Development and in-vitro characterization of an implantable flow sensing transducer for hydrocephalus

An implantable transducer for monitoring the flow of Cerebrospinal fluid (CSF) for the treatment of hydrocephalus has been developed which is based on measuring the heat dissipation of a local thermal source. The transducer uses passive telemetry at 13.56 MHz for power supply and read out of the measured flow rate. The in vitro performance of the transducer has been characterized using artificial Cerebrospinal Fluid (CSF) with increased protein concentration and artificial CSF with 10\% fresh blood. After fresh blood was added to the artificial CSF a reduction of flow rate has been observed in case that the sensitive surface of the flow sensor is close to the sedimented erythrocytes. An increase of flow rate has been observed in case that the sensitive surface is in contact with the remaining plasma/artificial CSF mix above the sediment which can be explained by an asymmetric flow profile caused by the sedimentation of erythrocythes having increased viscosity compared to artificial CSF. After removal of blood from artificial CSF, no drift could be observed in the transducer measurement which could be associated to a deposition of proteins at the sensitive surface walls of the packaged flow transducer. The flow sensor specification requirement of +-10\% for a flow range between 2 ml/h and 40 ml/h. could be confirmed at test conditions of 37 degrees C.

Identification of a fibronectin interaction site in the extracellular matrix protein ameloblastin

Mammalian teeth are composed of hydroxyapatite crystals that are embedded in a rich extracellular matrix. This matrix is produced by only two cell types, the mesenchymal odontoblasts and the ectodermal ameloblasts. Ameloblasts secrete the enamel proteins amelogenin, ameloblastin, enamelin and amelotin. Odontoblasts secrete collagen type I and several calcium-binding phosphoproteins including dentin sialophosphoprotein, dentin matrix protein, bone sialoprotein and osteopontin. The latter four proteins have recently been grouped in the family of the SIBLINGs (small integrin-binding ligand, N-linked glycoproteins) because they display similar gene structures and because they contain an RGD tripeptide sequence that binds to integrin receptors and thus mediates cell adhesion. We have prepared all the other tooth-specific proteins in recombinant form and examined whether they might also promote cell adhesion similar to the SIBLINGs. We found that only ameloblastin consistently mediated adhesion of osteoblastic and fibroblastic cells to plastic or titanium surfaces. The activity was dependent on the intact three-dimensional structure of ameloblastin and required de novo protein synthesis of the adhering cells. By deletion analysis and in vitro mutagenesis, the active site could be narrowed down to a sequence of 13 amino acid residues (VPIMDFADPQFPT) derived from exon 7 of the rat ameloblastin gene or exons 7-9 of the human gene. Kinetic studies and RNA interference experiments further demonstrated that this sequence does not directly bind to a cell surface receptor but that it interacts with cellular fibronectin, which in turn binds to integrin receptors. The identification of a fibronectin-binding domain in ameloblastin might permit interesting applications for dental implantology. Implants could be coated with peptides containing the active sequence, which in turn would recruit fibronectin from the patient's blood. The recruited fibronectin should then promote cell adhesion on the implant surface, thereby accelerating osseointegration of the implant.

Surface-acoustic-wave counterflow micropumps for on-chip liquid motion control in two-dimensional microchannel arrays

Fully controlled liquid injection and flow in hydrophobic polydimethylsiloxane (PDMS) two-dimensional microchannel arrays based on on-chip integrated, low-voltage-driven micropumps are demonstrated. Our architecture exploits the surface-acoustic-wave (SAW) induced counterflow mechanism and the effect of nebulization anisotropies at crossing areas owing to lateral propagating SAWs. We show that by selectively exciting single or multiple SAWs, fluids can be drawn from their reservoirs and moved towards selected positions of a microchannel grid. Splitting of the main liquid flow is also demonstrated by exploiting multiple SAW beams. As a demonstrator, we show simultaneous filling of two orthogonal microchannels. The present results show that SAW micropumps are good candidates for truly integrated on-chip fluidic networks allowing liquid control in arbitrarily shaped two-dimensional microchannel arrays.

