Resin-bonded fixed partial dentures (RBFPD) are used as a minimal invasive, tooth-preventing alternative for replacing anterior teeth. Zirconia cantilever restorations were supposed to show sufficient strength for a clinical application. The aim of this investigation was to determine the fracture characteristics of cantilever and two-retainer RBFPD, which are fabricated by computer-manufactured high-strength zirconia. Human incisors and canines were used to form three groups of 14 RBFPDs with different types of preparation: group 1, an invasive cantilever; group 2, a minimal-invasive cantilever and group 3, a two-retainer RBFPD control. After thermal cycling and mechanical loading, which was performed to simulate oral service, all restorations were loaded to fracture in a universal testing machine. One half of the specimens were investigated as a control without simulated service. Mode of failure was determined for the three designs. Both cantilever groups showed comparable fracture resistance of 227 N (no. 1) and 210 N (no. 2) before thermal cycling and mechanical loading. The resistance after aging was reduced to 210 N for the invasive cantilever RBFPD and to 179 N for the minimal invasive group. Three-unit RBFPDs showed a significantly higher (p < 0.02) fracture resistance than cantilever bridges before (426 N) as well as after aging (360 N). Predominant failure was FPD and retainer fracture for the invasive cantilever design, debonding for the minimal cantilever design and RBFPD fracture for the two-retainer design. The present study revealed a significantly higher fracture resistance for two-retainer RBFPDs than for cantilever RBFPDs. The frequency of adhesive debonding increased for non-retentive prepared cantilever RBFPDs.
Schon wiederholt ist die Beobachtung gemacht worden, dab bei Kurztagspflanzen Hemmungen in der Blfitenbildung auftreten, wenn ~ich Teile der Pfl~nze, besonders L~ubbl~tter, ira Langtag befinden. Das ist vor allem in Versttcheh festgestellt worden, bei denen angestrebt wurde, einen Bliihimpuls yon einem dem Kurztag ausgesetzten Ast ~uf einen sich im L~ngtag befindenden der gleichen Pflanze hiniiberzu]eiten, iJber solche das Bliihen hemmende Wirkungen durch BlOtter in der ,,verkehrten" Tagesl~nge (GARNER und ALLAR~ MEL-CriERS und LANG 1948) sind nachstehend einige Beobach~ungen an KaIanchog Blo[3/eldiana geschildert. I. Experimenteller Teil. A. Methodik.:Die zu den Vorsuchen verwendeten Pflanzen waren, wenn nicht anders angegeben, etwa 1/2 Jahr alt und hatten 10--12 Blattpaare. Dutch st~ndiges Abnehmen der Achselknosper~ wurden sic unverzweigt gehalten. Sie standen im 15-oder 16stiindigen Langt~g. Eines oder mehrere ihrer BlOtter wurden dutch t~gliches Uberziehen yon Sgckchen aus lichtdichtem Stoff in 8-odor 9stiindigen Kurztag (meistens yon 8--17 oder 18 Uhr) gebracht.Die Bl~itter sind, wenn n6tig, folgendermaBen bezeichnet (Abb. 1): Di~ Blattstellung ist bei Kalancho@ Blofi]eldiana kreuzgegenst~ndig; bei entsprechender Aufstellung der Pflanze weist also eine Zeile nach vorne zum Beschauer, eine nach hinten, und 2 stehen nach rechts und links. Die BlOtter in 'dieson Zeilen 9 sind nachstehend mit V, H, R und L bezeichnet. I)er Wirtel mit dem Versuchs-blat~paar (Kurztag) ist immer 0 genannt, der ngchst hShere 1, dann folgt 2 usw. Die unterhalb des Versuchsblattpaars s tehenden Blattpaare sind mit--1,--2 usw. bezeichnet. Wo nur 1 Blat~ in den Kurztag kam, wurde immer das nach links gerichtete genommen; es hat also die Bezeichnung 0L; im allgemeinen wurde dazu ein Blatt des 6. Knotens yon unten benutzt.
BACKGROUND Significant proportion of inflammatory bowel disease (IBD) patients continue to respond inconsistently to therapies, underscoring disease complexity and the need for efficacious treatment. Interleukin 21 (IL-21), which is known to support T helper (Th) cell function, is highly expressed within inflamed tissues of IBD patients compared to healthy controls. Also, inflammatory regulatory T cells (Tregs) have been linked to refractory human IBD, and the complete induction of IBD in mice has been shown to require IL-21. Given that healthy Tregs are critical for self-tolerance and prevention of IBD, we investigated the metabolic role of IL-21 in instigating Treg dysfunction and the therapeutic ramifications of targeting metabolic pathways during IBD. METHODS Human Tregs as well as relevant control Th cells were generated from naïve CD4+ T cells isolated from healthy blood donors. Microarray analysis was utilized for targeted transcriptional profiling. Immune phenotyping was assessed by fluorescence-activated cell sorting. Metabolic phenotyping of cells was assessed by Seahorse flux analysis and mass spectrometry-based targeted metabolomics. Colitis was induced in Rag1-/- (T and B cell deficient) mice by adoptive transfer of pathogenic naïve CD4+ T cells. RESULTS Acute IL-21 stimulation of human Tregs induced glycolysis and fluctuations in mitochondrial respiration (i.e. oxidative phosphorylation – OXPHOS), as assessed by Seahorse flux analysis. In agreement, microarray analysis, validated by qPCR, revealed IL-21-induced alterations in the expression of genes associated with glycolysis and OXPHOS metabolism. Prolonged IL-21 stimulation rendered Tregs susceptible to inflammatory response, as evidenced by the production of inflammatory Th cytokines such as interferon γ, tumor necrosis factor, IL-17A, and IL-17F. Exploring the mechanisms underlying IL-21-induced effects, we observed reduced expression of inactive glycogen synthase kinase 3 (GSK3) β, a protein known to prevent pyruvate entry into the mitochondria. This reduction in inactive GSK3β in response to IL-21 was accompanied by high abundance of intracellular pyruvate and lactate, as assessed by targeted metabolomics. Importantly, GSK3 inhibition or exogenous membrane-permeable methyl pyruvate abrogated IL-21-induced metabolic rewiring and Treg inflammatory response. Moreover, GSK3 inhibition diminished the metabolic and inflammatory function of Th cells. Lastly, GSK3 inhibition prevented pathogenic CD4+ T cell-induced colitis in mice, as evidenced by reduced Disease Activity Index, Mouse Colon Histology Index, and serum inflammatory cytokines. CONCLUSIONS IL-21 potently engages human Tregs in a metabolic state that subsequently augments an inflammatory phenotype. Therefore, desensitizing CD4+ T cells to detrimental cues, such as IL-21, may augment Treg function during human IBD.
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