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Evaluation of the radioisotopic purity of technetium-99m ( 99m Tc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 ( 100 Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states ( 9x Tc) present in the pertechnetate saline Na 99m TcO 4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate ( 99m Tc) injection 4801-3). Moreover, the impact of 9x Tc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99m Tc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99 Mo/ 99m Tc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E γ   >  200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99m Tc using 100 Mo(p,2n) 99m Tc reaction at a proton beam energy in the range 15.7-19.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99m Tc.

Background Literature concerning the lower limbs physiological venous haemodynamics is still lacking of reference velocity values and consequent impact on drainage direction. Aim of the present study is to assess the flow velocities in the different venous compartments, evaluating the possible Venturi effect role, thus finding clues for the identification of the physical model governing the flow direction. Methods Thirty-six lower limbs underwent a velocity and diameters echo-color-Doppler assessment in several anatomical point of analysis along both the deep and superficial venous systems. The investigation protocol included and compared two different manoeuvres to elicit the flow: manual calf compression/relaxation (CR) and active foot dorsiflexion (AFD). Both peak systolic (PSV) and time average velocities (TAV) were measured. Results The different venous segments demonstrated an overlap among the velocity values and the anatomical subdivision of the deep and superficial compartments. At the CR, TAV was 34 ± 12 cm/s in the deep venous system (N1), 15 ± 7 cm/s in the saphenous system (N2), 5 ± 2 cm/s in the saphenous tributaries (N3); PSV was 89 ± 35 cm/s in N1, 34 ± 16 cm/s in N2, 11 ± 4 cm/s in N3, p < 0.05. At the AFD, TAV was 33 ± 13 cm/s in N1, 15 ± 7 in N2, 9 ± 5 in N3; PSV was 83 ± 35 in N1, 32 ± 17 in N2, 15 ± 4 in N3, p < 0.05. A diameter decrease was reported from N1 to N3 ( p < 0.05). Conclusion This investigation provides evidences of the velocity decrease from the deepest to the most superficial compartments. These data introduce the Venturi effect as potential factor in the flow aspiration from the tributary to the deeper veins. The reported data represent a first step towards an objective evaluation of the physic laws governing the drainage. These values can constitute the basis for further investigations in pathological and post-procedural scenarios.

We investigate the evolution of the state of polarization of light propagating through bulk depoled composite ferroelectrics below the Curie temperature. In contrast to standard depoled ferroelectrics, where random birefringence causes depolarization and scattering, light is observed to suffer varying degrees of depolarization and remains fully polarized when linearly polarized along the crystal principal axes. The effect is found to be supported by the formation of polarized speckles organized into a spatial lattice and occurs as the ferroelectric settles into a spontaneous super-crystal, a three-dimensional coherent mosaic of ferroelectric clusters. The polarization lattices gradually disappear as the ferroelectric state reduces to a disordered distribution of polar nanoregions above the critical point.

JWH-018 and AKB48 are two synthetic cannabinoids (SCBs) belonging to different structural classes and illegally marketed as incense, herbal preparations, or chemical supply for theirs psychoactive cannabis-like effects. Clinical reports from emergency room reported psychomotor agitation as one of the most frequent effects in people assuming SCBs. This study aimed to investigate the psychostimulant properties of JWH-018 and AKB48 in male CD-1 mice and to compare their behavioral and biochemical effects with those caused by cocaine and amphetamine. In vivo studies showed that JWH-018 and AKB48, as cocaine and amphetamine, facilitated spontaneous locomotion in mice. These effects were prevented by CB 1 receptor blockade and dopamine (DA) D 1/5 and D 2/3 receptors inhibition. SPECT-CT studies on dopamine transporter (DAT) revealed that, as cocaine and amphetamine, JWH-018 and AKB48 decreased the [ 123 I]-FP-CIT binding in the mouse striatum. Conversely, in vitro competition binding studies revealed that, unlike cocaine and amphetamine, JWH-018 and AKB48 did not bind to mouse or human DAT. Moreover, microdialysis studies showed that the systemic administration of JWH-018, AKB48, cocaine, and amphetamine stimulated DA release in the nucleus accumbens (NAc) shell of freely moving mice. Finally, unlike amphetamine and cocaine, JWH-018 and AKB48 did not induce any changes on spontaneous [ 3 H]-DA efflux from murine striatal synaptosomes. The present results suggest that SCBs facilitate striatal DA release possibly with different mechanisms than cocaine and amphetamine. Furthermore, they demonstrate, for the first time, that JWH-018 and AKB48 induce a psychostimulant effect in mice possibly by increasing NAc DA release. These data, according to clinical reports, outline the potential psychostimulant action of SCBs highlighting their possible danger to human health.

