RESUMEN
This evaluation assessed the influence of a new implant shoulder design on cleanability using a now established in-vitro study model. Eight test (Botticelli, Di Meliora AG, Basel, Switzerland) and eight control implants (T3 Osseotite, ZimVie, Winterthur, Switzerland), were embedded in standardized defects in simulated bone. The implant surfaces were painted to be visually distinguishable and debrided with ultrasonic instruments (US) and an air powder waterjet device (AIR). Uncleaned implants served as positive controls. After the standardized cleaning, the implants were photographed and divided into three zones (upper marginal shoulder zone (A); lower marginal shoulder zone (B); fully threaded sub-shoulder zone (C)), and analyzed with an image processing software. On test implants, AIR was almost 100% efficacious compared to 80-90% with US, in both upper zones (A/B). In control implants, results of both AIR and US were almost 100% in zone A, but only 55-75% in zone B. In both implants, AIR showed statistically significant higher efficacy than US (P<0.05). Within the limitations of the present in-vitro model, a new macro-structured micro-rough dental implant shoulder with a new coronal vertical groove design shows similar cleanability in comparison to a smooth and machined surface.
RESUMEN
The succinic semialdehyde dehydrogenase (SSADH) null mouse (SSADH(-/-)) represents a viable animal model for human SSADH deficiency and is characterized by markedly elevated levels of both gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acid (GABA) in brain, blood, and urine. In physiological concentrations, GHB acts at the GHB receptor (GHBR), but in high concentrations such as those observed in the brains of children with SSADH deficiency, GHB is thought to be a direct agonist at the GABABR receptor (GABABR). We tested the hypothesis that both GHBR and GABABR-mediated function are perturbed in SSADH deficiency. Therefore, we examined the high affinity binding site for GHB as well as the expression and function of the GABABR in mutant mice made deficient in SSADH (SSADH(-/-)). There was a significant decrease in binding of the specific GABABR antagonist, [3H]CGP-54626A at postnatal day (PN)7 and PN14 in SSADH(-/-) when compared to wild type control animals (SSADH(+/+)), particularly in hippocampus. GABABR-mediated synaptic potentials were decreased in SSADH(-/-). Immunoblot analysis of GABABR1a, R1b, and R2 in SSADH(-/-) indicated a trend towards a region-specific and time-dependent decrease of GABABR subunit protein expression. There was no difference between SSADH(-/-) and wild type in binding of either [3H]GHB or a specific GHBR antagonist to the GHBR. These data suggest that the elevated levels of GABA and GHB that occur in SSADH(-/-) lead to a use-dependent decrease in GABABR-mediated function and raise the possibility that this GHB- and GABA-induced perturbation of GABABR could play a role in the pathogenesis of the seizures and mental retardation observed in SSADH deficiency.
Asunto(s)
Química Encefálica/genética , Encefalopatías Metabólicas Innatas/enzimología , Encéfalo/enzimología , Receptores de GABA-B/metabolismo , Succionato-Semialdehído Deshidrogenasa/deficiencia , Succionato-Semialdehído Deshidrogenasa/genética , Animales , Sitios de Unión/genética , Encéfalo/fisiopatología , Encefalopatías Metabólicas Innatas/genética , Encefalopatías Metabólicas Innatas/fisiopatología , Modelos Animales de Enfermedad , Antagonistas del GABA/farmacología , Hidroxibutiratos/metabolismo , Ratones , Ratones Noqueados , Subunidades de Proteína/genética , Receptores de GABA-B/genética , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/genética , Regulación hacia Arriba/genética , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Neurophysiological studies suggest that clozapine may facilitate γ-aminobutyric acid (GABAergic) neurotransmission. Therefore, we studied the interaction between clozapine and the GABAB receptor (GABABR). We showed that clozapine, and not N-desmethylclozapine, which is a metabolite of clozapine, increased the binding of the GABABR antagonist, [³H]-CGP54626A, at GABABRs. Linear regression analysis showed that the correlation between the dose of clozapine and the increase of [³H]-CGP54626A binding was significant. The curve of specific [³H]-CGP54626A binding in competition with different concentrations of GABA was left shifted in the presence of clozapine. With HEK293 cells overexpressing GABABR, we showed that clozapine had a significant increase of [³H]-CGP54626A binding at GABABR1 subunit, which provided a clue of the potential therapeutic target of clozapine.