa+ neutrophils on elderly individuals’ samples but lower when compared with neutrophils from young donors. We observed that LPS caused an increase in FcγRIIa expression on aging human neutrophils. In contrast, FcγRIIIb expression in response to CXCL8 and LPS stimulation was not altered in the four groups. CD11b expression was lower in neutrophils from elderly individuals even in response to LPS and CXCL8. In mice, we observed differences only regarding CD11b expression, which was increased on aged neutrophils. LPS exposure caused an increase in all FcγRs. Conclusions: Our results suggest that, in humans, the overall pattern of FcγR expression and integrin CD11b are altered during aging and immunosenescence might contribute to age-related infection

Randomized controlled clinical trial of long-term chemo-mechanical caries removal using PapacarieTM gel

Objectives: Compare the effectiveness of PapacarieTM gel for the chemo-mechanical removal of carious lesions on primary teeth to conventional caries removal with a low-speed bur with regard to execution time, clinical aspects and radiographic findings. Material and Methods: A randomized controlled clinical trial with a split-mouth design was carried out. The sample was composed of 20 children aged four to seven years, in whom 40 deciduous teeth were randomly divided into two groups: chemo-mechanical caries removal with PapacarieTM and removal of carious dentin with a low-speed bur. Each child underwent both procedures and served as his/her own control. Restorations were performed with glass ionomer cement. The time required to perform the procedure was also analyzed. The patients underwent longitudinal clinical and radiographic follow-up of the restorations. Results: No statistically significant difference between groups was found regarding the time required to perform the procedures and the radiographic follow up. Statistically significant differences between groups were found in the clinical evaluation at 6 and 18 months after treatment. Conclusion: PapacarieTM is as effective as the traditional method for the removal of carious dentin on deciduous teeth, but offers the advantages of the preservation of sound dental tissue as well as the avoidance of sharp rotary instruments and local anesthesia

Fresh or minimally processed vegetables in foodservices: what aspects should be considered when purchasing them?

Objetivo O objetivo do estudo foi avaliar as perdas ocorridas no processamento de hortaliças in natura, comparar o custo da aquisição de hortaliças in natura e das minimamente processadas e discutir as vantagens e desvantagens da utilização destas últimas. Métodos Foram calculados fatores de correção de sete hortaliças por meio da determinação do peso bruto e do peso líquido em triplicata e o peso aferido por balança digital. Foram calculados média, desvio-padrão e coeficiente de variação. Os custos do peso bruto, considerando a correção pelo seu rendimento líquido, foram comparados aos custos das hortaliças minimamente processadas fornecidos pelo fabricante em dois períodos. Resultados Os valores da abobrinha, cenoura, chuchu e mandioquinha minimamente processados foram, respectivamente, 8,6%, 14,1%, 4,6% e 13,5% menores em relação ao custo do alimento bruto no tempo 1, mas isso não se repetiu no tempo 2, quando os alimentos in natura apresentavam menor custo. Conclusão Conclui-se que inúmeros fatores inerentes ou externos aos alimentos influenciam diretamente na magnitude das perdas durante o processamento. Os métodos de trabalho e objetivos finais de cada unidade produtora é que devem definir qual produto é o mais vantajoso, considerando que os custos são variáveis, uma vez que a produção pode ser comprometida pela sazonalidade e pela oferta e procura dos alimentos, com repercussão na gestão de qualidade da unidade.Objective The objective of the present study was to assess the losses that occur when fresh vegetables are processed, to compare the cost of purchasing fresh and minimally processed vegetables, and to discuss the advantages and disadvantages of using minimally processed food items. Methods Correction factors for seven food items were calculated by determining their gross and net weights in triplicate with a digital scale. Mean, standard deviation and variation coefficient were calculated. The costs of gross weight considering the correction for net yield were compared with the costs of minimally processed vegetables supplied by the manufacturer during two different periods. Results The costs of minimally processed zucchini, carrot, chayote and arracacha were 8.6%, 14.1%, 4.6% and 13.5% lower than their respective fresh counterparts at time 1, a fact that did not repeat itself at time 2, when these vegetables were less expensive when bought fresh. Conclusion In conclusion, numerous factors associated or not with the food directly influence the magnitude of the losses that occur during processing. The working methods and final objectives of each foodservice should define which product is more advantageous since costs vary and production can be affected by seasonality and the supply and demand of the food item, with repercussions on the quality management of the foodservice

