The Role of Apoptotic Factors in Assessing Progression of Periodontal Disease.

BACKGROUND: The mechanisms responsible for periodontal disease progression remain unclear. However, recent studies suggest that apoptosis may be one mechanism underlying the pathophysiology of periodontal disease progression. This pilot study is the 3 month follow-up of our published baseline study on the presence of apoptotic factors in serum, saliva, and gingival crevicular fluid (GCF) and their association with periodontal disease severity and activity. METHODS: GCF samples were obtained from 37 adult patients with chronic periodontitis (CP) and 7 healthy controls. Clinical measurements, including probing depth (PD), clinical attachment level (CAL), and radiographs, were used to evaluate data by sites and to classify patients into healthy, mild, and moderate/severe CP groups. Enzyme-linked immunosorbent assays were used to measure apoptosis or DNA fragmentation levels in GCF. Western immunoblotting was used to detect several apoptotic proteins, Fas, FasL, sFasL, and caspase-3 expression and its cleavage products in GCF. RESULTS: At the patient level clinical and apoptotic measurements change minimally over time. At the site level, DNA fragmentation levels increase with increasing PDs at 3 months and baseline. Apoptotic protein expression exhibits increasing trends with increasing PDs at baseline and 3 months. FasL and Active FasL show a high specificity and PPV; low sensitivity and NPV. Caspase-3 products (ProCas35K and Active Cas) show a high PPV with moderate to high specificity; low sensitivity and NPV. ProCas70K shows a high PPV with moderate to high sensitivity; low specificity and NPV. CONCLUSION: Factors associated with apoptosis show minimal changes in expression in periodontitis groups in comparison to a healthy group over a short time interval (3 months). However, at the site level, apoptotic factors (DNA fragmentation and apoptotic proteins) exhibit significant increases or increasing trends with increasing PDs at any time point examined (baseline or 3 months). Several of these apoptotic factors also exhibit a high sensitivity and high positive predictive value. Thus, apoptotic molecules may be helpful biomarkers of disease status at any point in time.

Characterization of a bioprosthetic bicuspid venous valve hemodynamics: implications for mechanism of valve dynamics.

BACKGROUND: Chronic venous insufficiency (CVI) of the lower extremities is a common clinical problem. Although bioprosthetic valves have been proposed to treat severe reflux, clinical success has been limited due to thrombosis and neointima overgrowth of the leaflets that is, in part, related to the hemodynamics of the valve. A bioprosthetic valve that mimics native valve hemodynamics is essential. METHODS: A computational model of the prosthetic valve based on realistic geometry and mechanical properties was developed to simulate the interaction of valve structure (fluid-structure interaction, FSI) with the surrounding flow. The simulation results were validated by experiments of a bioprosthetic bicuspid venous valve using particle image velocimetry (PIV) with high spatial and temporal resolution in a pulse duplicator (PD). RESULTS: Flow velocity fields surrounding the valve leaflets were calculated from PIV measurements and comparisons to the FSI simulation results were made. Both the spatial and temporal results of the simulations and experiments were in agreement. The FSI prediction of the transition point from equilibrium phase to valve-closing phase had a 7% delay compared to the PD measurements, while the PIV measurements matched the PD exactly. FSI predictions of reversed flow were within 10% compared to PD measurements. Stagnation or stasis regions were observed in both simulations and experiments. The pressure differential across the valve and associated forces on the leaflets from simulations showed the valve mechanism to be pressure driven. CONCLUSIONS: The flow velocity simulations were highly consistent with the experimental results. The FSI simulation and force analysis showed that the valve closure mechanism is pressure driven under the test conditions. FSI simulation and PIV measurements demonstrated that the flow behind the leaflet was mostly stagnant and a potential source for thrombosis. The validated FSI simulations should enable future valve design optimizations that are needed for improved clinical outcome.

Role of sinus in prosthetic venous valve.

BACKGROUND: The majority of bioprosthetic venous valves do not have a sinus pocket and, in practice, they are often placed in non-sinus segments of the veins. The aim of this study is to investigate the effect of the sinus pocket on the flow dynamics in a prosthetic valve. METHODS: A bench top in vitro experiment was set up at physiological flow conditions to simulate the flow inside a venous system. Bicuspid bioprosthetic valves with different leaflet lengths (5 and 10 mm) were tested in tubes with and without a sinus pocket and the flows around the valve were visualized by particle image velocimetry (PIV). Velocity data measurements were made and the vorticity was calculated in the with- and without-sinus set-ups. RESULTS: PIV measurements showed that vortex structure was maintained by the sinus. For the 10-mm leaflet length design with sinus, the jet width at the exit of the valve was 59% of that without sinus. For the 5-mm design with sinus, the jet width was 73% of the valve without sinus. Flow from the sinus region was entrained into the main jet observed near the exit of the sinus and altered the flow at the near wall region. CONCLUSIONS: The sinus pocket alters the flow around the valve and functions as flow regulator to smooth the flow pattern around the valve. The vortical structure inside the sinus is maintained at the valve leaflet tip during the valve cycle. For the prosthetic valve designated to be placed without a sinus, a shorter leaflet length is preferable and performs more closely to the valve with sinus.