Bone Morphogenetic Protein-7 Enhances Degradation of Osteoinductive Bioceramic Implants in an Ectopic Model

Background: The aim of the present study was to evaluate the degradation pattern of highly porous bioceramics as well as the bone formation in presence of bone morphogenetic protein 7 (BMP-7) in an ectopic site. Methods: Novel calcium phosphate ceramic cylinders sintered at 1,300ºC with a total porosity of 92–94 vol%, 45 pores per inch, and sized 15 mm (Ø) × 5 mm were grafted on the musculus latissimus dorsi bilaterally in 10 Göttingen minipigs: group I (n = 5): hydroxyapatite (HA) versus biphasic calcium phosphate (BCP), a mixture of HA and tricalcium phosphate (TCP) in a ratio of 60/40 wt%; group II (n = 5): TCP versus BCP. A test side was supplied in situ with 250 μg BMP-7. Fluorochrome bone labeling and computed tomography were performed in vivo. Specimens were evaluated 14 weeks after surgery by environmental scanning electron microscopy, fluorescence microscopy, tartrate-resistant acid phosphatase, and pentachrome staining. Results: Bone formation was enhanced in the presence of BMP-7 in all ceramics (P = 0.001). Small spots of newly formed bone were observed in all implants in the absence of BMP-7. Degradation of HA and BCP was enhanced in the presence of BMP-7 (P = 0.001). In those ceramics, osteoclasts were observed. TCP ceramics were almost completely degraded independently of the effect of BMP-7 after 14 weeks (P = 0.76), osteoclasts were not observed

The influence of attachment style on marital interaction

Thesis (B.S.)--University of Illinois at Urbana-Champaign, 2000.Includes bibliographical reference (leaves 18-21)U of I OnlyTheses restricted to UIUC community onl

Bioavailability and metabolism of hydroquinone after intratracheal instillation in male rats.DrugMetab.Dispos

