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The subject of this present work is a group of nine historical pictures shot in Palermo by the Sicilian photographer E. Interguglielmi in 1912. They are nine matte-collodion prints mounted on the original cardboard supports and all of them show foxing stains affecting the paper surface. In order to characterise the chemical composition of the supports and investigate foxing spots, non-destructive and micro-destructive analysis were carried out. X-rays fluorescence (XRF) analysis was used to characterise the elemental composition of all the mounting boards, allowing a comparison between the foxing spots and non-affected areas. Laser-Induced Breakdown Spectroscopy was used to investigate the presence of lower atomic number elements, not detectable by XRF, while SEM imaging allowed the investigation of surface appearance and nature of original paper samples from the cardboards.

In recent years many papers about diagnostic applications of diffusion tensor imaging (DTI) have been published. This is because DTI allows to evaluate in vivo and in a non-invasive way the process of diffusion of water molecules in biological tissues. However, the simplified description of the diffusion process assumed in DTI does not permit to completely map the complex underlying cellular components and structures, which hinder and restrict the diffusion of water molecules. These limitations can be partially overcome by means of diffusion kurtosis imaging (DKI). The aim of this paper is the description of the theory of DKI, a new topic of growing interest in radiology. DKI is a higher order diffusion model that is a straightforward extension of the DTI model. Here, we analyze the physics underlying this method, we report our MRI acquisition protocol with the preprocessing pipeline used and the DKI parametric maps obtained on a 1.5 T scanner, and we review the most relevant clinical applications of this technique in various neurological diseases.

The radiation therapy carried out by means of heavy charged particles (such as carbon ions) and neutrons is rapidly becoming widespread worldwide. The success of these radiation therapies relies on the high density of energy released by these particles or by secondary particles produced after primary interaction with matter. The biological damages produced by ionising radiations in tissues and cells depend more properly on the energy released per unit pathlength, which is the linear energy transfer and which determines the radiation quality. To improve the therapy effectiveness, it is necessary to grasp the mechanisms of free radical production and distribution after irradiation with these particles when compared with the photon beams. In this work some preliminary results on the analysis of the spatial distributions of the free radicals produced after exposure of ammonium tartrate crystals to various radiation beams ((60)Co gamma photons and thermal neutrons) were reported. Electron spin resonance analyses were performed by the electron spin echo technique, which allows the determination of local spin concentrations and by double electron-electron resonance technique, which is able to measure the spatial distance distribution (range 1.5-8 nm) among pairs of radicals in solids. The results of these analyses are discussed on the basis of the different distributions of free radicals produced by the two different radiation beams used., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This paper reports on results obtained by electron paramagnetic resonance (EPR) measurements and Monte Carlo (MC) simulation on a blend of alanine added with low content of gadolinium oxide (5 % by weight) to improve the sensitivity to thermal neutron without excessively affecting tissue equivalence. The sensitivity is enhanced by this doping procedure of more an order of magnitude. The results are compared with those obtained with the addition of boric acid (50 % by weight) where boron is in its natural isotopic composition in order to produce low-cost EPR dosemeters. The gadolinium addition influences neutron sensitivity more than the boron addition. The presence of additives does not substantially change the fading of the EPR signal induced by neutrons. The MC simulations agree the experimental results in case of gadolinium addition., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This paper continues analyses on organic compounds for application in neutron dosimetry performed through electron spin resonance (ESR). Here, the authors present the results obtained by ESR measurements of a blend of ammonium tartrate dosemeters and gadolinium oxide (5 % by weight). The choice of low amount of Gd is due to the need of improving neutron sensitivity while not significantly influencing tissue equivalence. A study of the effect of gadolinium presence on tissue equivalence was carried out. The experiments show that the neutron sensitivity is enhanced by more than an order of magnitude even with this small additive content. Monte Carlo simulations on the increment of energy release due to gadolinium presence were carried, and the results were in good agreement with the experimental data., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This paper presents the results of an interlaboratory comparison of retrospective dosimetry using the electron paramagnetic resonance method. The test material used in this exercise was glass coming from the touch screens of smart phones that might be used as fortuitous dosimeters in a large-scale radiological incident. There were 13 participants to whom samples were dispatched, and 11 laboratories reported results. The participants received five calibration samples (0, 0.8, 2, 4, and 10 Gy) and four blindly irradiated samples (0, 0.9, 1.3, and 3.3 Gy). Participants were divided into two groups: for group A (formed by three participants), samples came from a homogeneous batch of glass and were stored in similar setting; for group B (formed by eight participants), samples came from different smart phones and stored in different settings of light and temperature. The calibration curves determined by the participants of group A had a small error and a critical level in the 0.37-0.40-Gy dose range, whereas the curves determined by the participants of group B were more scattered and led to a critical level in the 1.3-3.2-Gy dose range for six participants out of eight. Group A were able to assess the dose within 20 % for the lowest doses (<1.5 Gy) and within 5 % for the highest doses. For group B, only the highest blind dose could be evaluated in a reliable way because of the high critical values involved. The results from group A are encouraging, whereas the results from group B suggest that the influence of environmental conditions and the intervariability of samples coming from different smart phones need to be further investigated. An alongside conclusion is that the protocol was easily transferred to participants making a network of laboratories in case of a mass casualty event potentially feasible.

