In addition to the well-known signals of retinal image slip, floccular complex spikes (CSs) also convey nonvisual signals. We recorded eye movement and CS activity from Purkinje cells in awake ...rabbits sinusoidally oscillated in the dark on a vestibular turntable. The stimulus frequency ranged from 0.2 to 1.2 Hz, and the velocity amplitude ranged from 6.3 to 50°/s. The average CS modulation was evaluated at each combination of stimulus frequency and amplitude. More than 75% of the Purkinje cells carried nonvisual CS signals. The amplitude of this modulation remained relatively constant over the entire stimulus range. The phase response of the CS modulation in the dark was opposite to that during the vestibulo-ocular reflex (VOR) in the light. With increased frequency, the phase response systematically shifted from being aligned with contraversive head velocity toward peak contralateral head position. At fixed frequency, the phase response was dependent on peak head velocity, indicating a system nonlinearity. The nonvisual CS modulation apparently reflects a competition between eye movement and vestibular signals, resulting in an eye movement error signal inferred from nonvisual sources. The combination of this error signal with the retinal slip signal in the inferior olive results in a net error signal reporting the discrepancy between the actual visually measured eye movement error and the inferred eye movement error derived from measures of the internal state. The presence of two error signals requires that the role of CSs in models of the floccular control of VOR adaption be expanded beyond retinal slip.
Purpose
This study was designed to assess midterm outcome of uterine artery embolisation (UAE) for women with therapy-resistant adenomyosis using polyzene F-coated hydrogel microspheres.
Methods
...Between September 2006 and January 2010, 29 consecutive women with adenomyosis (15 in combination with fibroids) were treated with UAE using polyzene F-coated hydrogel microspheres. Junction zone thickness was assessed with MRI at baseline and 3 months. Women filled out the uterine fibroid symptom and quality of life questionnaire at baseline, 3 months and after a mean clinical follow-up of 37 months (median 35, range 29–64 months).
Results
At baseline, symptom severity score of 29 women was mean 67 (median 72, range 23–100). At 3 months, this score decreased to mean 22 (median 15, range 0–66) and mean 15 (median 17, range 0–34) at final follow-up. At final follow-up of mean 37 months (median 35, range 29–64 months), 22 of 29 (76 %) patients were asymptomatic. Of these 22 women, 3 underwent a second UAE at 6, 7, and 14 months. The remaining seven patients clinically improved but still had symptoms; one underwent a hysterectomy. There was no difference in outcome between women with pure adenomyosis and women with additional fibroids. The junction zone of 4 women with additional therapy was significantly thicker compared with the remaining 25 patients.
Conclusions
In women with therapy resistant adenomyosis, UAE using polyzene F-coated hydrogel microspheres resulted in 3 years preservation of the uterus in 28 of 29 (97 %) with good clinical outcome in the vast majority of patients. Initial thickness of the junction zone is related to additional therapy.
An experimental setup exploiting grating-coupled surface plasmon resonance (GCSPR) technique based on polarization modulation in conical mounting is presented for the first time. A metallic grating ...is azimuthally rotated in order to support excitation of surface plasmon polaritons (SPPs) with enhanced sensitivity. In correspondence of SPP resonance, a polarization scan of the incident light is performed and reflectivity is collected. Output signal exhibits harmonic dependence on polarization and the phase term is exploited as a parameter for sensing analysis. Since the sensing configuration is kept fixed during the analysis and the only degree of freedom is represented by the incident polarization, the mechanical complexity of this SPR system is significantly reduced with respect to other configurations. Moreover the setup assures competitive performance in refractive index sensitivity and resolution. The assembled prototype is tested for fluid analysis with an embedded glass/PDMS microfluidic cell fabricated by soft-lithography procedure. A model biorecognition assay based on avidin/biotin reaction was considered in order to test the detection performance of the presented setup.
Stability, defined as the reproducible behavior of a device upon its storage, is an important issue in pharmaceutical formulation. Silica xerogels obtained through the sol-gel route are relatively ...new as matrices for the controlled release of drugs. In some cases, it was observed that their behavior changes upon storage, so that they cannot always be defined as "stable". This occurs especially when gel processing is performed at mild temperatures, a procedure that may have to be used to prevent degradation of the embedded drug. This work investigated the use of inorganic catalysts as potential xerogel stability inducers when gel curing by heating is not applicable. Three compounds known to accelerate sol-gel polymerization, namely ammonia, sodium fluoride and sodium carbonate, were introduced during the polymerization of low-temperature processed inorganic and organically modified gels, and the effect of each compound on xerogel stability and drug release was monitored. The use of carbonate leads to formulations with good retention properties, as opposed to ammonia and NaF, which lead to poorly retentive xerogels in accordance with their known ability to increase porosity. Ammonia was shown to be a poor stability promoter independently of gel composition, as opposed to fluoride and carbonate, which both displayed stabilizing properties in a dose-dependent manner. No correlation was found between xerogel stability and drug release properties. An attempt was also made to correlate stability data with polymerization rates and wet gel syneresis time evolution with the purpose of identifying one or more synthesis parameters that could act as stability predictors for pre-formulation studies. No correlation was found between stability and syneresis data. A similar trend in the curve of gel time vs. catalyst concentration was observed for the two stabilizing catalysts, which was different for the non-stabilizing ammonia. It was concluded that the trend of this curve could potentially provide an indicator of catalyst stabilizing efficacy.
•Metallic gratings were fabricated by interferential lithography and replicated on resin substrates before metal evaporation.•The plasmonic platforms were exploited for a novel configuration of ...surface plasmon resonance.•A prototypal device was assembled implementing grating-coupled surface plasmon resonance with polarization modulation.•The sensing technique was tested with saline solutions flowing through an integrated microfluidic cell.•The sensing device was tested for the detection of a avidin/biotin binding reaction.
