Sao Leopoldo Mandic Institute

Swift, Brazil

Sao Leopoldo Mandic Institute

Swift, Brazil
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Alves C.F.,University of Uberaba | De Melo N.F.S.,University of Campinas | De Melo N.F.S.,São Paulo State University | Fraceto L.F.,University of Campinas | And 4 more authors.
British Journal of Pharmacology | Year: 2011

Background and Purpose: The PPAR-γ agonist 15d-PGJ 2 is a potent anti-inflammatory agent but only at high doses. To improve the efficiency of 15d-PGJ 2, we used poly(D,L-lactide-co-glycolide) nanocapsules to encapsulate it, and function as a drug carrier system. The effects of these loaded nanocapsules (15d-PGJ 2-NC) on inflammation induced by different stimuli were compared with those of free 15d-PGJ 2. Experimental Approach: Mice were pretreated (s.c.) with either 15d-PGJ 2-NC or unloaded 15d-PGJ 2 (3, 10 or 30 μg•kg -1), before induction of an inflammatory response by i.p. injection of either endotoxin (LPS), carrageenan (Cg) or mBSA (immune response). Key Results: The 15d-PGJ 2-NC complex did not display changes in physico-chemical parameters or drug association efficiency over time, and was stable for up to 60 days of storage. Neutrophil migration induced by i.p. administration of LPS, Cg or mBSA was inhibited by 15d-PGJ 2-NC, but not by unloaded 15d-PGJ 2. In the Cg model, 15d-PGJ 2-NC markedly inhibited serum levels of the pro-inflammatory cytokines TNF-α, IL-1β and IL-12p70. Importantly, 15d-PGJ 2-NC released high amounts of 15d-PGJ 2, reaching a peak between 2 and 8 h after administration. 15d-PGJ 2 was detected in mouse serum after 24 h, indicating sustained release from the carrier. When the same concentration of unloaded 15d-PGJ 2 was administered, only small amounts of 15d-PGJ 2 were found in the serum after a few hours. Conclusions and Implications: The present findings clearly indicate the potential of the novel anti-inflammatory 15d-PGJ 2 carrier formulation, administered systemically. The formulation enables the use of a much smaller drug dose, and is significantly more effective compared with unloaded 15d-PGJ 2. © 2011 The Authors.

Jee K.J.,University of Turku | Jee K.J.,University of Helsinki | Persson M.,Gothenburg University | Heikinheimo K.,University of Turku | And 11 more authors.
Modern Pathology | Year: 2013

Mucoepidermoid carcinoma is the most common salivary gland malignancy, and includes a spectrum of lesions ranging from non-aggressive low-grade tumors to aggressive high-grade tumors. To further characterize this heterogeneous group of tumors we have performed a comprehensive analysis of copy number alterations and CRTC1-MAML2 fusion status in a series of 28 mucoepidermoid carcinomas. The CRTC1-MAML2 fusion was detected by RT-PCR or fluorescence in situ hybridization in 18 of 28 mucoepidermoid carcinomas (64%). All 15 low-grade tumors were fusion-positive whereas only 3 of 13 high-grade tumors were fusion-positive. High-resolution array-based comparative genomic hybridization revealed that fusion-positive tumors had significantly fewer copy number alterations/tumor compared with fusion-negative tumors (1.5 vs 9.5; P=0.002). Twelve of 18 fusion-positive tumors had normal genomic profiles whereas only 1 out of 10 fusion-negative tumors lacked copy number alterations. The profiles of fusion-positive and fusion-negative tumors were very similar to those of low-and high-grade tumors. Thus, low-grade mucoepidermoid carcinomas had significantly fewer copy number alterations/tumor compared with high-grade mucoepidermoid carcinomas (0.7 vs 8.6; P<0.0001). The most frequent copy number alterations detected were losses of 18q12.2-qter (including the tumor suppressor genes DCC, SMAD4, and GALR1), 9p21.3 (including the tumor suppressor genes CDKN2A/B), 6q22.1-q23.1, and 8pter-p12.1, and gains of 8q24.3 (including the oncogene MAFA), 11q12.3-q13.2, 3q26.1-q28, 19p13.2-p13.11, and 8q11.1-q12.2 (including the oncogenes LYN, MOS, and PLAG1). On the basis of these results we propose that mucoepidermoid carcinoma may be subdivided in (i) low-grade, fusion-positive mucoepidermoid carcinomas with no or few genomic imbalances and favorable prognosis, (ii) high-grade, fusion-positive mucoepidermoid carcinomas with multiple genomic imbalances and unfavorable prognosis, and (iii) a heterogeneous group of high-grade, fusion-negative adenocarcinomas with multiple genomic imbalances and unfavorable outcome. Taken together, our studies indicate that molecular genetic analysis can be a useful adjunct to histologic scoring of mucoepidermoid carcinoma and may lead to development of new clinical guidelines for management of these patients. © 2013 USCAP, Inc. All rights reserved.