We experimentally demonstrate an electro-optic Gaussian-to-Bessel beam-converter miniaturized down to a 30×30  μm pixel in a potassium-lithium-tantalate-niobate (KLTN) paraelectric crystal. The converter is based on the electro-optic activation of a photoinduced and reconfigurable volume axicon lens achieved using a prewritten photorefractive funnel space-charge distribution. The transmitted light beam has a tunable depth of field that can be more than twice that of a conventional beam with the added feature of being self-healing.

OBIETTIVI: determinare i fattori associati ai ricoveri ripetuti per identificare i pazienti a rischio di riospedalizzazione entro i 30 giorni dalla dimissione. DISEGNO: analisi retrospettiva delle dimissioni nell'anno 2013 attraverso le schede di dimissione ospedaliera (SDO)., Setting E Partecipanti: 3.900 pazienti ricoverati presso il presidio ospedaliero "Fabrizio Spaziani" di Frosinone. PRINCIPALI MISURE DI OUTCOME: analisi bivariata per l'analisi dell'associazione tra variabili. La regressione logistica è stata utilizzata per identificare i fattori di rischio associati al ricovero ripetuto. RISULTATI: tra i 3.900 pazienti considerati, il 12,8% ha avuto una riammissione non programmata entro un mese dalla dimissione precedente per le stesse categorie diagnostiche principali (MCD). Sono state rilevate differenze statisticamente significative tra i pazienti con e senza ricovero ripetuto per età, durata della degenza, titolo di studio, condizione occupazionale e diagnosi. I fattori che aumentano la probabilità di una riospedalizzazione sono il vivere da solo, la condizione di pensionato o casalinga, una degenza più lunga e alcune diagnosi, fra cui malattie dell'apparato respiratorio, del sistema nervoso e dell'apparato urinario. CONCLUSIONE: alcune caratteristiche sociodemografiche e la diagnosi dei pazienti ospedalizzati sono associate al rischio di riospedalizzazione entro 30 giorni dalla dimissione. I dati disponibili nell'archivio delle SDO possono essere utilizzati per un'identificazione dei pazienti a rischio sui quali definire specifici piani di dimissione.

Purpose: Dual-energy image subtraction represents a useful tool to improve the detectability of small lesions, especially in dense breasts. A feature it shares with all x-ray imaging techniques is the appearance of fluctuations in the texture of the background, which can obscure the visibility of interesting details. The aim of the work is to investigate the main noise sources, in order to create a better performing subtraction mechanism. In particular, the structural noise cancellation was achieved by means of a suitable extension of the dual-energy algorithm., Methods: The effect of the cancellation procedure was tested on an analytical simulation of a target with varying structural composition. Subsequently, the subtraction algorithm was also applied to a set of actual radiographs of a breast phantom exhibiting a nonuniform background pattern. The background power spectra of the outcomes were computed and compared to the ones obtained from a standard subtraction algorithm., Results: The comparison between the standard and the proposed cancellations showed an overall suppression of the magnitudes of the spectra, as well as a flattening of the frequency dependence of the structural component of the noise., Conclusions: The proposed subtraction procedure provides an effective cancellation of the residual background fluctuations. When combined with the polychromatic correction already described in a companion publication, it results in a high performing dual-energy subtraction scheme for commercial mammography units.