The ability to discriminate the quality of ionizing radiation is important because the biological effects produced in tissue strongly depends on both absorbed dose and linear energy transfer (LET) of ionizing particles. Here we present an experimental electron spin resonance (ESR) analysis aimed at discriminating the effective LETs of various radiation beams (e.g., 19.3 MeV protons, (60)Co photons and thermal neutrons). The measurement of the intensities of the continuous wave spectrometer signal channel first harmonic in-phase and the second harmonic out-of-phase components are used to distinguish the radiation quality. A computational analysis, was carried out to evaluate the dependence of the first harmonic in-phase and second harmonic out-of-phase components on microwave power, modulation amplitude and relaxation times, and highlights that these components could be used to point out differences in the relaxation times. On the basis of this numerical analysis the experimental results are discussed. The methodology described in this study has the potential to provide information on radiation quality.

Feature detection in biomedical signals is crucial for deepening our knowledge about the involved physiological processes. To achieve this aim, many analytic approaches can be applied but only few are able to deal with signals whose time dependent features provide useful clinical information. Among the biomedical signals, the electroretinogram (ERG), that records the retinal response to a light flash, can improve our comprehension of the complex photoreceptoral activities. The present study is focused on the analysis of the early response of the photoreceptoral human system, known as a-wave ERG-component. This wave reflects the functional integrity of the photoreceptors, rods and cones, whose activation dynamics are not yet completely understood. Moreover, since in incipient photoreceptoral pathologies eventual anomalies in a-wave are not always detectable with a "naked eye" analysis of the traces, the possibility to discriminate pathologic from healthy traces, by means of appropriate analytical techniques, could help in clinical diagnosis. In the present paper, we discuss and compare the efficiency of various techniques of signal processing, such as Fourier analysis (FA), Principal Component Analysis (PCA), Wavelet Analysis (WA) in recognising pathological traces from the healthy ones. The investigated retinal pathologies are Achromatopsia, a cone disease and Congenital Stationary Night Blindness, affecting the photoreceptoral signal transmission. Our findings prove that both PCA and FA of conventional ERGs, don't add clinical information useful for the diagnosis of ocular pathologies, whereas the use of a more sophisticated analysis, based on the wavelet transform, provides a powerful tool for routine clinical examinations of patients., (Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

In-soil radon concentrations as well as climatic parameters (temperature, atmospheric pressure and relative humidity) were collected in St. Venerina (Eastern Sicily - Italy) from March 19th to May 22nd 2009, close to an active fault system called Timpe Fault System (TFS), which is strictly linked to the geodynamics of Mt. Etna. During the monitoring period no drastic climatic variations were observed and, on the other hand, important seismic events were recorded close to the monitoring site. A seismic swarm composed of 5 earthquakes was observed in the Milo area on March 25th (M(max) = 2.7) at just 5.1 km from the site, and on May 13th an earthquake of 3.6 magnitude was recorded in the territory of St. Venerina, at just 3.2 km from the site; the earthquake was felt by the population and reported by all local and regional media. The in-soil radon concentrations have shown anomalous increases possibly linked to the earthquakes recorded, but certainly not attributable to local meteorology. To verify this assumption the average radon concentration and the standard deviation (σ) have been calculated and the regions of ±1.5σ and ±2σ deviation from the average concentration have been investigated. Moreover, to further minimise the contribution of the meteorological parameters on the in-soil radon fluctuations, a multiple regressions method has been used. To distinguish those earthquakes which could generate in-soil radon anomalies as precursors, the Dobrovolsky radius has been applied. The results obtained suggests that a clear correlation between earthquakes and in-soil radon increases exist, and that the detection of the in-soil radon anomalies becomes surely simpler in particular favourable conditions: weather stability, earthquakes within the Dobrovolsky radius and close to the monitoring area. Moreover, the absence of large variations of the climatic parameters, which could generate incoherent noise components to the radon signal, has made the radon fluctuations more evident and so more legible., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In this study we analyzed the ESR signal of alanine dosimeters with gadolinium exposed to 6 MV linear accelerator photons. We observed that the addition of gadolinium brings about an improvement in the sensitivity to photons because of its high atomic number. The experimental data indicated that the addition of gadolinium increases the sensitivity of the alanine to 6 MV photons. This enhancement was better observed at high gadolinium concentrations for which the tissue equivalence is heavily reduced. However, information about the irradiation setup and of the radiation beam features allows one to correct for this difference. Monte Carlo simulations were carried out to obtain information on the expected effect of the addition of gadolinium on the dose absorbed by the alanine molecules inside the pellets. These results are compared with the experimental values, and the agreement is discussed.

Most biomedical signals are non-stationary. The knowledge of their frequency content and temporal distribution is then useful in a clinical context. The wavelet analysis is appropriate to achieve this task. The present paper uses this method to reveal hidden characteristics and anomalies of the human a-wave, an important component of the electroretinogram since it is a measure of the functional integrity of the photoreceptors. We here analyse the time-frequency features of the a-wave both in normal subjects and in patients affected by Achromatopsia, a pathology disturbing the functionality of the cones. The results indicate the presence of two or three stable frequencies that, in the pathological case, shift toward lower values and change their times of occurrence. The present findings are a first step toward a deeper understanding of the features of the a-wave and possible applications to diagnostic procedures in order to recognise incipient photoreceptoral pathologies., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements.

