Cytotoxic Effects on Gingival Mesenchymal Stromal Cells and Root Surface Modifications Induced by Some Local Antimicrobial Products Used in Periodontitis Treatment

(1) Background: this study aims to test the cytotoxicity of three antimicrobial products used in periodontitis treatment on gingival mesenchymal stem cells (gMSCs) and their influence on root surfaces and gMSC adhesion. We tested the null hypothesis that the effects of the antimicrobials did not differ. (2) Methods: the commercial products based on sulphonic/sulphuric acids, sodium hypochlorite and silver nanoparticles, in five different concentrations, were added to culture medium for growing gMSCs. Cell proliferation capacity was tested using the Cell Counting Kit-8 (CCK8) and their viability was determined by succinate dehydrogenase activity (MTT) assay. Scanning electron microscopy evaluated the adhesion of gMSCs on root samples treated mechanically and with commercial products. (3) Results: the products induced a dose-dependent cytotoxicity in terms of reduced proliferation and viability of gMSCs, as well as cell shape modifications. Significant differences in CCK8 values between the different commercial products were observed. Based on proliferation tests, the null hypothesis was rejected. When MTT values of the three products were compared with each other, no significant differences were observed for any of the five concentrations (p = 0.065, p = 0.067, p = 0.172, p = 0.256, p = 0.060). (4) Conclusions: the three antimicrobials had a certain degree of cytotoxicity on gMSCs. gMSCs repopulated treated root surfaces.     

Computational analysis of an axial flow pediatric ventricular assist device

Longer-term (>2 weeks) mechanical circulatory support will provide an improved quality of life for thousands of pediatric cardiac failure patients per year in the United States. These pediatric patients suffer from severe congenital or acquired heart disease complicated by congestive heart failure. There are currently very few mechanical circulatory support systems available in the United States as viable options for this population. For that reason, we have designed an axial flow pediatric ventricular assist device (PVAD) with an impeller that is fully suspended by magnetic bearings. As a geometrically similar, smaller scaled version of our axial flow pump for the adult population, the PVAD has a design point of 1.5 L/min at 65 mm Hg to meet the full physiologic needs of pediatric patients. Conventional axial pump design equations and a nondimensional scaling technique were used to estimate the PVAD's initial dimensions, which allowed for the creation of computational models for performance analysis. A computational fluid dynamic analysis of the axial flow PVAD, which measures approximately 65 mm in length by 35 mm in diameter, shows that the pump will produce 1.5 L/min at 65 mm Hg for 8000 rpm. Fluid forces (approximately 1 N) were also determined for the suspension and motor design, and scalar stress values remained below 350 Pa with maximum particle residence times of approximately 0.08 milliseconds in the pump. This initial design demonstrated acceptable performance, thereby encouraging prototype manufacturing for experimental validation.     

Design and transient computational fluid dynamics study of a continuous axial flow ventricular assist device

A ventricular assist device (VAD), which is a miniaturized axial flow pump from the point of view of mechanism, has been designed and studied in this report. It consists of an inducer, an impeller, and a diffuser. The main design objective of this VAD is to produce an axial pump with a streamlined, idealized, and nonobstructing blood flow path. The magnetic bearings are adapted so that the impeller is completely magnetically levitated. The VAD operates under transient conditions because of the spinning movement of the impeller and the pulsatile inlet flow rate. The design method, procedure, and iterations are presented. The VAD's performance under transient conditions is investigated by means of computational fluid dynamics (CFD). Two reference frames, rotational and stationary, are implemented in the CFD simulations. The inlet and outlet surfaces of the impeller, which are connected to the inducer and diffuser respectively, are allowed to rotate and slide during the calculation to simulate the realistic spinning motion of the impeller. The flow head curves are determined, and the variation of pressure distribution during a cardiac cycle (including systole and diastole) is given. The axial oscillation of impeller is also estimated for the magnetic bearing design. The transient CFD simulation, which requires more computer resources and calculation efforts than the steady simulation, provides a range rather than only a point for the VAD's performance. Because of pulsatile flow phenomena and virtual spinning movement of the impeller, the transient simulation, which is realistically correlated with the in vivo implant scenarios of a VAD, is essential to ensure an effective and reliable VAD design.     

Accelerated streptokinase and enoxaparin in ST-segment elevation acute myocardial infarction (the ASENOX study)

BACKGROUND: The streptokinase (SK) regimen (1.5 MU/60 min) has remained unchanged in the ST-segment elevation acute myocardial infarction (STEMI) for the last 20 years. AIM: To compare the efficacy of an accelerated SK (ASK) regimen combined with enoxaparin (Enox) or heparin (UFH) with the standard SK and UFH combination in STEMI. METHODS: 633 consecutive patients, aged 21-74 years, admitted within 6 hours after the onset of STEMI, were divided in three groups: (1) ASKEnox (n=165): Enox 40 mg. i.v. followed by SK 1.5 MU over 20 min, either as a full dose or a double infusion of 0.75 MU over 10 min. separated by 50 min. After SK infusion, Enox was administered 1 mg/kg s.c. every 12 hours for 5-7 days; (2) ASKUFH (n=264): the same ASK regimen plus UFH 1,000 IU/h for 48-72 hours, (3) SSKUFH (n=204): SK 1.5 MU/60 min. plus UFH 1,000 IU/h for 48-72 hours. All patients received aspirin. Three coronary reperfusion (CR) criteria were used: 1. rapid cessation of chest pain; 2. rapid reduction of ST-segment elevation by more than 50% of the initial value; 3. rapid increase in plasma CK and CK-MB with a peak in the first 12 hours. RESULTS: The rates of CR in the ASKEnox (77.6%) and the ASKUFH (73.5%) groups were similar but both were significantly higher than that observed in the SSKUFH group (62.2%) (p=0.002 and 0.013, respectively). The 30-day mortality rates were similar in the ASKEnox (6.06%) and the ASKUFH (6.81%) groups but both were significantly lower than in the SSKUFH group (12.74%) (p=0.048 and 0.044, respectively). SK-induced hypotension was more frequent in the ASKEnox (39.4%) and ASKUFH (38.3%) groups compared with the SSKUFH group (20.6%) (p<0.0001), but it was transient and well tolerated. Haemorrhagic stroke occurred in two patients from the SSKUFH and one patient from the ASKUFH groups. CONCLUSIONS: ASKEnox and ASKUFH regimens are safe and result in a significantly higher rate of CR and a lower in-hospital mortality compared with the traditional SSKUFH regimen.     