Purpose: The quality of a radiography system is affected by several factors, a major one being the focal spot size of the x-ray tube. In fact, the measurement of such size is recognized to be of primary importance during acceptance tests and image quality evaluations of clinical radiography systems. The most common device providing an image of the focal spot emission distribution is a pin-hole camera, which requires a high tube loading in order to produce a measurable signal. This work introduces an alternative technique to obtain an image of the focal spot, through the processing of a single radiograph of a simple test object, acquired with a suitable magnification., Methods: The radiograph of a magnified sharp edge is a well-established method to evaluate the extension of the focal spot profile along the direction perpendicular to the edge. From a single radiograph of a circular x-ray absorber, it is possible to extract simultaneously the radial profiles of several sharp edges with different orientations. The authors propose a technique that allows to obtain an image of the focal spot through the processing of these radial profiles by means of a pseudo-CT reconstruction technique. In order to validate this technique, the reconstruction has been applied to the simulated radiographs of an ideal disk-shaped absorber, generated by various simulated focal spot distributions. Furthermore, the method has been applied to the focal spot of a commercially available mammography unit., Results: In the case of simulated radiographs, the results of the reconstructions have been compared to the original distributions, showing an excellent agreement for what regards both the overall distribution and the full width at half maximum measurements. In the case of the experimental test, the method allowed to obtain images of the focal spot that have been compared with the results obtained through standard techniques, namely, pin-hole camera and slit camera., Conclusions: The method was proven to be effective for simulated images and the results of the experimental test suggest that it could be considered as an alternative technique for focal spot distribution evaluation. The method offers the possibility to measure the actual focal spot size and emission distribution at the same exposure conditions as clinical routine, avoiding high tube loading as in the case of the pin-hole imaging technique.

Purpose: Contrast-enhanced digital mammography is an image subtraction technique that is able to improve the detectability of lesions in dense breasts. One of the main sources of error, when the technique is performed by means of commercial mammography devices, is represented by the intrinsic polychromaticity of the x-ray beams. The aim of the work is to propose an iterative procedure, which only assumes the knowledge of a small set of universal quantities, to take into account the polychromaticity and correct the subtraction results accordingly., Methods: In order to verify the procedure, it has been applied to an analytical simulation of a target containing a contrast medium and to actual radiographs of a breast phantom containing cavities filled with a solution of the same medium., Results: The reconstructed densities of contrast medium were compared, showing very good agreement between the theoretical predictions and the experimental results already after the first iteration. Furthermore, the convergence of the iterative procedure was studied, showing that only a small number of iterations is necessary to reach limiting values., Conclusions: The proposed procedure represents an efficient solution to the polychromaticity issue, qualifying therefore as a viable alternative to inverse-map functions.

The purpose of the work described here was to investigate the feasibility of assessing the jugular venous pulse (JVP) using ultrasound (US) equipment. Three young healthy subjects underwent a B-mode US scan of the internal jugular vein (IJV) to acquire a sonogram sequence in the transverse plane. On each acquired sonogram, the IJV contour was manually traced, and both the cross-sectional area (CSA) and the perimeter were measured. The CSA data set represents the US jugular diagram (USJD). The arterial distension waveform of the subjects was compared with its USJD. The correlation between the CSA and the perimeter was assessed during the cardiac cycle to verify IJV distension. For each subject, a short sonogram sequence of a few seconds was recorded, and the USJD obtained exhibited periodic behavior. Furthermore, for all subjects, the CSA was found to be correlated with the perimeter (Pearson coefficient, R > 0.9), indicating that the IJV in supine position is distended. We compared 390 manually traced contours of the IJV cross-sectional area with corresponding values semi-automatically calculated by an algorithm developed in-house. For all subjects, the sensitivity, specificity and accuracy were around 95%, 85% and 90% respectively. We found that a diagram reflecting the JVP can be obtained by analyzing a B-mode sonogram sequence of the IJV; such a diagram can result in a new methodology to assess the IJV functionality., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