The wavelet analysis is a powerful tool for analyzing and detecting features of signals characterized by time-dependent statistical properties, as biomedical signals. The identification and the analysis of the components of these signals in the time-frequency domain, give meaningful information about the physiological mechanisms that govern them. This article presents the results of the wavelet analysis applied to the a-wave component of the human electroretinogram. In order to deepen and improve our knowledge about the behavior of the early photoreceptoral response, including the possible activation of interactions and correlations among the photoreceptors, we have detected and identified the stable time-frequency components of the a-wave, using six representative values of luminance. The results indicate the occurrence of three frequencies lying in the range 20-200 Hz. The lowest one is attributed to the summed activities of the photoreceptors. The others are weaker and at low luminance one of them does not occur. We relate them to the response of the rods and the cones whose aggregate activities are non-linear and typically exhibit self-organization under selective stimuli. The identification of the stable frequency components and of their times of occurrence helps us to shine light about the complex mechanisms governing the a-wave. The present results are promising toward the assessment of more refined model concerning the photoreceptoral activities.

Monte Carlo numerical calculations of the response of alanine and ammonium tartrate ESR (electron spin resonance) dosimeters exposed to neutron fields with different energy spectra are reported. Results have been obtained for various gadolinium concentrations inside the dosimeters. Furthermore, in order to simulate the in-phantom response we have carried out calculations by varying the depth of the dosimeter. We have found that a large enhancement is obtained for thermal neutrons, because of the very high capture cross section of gadolinium to thermal neutrons. A good enhancement was obtained for epithermal neutrons, whereas the sensitivity improvement in the case of fast neutron irradiation is poor. Furthermore, the simulations carried out by varying the depth suggests that an appreciable sensitivity to thermal and epithermal neutrons could be observed for in-phantom measurements in the 2-3 cm depth range. These results can provide useful insight for future experiments with epithermal neutron beams (such as those used in neutron capture therapy) and for future applications in neutron capture therapy dosimetry.

Using pulse electron paramagnetic resonance (EPR) on a series of l(+)-ammonium tartrate (AT) dosimeters exposed to radiations with different linear energy transfer (LET), we assessed the ability of pulse EPR spectroscopy to discriminate the quality of various radiation beams such as (60)Co gamma-ray photons, protons and thermal neutrons at various doses by analyzing the local radical distributions produced by the different beams. We performed two types of pulse EPR investigations: two-pulse electron spin echo decay obtained by varying the microwave power, and a double electron-electron resonance (DEER) study. Both methods provide information about the dipolar interactions among the free radicals and about their spatial distributions. The first method provided information on the instantaneous diffusion and hence the microscopic concentration of the radicals that is compared with the macroscopic one obtained by CW-EPR. The DEER spectra yielded the distributions of distances between pairs of radicals two to five crystal cells apart produced by the same radiation event, a result reported here for the first time. The inter-radical distributions given by the DEER results have been simulated by modeling the radical distributions according to the details of the matter-radiation interactions for the various beams. The results of both types of pulse experiments are strongly dependent on the radiation quality. This was also observed for samples giving indistinguishable CW-EPR spectral profiles. We conclude that the pulse EPR measurements can be valuable tools for distinguishing the LET of the radiation beams, an important parameter for radiobiological considerations.

Thermoluminescence dosimetry has been used to measure air kerma in 29 sites in Sicily. Four three month measurement campaigns have been carried out in order to assess seasonal variations. Average annual values between 20 and 90 nGy h(-1), after cosmic background subtraction, are reported. Average annual values are strongly dependent on site lithology, and we find that winter data are generally the highest, while spring and autumn rates are generally the lowest with very similar trends in any site. Summer values generally lay in between. Largest seasonal variations are found in sites along the southern coast of the island, probably because of stronger action of winds affecting radon, along with its progeny, concentrations at ground level.

Many efforts have been made to develop neutron capture therapy (NCT) for cancer treatment. Among the challenges in using NCT is the characterization of the features of the mixed radiation field and of its components. In this study, we examined the enhancement of the ESR response of pellets of alanine and ammonium tartrate with gadolinium oxide exposed to a thermal neutron beam. In particular, the ESR response of these dosimeters as a function of the gadolinium content inside the dosimeter was analyzed. We found that the addition of gadolinium improves the sensitivity of both alanine and ammonium tartrate. However, the use of gadolinium reduces or abolishes tissue equivalence because of its high atomic number (Z(Gd) = 64). Therefore, it is necessary to find the optimum compromise between the sensitivity to thermal neutrons and the reduction of tissue equivalence. Our analysis showed that a low concentration of gadolinium oxide (of the order of 5% of the total mass of the dosimeter) can enhance the thermal neutron sensitivity more than 13 times with an insignificant reduction of tissue equivalence.