Barreto I.,University of Campinas | Costa A.F.,University of Campinas | Martins M.T.,University of Sao Paulo | Furuse C.,Sao Leopoldo Mandic Institute | And 2 more authors.
Virchows Archiv | Year: 2011

Tonsillar polyps are nonneoplastic lesions usually composed of variable amounts of lymphoid and vascular and connective tissues. All of them are generally assumed to be hamartomatous proliferations, but the profile of vascular and connective components has yet to be explored. The vascular system of the tonsils is complex and includes highly specialized structures (i.e., high endothelial venules (HEVs)) involved in lymphocyte homing into lymphoid tissues. In 14 tonsillar polyps and 26 control tonsils, an immunohistochemical study was performed using CD34 (blood vessels and HEVs), MECA-79 (HEVs), D2-40 (lymphatic vessels), Ki-67, collagens I and III, fibronectin, and tenascin-C. The polyps showed increased total lymphatic area, whereas the number of blood vessels and lymphatics and the blood vascular area did not differ significantly from those of control tonsils. Rare Ki-67+ endothelial cells were found. In the polyps, we detected, possibly for the first time, HEVs amid lymphoid tissue, and that the amount of the latter correlated positively with HEV density. The polyps also presented lesser amounts of fibronectin and collagens I and III than in normal tonsils, which were distributed in a disorganized fashion. Tenascin-C expression was uncommon in the polyps and control tonsils. Tonsillar polyps are composed of disorganized connective tissue and lymphatic channels which can be considered hamartomatous proliferations. However, the lymphoid component is possibly reactive due to its relationship with the HEVs. The highly differentiated phenotype of the HEVs and their complex biology are not in agreement with what would be expected for a component of hamartomatous nature. © 2011 Springer-Verlag.

Lepri T.P.,University of Sao Paulo | Colucci V.,University of Sao Paulo | Turssi C.P.,Sao Leopoldo Mandic Institute | Corona S.A.M.,University of Sao Paulo
Lasers in Medical Science | Year: 2013

This study evaluated the combined effect of fluoride compounds and CO 2 laser in controlling the permeability of eroded enamel. Bovine enamel slabs (3 × 2 mm) were cycled twice through an alternating erosion and remineralization regimen. Slabs were immersed in 20 ml of orange juice (pH 3.84) for 5 min under agitation, rinsed with deionized water, and stored in artificial saliva for 4 h to form erosive lesions. Specimens were then divided into four groups (n = 10), which were treated for 1 min with either a control or with one of the following gels: amine fluoride (AmF), titanium tetrafluoride (TiF4), or sodium fluoride (NaF). Half of the specimens were irradiated with a CO2 laser (λ = 10.6 μm; 2.0 W). Specimens were cycled two more times through the aforementioned erosion-remineralization regimen and were subjected to permeability assessment. ANOVA demonstrated a significant interaction between fluoride and laser treatment (p = 0.0152). Tukey's test showed that when fluoride was applied alone, TiF4 resulted in lower enamel permeability than that observed after application of the placebo gel. Intermediate permeability values were noted after NaF and AmF had been used. A significant reduction in enamel permeability was obtained when fluoride was combined with CO2 laser treatment, with no difference between fluoride gels. Permeability of eroded enamel may be reduced by combining the application of fluoride gels with CO2 laser irradiation. © 2012 Springer-Verlag London Ltd.

