Periodontal ligament and gingival fibroblasts participate in the production of TGF-β, interleukin (IL)-8 and IL-10. Morandini AC, Sipert CR, Ramos-Junior ES, Brozoski DT, Santos CF Braz Oral Res. 2011 Apr;25(2):157-62.PMID: 21537641 [PubMed - indexed for MEDLINE]
Abstract: The aim of this study was to quantify and compare the production of transforming growth factor beta (TGF-β), interleukin (IL)-8 and IL-10 by human cultured periodontal ligament and gingival fibroblasts both obtained from the same donors challenged with lipopolysaccharide (LPS) from Porphyromonas gingivalis. Fibroblasts were exposed to 0.1-10µg/mL of LPS from P. gingivalis and after 24 h the supernatants were collected and analyzed by enzyme-linked immunosorbent assay (ELISA). TGF-β protein production was upregulated in a concentration-dependent manner, mainly in gingival fibroblasts, which was statistically significant when challenged by 10µg/mL LPS. Additionally, at this concentration, gingival fibroblasts had almost a two-fold increase in the amount of TGF-β when compared to periodontal ligament fibroblasts. Both periodontal ligament and gingival fibroblasts showed an increase in IL-8 production when challenged with 1µg/mL and 10µg/mL LPS. IL-10 production remained unaffected when challenged by any of the LPS concentrations tested in either periodontal ligament or gingival fibroblasts. Our results demonstrate that periodontal ligament and gingival fibroblasts when challenged by LPS from P. gingivalis with 24 h may play a critical role in producing TGF-β and IL-8 but not IL-10.
Trypanosoma cruzi invades host cells through the activation of endothelin and bradykinin receptors: a converging pathway leading to chagasic vasculopathy.Dos Santos Andrade D, Serra RR, Svensjö E, de Araújo Lima AP, Junior ES, da Silva de Azevedo Fortes F, de Faria Morandini AC, Morandi V, de Nazaré Correia Soeiro M, Tanowitz HB, Scharfstein J . Br J Pharmacol. 2011 Jul 28. [Epub ahead of print] PubMed PMID: 21797847
Abstract: Independent studies in experimental models of Trypanosoma cruzi appointed different roles for endothelin-1 (ET-1) and bradykinin (BK) in the immunopathogenesis of Chagas disease. Here we addressed the hypothesis that pathogenic outcome is influenced by functional interplay between endothelin receptors (ET(A) R and ET(B) R) and bradykinin receptors (B(2) R). Experimental approach: Intravital microscopy was used to determine whether ETR/B(2) R drives the accumulation of rhodamine-labeled leukocytes in the hamster cheek pouch (HCP). Inflammatory edema was measured in the infected BALB/c paw. Parasite invasion was assessed in CHO overexpressing ETRs, mouse cardiomyocytes, endothelium (HUVECs) or smooth muscle cells (HSMCs), in the presence/absence of antagonists of B(2) R (HOE-140), ET(A) R (BQ-123) and ET(B) R (BQ-788); specific IgG antibodies to each GPCRs; cholesterol or calcium-depleting drugs. RNA interference (ET (A) R or ET(B) R genes) in parasite infectivity was investigated in HSMCs. Key results: BQ-123, BQ-788 and HOE-140 reduced leukocyte accumulation in HCP topically exposed to trypomastigotes and blocked edematogenic inflammation in infected mice. Acting synergistically, ET(A) R and ET(B) R antagonists reduced parasite invasion of HSMCs to the same extent as HOE-140. Exogenous ET-1 potentiated T. cruzi uptake by HSMCs via ETRs/B(2) R whereas RNA interference of ET(A) R and ET(B) R genes conversely reduced parasite internalization. ETRs/B(2) R-driven infection in HSMCs was reduced in HSMC pretreated with MβCD, a cholesterol depleting drug, or in thapsigargin or verapamil treated target cells. Conclusions and Implications: Our findings suggest that plasma leakage, a neutrophil-driven inflammatory response evoked by trypomastigotes via the kinin/endothelin pathways, may offer a window of opportunity for enhanced parasitism of cardiovascular cells.