NMR relaxation time distributions, obtained with laboratory and portable devices, are utilized to characterize the pore-size distributions of building materials coming from the Roman remains of the Greek-Roman Theatre of Taormina. To validate the interpretation of relaxation data in terms of pore-size distribution, comparison of results from standard and in situ NMR experiments with results of the mercury intrusion porosimetry (MIP) has been made. Although the pore-size distributions can be obtained by NMR in terms of either longitudinal (T(1)) or transverse (T(2)) relaxation times distributions, the shorter duration of the T(2) measurement makes it, in principle, preferable, although the determination of T(2) distributions is not necessarily an easy alternative to finding T(1) distributions. Among other things, the T(1) distribution is almost independent of the inhomogeneity of the magnetic field, while the T(2) distribution is strongly influenced by it. This paper was aimed at answering two questions: what are the validity limits to interpret NMR data in terms of pore-size distributions and whether the portable device can successfully be applied as a non-destructive and non-invasive tool for in situ NMR analysis of building materials, particularly those of Cultural Heritage interest.

In this paper, the addition of gadolinium is proposed as a useful tool to enhance the electron spin resonance (ESR) sensitivity of organic compounds to thermal neutrons. The target of this work is the detection, through the ESR technique, of the thermal neutron fluence in a mixed field of photons and neutrons. Gadolinium was chosen because it has a very high capture cross section to thermal neutrons; its nuclear reaction with thermal neutrons induces complex inner shell transitions that generate, besides other particles, Auger electrons, which in turn release their energy in the neighborhood (only several nanometers) of the place of reaction. Gadolinium was added to two organic molecules: alanine and ammonium tartrate. The main result obtained was a greater neutron sensitivity for dosimeters with gadolinium than for those without gadolinium for both organic molecules used. Since a dosimeter pair is required to discriminate between the two components of a mixed field, we studied the response of each dosimeter pair irradiated in a mixed field. Through a blind test we verified the usefulness of this dosimetric system and we obtained an estimate of the fluence in the mixed field with a relative uncertainty of 3%, when the pair composed of an alanine dosimeter and a dosimeter with alanine and gadolinium is used.

Nuclear magnetic resonance (NMR) portable devices are now being used for nondestructive in situ analysis of water content, pore space structure and protective treatment performance in porous media in the field of cultural heritage. It is a standard procedure to invert T(1) and T(2) relaxation data of fully water-saturated samples to get "pore size" distributions, but the use of T(2) requires great caution. It is well known that dephasing effects due to water molecule diffusion in a magnetic field gradient can affect transverse relaxation data, even if the smallest experimentally available half echo time tau is used in Carr-Purcell-Meiboom-Gill experiments. When a portable single-sided NMR apparatus is used, large field gradients due to the instrument, at the scale of the sample, are thought to be the dominant dephasing cause. In this paper, T(1) and T(2) (at different tau values) distributions were measured in natural (Lecce stone) and artificial (brick samples coming from the Greek-Roman Theatre of Taormina) porous media of interest for cultural heritage by a standard laboratory instrument and a portable device. While T(1) distributions do not show any appreciable effect from inhomogeneous fields, T(2) distributions can show strong effects, and a procedure is presented based on the dependence of 1/T(2) on tau to separate pore-scale gradient effects from sample-scale gradient effects. Unexpectedly, the gradient at the pore scale can be, in some cases, strong enough to make negligible the effects of gradients at the sample scale of the single-sided device.

ESR response to gamma-irradiation (1-50 Gy) of blends containing alanine and either B(OH)(3) or Gd(2)O(3) is reported. The sensitivity of the alanine--B(OH)(3) blend is comparable to the sensitivity of pure alanine, although its lowest detectable dose, LDD, is smaller ( approximately 1.3 Gy) than that of pure alanine ( approximately 2.9 Gy). Alanine with Gd(2)O(3) is about two times more sensitive than pure alanine, and its LDD is 0.8 Gy. The better sensitivity and LDD are probably due to the high atomic number (Z=64) of gadolinium, which enhances the interaction probability with photons and, consequently, the radical yield. This study suggests that other high-Z atoms may be useful for increasing the sensitivity of the response of alanine to gamma-radiation.

In this paper, the results of a study on the electron spin resonance (ESR) dosimetry to measure thermal neutron fluence in a mixed radiation field (neutron and photons) are presented. The ESR responses of alanine dosemeters with different additives are compared. In particular, the (10)B-acid boric and the Gd-oxide were chosen to enhance the sensitivity of alanine dosemeters to thermal neutrons. Irradiations were carried out inside the thermal column of the TAPIRO reactor of the ENEA center, Casaccia Rome. The main results are a greater neutron sensitivity and a smaller lowest detectable fluence for the dosemeters with gadolinium than for dosemeters of alanine with (10)B, which is well known to be much more sensitive to thermal neutrons than simple alanine.

The glow curves of thermoluminescent dosimeters (TLD600, TLD700 and MCP), exposed to a mixed field of thermal neutrons and gamma photons are analysed. The fluence values of thermal neutrons used, comparable with those used in radiotherapy, allow one to define the reliability of the TLDs, in particular the most sensitive MCP, in this radiation field and to get information on the dose absorbed values. The glow curves obtained have been deconvoluted using general order kinetics and the observed differences for the different LET components have been analysed. In particular, the ratio of the n(0) parameter of two different peaks seems to allow to discriminate the different contributions of neutrons and gamma photons in the beam.