Differential roles for endothelial ICAM-1, ICAM-2, and VCAM-1 in shear-resistant T cell arrest, polarization, and directed crawling on blood-brain barrier endothelium

Endothelial ICAM-1 and ICAM-2 were shown to be essential for T cell diapedesis across the blood-brain barrier (BBB) in vitro under static conditions. Crawling of T cells prior to diapedesis was only recently revealed to occur preferentially against the direction of blood flow on the endothelial surface of inflamed brain microvessels in vivo. Using live cell-imaging techniques, we prove that Th1 memory/effector T cells predominantly crawl against the direction of flow on the surface of BBB endothelium in vitro. Analysis of T cell interaction with wild-type, ICAM-1-deficient, ICAM-2-deficient, or ICAM-1 and ICAM-2 double-deficient primary mouse brain microvascular endothelial cells under physiological flow conditions allowed us to dissect the individual contributions of endothelial ICAM-1, ICAM-2, and VCAM-1 to shear-resistant T cell arrest, polarization, and crawling. Although T cell arrest was mediated by endothelial ICAM-1 and VCAM-1, T cell polarization and crawling were mediated by endothelial ICAM-1 and ICAM-2 but not by endothelial VCAM-1. Therefore, our data delineate a sequential involvement of endothelial ICAM-1 and VCAM-1 in mediating shear-resistant T cell arrest, followed by endothelial ICAM-1 and ICAM-2 in mediating T cell crawling to sites permissive for diapedesis across BBB endothelium.

In vivo evaluation of the first dedicated combined flow-restoration and mechanical thrombectomy device in a swine model of acute vessel occlusion

The use of self-expanding retrievable stents is an emerging and promising treatment strategy for acute stroke treatment. The concept combines the advantages of stent deployment with immediate flow-restoration and of mechanical thrombectomy with definitive thrombus removal. The present study was performed to gain more knowledge about the principle of combined flow restoration and thrombectomy in an established animal model using radiopaque thrombi evaluating efficiency, thrombus-device interaction and possible complications of the first dedicated flow-restoration and mechanical thrombectomy device.

Dental erosion--an overview with emphasis on chemical and histopathological aspects

The quality of dental care and modern achievements in dental science depend strongly on understanding the properties of teeth and the basic principles and mechanisms involved in their interaction with surrounding media. Erosion is a disorder to which such properties as structural features of tooth, physiological properties of saliva, and extrinsic and intrinsic acidic sources and habits contribute, and all must be carefully considered. The degree of saturation in the surrounding solution, which is determined by pH and calcium and phosphate concentrations, is the driving force for dissolution of dental hard tissue. In relation to caries, with the calcium and phosphate concentrations in plaque fluid, the 'critical pH' below which enamel dissolves is about 5.5. For erosion, the critical pH is lower in products (e.g. yoghurt) containing more calcium and phosphate than plaque fluid and higher when the concentrations are lower. Dental erosion starts by initial softening of the enamel surface followed by loss of volume with a softened layer persisting at the surface of the remaining tissue. Dentine erosion is not clearly understood, so further in vivo studies, including histopathological aspects, are needed. Clinical reports show that exposure to acids combined with an insufficient salivary flow rate results in enhanced dissolution. The effects of these and other interactions result in a permanent ion/substance exchange and reorganisation within the tooth material or at its interface, thus altering its strength and structure. The rate and severity of erosion are determined by the susceptibility of the dental tissues towards dissolution. Because enamel contains less soluble mineral than dentine, it tends to erode more slowly. The chemical mechanisms of erosion are also summarised in this review. Special attention is given to the microscopic and macroscopic histopathology of erosion.

Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia

Insufficient cardiac preload and impaired contractility are frequent in early sepsis. We explored the effects of acute cardiac preload reduction and dobutamine on hepatic arterial (Qha) and portal venous (Qpv) blood flows during endotoxin infusion. We hypothesized that the hepatic arterial buffer response (HABR) is absent during preload reduction and reduced by dobutamine. In anesthetized pigs, endotoxin or vehicle (n = 12, each) was randomly infused for 18 h. HABR was tested sequentially by constricting superior mesenteric artery (SMA) or inferior vena cava (IVC). Afterward, dobutamine at 2.5, 5.0, and 10.0 μg/kg per minute or another vehicle (n = 6, each) was randomly administered in endotoxemic and control animals, and SMA was constricted during each dose. Systemic (cardiac output, thermodilution) and carotid, splanchnic, and renal blood flows (ultrasound Doppler) and blood pressures were measured before and during administration of each dobutamine dose. HABR was expressed as hepatic arterial pressure/flow ratio. Compared with controls, 18 h of endotoxin infusion was associated with decreased mean arterial blood pressure [49 ± 11 mmHg vs. 58 ± 8 mmHg (mean ± SD); P = 0.034], decreased renal blood flow, metabolic acidosis, and impaired HABR during SMA constriction [0.32 (0.18-1.32) mmHg/ml vs. 0.22 (0.08-0.60) mmHg/ml; P = 0.043]. IVC constriction resulted in decreased Qpv in both groups; whereas Qha remained unchanged in controls, it decreased after 18 h of endotoxemia (P = 0.031; constriction-time-group interaction). One control and four endotoxemic animals died during the subsequent 6 h. The maximal increase of cardiac output during dobutamine infusion was 47% (22-134%) in controls vs. 53% (37-85%) in endotoxemic animals. The maximal Qpv increase was significant only in controls [24% (12-47%) of baseline (P = 0.043) vs. 17% (-7-32%) in endotoxemia (P = 0.109)]. Dobutamine influenced neither Qha nor HABR. Our data suggest that acute cardiac preload reduction is associated with preferential hepatic arterial perfusion initially but not after established endotoxemia. Dobutamine had no effect on the HABR.

Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura

It has been shown that β(2) -glycoprotein I (β(2) GPI) interacts with von Willebrand factor (VWF) in a glycoprotein (GP)Ib binding state. Given the presence of active VWF multimers in thrombotic thrombocytopenic purpura (TTP), we speculated that β(2) GPI might play a role in TTP. We found that β(2) GPI plasma levels were significantly lower in acute and remission TTP patients than in normal controls, showing a direct correlation with ADAMTS 13 levels and an inverse correlation with the extent of VWF activation. In vitro flow experiments demonstrated that β(2) GPI can block platelet adhesion to endothelial cell-derived VWF strings. We confirmed the direct binding of β(2) GPI to VWF by surface plasmon resonance, and determined that domain I of β(2) GPI is the binding site of VWF A1 domain. Adhesion of β(2) GPI to erythrocytes and platelets was increased in the presence of active VWF, indicating that β(2) GPI may be cleared from the circulation during TTP episodes together with blood cells. Our findings suggest that β(2) GPI may protect from the effects of hyper-functional VWF by inhibiting its interaction with platelets.

Iodide interaction with natural pyrite

29I is one of the major dose-determining nuclides in the safety analysis of deep storage of radioactive waste. Iodine forms anionic species that hardly sorb on the surfaces of common host-rock minerals. Recently, interest has arisen on the role of pyrite, an accessory mineral capable of binding anionic selenium. Whereas the interaction of selenium with pyrite is well documented, corresponding results on iodine sorption are still scarce and controversial. Pyrite is present in argicilleous rocks which are being considered in many countries as potential host rocks for a radioactive waste repository. The uptake of iodide (I−) on natural pyrite was investigated under nearly anoxic conditions (O2 < 5 ppm) over a wide concentration range (10−11–10−3 M total I−) using 125I as the radioactive tracer. Weak but measurable sorption was observed; distribution coefficients (R d) were less than 0.002 m3 kg−1 and decreased with increasing total iodide concentration. Iodide sorption was connected to the presence of oxidized clusters on the pyrite surface, which were presumably formed by reaction with limited amounts of dissolved oxygen. The results obtained indicated that pyrite cannot be considered as an effective scavenger of 129I under the geochemical conditions prevailing in underground radioactive waste geologic storage.