Bueno-Silva B.,University of Campinas | Alencar S.M.,University of Sao Paulo | Koo H.,University of Rochester | Ikegaki M.,Federal University of Alfenas | And 3 more authors.
Journal of Agricultural and Food Chemistry | Year: 2013

The objective of this study was to evaluate anti-inflammatory and antimicrobial activities of neovestitol and vestitol isolated from Brazilian red propolis (BRP). BRP ethanolic extract (EEP), neovestitol, and vestitol were evaluated by anti-inflammatory properties using a neutrophil migration assay. The antimicrobial activity was evaluated by minimal inhibitory and bactericidal concentrations (MIC and MBC) against Streptococcus mutans, Streptococcus sobrinus, Staphylococcus aureus, and Actinomyces naeslundii. Neovestitol, vestitol, and EEP inhibited neutrophil migration at a dose of 10 mg/kg. Regarding antimicrobial activity, neovestitol showed MICs ranging from <6.25 to 25-50 μg/mL and MBCs ranging from 25-50 to 50-100 μg/mL, while vestitol showed MICs ranging from 25-50 to 50-100 μg/mL and MBCs ranging from 25-50 to 50-100 μg/mL. Both isoflavonoids neovestitol and vestitol are consistent bioactive compounds displaying anti-inflammatory and antimicrobial activities that can strongly act in a low dose and concentration and have a promising potential to be applied in the pharmaceutical and food industries. © 2013 American Chemical Society.

Severino V.O.,Federal University of Triângulo Mineiro | Napimoga M.H.,University of Uberaba | Napimoga M.H.,Sao Leopoldo Mandic Institute | De Lima Pereira S.A.,Federal University of Triângulo Mineiro | De Lima Pereira S.A.,University of Uberaba
Archives of Oral Biology | Year: 2011

Objectives: The aim of this study was to compare the levels of cytokines IL-6, IL-10 and IL-17 and the chemokine IL-8 in the peri-implant crevicular fluid (PCF) between the group of patients with peri-implantitis (PP) and peri-implantar healthy patients (HP). Design: The PCF was collected from 40 implants regarding 25 patients, being 14 patients with PP and 11 HP totalizing 20 implants from each group. The PCF samples collected from each patient were quantified for IL-6, IL-17, IL-8 and IL-10 using the enzymatic immunosorbent assay (ELISA). Results: The expression of IL-17 was significantly higher in the PP group when compared to HP (p < 0.05). There was no significant difference when comparing the levels of IL-6, IL-8 and IL-10 between both groups HP and PP. Also, there was a significant positive correlation between levels of IL-6 and IL-8 in the PP group. Conclusions: This study demonstrates that in patients with peri-implantitis there is an increase of IL-17 which may induce the production of other inflammatory cytokines, contributing to the pathogenesis of bone loss in peri-implantitis. © 2011 Elsevier Ltd. All rights reserved.

Leal R.C.,Sao Leopoldo Mandic Institute | Amaral F.L.B.,Sao Leopoldo Mandic Institute | Franc a F.M.G.,Sao Leopoldo Mandic Institute | Basting R.T.,Sao Leopoldo Mandic Institute | Turssi C.P.,Sao Leopoldo Mandic Institute
Angle Orthodontist | Year: 2014

Objective: To evaluate the effect of different lubricants on friction between orthodontic brackets and archwires. Materials and Methods: Active (Quick, Forestadent) and passive (Damon 3MX, Ormco) self-ligating brackets underwent friction tests in the presence of mucin- and carboxymethylcellulose (CMC)-based artificial saliva, distilled water, and whole human saliva (positive control). Dry friction (no lubricant) was used as the negative control. Bracket/wire samples (0.014 x 0.025 inch, CuNiTi, SDS Ormco) underwent friction tests eight times in a universal testing machine. Results: Two-way analysis of variance showed no significant interaction between bracket type and lubricant (P = .324). Friction force obtained with passive self-ligating brackets was lower than that for active brackets (P < .001). Friction observed in the presence of artificial saliva did not differ from that generated under lubrication with natural human saliva, as shown by Tukey test. Higher friction forces were found with the use of distilled water or when the test was performed under dry condition (ie, with no lubricant). Conclusion: Lubrication plays a role in friction forces between self-ligating brackets and CuNiTi wires, with mucin- and CMC-based artificial saliva providing a reliable alternative to human natural saliva. © 2014 by The EH Angle Education and Research Foundation, Inc.