In this paper we present an investigation of the electron spin resonance (ESR) line shape of ammonium tartrate (AT) dosimeters exposed to radiation with different linear energy transfer (LET). We exposed our dosimeters to gamma-ray photons ((60)Co), 7 MeV and 14 MeV initial energy electrons, and 19.3 MeV initial energy protons. The differences in the power saturation behavior of ESR spectra of AT irradiated with photons, electrons and protons could be correlated to the effective LET of the radiation beams. We analyzed the behavior of peak-to-peak amplitude as a function of microwave power, and we developed a fitting procedure that permits us to obtain the dependence of the homogeneity parameter of the line shape on the LET of the radiation using the Castner saturation theory. This simple procedure allows us to distinguish the LET of the radiation beam.

The a-wave is one of the main issues of research in the field of ocular electrophysiology, since it is strictly connected with early photoreceptoral activities. The present study proposes mathematical methods that analyse this component in human subjects, and supports experimental evidence relating to possible correlations among the responses of photoreceptoral units under a light stimulus. The investigation is organized in two parts: the first part concerns the onset and the initial slope, up to the first minimum (about 10-15 ms), the second part deals with the main portion of the wave, up to about 30 ms. In both cases, the a-waves, recorded at various levels of luminance, have been fitted with a set of appropriate functions representing possible models of physiological behaviour which would take place in the early stages of phototransduction. The statistical nature of the underlying processes is also discussed. The results indicate that correlations occur in the early stages, whereas random processes are set up later.

We show that Posidonia oceanica is able to reliably monitor the variability of environmental lead (Pb). We analyze lead concentration measured in the scales and rhizomes of Posidonia oceanica collected in seven sites along the coasts of the Sicily island and subsequently fractioned them according to a lepidochronological analysis. We measure lead concentration in Posidonia oceanica tissues by using the flame atomic absorption spectrophotometry technique. We compare the measured lead concentration with the estimated lead emission in air due to the gasoline sold and used for combustion in car engines in Sicily. By computation of the Pearson cross-correlation coefficient, we show that lead concentration, which is measured in the scales of Posidonia oceanica, is statistically correlated to lead emission in air and reflects the level of lead pollution in the coastal marine environment.

Magnetic Resonance Relaxation (MRR) and Magnetic Resonance Imaging (MRI) are powerful tools to obtain detailed information on the pore space structure that one is unlikely to obtain in other ways. These techniques are particularly suitable for Cultural Heritage materials, because they use water 1H nuclei as a probe. Interaction with water is one of the main causes of deterioration of materials. Porous structure in wood, for example, favours the penetration of water, which can carry polluting substances and promote mould growth. A particular case is waterlogged wood from underwater discoveries and moist sites; in fact, these finds are very fragile because of chemical, physical and biological decay from the long contact with the water. When wood artefacts are brought to the surface and directly dried in air, there is the collapse of the cellular structures, and wood loses its original form and dimensions and cannot be used for study and museum exhibits. In this work we have undertaken the study of some wood finds coming from Ercolano's harbour by MRR and MRI under different conditions, and we have obtained a characterization of pore space in wood and images of the spatial distribution of the confined water in the wood.

Ionizing radiation can be used as a drug sterilization technique, provided that the drug itself is not modified and that no toxic products are produced; moreover, if the irradiated product is a drug delivery system, the drug release characteristics must not be significantly altered by radiation. The aim of this work was to study the effects of sterilization by ionizing radiation on hydroxyethylcellulose/trehalose spherical micromatrices, containing the antibiotic vancomycin. Our experimental results showed that gamma-rays did not alter the chromophore groups of vancomycin (UV measurements), and did not modify the kinetic behavior of drug release from microspheres. Moreover, no significant changes in the shape and in the size distribution of microspheres were found after irradiation. The electron spin resonance (ESR) spectroscopy was proven to be a valid identification method of the executed radiation treatment, even after 5 years. The experimental results showed that the therapeutic application of the pharmacological system investigated was not compromised by irradiation, and that ESR spectroscopy can be used to distinguish irradiated from non-irradiated products.

The dosimetric technique described in this paper is based on electron spin resonance (ESR) detectors using an alanine-boric compound acid enriched with (10)B, and beryllium oxide thermoluminescent (TL) detectors; with this combined dosimetry, it is possible to discriminate the doses due to thermal neutrons and gamma radiation in a mixed field. Irradiations were carried out inside the thermal column of a TRIGA MARK II water-pool-type research nuclear reactor, also used for Boron Neutron Capture therapy (BNCT) applications, with thermal neutron fluence from 10(9) to 10(14) nth cm(-2). The ESR dosemeters using the alanine-boron compound indicated ESR signals about 30-fold stronger than those using only alanine. Moreover, a negligible correction for the gamma contribution, measured with TL detectors, almost insensitive to thermal neutrons, was necessary. Therefore, a simultaneous analysis of our TL and ESR detectors allows discrimination between thermal neutron and gamma doses, as required in BNCT.