Interaction of the solar wind with them Moon: An overview on the results from the SARA experiment aboard Chandrayaan-1

The results from the Sub-keV Atom Reflecting Analyzer (SARA) experiment onboard Chandrayaan-1 have revealed several hitherto unknown and interesting aspects about the interaction of solar wind with the Moon. The SARA experiment had two sensors — CENA and SWIM. The Chandrayaan-1 energetic neutrals analyzer (CENA), detected energetic neutral atoms (ENAs), and the Solar Wind Monitor (SWIM) measured ions of solar wind origin. In this review, we summarize the observations made by the SARA experiment, which are: (1) substantial (~20%) and sustained backscattering of solar wind protons from lunar surface as energetic neutral hydrogen,1 (2) minimagnetosphere around magnetic anomalies on Moon using the backscattered ENAs,2 (3) reflection of solar wind protons from the Moon surface,3 (4) huge (~50%) deflection of solar wind protons over strong magnetic anomalies,4 and (5) presence of protons in the near-lunar plasma wake.5 These results have implications on the lunar plasma environment, implantation of solar wind hydrogen on lunar surface, and behavior of small scale magnetic anomalies on planetary bodies. The SARA observations suggest that similar processes may happen on other airless bodies covered with regolith in the solar system as well as in extra-solar system. This paper presents a review of the results obtained from the SARA observation.

Interaction of fine particles and nanoparticles with red blood cells visualized with advanced microscopic techniques

So far, little is known about the interaction of nanoparticles with lung cells, the entering of nanoparticles, and their transport through the blood stream to other organs. The entering and localization of different nanoparticles consisting of differing materials and of different charges were studied in human red blood cells. As these cells do not have any phagocytic receptors on their surface, and no actinmyosin system, we chose them as a model for nonphagocytic cells to study how nanoparticles penetrate cell membranes. We combined different microscopic techniques to visualize fine and nanoparticles in red blood cells: (I) fluorescent particles were analyzed by laser scanning microscopy combined with digital image restoration, (II) gold particles were analyzed by conventional transmission electron microscopy and energy filtering transmission electron microscopy, and (III) titanium dioxide particles were analyzed by energy filtering transmission electron microscopy. By using these differing microscopic techniques we were able to visualize and detect particles < or = 0.2 microm and nanoparticles in red blood cells. We found that the surface charge and the material of the particles did not influence their entering. These results suggest that particles may penetrate the red blood cell membrane by a still unknown mechanism different from phagocytosis and endocytosis.

The well-being model: a new drug interaction model for positive and negative effects

BACKGROUND: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account. METHODS: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs. RESULTS: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed. CONCLUSIONS: The model is consistent with clinical knowledge and supports previously published experimental results on optimal drug combinations. This new framework improves understanding of the characteristics of drug combinations used in clinical practice and can be used in clinical research to identify optimal drug dosing.

Kinetics of the interaction of desAABB-fibrin monomer with immobilized fibrinogen

The soluble and stable fibrin monomer-fibrinogen complex (SF) is well known to be present in the circulating blood of healthy individuals and of patients with thrombotic diseases. However, its physiological role is not yet fully understood. To deepen our knowledge about this complex, a method for the quantitative analysis of interaction between soluble fibrin monomers and surface-immobilized fibrinogen has been established by means of resonant mirror (IAsys) and surface plasmon resonance (BIAcore) biosensors. The protocols have been optimized and validated by choosing appropriate immobilization procedures with regeneration steps and suitable fibrin concentrations. The highly specific binding of fibrin monomers to immobilized fibrin(ogen), or vice versa, was characterized by an affinity constant of approximately 10(-8)M, which accords better with the direct dissociation of fibrin triads (KD approximately 10(-8) -10(-9) M) (J. R. Shainoff and B. N. Dardik, Annals of the New York Academy of Science, 1983, Vol. 27, pp. 254-268) than with earlier estimations of the KD for the fibrin-fibrinogen complex (KD approximately 10(-6) M) (J. L. Usero, C. Izquierdo, F. J. Burguillo, M. G. Roig, A. del Arco, and M. A. Herraez, International Journal of Biochemistry, 1981, Vol. 13, pp. 1191-1196).