Egal E.S.A.,University of Campinas | Mariano F.V.,University of Campinas | Blotta M.H.,University of Campinas | Pina A.R.,University of Campinas | And 3 more authors.
Placenta | Year: 2014

Introduction: ICAM-1 expression on the villous syncytiotrophoblast (ST) is believed to participate in migration of maternal cells into the inflamed villi regardless of villitis etiology. However, its expression on immune cells in chronic villitis (CV) has yet to be analyzed. ICAM-1 induces cellecell adhesion allowing intercellular communication, T cell-mediated defense mechanism, and inflammatory response. Material and methods: 21 cases of CV (all without an identifiable etiologic agent) and 3 control placentas were analyzed using ICAM-1, and for immune cells CD45, CD3 and CD68. These cells were subdivided according to their location in inflamed villi: a) within the inflamed villi and b) outside forming perivillous aggregates. Results: Large amounts of CD45, CD3 and CD68 were found within the inflamed villi and forming perivillous aggregates attached to areas of trophoblastic loss. Inflamed villi usually showed ICAM-1+ ST. The majority of immune cells surrounding areas of trophoblastic rupture presented marked expression of ICAM-1. In contrast, a small number of immune cells within the inflamed villi exhibited ICAM-1 expression. Only some (<5%) inflamed villi without trophoblastic rupture and with ICAM-1+ ST presented adherence of immune cells. Discussion: In inflamed villi of chronic villitis, the level of ICAM-1 expression on immune cells depends on their location: high in number of cells in the perivillous region and low within the villi. The strongest expression of ICAM-1 on immune cells attached to areas of trophoblastic rupture suggests that the loss of trophoblast can lead to an amplification of the inflammatory response. Copyright © 2014 Elsevier Ltd. All rights reserved.

Simoes D.M.S.,Sao Leopoldo Mandic Institute | Basting R.T.,Sao Leopoldo Mandic Institute | Amaral F.L.B.,Sao Leopoldo Mandic Institute | Turssi C.P.,Sao Leopoldo Mandic Institute | Franca F.M.G.,Sao Leopoldo Mandic Institute
Operative Dentistry | Year: 2014

The aim of this study was to evaluate the effect of a chlorhexidine and/or ethanol application on the bond strength of an etch-and-rinse, hydrophobic adhesive system either under in vitro aging or in situ cariogenic challenge. The dentin surface of 36 human third molars were flattened and allocated into four groups to be treated with chlorhexidine, ethanol, or chlorhexidine + ethanol or left unexposed to any solution (control) (n=9). Then, a resin composite restoration was made on the dentin surface and longitudinal sticks were obtained. Sticks from each tooth were assigned to three test conditions: stored in water in vitro for 24 hours, stored in water in vitro for 6 months, or worn in situ for 14 days. During in situ wear time, a high-cariogenic challenge condition was simulated. Specimens were tested for microtensile bond strength (lTBS). Multivariate analysis of variance and Tukey'stest showedthat chlorhexidine,ethanol, or chlorhexidine + ethanol did not affect the lTBS. The in vitro lTBS values were significantly lower for the specimens stored for 6 months than for those stored for 24 hours. Intermediate lTBS values were shownby the specimens worn in situ. Thus, use of chlorhexidine and/or ethanol was incapable of containing the degradation at the bond interface in the in vitro model. The in situ model was capable of reducing bond strength similarly to the in vitro/6 months model. Despite this, the in situ bond strength was still similar to that of the in vitro/24-hour model.

PubMed | Sao Leopoldo Mandic Institute
Type: Journal Article | Journal: Clinical implant dentistry and related research | Year: 2016

To evaluate in vitro, the efficacy of gutta-percha (GP) and polytetrafluoroethylene (PTFE) tape to act as a seal against the penetration of Escherichia coli through prosthetic implant abutments (PIA) with external hexagon (EH) and morse taper (MT) connections.120 sets of implant analogs with their respective PIA were used. 60 sets from each system were divided into four groups (n=15): I - GP sealing; II - PTFE tape sealing; III - no sealing (NS) and IV - negative control. Microbiological challenge was performed by placing bacterial colonies inside the titanium PIA before screwing them into their respective analogs. Each set was immersed in 5mL of BHI and incubated for 14 days with daily checks for contamination, according to the nutrient medium turbidity.The type of seal used influenced microbial penetration at all evaluation times (p<0.05). Compared to GP, PTFE led to an increase in turbidity and its effectiveness against microbial penetration was equivalent to group NS. When the sealing efficacy of each group was compared in terms of time, Cochrans Q test revealed that in the two groups sealed with PTFE, there was a progressive increase in the number of turbid nutrient media (p<0.0001), while in the group sealed with GP, this was only observed in the MT system (p=0.0310).Sealing the PIA channel with GP was a significantly superior approach to sealing it with PTFE tape. PTFE tape or NS led to a progressive increase in microbiological leakage over time in PIA channels, however, this only occurred with GP in the MT system.

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