Development and characterization of an implantable biosensor for telemetric monitoring of ethanol in the brain of freely moving rats

Ethanol is one of the most widespread psychotropic agents in western society. While its psychoactive effects are mainly associated with GABAergic and glutamatergic systems, the positive reinforcing properties of ethanol are related to activation of mesolimbic dopaminergic pathways resulting in a release of dopamine in the nucleus accumbens. Given these neurobiological implications, the detection of ethanol in brain extracellular fluid (ECF) is of great importance. In this study, we describe the development and characterization of an implantable biosensor for the amperometric detection of brain ethanol in real time. Ten different designs were characterized in vitro in terms of Michaelis-Menten kinetics (V(MAX) and K(M)), sensitivity (linear region slope, limit of detection (LOD), and limit of quantification (LOQ)), and electroactive interference blocking. The same parameters were monitored in selected designs up to 28 days after fabrication in order to quantify their stability. Finally, the best performing biosensor design was selected for implantation in the nucleus accumbens and coupled with a previously developed telemetric device for the real-time monitoring of ethanol in freely moving, untethered rats. Ethanol was then administered systemically to animals, either alone or in combination with ranitidine (an alcohol dehydrogenase inhibitor) while the biosensor signal was continuously recorded. The implanted biosensor, integrated in the low-cost telemetry system, was demonstrated to be a reliable device for the short-time monitoring of exogenous ethanol in brain ECF and represents a new generation of analytical tools for studying ethanol toxicokinetics and the effect of drugs on brain ethanol levels.     

Experimental tests of a new hysteretic damper made of buckling inhibited shear panels

Metal shear panels represent a highly performing anti seismic system for medium–high rise buildings located in strong earthquake prone zones. A new configuration of dissipative shear panel is presented in the current paper. The base shear plate is made of a low-strength material, namely the heath treated EN-AW-1050A aluminium alloy, which has been already used by the authors for other types of dissipative shear panels. In this proposed new system, the main buckling modes are inhibited by the application of external devices placed in parallel to the base plate and not directly loaded by the external forces. Two shear panel samples are tested as prototypes, which are based on two different plate buckling inhibition strategies. In the former the out-of-plane displacements of only some parts of the base plate are restrained, whereas in the latter the restraining action of the external device is extended to the whole base plate. Experimental tests are presented in order to prove the performance of the proposed devices in terms of dissipative capacity and stiffness. In addition, the obtained results are compared with the ones related to other more conventional shear panel typologies, characterized by the same geometry and material, but in which buckling phenomena were mitigated by means of welded stiffeners, according to a more traditional practice.     

Service life prediction for refractory materials

Ultrasonic pulse velocity testing and image analysis were used to predict the thermal stability of cordierite–mullite refractories. Two compositions used as substrates in fast firing of porcelain whiteware, characterized by different microstructure and crack propagation behavior, were investigated. Fracture strength and fracture toughness values were obtained from three point bending test and chevron notched specimen technique, respectively. The measurement of the ultrasonic velocity was used to assess the material degradation with increasing number of thermal-shock cycles and specimen damage was monitored using image analysis to obtain further evidence of material degradation. The correlation between thermo-mechanical properties, ultrasonic velocity, microstructure, crack-propagation behavior and thermal-shock resistance was discussed. A remarkable similarity was found between the variation of ultrasonic velocity (when measured through the length of the refractory plates) and fracture strength with number of thermal shock cycles. On the other hand, the development of surface microcracking, as monitored by image analysis, is in good agreement with the variation of K _IC with the number of thermal-shock cycles. The variation of the ratio with number of thermal-shock cycles shows the highest gradient of the investigated trends and it is proposed as a promising parameter to differentiate refractory materials regarding their different thermal shock behavior. Service life prediction models for refractory plates, from measured values of ultrasonic velocity and surface damage analysis, were proposed and validated.     

Analysis of computational problems expressing the overall uncertainties: photons, neutrons and electrons

In the frame of the EU Coordination Action CONRAD (coordinated network for radiation dosimetry), WP4 was dedicated to work on computational dosimetry with an action entitled 'Uncertainty assessment in computational dosimetry: an intercomparison of approaches'. Participants attempted one or more of eight problems. This paper presents the results from problems 4-8-dealing with the overall uncertainty budget estimate; a short overview of each problem is presented together with a discussion of the most significant results and conclusions. The scope of the problems discussed here are: the study of a (137)Cs calibration irradiator; the manganese bath technique; the iron sphere experiment using neutron time-of-flight technique; the energy response of a RADFET detector and finally the sensitivity and uncertainty analysis for the recoil-proton telescope discussed in the companion paper.     