Understanding the impact of divalent cation substitution on hydroxyapatite: an in vitro multiparametric study on biocompatibility. de Lima IR, Alves GG, Soriano CA, Campaneli AP, Gasparoto TH, Ramos ES Jr, de Sena LÁ, Rossi AM, Granjeiro JM. J Biomed Mater Res A. 2011 Sep 1;98(3):351-8. doi: 10.1002/jbm.a.33126 PMID:21626666 [PubMed - indexed for MEDLINE]
Abstract. Hydroxyapatite (HA), a stable and biocompatible material for bone tissue therapy, may present a variable stoichiometry and accept a large number of cationic substitutions. Such substitutions may modify the chemical activity of HA surface, with possible impact on biocompatibility. In this work, we assessed the effects of calcium substitution with diverse divalent cations (Pb(2+), Sr(2+), Co(2+), Zn(2+), Fe(2+), Cu(2+), or Mg(2+)) on the biological behavior of HA. Physicochemical analyses revealed that apatite characteristics related to crystallinity and calcium dissolution/uptake rates are very sensitive to the nature of cationic substitution. Cytocompatibility was evaluated by mitochondrial activity, membrane integrity, cell density, proapoptotic potential, and adhesion tests. With the exception of Zn-HA, all the substituted HAs induced some level of apoptosis. The highest apoptosis levels were observed for Mg-HA and Co-HA. Cu-HA was the only material to impair simultaneously mitochondrial activity, membrane integrity, and cell density. The highest relative cell densities after exposure to the modified HAs were observed for Mg-HA and Zn-HA, while Co-HA significantly improved cell adhesion onto HA surface. These results show that changes on surface dissolution caused by cationic substitution, as well as the increase of metal species released to biological media, were the main responsible factors related to alterations on HA biocompatibility.
The role of toll-like receptor 2 in the recognition of Aggregatibacter actinomycetemcomitans. Gelani V, Fernandes AP, Gasparoto TH, Garlet TP, Cestari TM, Lima HR, Ramos ES, de Souza Malaspina TS, Santos CF, Garlet GP, da Silva JS, Campanelli AP. J Periodontol 2009 Dec;80(12):2010-9. PMID:19961384 [PubMed - indexed for MEDLINE]
Abstract. 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.
Research in humans: medical, legal, psychological and religious aspects. Marsicano, JA; Ramos-Junior ES; Assumpção, TS; Sales Peres, SHC; Sales Peres, A.RGO, Porto Alegre, 2008. jul./set: 56(3):327-32. [Article in Portuguese].
Abstract: Modern society is witnessing unprecedented technological and scientific progress. The development in medicine can partly be attributed to research in human beings, but this can frequently interfere in a manner that is harmful to the research subjects. Several factors had a great historical impact, and imposed the need for discussions of an ethical nature, such as the atrocious experiments conducted by scientists in prisoners during the last World War, which motivated the publication of the Nuremberg Code, which for the first time, established rules to be observed in research involving human beings. From this, other regulations appeared in response to the atrocities committed in research, with principles inherent to any ethical or mandatory code. However, moral values differ from one society to another, generating dilemmas that involve technological, biological, belief and theological revolutions. Thus, ethicists have been obliged to consider disciplines beyond their specificities, in order to establish frontiers with various fields of knowledge, as the progress achieved up to now, has raised ethical questions to which knowledge itself frequently has no satisfactory answers. This study examines the words of ethics and morality with a medical, religious legal and psychological focus, in a practical manner, endeavoring the delineation their differences and similarities.
Oral health and presence of Candida in the oral cavity of patients under treatment in dental clinics of UEPG. Publicatios UEPG – Biological and Health Science, *(1): 57-73, 2002 [Article in Portuguese].