Therapy with mesenchymal stromal cells or conditioned medium reverse cardiac alterations in a high-fat diet-induced obesity model.

BACKGROUND: Obesity is associated with numerous cardiac complications, including arrhythmias, cardiac fibrosis, remodeling and heart failure. Here we evaluated the therapeutic potential of mesenchymal stromal cells (MSCs) and their conditioned medium (CM) to treat cardiac complications in a mouse model of high-fat diet (HFD)-induced obesity. METHODS: After obesity induction and HFD withdrawal, obese mice were treated with MSCs, CM or vehicle. Cardiac function was assessed using electrocardiography, echocardiography and treadmill test. Body weight and biochemical parameters were evaluated. Cardiac tissue was used for real time (RT)-polymerase chain reaction (PCR) and histopathologic analysis. RESULTS/DISCUSSION: Characterization of CM by protein array showed the presence of different cytokines and growth factors, including chemokines, osteopontin, cystatin C, Serpin E1 and Gas 6. HFD-fed mice presented cardiac arrhythmias, altered cardiac gene expression and fibrosis reflected in physical exercise incapacity associated with obesity and diabetes. Administration of MSCs or CM improved arrhythmias and exercise capacity. This functional improvement correlated with normalization of GATA4 gene expression in the hearts of MSC- or CM-treated mice. The gene expression of connexin 43, troponin I, adiponectin, transforming growth factor (TGF) ß, peroxisome proliferator activated receptor gamma (PPARγ), insulin-like growth factor 1 (IGF-1), matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1) were significantly reduced in MSCs, but not in CM-treated mice. Moreover, MSC or CM administration reduced the intensity of cardiac fibrosis. CONCLUSION: Our results suggest that MSCs and CM have a recovery effect on cardiac disturbances due to obesity and corroborate to the paracrine action of MSCs in heart disease models.

Influence of matrix metalloproteinase synthetic inhibitors on dentin microtensile bond strength of resin cements.

This study evaluated the effect of dentin pretreatment with 2% chlorhexidine (CHX) or 24% ethylenediamine tetra-acetic acid gel (EDTA) on the dentin microtensile bond strength (µTBS) of resin cements. Composite blocks were luted to superficial noncarious human dentin (n=10) using two resin cements (RelyX ARC [ARC] and RelyX U100 [U100]) and three dentin pretreatments (without pretreatment-control, CHX, and EDTA). CHX was applied for 60 seconds on the acid-etched dentin in the ARC/CHX group, and for the same time on smear layer-covered dentin in the U100/CHX group. EDTA was applied for 45 seconds on smear-covered dentin in the U100/EDTA group, and it replaced phosphoric acid conditioning in the ARC/EDTA group for 60 seconds. After storage in water for 24 hours, specimens were prepared for microtensile bond strength testing. The results were submitted to two-way analysis of variance (ANOVA) followed by Tukey test. ARC produced significantly higher µTBS (p<0.05) compared to the U100, except when EDTA was used. For ARC, no pretreatment and CHX produced higher µTBS than EDTA. For U100, EDTA produced higher µTBS; no statistical difference occurred between CHX pretreatment and when no pretreatment was performed. While CHX did not affect immediate dentin bond strength of both cements, EDTA improved bond strength of U100, but it reduced dentin bond strength of ARC.

Dentin Bonding Testing Using a Mini-interfacial Fracture Toughness Approach.

Measurement of interfacial fracture toughness (iFT) is considered a more valid method to assess bonding effectiveness as compared with conventional bond strength testing. Common fracture toughness tests are, however, laborious and require a relatively bulky specimen size. This study aimed to evaluate a new simplified and miniaturized iFT (mini-iFT) test. Four dentin adhesives, representing the main adhesive classes, and 1 glass ionomer cement were applied onto flat dentin. Mini-iFT (1.5 × 2.0 × 16 to 18 mm) and microtensile bond strength (µTBS; 1.5 × 1.5 × 16 to 18 mm) specimens were prepared from the same tooth. For the mini-iFT specimens, a single notch was cut at the adhesive-dentin interface with a 150-µm diamond blade under water cooling; the specimens were loaded until failure in a 4-point bending test setup. Finite element analysis was used to analyze stress distribution during mini-iFT testing. The correlation between the mean mini-iFT and µTBS was examined and found to be significant; a strong positive correlation was found (r(2) = 0.94, P = 0.004). Weibull data analysis suggested the mini-iFT to vary less than the µTBS. Both the mini-iFT and the µTBS revealed the same performance order, with the 3-step etch-and-rinse adhesive outperforming the 2-step self-etch and 2-step etch-and-rinse adhesive, followed by the 1-step SE adhesive and, finally, the glass ionomer cement. Scanning electron microscopy failure analysis revealed the adhesive-dentin interface to fail more at the actual interface with the mini-iFT test, while µTBS specimens failed more within dentin and composite. This finding was corroborated by finite element analysis showing stress to concentrate at the interface during mini-iFT loading and crack propagation. In conclusion, the new mini-iFT test appeared more discriminative and valid than the µTBS to assess bonding effectiveness; the latter test nevertheless remains more versatile. Specimen size and workload were alike, making the mini-iFT test a valid alternative for the popular µTBS test.

Incremental filling technique and composite material--part II: shrinkage and shrinkage stresses.

OBJECTIVES: Finite element analysis (FEA) was used to study polymerization shrinkage stress in molars restored with composites and to correlate those stresses with experimentally measured tooth deformation. METHODS: Three composites (Filtek LS, Aelite LS Posterior, Filtek Supreme) and three filling techniques (bulk, 2.0-mm increments, and 1.0-mm increments) for restoring a molar were simulated in a two-dimensional FEA. Polymerization shrinkage was modeled using post-gel shrinkage, which was measured using the strain gauge technique (n=10). Cuspal tooth deformation, measured at the buccal and lingual surfaces with strain gauges in a laboratory study, was used to validate the analysis. Residual shrinkage stresses were expressed in modified von Mises equivalent stresses. Linear Pearson correlations were determined between the laboratory and FEA results. RESULTS: Post-gel shrinkage values (in volume %) were: Filtek LS (0.11 ± 0.03) < Aelite LS Posterior (0.51 ± 0.02) < Filtek Supreme (0.62 ± 0.09). The 1.0-mm increment filling caused substantially higher stresses and strains in the cervical enamel region. Significant correlations were found between: elastic modulus and FEA strain, elastic modulus and FEA stress, post-gel shrinkage and FEA strain, post-gel shrinkage and FEA stress, FEA strain and cuspal deformation by strain gauge, and FEA stress and cuspal deformation by strain gauge (p<0.05). CONCLUSIONS: Increasing the number of increments and high post-gel shrinkage and/or elastic modulus values caused higher stresses in the remaining tooth structure and tooth/restoration interface. Cuspal deformation measured with the strain gauge method validated the finite element analyses.