HPGe gamma spectrometry, thermoluminescence dosimetry, X-ray diffractometry and fluorescence techniques have been used to analyze the natural radionuclides content of soil and rock samples, air kerma and geochemical features on the island of Stromboli, belonging to the Aeolian Islands, in the Mediterranean Sea. The 214Bi, 238Ac, and 40K contents obtained are in agreement with the magmatic evolution of the rock formation, as shown by the correlations between radionuclide and chemical elements abundacies, depending on the various magmatic differentiation mechanisms. Correlations between radiometric, lithological and geochemical data have been assessed in order to obtain some hints on the geochronology of the magmatic products.

A high-purity germanium detector has been used to measure the abundance of radium (Ra), thorium (Th) and potassium (K) in building materials used in Sicilian dwellings. The measurements were performed to evaluate which material was suitable for the construction of an enclosure, which would have a low background emission. The materials examined in this work showed concentrations of 226Ra, 232Th and 40K dramatically variable depending on the lithologies, particularly in the case of blocks, sands and aggregates commonly used in building materials in Sicily. The results are discussed and a criterion is indicated to reduce the radiation dose to humans. Since radon inlet is a major health problem, all the radiometric data and the geochemical features have been used to determine the radon exhalation, which arises from the disintegration of 226Ra in soils and walls of houses. From our experimental data it can be seen out that one of the geochemical parameters, Total Alkali (TA), may be an appropriate index to select materials of low radiological risk.

Air kerma was measured in the "Vulcano Porto" area of the Vulcano Island, belonging to the Aeolian Islands, in the Mediterranean Sea. Measurements were carried out using thermoluminescence dosimeters. The relationship between observed dose values and source lithology has been assessed. Data show a seasonal variation due to weather conditions but also probably related to features of the soils, making the variation more evident.

Solid state pellets (1 mm thick) for electron spin resonance (ESR) dosimetry were made using ammonium tartrate as the radiation-sensitive substance. Their behaviour was experimentally investigated as a function of dose with 60Co gamma rays. The calibration function obtained permits measurements of absorbed dose in the 2-50 Gy range, with a combined uncertainty of +/-4%. The lowest detectable dose was about 0.5 Gy. These properties are comparable with or even better than those of ESR dosimeters made from other materials. The time stability of the ESR signal of ammonium tartrate dosimeters at different storage conditions after irradiation was studied. A rather complex behaviour was observed, which suggests that more species of free radicals are produced by radiation and that migration processes may be effective. No dependence of the response on beam quality was found for high-energy photon and electron beams produced by a linear accelerator used in radiotherapy, whereas dose was underestimated with low-energy x-rays.

The aim of this study was to examine the complement system and the distribution of some human leukocyte antigen (HLA) class III alleles (C4, BF) in healthy aged people (77 centenarians and 89 elderly subjects). We have also studied the alleles of C3, a complement component genetically unrelated to HLA, the immunochemical levels of C4 and C3 and serum functional hemolytic activity for classical (CH50) and alternative (AP50) complement pathway. The levels of C3 and C4 and the CH50 and AP50 were found to be within the normal range. The frequencies of C3, BF, and C4A alleles were similar in the cohorts that have been studied. For C4B null allele (C4BQ0) a trend toward an increase in the older cohort was observed, although the differences were not significant after statistical correction. Our data suggest that the complement system is well preserved in centenarians and elderly subjects and class III HLA antigens are equally distributed in aged cohorts and in young healthy individuals.

The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.

Complement receptor type 1 (CR1) is an integral membrane protein of many haematopoietic cells and plays an important role in the clearance of complement-associated immune complexes, favouring their transport to liver and spleen macrophages. A small amount of soluble CR1 (sCR1) is also found in plasma and might originate directly from release of leucocytes and other circulating cells. In previous studies, an increase in serum sCR1 level has been observed in liver cirrhosis and end-stage renal failure. High levels have also been found in patients with some haematologic malignancies. sCR1 serum levels were measured using a specific double sandwich ELISA assay. The present study demonstrates the correlation between mean serum sCR1 concentrations and disease severity in patients with chronic liver disease. In patients with liver cirrhosis, grouped according to the Child-Pugh classification, sCR1 rose as liver function decreased. The presence of neoplastic growth in the liver apparently does not play a role in the increase of sCR1. Serum sCR1 was not elevated in other solid malignancies. Since sCR1 accumulates in liver diseases, evaluation of its serum levels could be useful as a liver function test.

