Over-nutrition and metabolic cardiomyopathy

Cardiovascular disease, which accounts for the highest morbidity and mortality in the United States, has several major risk factors, including aging and diabetes. Overweight and obesity, especially abdominal obesity, have been increasingly implicated as independent risk factors in the development of cardiovascular disease. Metabolic and/or diabetic cardiomyopathy has been especially associated with excess body weight caused by chronic over-nutrition and high-fat feeding. In the initial stages, obesity is now understood to cause significant dysregulation of cardiac fatty acid and glucose metabolism. These abnormalities are due, in part, to increased oxidative stress, which in turn can cause deleterious effects on intracellular signaling pathways that control cellular growth and proliferation. This increase in oxidative stress is coupled with reduced anti-oxidant species and dysregulation of metabolic signaling pathways. The cardiomyopathy seen with obesity is associated with increased interstitial fibrosis and diastolic dysfunction. Over time, evolving abnormalities include hypertrophy and systolic dysfunction, eventually leading to heart failure.     

Addition of zinc methacrylate in dental polymers: MMP-2 inhibition and ultimate tensile strength evaluation

This study evaluated the effect of zinc methacrylate (ZM) on the inhibition of matrix metalloproteinase 2 (MMP-2) and the ultimate tensile strength (UTS) of an experimental polymer. Enzymes secreted from mouse gingival tissues were analyzed by gelatin zymography in buffers containing 5 mM CaCl₂ (Tris–CaCl₂) in 50 mM Tris–HCl buffer with various concentrations of ZM (0.5, 1, 2, 4, 8, and 16 mM). The matrix metalloproteinases present in the conditioned media were characterized by immunoprecipitation. The polymer UTS evaluation was performed in eight groups with various concentrations of ZM (0, 0.5, 1, 2.5, 5, 10, 20, and 30 wt.%), in a mechanical testing machine. MMP-2 (62 kDa) was detected in the zymographic assays and inhibited by ZM in all tested concentrations. UTS data were submitted to one-way ANOVA and Tukey's test (α = 0.05), and no significant differences were observed among groups, except in the polymer containing 30% ZM, presenting a significantly lower value when compared with the control group (p < 0.05). The results suggest that ZM inhibits MMP-2 expression in all concentrations tested, while small concentrations did not affect the ultimate tensile strength of the polymer. Zinc methacrylate is a metalloproteinase inhibitor that can be copolymerized with other methacrylate monomers. Yet, the addition of ZM did not affect the resin bond strength. Thus, in vivo tests should be performed to evaluate the performance of this material.     

A randomized double-blind clinical trial of posterior composite restorations with or without bevel: 1-year follow-up

Objective

This randomized double-blind clinical trial compared the performance of posterior composite restorations with or without bevel, after 1-year follow-up.

Material and Methods

Thirteen volunteers requiring at least two posterior composite restorations were selected. Twenty-nine cavities were performed, comprising 14 without bevel (butt joint) and 15 with bevel preparation of the enamel cavosurface angle. All cavities were restored with simplified adhesive system (Adper Single Bond) and composite resin (Filtek P60). A halogen light curing unit was used through the study. Restorations were polished immediately. Analysis was carried out at baseline, after 6 months and after 1 year by a calibrated evaluator (Kappa), according to the FDI criteria. Data were statistically analyzed by Mann-Whitney test (p<0.05).

Results

Beveled and non-beveled cavities performed similarly after 1 year follow-up, regarding to fractures and retention, marginal adaptation, postoperative hypersensitivity, recurrence of caries, surface luster and anatomic form. However, for surface and marginal staining, beveled cavities showed significantly better performance (p<0.05) than butt joint restorations.

Conclusions

It was concluded that the restorations were acceptable after 1 year, but restorations placed in cavities with marginal beveling showed less marginal staining than those placed in non-beveled cavities.     

Effects of long-term water storage on the microtensile bond strength of five experimental self-etching adhesives based on surfactants rather than HEMA

Objectives

The purpose of this study is to evaluate the hypothesis that replacing 2-hydroxyethyl methacrylate (HEMA) for surfactant dimethacrylates (SD) does not affect the immediate and long-term microtensile bond strength (μTBS) of experimental two-step self-etch HEMA-free adhesive systems applied on dentin.

Materials and methods

Five experimental HEMA-free two-step self-etching systems containing different SD (ethoxylated bisphenol A diglycidyl dimethacrylate (Bis-EMA 10, B10), Bis-EMA 30 (B30), poly-ethyleneglycol (400) dimethacrylate (PEG 400, P400), PEG 1000 (P1000), and PEG 400 urethane dimethacrylate (UDMA) (UP400)) and a HEMA-containing system (control) (HA) were formulated. Specimens were subjected to the μTBS test after 24 h and 6 and 12 months of storage. Data (in megapascals) were analyzed by Kruskal–Wallis and Dunn tests (α?=?0.05).