An experimental prototype exploiting Grating-Coupled Surface Plasmon Resonance (GCSPR) based on polarization modulation has been assembled and tested for sensing purposes. The plasmonic gratings are azimuthally rotated in order to exploit the symmetry breaking for the excitation of highly sensitive Surface Plasmon Polaritons in conical mounting. By exploiting the optimal-polarization shift, a scan of the incident polarization is performed and reflectivity data are collected. The output signal exhibits a harmonic dependence on polarization and the phase term is considered as a parameter for sensing. Since the optical configuration is fixed during the analysis and the only degree of freedom is represented by the incident polarization, this setup provides a more compact and simplified architecture with respect to other commercial SPR techniques, however assuring at the same time competitive performances in refractive index sensitivity and resolution. The employed metallic gratings are fabricated by interferential lithography and replicated onto resin substrates by soft-lithography techniques, thus thermally evaporated.
Corrugated gratings coated with thin films of noble metals have been recognized to be useful substrates for bio-detection by means of the excitation of surface plasmon polaritons (SPP). These ...substrates show superior performances in terms both of detection limit and of simplicity of detection configuration compared to the classical Kretschmann SPP. A 1D sinusoidal corrugation of the metal-air interface has been fabricated by means of laser interference lithography and metal evaporation. In this paper we report progress in the optimization of the sinusoidal grating surface profile. The quality of the fabricated samples has been proved by the good agreement between experimental and simulated results.
In this work, we investigated a sol-gel derived silica matrix as a delivery system for the prolonged release of different molecular weight heparins, which allows the glycosaminoglicons to retain ...their whole biological activity. Several xerogels were obtained by embedding different molecular weight heparins into matrices prepared by using different amount of NH4OH as a catalyst during gel formation. Gel synthesis parameters, drug release properties, and xerogels surface area were evaluated. Unfractionated, low and oligo-molecular weight heparins were embedded into xerogels and the effect of the molecular weight on the release kinetics and the retained biological activity has been investigated. The results show that the surface area of the matrix is a determinant parameter affecting drug release kinetics. This structural feature can be modified by varying the catalyst tetraethoxysilane molar ratio used during the matrix synthesis. In most cases release kinetics fitted the Higuchi diffusive model and a lower diffusion rate was observed from silica matrices characterized by a smaller surface area. In the case of matrices with lower surface area, loaded with unfractionated heparin, zero order kinetics was observed. In this paper, we have defined a heparin release silica xerogel system and we have pointed out how modulation of its synthesis parameters allows adjusting the release of heparin according to therapeutic needs.
The addition of surfactants to suppository formulations is referred to in the scientific literature, but their effects on drug availability remain uncertain. Surfactants are reported to improve drug ...dispersion into hard fatty excipients, to increase the spreading of the melted suppository on the rectal mucosa leading to a greater contact surface, to reduce the viscosity of the molten mass and to reduce the pathway of drug particles to the interface. In the present study a systematic investigation based on tensiometric and rheological methods was carried out to evaluate the effects of nonionic surfactants with different HLBs (hydrophilic-lipophilic-balance) on drug availability and to clarify the possible mechanisms involved in the release process. The relationship between the melted suppositories and a membrane simulating the rectal barrier were investigated in the course of the in vitro release test by measuring their energy characteristics. At the same time, the potential influences of such interactions on drug release were investigated in suppositories formulated with different kinds and concentrations of surfactant additives. Drug availability was influenced not only by the interaction between the suppository and the rectal membrane but also by the interaction between surfactant, lipophilic excipient and suspended drug particles. Such interactions appear to greatly influence drug release from suppositories, which, in turn, is the main parameter determining drug availability.
Background.The effect of alteplase versus heparin in pulmonary embolism has not been studied extensively with serial pulmonary angiograms.
Objectives.The aim of this randomized, open trial was to ...evaluate the efficacy and safety of alteplase followed by heparin, versus heparin alone, in 30 patients with angiographically documented pulmonary embolism.
Methods.Twenty patients were allocated randomly to a 2-h infusion of alteplase (10 mg bolus, then 90 mg over 2 h) followed by heparin; the other 16 patients were given intravenous heparin at a continuous infusion rate of 1,750 IU/h.
Results.The vascular obstruction, assessed by the Miller index at pulmonary angiography, decreased significantly in alteplasetreated patients (p < 0.01) from a baseline of 28.3 ± 2.9 to a value of 24.8 ± 5.2 2 h after the start of infusion; in the heparin group there was no change (from 25.3 ± 5.3 to 25.2 ± 5.4). Mean pulmonary artery pressure decreased significantly from a baseline of 30.2 ± 7.8 mm Hg to 21.4 ± 6.7 in the alteplase group and increased in the heparin group (from 22.3 ± 10.5 to 24.8 ± 11.2 mm Hg). For a subset of patients, lung scans were performed at baseline and on days 7 and 30. There were no differences between the two groups in the follow-up lung scans, but there were significant decreases from the baseline values. Bleeding occurred in 14 of 20 alteplase-treated patients and in 6 of 16 in the heparin group (p = NS). There were three major bleeding episodes in the alteplase group and two in the heparin group. Two patients died after fibrinolysis (one of acute renal failure after cardiac tamponade and one of cardiac arrest after cerebral hemorrhage) and one patient in the heparin group died of recurrent pulmonary embolism.
Conclusions.Alteplase resulted in a greater and faster improvement of the angiographic and hemodynamic variables compared with heparin. However, the high frequency of bleeding observed with alteplase in this trial suggests that patients should be carefully selected before thrombolytic therapy is given.
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