Here we investigate the effects of tetracycline base and of a semi-synthetic tetracycline derivative, doxycycline, on the induction of inducible nitric oxide synthase and, hence, on the production of nitric oxide (NO) by lipopolysaccharide in J774 macrophage cultured in vitro. The treatment of J774 line with tetracycline base (6.25-250 microM) or doxycycline (5-50 microM) dose-dependently decreased the lipopolysaccharide-stimulated (1 microg/ml) inducible NO synthase activity and, consequently, nitrite formation. For instance, the inhibition was 70% for tetracycline base at 250 microM and 68% for doxycycline at 50 microM. The inhibitory effect of tetracyclines was due neither to a reduction in the viability of the cells, studied as colorimetric 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay, nor to an indiscriminate inhibition of total protein synthesis, but to a specific decrease in inducible NO synthase protein content in the cells, as attested by the significant reduction of the expression of inducible NO synthase, assayed by sodium-dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. However, no effect of tetracyclines on inducible NO synthase mRNA accumulation could be demonstrated in lipopolysaccharide-stimulated macrophage line, suggesting that the inhibitory effect of tetracyclines on NO synthesis involves post-transcriptional events. The reduction in lipopolysaccharide-stimulated nitrite accumulation produced by tetracyclines was significantly less when they were applied 6 h after lipopolysaccharide and absent 12 h after lipopolysaccharide, indicating that tetracyclines modify an early event in inducible NO synthase activation operating after mRNA transcription. The findings presented in this study indicate that the modulation of NO synthesis is another possible pathway by which tetracyclines may function as anti-inflammatory compounds.

A complete mutational scan of the gene coding for the serpin C1 inhibitor, comprising all eight exons and adjacent intron sequences and 550 bp preceding the transcription start site, was rapidly accomplished in 36 unrelated angioedema patients by using fluorescence-assisted mismatch analysis (FAMA). Mutations accounting for C1 inhibitor deficiency were identified in every one of 34 patients, with two failures turning out to be spurious cases. Two new substitution dimorphisms were also detected in introns. Changes affecting the C1 inhibitor protein, distributed throughout the seven coding exons, provide new insights into the molecular pathology of serpins. Six different splice-site and two promoter mutations were also found. Among the latter, a C-->T transition within one of two putative CAAT boxes of this TATA-less promoter, the sole idiomorphic nucleotide change in this kindred, was found homozygous in the proband, at variance with the dominant mode of transmission observed for structural mutations. FAMA, in the chemical probes configuration used in this study, is a rapid and robust mutation-scanning procedure, applicable to large DNA segments or transcripts and proved capable of 100% detection. Moreover, it provides accurate positional information--and hence recognition of multiple substitutions, precise relationship with those already known, and often immediate identification of the nucleotide change.

In Italy a rather high number of homozygotes with late complement component defects has been found among patients with meningococcal disease. It seems that clinical manifestations of meningococcal disease are less severe in patients with complement deficiency than in normal individuals. This situation could even be more evident in the heterozygous carriers for whom a selective advantage is discussed. In this study we have screened a cohort of 527 Italian blood donors from western Sicily for the presence of C8B mutated allele. Heterozygotes for C8 beta deficiency were identified using a specific PCR assay to detect a C-->T transition in exon 9 of the C8B gene. This mutation represents the most frequent genetic mechanism for C8 beta deficiency in Caucasians. A rapid PCR screening test was performed on DNA extracted from pooled blood samples of up to 8 individuals. A single male individual with heterozygous C8 beta deficiency was detected. In the family studies it was shown that his two brothers and the mother were heterozygous carriers too. Functional activity of the classical and alternative complement pathways were normal. No neisserial infections or inflammatory diseases were found in the family history. It was shown that the allele-specific PCR is a sensitive and rapid method to examine large numbers of DNA samples. It permitted to assess the real prevalence of the C8B mutated null allele in the general population free of ascertainment bias.

To ensure the effectiveness of radiation-therapy treatments, both in-phantom and in-patient reliable dose measurements are required. Thermoluminescence dosimeters are used commonly for both applications. Among the various available materials, the relatively new LiF:Mg,Cu,P phosphor is a suitable candidate for quality control of in vivo dosimetry in electron-beam therapy. The response behaviour of LiF:Mg,Cu,P chips to 6-21 MeV electron beams used in radiotherapy was studied. Batch homogeneity, dose linearity, sensitivity change after use, dose and dose-rate response, energy dependence and fading characteristics were investigated. The contribution from each factor to the overall uncertainty in dose measurement was evaluated. The results of this work show that the LiF:Mg,Cu,P chips are comparable to the commonly used LiF:Mg,Ti ones, and support their use for in vivo electron-beam dosimetry to an accuracy within +/- 10%.

The aim of this work was to perform an immunological study in six patients with 21 hydroxylase deficiency in mild form (M210HD) and in 2 patients with 21-hydroxylase deficiency in classical form (C210HD) and in their parents, in whom a previous HLA,C4,Bf typing demonstrated high prevalence of DR5 and phenotypic absence of fraction C4B of complement (C4BQO). This study contains the evaluation of C3, IgA, IgG, IgM levels, anticardiolipin antibodies (IgG and IgM) and circulating immunocomplexes. A study of lymphocyte subsets was also performed. Among M210HD 1 patient showed presence of anticardiolipin antibodies both IgM and IgG; this patient had shown antinuclear antibodies in a previous study. Among parents, some subjects showed presence of anticardiolipin antibodies and high levels of circulating immunocomplexes. No alterations in C3 and Ig levels were observed. A reduced percentage of CD4 suppressor-inducer (CD4-SI) (p < 0.05 in M210HD and in parents vs controls) and increased percentage of CD4 helper-inducer (CD4-HI) (p < 0.05 in both groups vs controls) were found. No alterations were evidenced in C210HD patients. Data about association between 21-hydroxylase deficiency and autoimmune diseases are rare. Our results confirm that 210HD could be associated to an unbalancement of immune system function and suggest that non immune genes, like 21-hydroxylase one, may influence the expression of autoimmune diseases at least in presence of peculial extended haplotypes.