HGMB1 and RAGE as Essential Components of Ti Osseointegration Process in Mice

The release of the prototypic DAMP High Mobility Group Box 1 (HMGB1) into extracellular environment and its binding to the Receptor for Advanced Glycation End Products (RAGE) has been described to trigger sterile inflammation and regulate healing outcome. However, their role on host response to Ti-based biomaterials and in the subsequent osseointegration remains unexplored. In this study, HMGB1 and RAGE inhibition in the Ti-mediated osseointegration were investigated in C57Bl/6 mice. C57Bl/6 mice received a Ti-device implantation (Ti-screw in the edentulous alveolar crest and a Ti-disc in the subcutaneous tissue) and were evaluated by microscopic (microCT [bone] and histology [bone and subcutaneous]) and molecular methods (ELISA, PCR array) during 3, 7, 14, and 21 days. Mice were divided into 4 groups: Control (no treatment); GZA (IP injection of Glycyrrhizic Acid for HMGB1 inhibition, 4 mg/Kg/day); RAP (IP injection of RAGE Antagonistic Peptide, 4 mg/Kg/day), and vehicle controls (1.5% DMSO solution for GZA and 0.9% saline solution for RAP); treatments were given at all experimental time points, starting 1 day before surgeries. HMGB1 was detected in the Ti-implantation sites, adsorbed to the screws/discs. In Control and vehicle groups, osseointegration was characterized by a slight inflammatory response at early time points, followed by a gradual bone apposition and matrix maturation at late time points. The inhibition of HMGB1 or RAGE impaired the osseointegration, affecting the dynamics of mineralized and organic bone matrix, and resulting in a foreign body reaction, with persistence of macrophages, necrotic bone, and foreign body giant cells until later time points. While Control samples were characterized by a balance between M1 and M2-type response in bone and subcutaneous sites of implantation, and also MSC markers, the inhibition of HMGB1 or RAGE caused a higher expression M1 markers and pro-inflammatory cytokines, as well chemokines and receptors for macrophage migration until later time points. In conclusion, HMGB1 and RAGE have a marked role in the osseointegration, evidenced by their influence on host inflammatory immune response, which includes macrophages migration and M1/M2 response, MSC markers expression, which collectively modulate bone matrix deposition and osseointegration outcome

Regulatory T cells in the actinic cheilitis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109303/1/jop12207.pd

Inflammasome activation is critical to the protective immune response during chemically induced squamous cell carcinoma

Chronic inflammation affects most stages of tumorigenesis, including initiation, promotion, malignant differentiation, invasion and metastasis. Inflammasomes have been described as involved with persistent inflammation and are known to exert both pro and antitumour effects. We evaluated the influence of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase (CASP)-1 in the antitumor immune response using a multistage model of squamous cell carcinoma (SCC) development. Absence of ASC and CASP-1 resulted in an earlier incidence and increased number of papilloma. Loss of inflammassome function in mice resulted in decreased presence of natural killer (NK), dendritic (DC), CD4+, CD8+ and CD45RB+ T cells in the tumor lesions as well as in lymph nodes (LN) compared with WT mice. Increased percentage of CD4+CD25+Foxp3+ T cells was associated with association with inflammasome loss of function. Moreover, significant differences were also found with neutrophils and macrophage infiltrating the lesions. Myeloperoxidase (MPO), but not elastase (ELA), activity oscillated among the groups during the SCC development. Levels of proinflammatory cytokines IL-1β, IL-18, Tumor Necrosis Factor (TNF)-α and Interferon (IFN)-γ were decreased in the tumor microenvironment in the absence of inflammasome proteins. These observations suggest a link between inflammasome function and SCC tumorigenesis, indicating an important role for inflammasome activation in the control of SCC development.Fil: Gasparoto, Thais Helena. Universidad de São Paulo. Faculdade de Odontologia de Bauru. Departamento de Ciencias Biológicas; BrasilFil: Ervolino de Oliveira, Carine. Universidad de São Paulo. Faculdade de Odontologia de Bauru. Departamento de Ciencias Biológicas; BrasilFil: Thomazini de Freitas, Luisa. Universidad de São Paulo. Faculdade de Odontologia de Bauru. Departamento de Ciencias Biológicas; BrasilFil: Ramos Pinheiro, Claudia. Universidad de São Paulo. Faculdade de Odontologia de Bauru. Departamento de Ciencias Biológicas; BrasilFil: Issa Hori, Juliana. University of São Paulo. Faculdade de Medicina de Ribeirão Preto; BrasilFil: Pompermaier Garlet, Gustavo. Universidad de São Paulo. Faculdade de Odontologia de Bauru. Departamento de Ciencias Biológicas; BrasilFil: Cavassani, Karen Angélica. University Of Michigan; Estados UnidosFil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Santana Da Silva, Joao. University of São Paulo. Faculdade de Medicina de Ribeirão Preto; BrasilFil: Simmões Zamboni, Darío. University of São Paulo. Faculdade de Medicina de Ribeirão Preto; BrasilFil: Campanelli, Ana Paula. Universidad de São Paulo. Faculdade de Odontologia de Bauru. Departamento de Ciencias Biológicas; Brasi

Antimicrobial activity of calcium hydroxide and chlorhexidine on intratubular Candida albicans

This study investigated the efficacy of calcium hydroxide and chlorhexidine gel for the elimination of intratubular Candida albicans (C. albicans). Human single-rooted teeth contaminated with C. albicans were treated with calcium hydroxide, 2% chlorhexidine gel, calcium hydroxide plus 2% chlorhexidine gel, or saline (0.9% sodium chloride) as a positive control. The samples obtained at depths of 0–100 and 100–200 µm from the root canal system were analyzed for C. albicans load by counting the number of colony forming units and for the percentage of viable C. albicans using fluorescence microscopy. First, the antimicrobial activity of calcium hydroxide and the 2% chlorhexidine gel was evaluated by counting the number of colony forming units. After 14 days of intracanal medication, there was a significant decrease in the number of C. albicans colony forming units at a depth of 0–100 µm with chlorhexidine treatment either with or without calcium hydroxide compared with the calcium hydroxide only treatment. However, there were no differences in the number of colony forming units at the 100–200 µm depth for any of the medications investigated. C. albicans viability was also evaluated by vital staining techniques and fluorescence microscopy analysis. Antifungal activity against C. albicans significantly increased at both depths in the chlorhexidine groups with and without calcium hydroxide compared with the groups treated with calcium hydroxide only. Treatments with only chlorhexidine or chlorhexidine in combination with calcium hydroxide were effective for elimination of C. albicansFAPESP 2007/00306-1FAPESP 2007/003061CAPESCAPE