This study describes the preparation, characterization, and biodistribution of radiolabelled nanostructured lipid carriers (NLCs) especially designed for in vivo tomographic study. A preliminary formulative study was conducted in order to incorporate (99m)Tc based tracer in NLCs. At this aim a (99m)Tc complex containing a terminal (99m)Tc ≡ N multiple bond ([(99m)Tc]N-DBODC2) has been synthesized and included in NLCs produced by a stirring and ultrasonication method. The morphological and dimensional characteristics of the produced NLCs have been accurately investigated by a number of specific techniques, including: cryogenic transmission electron microscopy, X-ray, photon correlation spectroscopy and sedimentation field flow fractionation. The obtained NLCs were employed for achieving in vivo tomographic images of the rat body by small-animal SPECT scanner that enabled the investigation of NLC biodistribution after intraperitoneal, intravenous, intranasal and oral administration. NLC production protocol allowed to firmly encapsulate the radiotracer within the nanoparticles. In vivo studies evidenced that NLC remained stable in vivo, suggesting their suitability as controlled release system for drugs and radiochemical for therapeutic and diagnostic purposes. Moreover the high resolution images obtained by the SPECT technique allowed to detect NLC presence in brown fat tissue, suggesting NLC therapeutic application for treating human obesity and related metabolic disorders., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: New (188)Re and (99m)Tc peptide conjugates with substance- P (SP) were prepared and biologically evaluated. The radiopharmaceuticals have been labelled with the [M≡N](2+) (M=(99m)Tc, (188)Re) core using a combination of π-donor tridentate and π-acceptor monodentate ancillary ligands., Methods: The new radiopharmaceuticals have been prepared through a two-step reaction by simultaneous addition of the tridentate and monodentate ligands to a vial containing a preformed [M≡N](2+) core. The tridentate ligand was formed by linking two cysteine residues to the terminal arginine of the undecapeptide SP, whereas the monodentate ligand was a tertiary phosphine. The preparation of the corresponding Re-188 derivative required developing a more complex chemical procedure to obtain the [Re≡N](2+) core in satisfactory yields. Characterization of the resulting products was obtained by chromatographic methods. Biological evaluation was performed for both Tc-99m and Re-188 derivatives by in-vitro studies on isolated cells expressing NK1-receptors. In-vivo imaging in mice was carried out using a small-animal YAP(S)PET tomograph., Conclusion: New Tc-99m and Re-188 peptide radiopharmaceuticals with SP have been prepared in high-yield and with high-specific activity. Both Tc-99m and Re-188 peptide radioconjugates exhibit high affinity for NK1 receptors, thus giving further evidence to the empirical rule that structurally related Tc-99m and Re-188 radiopharmaceuticals exhibit identical biological properties., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Endothelial Progenitor Cells (EPCs), a minor subpopulation of the mononuclear cell fraction in peripheral blood, play a critical role in cancer development as they contribute to angiogenesis-mediated pathological neovascularization. In response to tumor cytokines, including VEGF, EPCs mobilize from the bone marrow into the peripheral circulation and move to the tumor bed where they incorporate into sprouting neovessels. In the present study, we evaluated the effects of everolimus (Afinitor, Novartis), a rapamycin analogue, alone or in combination with chloroquine, a 4-alkylamino substituted quinoline family member, one of the autophagy inhibitors, on EPCs biological functions. We found that either everolimus or chloroquine induce growth inhibition on EPCs in a dose-dependent manner after 72 h from the beginning of incubation. The combined administration of the two drugs to EPC was synergistic in inducing growth inhibition; in details, the maximal pharmacological synergism between everolimus and chloroquine in inducing growth inhibition on EPCs cells was recorded when chloroquine was administered 24 h before everolimus. Moreover, we have studied the mechanisms of cell death induced by the two agents alone or in combination on EPCs and we have found that the synergistic effect of combination on EPC growth inhibition was paralleled by increased apoptosis induction and reduced autophagy. These effects occurred together with biochemical features that are typical of reduced autophagic death such as increased co-immunoprecipitation between Beclin 1 and Bcl-2. Chloroquine antagonized the inhibition of the activity of Akt→4EBP1 axis mediated by everolimus and at the same time it blocked the feed-back activation of Erk-1/2 induced by RAD in EPCs. These data suggest a new strategy in order to block angiogenesis in tumours in which this process plays a key role in both the sustainment and spreading of cancer cells.