New perspectives for the Barkhausen effect

The precise connections between the Barkhausen effect and non-equilibrium critical phenomena and self-organized criticality (SOC) have been strongly debated in the past few years. We review the recent theoretical studies of the Barkhausen effect and discuss their relevance to quantitatively understand the experiments. We compare the results of disordered spin models, micromagnetic equations, and models for rigid and flexible domain walls with experiments on amorphous and polycrystalline ferromagnetic alloys. In particular, we discuss the theoretical predictions for the critical exponents of the power law decay and for the cutoff of the avalanche distributions. We conclude that models based on the dynamics of a flexible domain wall are the most successful in explaining existing experimental data.     

Dry versus hydrated collagen scaffolds: are dry states representative of hydrated states?

Collagen composite scaffolds have been used for a number of studies in tissue engineering. The hydration of such highly porous and hydrophilic structures may influence mechanical behaviour and porosity due to swelling. The differences in physical properties following hydration would represent a significant limiting factor for the seeding, growth and differentiation of cells in vitro and the overall applicability of such hydrophilic materials in vivo. Scaffolds based on collagen matrix, poly(DL-lactide) nanofibers, calcium phosphate particles and sodium hyaluronate with 8 different material compositions were characterised in the dry and hydrated states using X-ray microcomputed tomography, compression tests, hydraulic permeability measurement, degradation tests and infrared spectrometry. Hydration, simulating the conditions of cell seeding and cultivation up to 48?h and 576?h, was found to exert a minor effect on the morphological parameters and permeability. Conversely, hydration had a major statistically significant effect on the mechanical behaviour of all the tested scaffolds. The elastic modulus and compressive strength of all the scaffolds decreased by ~95%. The quantitative results provided confirm the importance of analysing scaffolds in the hydrated rather than the dry state since the former more precisely simulates the real environment for which such materials are designed.

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Pulmonary function tests as a predictor of chronic lung disease in ventilated preterm infants

BACKGROUND: The objective of this study was to determine if the value of respiratory system compliance and lung resistance could be a good predictor of chronic lung disease (CLD) in an early stage of this disease. METHODS: The study was carried out on 48 preterms infant (BW < 1500 g) who were ventilated for respiratory distress, calculating pulmonary mechanics at 3, 5, 7 and 10 days of life with a standardized protocol of measurements. RESULTS: Infants who did not develop CLD showed higher values of respiratory system dynamic compliance (Crsdyn) than the CLD group since the 5th day of life (p < 0.001). The values of lung resistance show a statistical significant difference between groups since the 7th day of life. CONCLUSIONS: These findings indicate that, with a well standardized method of measurements, the value of Crsdyn can well be a good predictor and a sensible prognostic factors for CLD.     

Oral keratinocyte immune responses in HIV-associated candidiasis

Technetium-99m is the most commonly used radionuclide in routine nuclear medicine imaging procedures. Development of 99mTc-labeled receptor-specific imaging agents for studying the central nervous system is potentially useful for evaluation of brain function in normal and disease states. A novel 99mTc-labeled tropane derivative, [99mTc]TRODAT-1, which is useful as a potential CNS dopamine transporter imaging agent, was evaluated and characterized. After i. v. injection into rats, [99mTc]TRODAT-1 displayed specific brain uptake in the rat striatal region (striatum-cerebellum/cerebellum ratio 1.8 at 60 min), where dopamine neurons are concentrated. The specific striatal uptake could be blocked by pretreating rats with a dose of competing dopamine transporter ligand, beta-CIT (or RTI-55, i.v., 1 mg/kg). However, the specific striatal uptake of [99mTc]TRODAT-1 was not affected by co-injection of excess free ligand (TRODAT-1, up to 200 microg per rat) or by pretreating the rats with haloperidol (i.v., 1 mg/kg). The specific uptake in striatal regions of rats that had prior 6-hydroxydopamine lesion in the substantia nigra area showed a dramatic reduction. The radioactive material recovered from the rat striatal homogenates at 60 min after i.v. injection of [99mTc]TRODAT-1 showed primarily the original compound (>95%), a good indication of in vivo stability in brain tissue. Similar and comparable organ distribution patterns and brain regional uptakes of [99mTc]TRODAT-1 were obtained for male and female rats. Ex vivo autoradiography results of rat brain sections further confirmed the high uptake and retention of [99mTc]TRODAT-1 in the striatal region. In vitro binding studies measuring the affinity to dopamine transporters for the free ligand, TRODAT-1, and a nonradioactive rhenium derivative, Re-TRODAT-1, showed Ki values of 9.7 nM and 14.1 nM, respectively. Behavioral studies in rats using the free ligand, TRODAT-1 and Re-TRODAT-1 indicated that, unlike other tropane derivatives, they displayed no effect on locomotor activity, suggesting low toxicity. These results strongly support the conclusions that this novel 99mTc radioligand binds selectively to dopamine transporters in the brain and that is is potentially useful for in vivo assessment of the loss of dopamine neurons in Parkinson's and other neurodegenerative diseases.