This paper is available online at http://www.dmd.org ABSTRACT: The purpose of this study was to investigate the rate and extent of hydroquinone (HQ) absorption and first pass metabolism in the lungs of male rats in vivo. This study investigated the rate and extent of hydroquinone (HQ) 1 absorption and first pass metabolism in the lungs of rats, and subsequent systemic metabolism after intratracheal instillation of a small amount of the chemical in physiological saline. HQ is both a naturally occurring substance HQ is known to be biotransformed systemically in the rat to sulfate, glucuronide, and glutathione conjugates The relatively large amount of chemical required for an inhalation exposure and the potential for radiochemical contamination in the generation of a [ 14 C]-labeled dust precluded the execution of an animal inhalation exposure to [ 14 C]HQ. As an alternative, [ 14 C]HQ in a physiological saline solution was administered intratracheally via an indwelling endotracheal tube to conscious rats to simulate exposure by inhalation of HQ dust and its subsequent dissolution in the fluid of the respiratory membrane. Bioavailability of HQ was determined by blood sampling simultaneously at arterial and venous sites at short intervals beginning immediately after intratracheal instillation. The extent of pulmonary metabolism was determined by differences observed in blood concentrations of parent compound and metabolites measured in venous and arterial blood samples after intratracheal administration of HQ over a range of concentrations. The rate of pulmonary absorption and systemic metabolism of HQ was estimated from the HQ concentration in both arterial and venous blood over time and from the decline in parent compound concentration and increase in metabolite concentrations over time. Materials and Methods Animals 442 Laboratories, Inc. (Zelienople, PA). The animals were prepared by the vendor with arterial and venous cannulae and an endotracheal tube. The arterial cannula was placed in the left carotid artery and threaded into the artery so as to position the cannula tip within the aortic arch. This allowed sampling of blood returning from the lung, having passed through the left side of the heart before systemic distribution. The venous cannula was placed in a jugular vein and threaded into the vein so as to position the cannula tip as near to the right atrium as possible; therefore, the blood samples collected from this cannula are returning from systemic circulation. The patency of both cannulae was maintained by daily aspiration and refill of each with a viscous solution of 50% (w/w) polyvinylpyrrolidone (Sigma catalog no. PVP-40; mw 40,000) in sterile saline containing 250 IU/ml sodium heparin (Elkins-Sinn, Inc., Cherry Hill, NJ). An endotracheal tube consisting of 0.012 inches inside diameter ϫ 0.025 inches outside diameter Micro-Renathane tubing (Braintree Science, Inc., Braintree, MA) was inserted through the wall of the trachea and permanently secured using medical grade cyanoacrylate and suturing to the osmohyoid muscles. The tube was then coupled to 0.020 inches inside diameter x 0.037 inches outside diameter Micro-Renathane tubing and tunneled s.c. below the nape of the neck. Both cannulae and the endotracheal tube were externalized at the top of the head and mounted in dental acrylic. The use of arterial and venous cannulated rats allowed rapid and accurate serial blood sampling and the presence of the endotracheal tube allowed the dosings to be conducted in conscious animals that were not affected by the respiratory and circulatory depression caused by anesthetics. Test Chemicals. Unlabeled HQ (CAS 123-31-9) was obtained from Eastman Kodak Company (Rochester, NY) and its structure and purity were confirmed by gas chromatography with mass selective detection 14 C] concentration between whole blood and ultrafiltrate was suspected to be due to HQ reversibly bound to protein in the blood. This was investigated by spiking whole blood with [ 14 C]HQ approximating the maximum concentrations of free HQ seen in blood after the 1 mg/kg intratracheal administration. The samples were processed both by ultrafiltration and by ethyl acetate extraction and the recovered [ 14 C] was assayed by LS counting and by HPLC for quantitation and characterization (see Results). HPLC Radiochemical Analysis for HQ and Metabolites. Injections of the clear ultrafiltrate (100 l) were analyzed for parent compound and metabolites on an HP 1090 HPLC using a reversed phase column (Supelcosil LC-18, 5 m, 4.6 ϫ 170 mm) and an isocratic mobile phase consisting of 50 mM sodium formate buffer (pH 4.5) at 1 ml/min. The column effluent was directed through the UV absorbance detector and then through the radiochemical detector, which was fitted with a 500 l scintillant-mix flow cell. The 1 ml/min column effluent was mixed with 2 ml/min scintillant (Ultima-Flo M, Packard Instrument Co., Meriden, CT) before passage through the radiochemical detector flow cell. The area percent value for each peak provided by this analysis was multiplied by the radiochemical concentration of the blood ultrafiltrate and then divided by the HQ dose-specific radioactivity to derive a mass quantitation (g equivalents/g blood ultrafiltrate) for the parent compound and each metabolite. HQ-sulfate and HQ-glucuronide metabolite standards were obtained from rat urine collected after a 25 mg/kg oral administration of [ 14 C]HQ. Their identities were established previously by negative ion fast atom bombardment mass spectrometry and by specific enzyme hydrolysis. Standards of the mono-, di-, tri-, and tetraglutathione conjugates of HQ were prepared as described previously in the literature Pharmacokinetic Descriptions. A nonlinear least-squares data-fitting program (PKAnalyst, Version 1.0; MicroMath Scientific Software, Salt Lake City, UT) was used to derive pharmacokinetic parameters for total HQ concentrations in blood. A two-compartment model with bolus input and first order output described by the equation C t ϭ Ae Ϫ␣t ϩ Be Ϫ␤t was fitted to total HQ concentrations in arterial blood over time, where C t represents the concentration at time t, A and B represent the y intercepts for the initial and terminal segments of the curve, respectively, and ␣ and ␤ are their respective rate constants. The following parameters were calculated: A, ␣, B, ␤, area under the curve (AUC), the half-life of elimination (T 1/2 ), and volume of distribution (V area ) defined as V area ϭ Dose/␤ ϫ AUC, which is valid for a non-i.v. administration assuming complete absorption and bioavailability Results The intratracheal instillation of 0.1, 1.0, or 10 mg/kg [ 14 C]HQ to male rats resulted in very rapid absorption and systemic distribution of HQ as indicated by the early detection of [ 14 C] in the blood. Free HQ appeared in the arterial and venous blood within 5 to 10 s after dose administration. Reversibly bound HQ was also present in the earliest samples. The mean concentrations of free plus reversibly bound HQ (total HQ) in the 5-to 10-s arterial blood samples were consistently higher than those in the corresponding venous samples at all dose levels, but showed large interanimal variability The glucuronic acid conjugate of HQ was the major metabolite at all dose levels, detected in both arterial and venous blood samples at comparable concentrations beginning at 45 s postdosing and at increasing concentrations in subsequent samples The limit of detection for pulmonary metabolites in the initial arterial blood samples depended on the radiochemical content of the dose, the rate of pulmonary absorption, and the rate of blood flow in the pulmonary vein. All three of these parameters were reflected in the [ 14 C] concentration of the initial arterial blood sample; therefore, the limit of detection can be expressed in terms of the blood total [ 14 C] concentration in this sample. At the 0.1 mg/kg dose level, the radiochemical concentration of the dose was limited by the specific activity of the stock [ 14 C]HQ and the mean initial arterial blood [ 14 C] concentration was 51,620 dpm/g. The detection limit of the radiochemical flow detector was approximately 3000 dpm/g (as a single peak, 100 l injection); therefore, a metabolite peak of approximately 5.8% of the whole blood concentration would be detected. For the 1.0 and 10 mg/kg dose levels, the mean initial arterial blood [ 14 C] concentration was 428,500 dpm/g. Factoring in the detection limit from above, a peak of 0.7% of the initial whole blood concentration would be detectable. The efficiency of [ 14 C] recovery by the blood ultrafiltration procedure was proportional to the sampling time. In the initial blood samples collected 5 to 10 s after dose administration, the concentration ratio of [ 14 C] in blood ultrafiltrate compared to that in whole blood was 0.32 to 0.38 at all dose levels. This ratio steadily increased at later time points to means of 0.92, 0.95, and 0.77 at 12 min for the 0.1, 1.0, and 10 mg/kg dose levels, respectively. To investigate the nature of the [ 14 C] not recovered after ultrafiltration at the early time points, methods experiments were conducted in which whole blood spiked with [ 14 C]HQ in vitro or collected in vivo at 5 to 10 s from rats dosed intratracheally with [ 14 C]HQ was extracted with ethyl acetate. The ethyl acetate extracts contained 98% and 92% of the whole blood [ 14 C] in the in vitro and in vivo experiments, respectively. HPLC analysis of these extracts detected HQ as the only radiolabeled component Discussion Initial arterial and venous blood samples were collected between 5 and 10 s after intratracheal dosing with [ 14 C]HQ. The very short interval between intratracheal administration and collection of the initial blood samples was designed to detect first pass metabolism in the lung. The arterial cannula was placed to allow sampling of blood returning from the lung before systemic distribution. The initial arterial blood samples were generally higher in [ 14 C] concentration than the corresponding venous samples, indicating pulmonary absorption of the dose had occurred but systemic distribution was incomplete. The initial arterial samples could, therefore, be expected to contain putative pulmonary metabolites, not diluted or masked by hepatic or other systemic metabolism. HPLC characterization of the [ 14 C] in these initial arterial blood samples revealed no metabolic products, with only free and reversibly bound HQ detected at the 0.1, 1.0, and 10 mg/kg dose levels. In corresponding arterial and venous blood samples collected at later time points and containing roughly equal total [ 14 C] concentrations, HQ-glucuronide, the major metabolite, was detected at equal concentrations in both venous and arterial blood The observation that [ 14 C] recovery by the blood ultrafiltration procedure was proportional to the sampling time lead to experiments to determine the nature of the [ 14 C] not recovered by ultrafiltration in the early samples. These methods experiments established that the [ 14 C] not recovered by ultrafiltration is readily extractable and consists predominantly of [ 14 C]HQ reversibly bound (i.e., hydrogen bonding) to blood proteins in both the plasma and cellular fraction of the blood 14 C] at later sampling times reflect the increasing presence of conjugated metabolites of HQ TABLE 1 Pharmacokinetic analysis of total HQ concentrations in blood after intratracheal dosing Summary of pharmacokinetic parameter estimates derived from nonlinear least squares fitting (PKAnalyst, MicroMath Scientific Software, Salt Lake City, UT, 1995) of arterial blood total HQ concentration after intratracheal administration of [ 14 C]HQ at 0.1, 1.0, and 10 mg/kg in male Sprague-Dawley rats. The form of the equation is C t ϭ Ae Ϫ␣t ϩ Be Ϫ␤