This article reports on the characterization of cryogenic sapphire oscillators (CSOs), and on the first test of a CSO in a real field installation, where ultimate frequency stability and continuous operation are critical issues, with no survey. Thanks to low-vibration liquid-He cryocooler design, Internet monitoring, and a significant effort of engineering, these oscillators could bridge the gap from an experiment to a fully reliable machine. The cryocooler needs scheduled maintenance every 2 years, which is usual for these devices. The direct comparison of two CSOs demonstrates a frequency stability of 5 × 10(-16) for 30 s ≤ τ ≤ 300 s integration time, and 4.5 × 10(-15) at 1 day (1 × 10(-14) typical). Two prototypes are fully operational, codenamed ELISA and ULISS. ELISA has been permanently installed the new deep space antenna station of the European Space Agency in Malargüe, Argentina, in May 2012. ULISS is a transportable version of ELISA, modified to fit in a small van (8.5 m(2) footprint). Installation requires a few hours manpower and 1 day of operation to attain full stability. ULISS, intended for off-site experiments and as a technology demonstrator, and has successfully completed two long-distance travels.

Laser frequency fluctuations can be characterized either comprehensively by the frequency noise spectrum or in a simple but incomplete manner by the laser linewidth. A formal relation exists to calculate the linewidth from the frequency noise spectrum, but it is laborious to apply in practice. We recently proposed a much simpler geometrical approximation applicable to any arbitrary frequency noise spectrum. Here we present an experimental validation of this approximation using laser sources of different spectral characteristics. For each of them, we measured both the frequency noise spectrum to calculate the approximate linewidth and the actual linewidth directly. We observe a very good agreement between the approximate and directly measured linewidths over a broad range of values (from kilohertz to megahertz) and for significantly different laser line shapes.

The frequency instability of a shot-noise limited atomic fountain clock is inversely proportional to its signal-tonoise ratio. Therefore, increasing the atomic flux is a direct way to improve the stability. Nevertheless, in pulsed operation, the local oscillator noise limits the performance via the Dick effect. We experimentally demonstrate here that a continuous atomic fountain allows one to overcome this limitation. In this work, we take advantage of two-laser optical pumping on a cold cesium beam to increase the useful fountain flux and, thus, to reduce the frequency instability below the Dick limit. A stability of 6 × 10(-14)τ(-1/2) has been measured with the continuous cesium fountain FOCS-2.

We describe a radio-frequency (RF) discriminator, or frequency-to-voltage converter, based on a voltage-controlled oscillator phase-locked to the signal under test, which has been developed to analyze the frequency noise properties of an RF signal, e.g., a heterodyne optical beat signal between two lasers or between a laser and an optical frequency comb. We present a detailed characterization of the properties of this discriminator and we compare it to three other commercially available discriminators. Owing to its large linear frequency range of 7 MHz, its bandwidth of 200 kHz and its noise floor below 0.01 Hz(2)/Hz in a significant part of the spectrum, our frequency discriminator is able to fully characterize the frequency noise of a beat signal with a linewidth ranging from a couple of megahertz down to a few hertz. As an example of application, we present measurements of the frequency noise of the carrier envelope offset beat in a low-noise optical frequency comb.

We report the first full stabilization of an optical frequency comb generated from a femtosecond diode-pumped solid-state laser (DPSSL) operating in the 1.5-μm spectral region. The stability of the comb is characterized in free-running and in phase-locked operation by measuring the noise properties of the carrier-envelope offset (CEO) beat, of the repetition rate, and of a comb line at 1558 nm. The high Q-factor of the semiconductor saturable absorber mirror (SESAM)-modelocked 1.5-µm DPSSL results in a low-noise CEO-beat, for which a tight phase lock can be much more easily realized than for a fiber comb. Using a moderate feedback bandwidth of only 5.5 kHz, we achieved a residual integrated phase noise of 0.72 rad rms for the locked CEO, which is one of the smallest values reported for a frequency comb system operating in this spectral region. The fractional frequency stability of the CEO-beat is 20‑fold better than measured in a standard self-referenced commercial fiber comb system and contributes only 10(-15) to the optical carrier frequency instability at 1 s averaging time., (© 2011 Optical Society of America)

Frequency fluctuations of lasers cause a broadening of their line shapes. Although the relation between the frequency noise spectrum and the laser line shape has been studied extensively, no simple expression exists to evaluate the laser linewidth for frequency noise spectra that does not follow a power law. We present a simple approach to this relation with an approximate formula for evaluation of the laser linewidth that can be applied to arbitrary noise spectral densities.