Computational design and experimental testing of a novel axial flow LVAD

Thousands of cardiac failure patients per year in the United States could benefit from long-term mechanical circulatory support as destination therapy. To provide an improvement over currently available devices, we have designed a fully implantable axial-flow ventricular assist device with a magnetically levitated impeller (LEV-VAD). In contrast to currently available devices, the LEV-VAD has an unobstructed blood flow path and no secondary flow regions, generating substantially less retrograde and stagnant flow. The pump design included the extensive use of conventional pump design equations and computational fluid dynamics (CFD) modeling for predicting pressure-flow curves, hydraulic efficiencies, scalar fluid stress levels, exposure times to such stress, and axial fluid forces exerted on the impeller for the suspension design. Flow performance testing was completed on a plastic prototype of the LEV-VAD for comparison with the CFD predictions. Animal fit trials were completed to determine optimum pump location and cannulae configuration for future acute and long-term animal implantations, providing additional insight into the LEV-VAD configuration and implantability. Per the CFD results, the LEV-VAD produces 6 l/min and 100 mm Hg at a rotational speed of approximately 6300 rpm for steady flow conditions. The pressure-flow performance predictions demonstrated the VAD's ability to deliver adequate flow over physiologic pressures for reasonable rotational speeds with best efficiency points ranging from 25% to 30%. The CFD numerical estimations generally agree within 10% of the experimental measurements over the entire range of rotational speeds tested. Animal fit trials revealed that the LEV-VAD's size and configuration were adequate, requiring no alterations to cannulae configurations for future animal testing. These acceptable performance results for LEV-VAD design support proceeding with manufacturing of a prototype for extensive mock loop and initial acute animal testing.     

Personal risk perception, HIV knowledge and risk avoidance behavior, and their relationships to actual HIV serostatus in an urban African obstetric population

One quarter of pregnant women in Zambia are infected with HIV. Understanding how knowledge of HIV relates to personal risk perception and avoidance of risky behaviors is critical to devising effective HIV prevention strategies. In conjunction with a large clinical trial in Lusaka, Zambia, we surveyed postpartum women who had been tested for HIV but did not know their status before undergoing the questionnaire. Of 858 women for whom complete data were available, 248 (29%) were HIV infected. Women 22 years of age or older (adjusted odds ratio [AOR], 1.7; 95% confidence interval [CI], 1.1-2.5), women reporting > or =2 sexual partners in their lifetime (AOR, 1.8; 95% CI, 1.3-2.5), and women reporting a history of a sexually transmitted infection (AOR, 2.7; 95% CI, 1.7-4.3) were more likely to be HIV infected. Having had > or =2 lifetime sexual partners was a marker for perception of high personnel risk for HIV infection (AOR, 1.5; 95% CI, 1.1-2.1). However, there was no relationship between perceived risk of HIV infection and actual HIV status. In fact, 127 (52%) of 245 women who stated that they were at no or low risk for HIV infection were HIV infected. Living in an area of high HIV seroprevalence like Zambia seems to be the greatest risk factor for infection in unselected pregnant women. Before significant inroads can be made in decreasing the incidence of HIV infection among pregnant women, population-based strategies that involve men must be implemented.     

ATP released via pannexin-1 hemichannels mediates bladder overactivity triggered by urothelial P2Y6 receptors

In contrast to the well-known signaling role of urothelial ATP to control bladder function, the hypothesis that uracil nucleotides (UTP and/or UDP) also exert autocrine/paracrine actions only recently gained experimental support. Urothelial cells express UDP-sensitive P2Y₆ receptors, yet their role in the control of bladder activity has been mostly neglected. This study was designed to investigate the ability of PSB0474, a stable UDP analogue which exhibits selectivity for P2Y₆ receptors, to modulate urodynamic responses in the anaesthetized rat in vivo. Instillation of PSB0474 into the bladder increased the voiding frequency (VF) without affecting the amplitude (A) and the duration (Δt) of bladder contractions. PSB0474-induced bladder overactivity was prevented by the selective P2Y₆ antagonist, MRS2578. The increase in the VF produced by PSB0474 was also blocked by inhibitors of pannexin-1 hemichannels, ¹⁰Panx or carbenoxolone, when these drugs were applied inside the bladder lumen but not when they were administered intravenously. Reduction of hemichannels pore permeability with H1152 also prevented PSB0474-induced bladder overactivity, but the exocytosis inhibitor, Exo-1, was inactive. PSB0474 increased by 3-fold the urinary ATP content. Implication of hemichannels permeability on PSB0474-induced ATP release was demonstrated by real-time fluorescence video-microscopy measuring the uptake of propidium iodide by intact urothelial cells in the absence and in the presence of MRS2578 or carbenoxolone. Confocal microscopy studies confirmed the co-localization of pannexin-1 and P2Y₆ receptors in the rat urothelium. Data indicate that activation of P2Y₆ receptors causes bladder overactivity in the anaesthetized rat indirectly by releasing ATP from the urothelium via pannexin-1 hemichannels.