The effect of different viewing devices for the sense of presence and immersion in virtual environments: A comparison of stereoprojections based on monitors, HMDs, and screen

Displays for virtual environments (VE) are in focus of many discussions in ergonomics. Some tests have been performed in the field of ergonomics of head mounted displays (HMD) but there is no comparison between different immersive viewing devices for VEs. This paper gives an overview of two experiments we conducted to compare different viewing devices for VEs like HMDs, monitors, and screen based projections (SBP) in combination with shutter techniques for time-multiplexed images. Since we included a stereoprojection with large screens and the fact that those devices are actually not a typical work environment, we performed the experiments under laboratory conditions. We supplied the experiments by query techniques in form of questionnaires. We paid attention to the "socially desirable" meaning of the words in the questionnaires to avoid mistakes. From the literature, most usability test or evaluation of user interfaces use inexperienced participants who perform determined tasks and fi lled out questionnaires . In this study, Immersive projection technologies (IPTs) should be compared in an interactive environment. In such VEs there are different view projection paradigms with either a fixed eye-point model (camera view) or a moving eye-point model (off-axis projection). Normally, HMDs are using the camera view. Monitors and SBP for example use single or connected off-axis projections. For both of the techniques, a device for most precise tracking the head position and orientation should be used. Actually an electromagnetic tracker is used with a filter for the cached data. Since there were a lot of tasks for improvements, these experiments should be understood as a preliminary investigation only

Performance evaluation of input devices in virtual environments

The user interface approach of virtual reality promises to be superior to two-dimensional approaches. Therefore, there is a need to perform experiments with different input devices. We developed a virtual environment test bed which integrates different input devices and modules for rapid modelling tests and evaluation. Our focus of the tests was a comparison between a conventional computer mouse, a space mouse and an electromagnetically tracked device. With the tests, we tried to measure the accuracy and performance of grabbing and positioning virtual objects