Serum concentrations of interleukin-6 (IL-6), IL-6-soluble receptor (sIL-6R), IL-6 gp130-soluble receptor (sgp130), ligand of receptor activator of nuclear factor (NF)-kappaB (RANKL), and osteoprotegerin (OPG) were determined in 42 patients with polyostotic Paget's disease of bone (PDB) and acquired resistance to clodronate (M/F ratio 23:19; mean age 58.5 +/- 9.4 years) in acute phase of disease and after oral risedronate treatment (30 mg/day for 8 weeks). At baseline, pagetic patients showed higher levels of OPG, sIL-6R, and IL-6 with lower levels of sgp130 compared to 24 age- and sex-matched controls (respectively, 4.69 +/- 1.27 vs. 2.87 +/- 0.54 pmol/L; 40.89 +/- 8.61 vs. 30.98 +/- 4.24 ng/ml; 3.59 +/- 0.97 vs. 1.8 +/- 0.9 pg/ml; 327.34 +/- 43.41 vs. 411.7 +/- 79.5 ng/ml). Response to treatment is related to a significant increase of OPG levels in all patients (from 4.69 +/- 1.27 to 5.48 +/- 1.31 pmol/L). The disease remission, that is, total alkaline phosphatase (tALP) levels within the normal range after therapy, was associated with a simultaneous increase in OPG and sgp130 levels. In patients with tALP higher than the normal range after therapy, the OPG increase was associated with a parallel increase in RANKL levels. Our data suggest that serum levels of components of RANKL/OPG and IL-6 systems, before and after treatment, may be used to better define a therapeutical strategy in pagetic patients.

Commercially pure titanium implants presenting a relatively smooth, machined surface or a roughened endosseous surface show a large percentage of clinical success. Surface properties of dental implants seem to affect bone cells response. Implant topography appears to modulate cell growth and differentiation of osteoblasts affecting the bone healing around the titanium implant. The aim of the present study was to examine the effects of 1cm diameter and 1mm thick titanium disks on cellular morphology, adhesion and bone phenotypic expression of human osteoblast-like cells, SaOS-2. SaOS-2 cells were cultured on commercially 1 cm pure titanium disks with three different surface roughness: smooth (S), sandblasted (SB) and titanium plasma sprayed (TPS). Differences in the cellular morphology were found when they were grown on the three different surfaces. An uniform monolayer of cells recovered the S surface, while clusters of multilayered irregularly shaped cells were distributed on the rough SB and TPS surfaces. The adhesion of SaOS-2 cells, as measured after 3h of culture, was not affected by surface roughness. ECM components such as Collagen I (CoI), Fibronectin (FN), Vitronectin (VN) and Tenascin (TN) were secreted and organized only on the SB and TPS surfaces while they remained into the cytoplasm on the S surfaces. Osteopontin and BSP-II were largely detected on the SB and TPS surfaces, while only minimal production was observed on the S ones. These data show that titanium surface roughness affects bone differentiation of osteoblast like-cells, SaOS-2, indicating that surface properties may be able to modulate the osteoblast phenotype. These observations also suggest that the bone healing response around dental implants can be affected by surface topography.

