Considerations for long-term clinical performance of partial restorations:exploring the pathway to success

Restorative dentistry has evolved significantly, emphasizing the importance of partial restorations in preserving natural tooth structure. Advances in adhesive systems play a pivotal role in extending their longevity and promoting minimally invasive dentistry. The second chapter of the thesis, a systematic review, revealed that intracoronal gold restorations outperform indirect resin composites, while lithium disilicate shows promise as a dental material. Laboratory studies on direct composite and lithium disilicate partial restorations in chapters 3, 4, and 5 show good results, which argue for minimal invasive preparation. The use of immediate dentin sealing improves the fracture strength of the restorations. The clinical studies included in this thesis report long-term follow-up. A retrospective clinical study in chapter 6, spanning 15 years, highlights the remarkable longevity of extensive direct resin composite restorations after replacing amalgams. A long-term randomized clinical trial in chapter 7 showcases the suitability of both direct and indirect resin composites for restoring maxillary premolars with cusp-replacing restorations. Chapter 8 focuses on long-term partial indirect lithium disilicate restorations, exhibiting excellent clinical survival over 7.5 years, with specific patient factors impacting their longevity. Chapter 9 highlights the medium-term clinical excellence of indirect lithium disilicate restorations, where no influence of preparation characteristics on the survival and success of the restorations was seen. Chapter 10 discusses the individual chapters, the connections, and correlations between the studies, as well as the limitations in the aforementioned chapters. Additionally, recommendations for future research were made, and some considerations for the daily application of partial restorations were formulated

The Influence of Dentin Wall Thickness and Adhesive Surface in Post and Core Crown and Endocrown Restorations on Central and Lateral Incisors

Purpose: The main purpose of this study was to determine the influence of dentin wall thickness (DWT) and adhesive surface on the fracture strength and failure mode in maxillary incisors restored with post and core crowns or endocrowns. Methods and Materials: Forty-eight sound maxillary incisors were selected and randomly divided into four groups (n=12): lateral incisor endocrown, lateral incisor post and core, central incisor endocrown, and central incisor post and core. All specimens obtained an endodontic treatment and were decoronated (2 mm ferrule remained). Chamfer outlines ended at the cementoenamel junction (outline in dentin). Dentin wall thickness (mm) was measured on 12 points per sample using a modified digital calliper. Fiber posts and cores were placed in two groups, and an immediate dentin sealing was applied on exposed dentin in all groups before taking digital impressions. Digital impressions were analyzed and the adhesive surface (mm(2)) was measured. Indirect restorations were made of lithium disilicate (IPS e.max, computer-aided design/computer-aided manufacturing). The restorations were luted after surface conditioning the crowns and teeth. Thermocyclic aging was performed (10,000 times in baths of 5 degrees C and 55 degrees C) and the specimens were loaded until fracture. Fractures were specified on failure mode and repairability, and they were analyzed with one-way ANOVA, chi(2)-test, and linear regression analysis in SPSS (alpha=0.05). Results: There was no significant difference in fracture strength and failure mode between all groups. Endocrown restorations on central incisors had significantly more repairable fractures than the post and core crowns. Regression analyses showed a statistically significant positive correlation between DWT/adhesive surface and fracture strength in the post and core groups. Conclusions: Both endocrowns and post and core crowns on the central and lateral incisors obtained clinically applicable fracture strengths. In the central incisor groups, the endocrown restorations had significantly more repairable failures. When the walls were thicker, or when the adhesive surface was larger, higher fracture strengths were obtained in the post and core groups

Recombinant hirudin: kinetic mechanism for the inhibition of human thrombin

Recombinant hirudin variant-2(Lys47 ), was found to be a competitive inhibitor of human α-thrombin with respect to peptidyl p-Miitroanilide substrates. These results contrast with those of Degryse and coworkers that suggest that recombinant hirudin variant-2(Lys47) inhibited thrombin by a non-competitive mechanism [Degryse et al. (1989) Protein Engng, 2, 459-465], γ-Thrombin, which can arise from α-thrombin by autolysis, was shown to have an affinity for recombinant hirudin variant-2(Lys47) that was four orders of magnitude lower than that of α-thrombin. It was demonstrated that the apparent noncompetitive mechanism observed previously was probably caused by a contamination of the thrombin preparation by γ-thrombin. Comparison of the inhibition of α-thrombin by recombinant hirudins variant-2(Lys47) and variant-1, which differ from one another in eight out of 65 amino acids, indicated that the two variants have essentially the same kinetic parameter

Caveolin-1 interacts with the chaperone complex TCP-1 and modulates its protein folding activity