Results

Medians of the μTBS data after 24 h of storage are: HA?=?57.2^A, B10?=?26.2^BC, B30?=?24.0^C, P400?=?32.6^BC, P1000?=?37.3^B, and UP400?=?57.9^A; after 6 months are: HA?=?47.9^A, B10?=?18.5^B, B30?=?7.8^C, P400?=?16.1^B, P1000?=?14.6^BC, and UP400?=?51.6^A; and after 12 months are: HA?=?31.2^A, B10?=?15.2^B, B30?=?9.0^B, P400?=?9.1^B, P1000?=?13.3^B, and UP400?=?35.7^A. Between the HEMA-free groups, the adhesive system formulated with PEG 400 UDMA produced similar μTBS to the HEMA-containing group. Also, the storage of specimens decreased the μTBS (p?<?0.05).

Conclusion

Replacing HEMA for PEG 400 UDMA in an adhesive system formulation generated a satisfactory μTBS to dentin.

Clinical relevance

Surfactant dimethacrylates have a potential use in the development of HEMA-free self-etching adhesive systems, which are more chemically stable.     

Effect of cariogenic biofilm challenge on the surface hardness of direct restorative materials in situ

Objectives

The presence of cariogenic biofilm could result in surface degradation of composite and ionomeric restorative materials. Thus, this study evaluated in situ the alterations in the surface microhardness of these materials under biofilm accumulation and cariogenic challenge.

Methods

In a split-mouth, double-blind, cross-over study, 10 volunteers wore palatal intra-oral devices containing bovine enamel slabs restored with composite resin (CR – Z250) or resin-modified glass ionomer (RMGI – Vitremer). Two phases of 14 days were carried out, one for each restorative material. In one side of the device, biofilm was allowed to accumulate under a plastic mesh, whereas in the opposing side, regular brushing was carried out 3 times/day with a dentifrice containing 1100 μg F/g as NaF. A 20% sucrose solution was applied extra-orally 10×/day on each restored dental slab. Knoop microhardness was used to calculate the percentage of surface hardness loss (%SHL).

Results

All materials showed a decrease in surface hardness after the in situ period. The restorative materials presented the following average for %SHL: RMGI without biofilm accumulation = 8.9 and with biofilm accumulation = 25.6, CR without biofilm accumulation = 14.7 and with biofilm accumulation = 17.0.

Conclusion

Biofilm accumulation and the presence of cariogenic challenge promoted faster degradation of ionomeric materials, but this was not observed for composite resin.

Clinical significance

The oral environment affects the surface hardness of aesthetic restorative materials. Biofilm accumulation and cariogenic challenge promote surface degradation for ionomeric materials, but not for composite resin.     

Murine FLIP transgene expressed on thyroid epithelial cells promotes resolution of granulomatous experimental autoimmune thyroiditis in DBA/1 mice

Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by mouse thyroglobulin-sensitized splenocytes activated in vitro with mouse thyroglobulin and interleukin-12. In wild-type (WT) DBA/1 recipients of WT donor splenocytes, thyroid lesions reach maximal severity at day 20, with ongoing inflammation and extensive fibrosis at day 60. Our previous studies indicated the site of expression of FLIP and Fas ligand [thyroid epithelial cells (TECs) versus inflammatory cells] differed in mice when lesions would resolve or progress to fibrosis. To test the hypothesis that expression of FLIP by TECs would promote earlier G-EAT resolution in DBA/1 mice, transgenic (Tg) DBA/1 mice expressing FLIP on TECs were generated. In FLIP Tg(+) and Tg(-) littermate recipients of WT donor splenocytes, G-EAT severity was comparable at day 20, but fibrosis was decreased, and many lesions resolved by day 60 in Tg(+) but not Tg(-) recipients. FLIP and Fas ligand were primarily expressed by TECs in Tg(+) recipients and by inflammatory cells in Tg(-) recipients at day 60. Apoptosis of inflammatory cells was greater, and expression of proinflammatory cytokines was decreased in thyroids of Tg(+) compared with Tg(-) recipients. These results are consistent with the hypothesis that transgenic expression of FLIP on thyroid epithelial cells promotes earlier resolution of granulomatous experimental autoimmune thyroiditis.     

Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients

The molecular characterization of the mutations in hemophilia A patients is hampered by the large size of the factor VIII gene and the great heterogeneity of mutations. In this study, we have performed a protocol involving multiplex polymerase chain reaction in which 19 exons were amplified in four different combinations followed by nonradioactive single-strand conformational polymorphism (SSCP) to screen for mutations. Southern blotting was used to detect inversion of the factor VIII gene resulting from recombination between copies of the gene A (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VIII occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed after Southern blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectively. Sixteen different mutations were identified. Eleven mutations were novel and comprised 9 point mutations and 2 small deletions. This study shows that the methodology used is safe and rapid and has potential for detecting almost all of the genetic defects of the studied hemophilia A patients.