Unlabelled: The preparation, characterization, and first biologic evaluation in rats of a novel class of monocationic (99m)Tc heart imaging agents are reported. The complexes are represented by the general formula [(99m)Tc(N)(PNP)(L)](+), where L is the monoanionic form of a dithiocarbamate ligand of the type [R(1)(R(2))-N-C(=S)S](-), PNP is a diphosphine ligand of the type [(R(3))(2)P-(CH(2))(2)](2)-N(R(4)), and R(1)-R(4) are organic functional groups., Methods: The new complexes were prepared by use of both liquid and freeze-dried formulations through a 2-step procedure. The first step involved the formation of the [TcN](2+) group through the reaction of (99m)TcO(4)(-) with succinic dihydrazide as a donor of nitride nitrogen atoms (N(3-)) in the presence of Sn(2+) ions. This step was followed by the simultaneous addition to the reaction solution of the ligand PNP and of the sodium salt of the dithiocarbamate ligand (NaL) to afford the final products, [(99m)Tc(N)(PNP)(L)](+). The chemical identities of the resulting (99m)Tc complexes were determined by comparing their chromatographic properties with those of the corresponding (99g)Tc analogs prepared by use of the long-lived isotope (99g)Tc and characterized by spectroscopic and crystallographic techniques. Ex vivo biodistribution studies were conducted in rats. In vivo tomographic images of the rat heart were obtained by use of a small-animal SPECT scanner., Results: The [(99m)Tc(N)(PNP)(L)](+) complexes are monocationic and possess a distorted square-pyramidal geometry in which the TcN multiple bond occupies an apical position and the diphosphine and dithiocarbamate ligands span the residual 4 coordination positions on the basal plane through the 2 phosphorus atoms and the 2 sulfur atoms, respectively. Imaging and biodistribution studies demonstrated that these radiopharmaceuticals localize selectively in the myocardium of rats and are retained in this region for a prolonged time. The kinetics of heart uptake and clearance were found to be influenced by variations in the lateral R(1)-R(4) groups. Blood and lung washouts were extremely fast. Elimination occurred mostly through the kidneys and the liver. Surprisingly, at 1 h after injection, liver activity was almost negligible. Analysis of heart-to-liver and heart-to-lung uptake ratios showed that these values increased exponentially over time and became much higher than those determined for (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. These findings were confirmed by analysis of high-quality SPECT images collected in rats for the new complexes and compared with images obtained with (99m)Tc-sestamibi and (99m)Tc-tetrofosmin., Conclusion: The high myocardial uptake and the very high heart-to-lung and heart-to-liver uptake ratios indicate that the [(99m)Tc(N)(PNP)(L)](+) complexes exhibit very favorable distribution properties and could be used to obtain SPECT cardiac images with improved quality.

Background: The aim of the present study was to perform an immunophenotypic analysis of human gingival fibroblast cells and its eventual modulation by Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)., Methods: Gingival fibroblasts were derived from gingival biopsy of 15 healthy subjects. The presence of fibroblast cells in culture and the absence of epithelial cells was performed with fluorescence microscopy using vimentin and cytokeratin markers, respectively. Molecular expression of gingival fibroblast cell membrane was carried out with monoclonal antibodies by flow cytometry analysis. Human recombinant GM-CSF at the concentration of 200 ng/ml was used for the in vitro stimulation of gingival fibroblasts. Statistical analysis was performed using the Student "t"-test., Results: Human gingival fibroblasts express a wide surface molecular panel including mainly CD59, CD99, CD9, CD95, CD55, CD63, CD26, CD117, CD71 and CD86. The GM-CSF seems to regulate the CD49B expression positively and the CD40 and CD103 expression negatively., Conclusions: Results show that GM-CSF is able to modulate the in vitro expression of some membrane molecules of gingival fibroblasts and therefore it may regulate, in vivo, peculiar specific biological functions of gingival tissue.

We investigated the effects of human granulocyte macrophage-colony stimulating factor (GM-CSF) on the relation between differentiation and apoptosis in SaOS-2 cells, an osteoblast-like cell line. To determine the relationship between these cellular processes, SaOS-2 cells were treated in vitro for 1, 7 and 14 days with 200 ng/mL GM-CSF and compared with untreated cells. Five nM insulin-like growth factor (IGF-I) and 30 nM okadaic acid were used as negative and positive controls of apoptosis, respectively. Effects on cell differentiation were determined by ECM (extracellular matrix) mineralization, morphology of some typical mature osteoblast differentiation markers, such as osteopontin and sialoprotein II (BSP-II), and production of bone ECM components such as collagen I. The results showed that treatment with GM-CSF caused cell differentiation accompanied by increased production of osteopontin and BSP-II, together with increased ECM deposition and mineralization. Flow cytometric analysis of annexin V and propidium iodide incorporation showed that GM-CSF up-regulated apoptotic cell death of SaOS-2 cells after 14 days of culture in contrast to okadaic acid, which stimulated SaOS-2 apoptosis only during the early period of culture. Endonucleolytic cleavage of genomic DNA, detected by "Aúladdering analysis"Aù, confirmed these data. The results suggest that GM-CSF induces osteoblastic differentiation and long-term apoptotic cell death of the SaOS-2 human osteosarcoma cell line, which in turn suggests a possible in vivo physiological role for GM-CSF on human osteoblast cells.