Abstract.: We report that caveolin-1, one of the major structural protein of caveolae, interacts with TCP-1, a hetero-oligomeric chaperone complex present in all eukaryotic cells that contributes mainly to the folding of actin and tubulin. The caveolin-TCP-1 interaction entails the first 32 amino acids of the N-terminal segment of caveolin. Our data show that caveolin-1 expression is needed for the induction of TCP-1 actin folding function in response to insulin stimulation. Caveolin-1 phosphorylation at tyrosine residue 14 induces the dissociation of caveolin-1 from TCP-1 and activates actin folding. We show that the mechanism by which caveolin-1 modulates TCP-1 activity is indirect and involves the cytoskeleton linker filamin. Filamin is known to bind caveolin-1 and to function as a negative regulator of insulin-mediated signaling. Our data support the notion that the caveolin-filamin interaction contributes to restore insulin-mediated phosphorylation of caveolin, thus allowing the release of active TCP-

Recombinant human interleukin-12 is the second example of a C-mannosylated protein

The β-chain of human interleukin 12 (IL-12) contains at position 319-322, the sequence Trp-x-x-Trp. In human RNase 2 this is the recognition motif for a new, recently discovered posttranslational modification, i.e., the C-glycosidic attachment of a mannosyl residue to the side chain of tryptophan. Analysis of C-terminal peptides of recombinant IL-12 (rHuIL-12) by mass spectrometry and NMR spectroscopy revealed that Trp-319β is (partially) C-mannosylated. This finding was extended by in vitro mannosylation experiments, using a synthetic peptide derived from the same region of the protein as an acceptor. Furthermore, human B-lymphoblastoid cells, which secrete IL-12, were found to contain an enzyme that carries out the C-mannosylation reaction. This shows that nonrecombinant IL-12 is potentially C-mannosylated as well. This is only the second report on a C-mannosylated protein. However, the occurrence of the C-mannosyltransferase activity in a variety of cells and tissues, and the presence of the recognition motif in many proteins indicate that more C-mannosylated proteins may be foun

Effect of immediate dentine sealing on the aging and fracture strength of lithium disilicate inlays and overlays

Objectives: The objectives of this study were to compare the in vitro, laboratory aging, fracture strength, failure mode and reparability of molars restored with lithium disilicate inlays and overlays in conjunction with or without immediate dentin sealing (IDS). Methods: Forty extracted, sound human molars were selected and divided into four groups: 1) Inlays with IDS; 2) Inlays without IDS; 3) Overlays with IDS; 4) Overlays without IDS. Standard MOD preparations were made (3 mm wide, 5 mm deep) and in groups 2 and 4, all the cusps were reduced by 2 mm. Directly following tooth preparation, IDS was applied in specimens belonging to groups 1 and 3. The indirect restorations were luted with a heated composite. The restored teeth were subsequently challenged during aging (1.2 million cycles) and thermocycling loading (8000 cycles, 5–55 degrees C). Subsequently, the fracture strength was tested by a load to failure test at 45°. A failure analysis was performed using light- and scanning electron microscopy. The results were analyzed using two-way ANOVA and a Fisher exact test. Results: Mean fracture load + SD (N) were: Group 1 (n = 12): 1610 ± 419; Group 2 (n = 12): 1115 ± 487; Group 3 (n = 12): 2011 ± 496; Group 4 (n = 12): 1837 ± 406. Teeth restored with an onlay were stronger than those restored with an inlay restoration (p <.001). Teeth with IDS were stronger overall than those without IDS (p =.026). The interaction between preparation type and the mode of dentin conditioning had no statistically significant influence on fracture strength (p =.272). Subsequently, custom hypothesis tests showed that there was no statistically significant difference in fracture strength between inlays with IDS and overlays without IDS (p =.27). Overlays tend to fail in a more destructive, non-reparable way (p =.003). Significance: Both variables IDS and overlay preparation improve overall fracture strength. Inlays with IDS and overlays without IDS didn't differ in fracture strength. Both inlays and overlays are strong enough to withstand physiological chewing forces

C-mannosylation supports folding and enhances stability of thrombospondin repeats.

Previous studies demonstrated importance of C-mannosylation for efficient protein secretion. To study its impact on protein folding and stability, we analyzed both C-mannosylated and non-C-mannosylated thrombospondin type 1 repeats (TSRs) of netrin receptor UNC-5. In absence of C-mannosylation, UNC-5 TSRs could only be obtained at low temperature and a significant proportion displayed incorrect intermolecular disulfide bridging, which was hardly observed when C-mannosylated. Glycosylated TSRs exhibited higher resistance to thermal and reductive denaturation processes, and the presence of C-mannoses promoted the oxidative folding of a reduced and denatured TSR in vitro. Molecular dynamics simulations supported the experimental studies and showed that C-mannoses can be involved in intramolecular hydrogen bonding and limit the flexibility of the TSR tryptophan-arginine ladder. We propose that in the endoplasmic reticulum folding process, C-mannoses orient the underlying tryptophan residues and facilitate the formation of the tryptophan-arginine ladder, thereby influencing the positioning of cysteines and disulfide bridging