Serum samples from members of two Italian families with complement C8 beta deficiency were studied by SDS-PAGE under nonreducing conditions and by IEF. The proband of family I had suffered from two episodes of purulent meningitis and two of her uncles had suffered from only one episode, while the proband of family II had suffered from three different episodes. In contrast to previous findings, where C8 beta deficiency was cosegregating with C8A (alpha-gamma) allotype A, the proband of family II had the C8A allotype B. In addition, in one of her sons a novel variant of the C8 beta chain was detected. Studies at the DNA level in family I, using a recently described PCR system, demonstrate the presence of a C-T exchange, which creates a stop codon in exon 9 of the C8B gene, as cause for the C8 beta deficiency. The mutated allele does not carry the TaqI polymorphic restriction site located in intron 11 of the C8B gene. These findings provide evidence for multiple recombination events within the genetic region of the defective C8B gene.

The complement system is an important part of non clonal or innate immunity that collaborates with acquired immunity to kill pathogens and to facilitate the clearance of immune complexes. The complement is made up of 20 distinct plasma proteins and 9 different membrane proteins. Three components, factor B, C2 and C4 (with 2 isotypes), are coded by polymorphic HLA-linked genes and are sometimes referred to as class III antigens, inherited as compact units called complotypes. The C4 genes are the most polymorphic, including a common null allele (Q0) at both the C4A and C4B loci. Other polymorphic complement factors (not linked to HLA) are C3 (2 common alleles), C6 and C7 (closely linked, with 3 and 2 alleles, respectively). A certain degree of polymorphism has also been described for complement receptors and membrane control proteins. No differences in functional activity are usually detected among different alleles. Immune-mediated diseases are associated with C4Q0, in particular: systemic lupus erythematosus and discoid-systemic lupus erythematosus, insulin-dependent diabetes mellitus, liver cirrhosis, celiac disease and IgA/IgG4 deficiency. Even if optimal HLA markers do become available, genetic counselling is usually not the ultimate goal for dealing with most of the HLA-associated common diseases, although their study could help to better delineate disease pathogenesis.

Patients with defects of terminal complement components are particularly exposed to the risk of developing neisserial infections and seem to respond poorly to meningococcal capsular polysaccharide (PS) C via natural immunization. The sole meningococcal PSC is, on the other hand, an excellent immunogen in normal people. Considering the great importance of vaccine prophylaxis for the prevention of meningococcal infections in patients with complement defects, it is crucial to study the antibody response to the sole meningococcal PS in these patients. We therefore analysed the levels of anti-PSA and PSC antibodies in the members of four families including patients with homozygous and heterozygous defects of C7, C8 or factor H, before and after vaccination with the sole PSA + C. Surprisingly, we found the highest levels of antibodies before vaccination in homozygous subjects, followed by heterozygous and normal controls, whereas, after vaccination, homozygous subjects showed the lowest increase of specific antibodies, indicating their relative incapability to respond to sole meningococcal PS. In conclusion, this study demonstrates (1) the capacity to respond to meningococcal PS via natural immunization by patients with total complement defects, and (2) the low responsiveness to meningococcal PS via vaccine immunization by the same patients. We propose that vaccination should be given to patients lacking specific antibodies and their serological response should be assessed. In addition this study confirms previous observations on a likely lower immunogenic power of meningococcal serogroup C via natural immunization compared with the better immunogenicity of the sole PSC.

Broadband ultrasonic absorption spectra are discussed for some aqueous solutions of single-walled phospholipid bilayer vesicles. It is shown that the excess absorption found with all samples can be represented by a sum of a Debye-type relaxation term with discrete relaxation time and a Fixman-Kawasaki term. The former term reflects the kinetics of structural isomerization of the hydrocarbon chains. The values of its relaxation time (0.09-0.56 ns) agree with those for pure n-alkanes of comparable length. The latter terms seems to be due to density fluctuations in the hydrocarbon part of the double layer. Fluctuation correlation lengths between 1 and 30 A result from the analysis of the ultrasonic spectra.

The nonlinear relation between stimulus intensity and response amplitude of the electroretinogram (ERG) scotopic b wave can be described by a curve based on the Naka-Rushton (NR) equation. Up to now, the NR equation has been used to assess the features of the normal and pathological ERG, but the best approach for a correct evaluation of the parameters is still debatable. The parameters are thought to be related to the different conditions of retinal activities. The method is well known in experimental laboratories but is quite unusual at the clinical level. In the present paper the derivative analysis of the NR function is proposed as an easier approach to understand the variations of the NR parameters in selected pathologies.

The population exposure to those living on the island of Pantelleria, Italy, was estimated by measuring the natural gamma background. Gamma spectra of natural rocks and measurements of absorbed dose in air were taken. A correlation was found between the mean gamma exposure rate and the mean values of natural radionuclide concentrations in the investigated rocks.