Objective: Interleukin-6 (IL-6) and its soluble receptor (sIL-6R) stimulate osteoclast formation and activity. The primary cell abnormality in Paget's disease of bone (PDB) involves osteoclasts. Pagetic osteoclasts overproduce IL-6 and IL-6 receptor in vitro. In vivo, IL-6 serum levels are very high in the acute phase of PDB. The aim of this study was to evaluate the modification in the serum levels of IL-6, sIL-6R and osteotropic hormones (parathormone, 25OHD3 and 1,25(OH)2D3) as a in long-term response to clodronate treatment in patients with PDB., Methods: 16 patients (8 females) with polyostotic PDB were studied. IL-6, sIL-6R and osteotropic hormones serum levels were evaluated in active PDB and after clodronate treatment (300 mg injected intravenously for 5 consecutive days). The sequential changes in total alkaline phosphatase (tALP) serum levels were used to assess the maximal pharmacological response to treatment., Results: In untreated pagetic patients, mean serum levels of IL-6 (3.20+/-1.18 pg/ml) and sIL-6R (35.02+/-8.33 ng/ml) were significantly increased. Serum osteotropic hormone levels fell within the normal range. Eight weeks after treatment, the maximal pharmacological response to clodronate was associated with a significant reduction of sIL-6R serum levels in all patients, without a significant variation in serum IL-6 and osteotropic hormone levels. Moreover, we observed a correlation between lower sIL-6R serum levels before clodronate therapy and complete remission of PBD, defined as a decrease of tALP serum levels within the normal range., Conclusion: The decrease in serum sIL-6R levels could be one of the molecular mechanisms that play a role in the clinical response to clodronate treatment in PDB.

The suitability of introducing molecular interference effects into coherent scattering phenomenology is considered here in the case of X and gamma photon transport in biological tissues. In order to make its implementation practicable in most of the existing open user Monte Carlo codes, a self-consistent basic set of tabulations for the linear differential scattering coefficient was proposed. The tabulations were critically reviewed by testing their validity over the entire range of the momentum transfer variable from 0 to 10(10) nm(-1). Implementation in three different Monte Carlo codes was performed, and they proved to be reliable.

A multivariate approach based on Principal Component Analysis (PCA) was used to analyze the energy distribution of n Monte Carlo simulated Compton scattered photon spectra describing the electron density of large layers. Three to five layers with different density distribution were used to test the algorithm; each layer was obtained by collecting 25 Compton spectra coming from sensitive volumes (SVs) where the complementary conditions of high and low density were realized (respectively full and void SV). The density variation inside a single layer is described by a two principal components (PCs) linear model that depicts the electron density of each SV: the layer density distribution appears to be correctly described even in the presence of very low signal-to-noise Compton spectra. Density profiles for layers at different depths were comparatively analyzed in order to show that, at least within one mean-free-path distance, it is possible to describe the layer density distribution by the PCA without any correction for the beam attenuation.

The purpose of this study was to analyze 19 patients infected with Human Papilloma Virus (HPV), in order to determine the most frequent subtype. Subjects were patients of the National Institute of Perinatology (INPer), between 1991-1992. All the patients had positive cytology, cervical biopsy was done through colposcopy control. Sample characteristics were: Mean age 29 years, married; most of them multiparous (9/19) and 7 were monogamous. Six out of 12 cytologies were positive for HPV, 12 out of 19 had an inespecific inflammatory reaction and one patient had NICIII. The histopathologic study showed in 15 cases a positive reaction to HPV, 2 out of 19 had both dysplasia and condyloma, two cases had moderate and severe dysplasia. All the cases were studied with in situ hybridization with biotinilaty probes, two cases were positive to Subtype 18 and one to Subtype 16. Positive cases were selected for electron microscopy in order to confirm viral particles. This study suggests that subtype 18 and 16 positivity must be considered as high risk of cancer.

Differences of frequency and morphology of carotid plaques are studied in 39 patients with ischemic cardiopathy matched for sex and age with 39 patients with various cardiopathies and 78 controls without heart diseases. Ischemic patients have more plaques, and these are more extended along the vessels. The plaques of the other cardiopathies reach greater thickness and degree of stenosis.