Numerical simulation of experimental tests performed on ZAO® non-evaporable-getter pump designed for neutral beam injector applications.

Vacuum systems of neutral beam injectors have very demanding requirements in terms of pumping speed, throughput, and capacity. Due to their high affinity to hydrogenic species, porous sintered Non-Evaporable Getters (NEG) are a possible candidate for deployment in giant hydrogen ion sources and neutral beam injectors for fusion. This paper presents the numerical interpretation of experimental tests on a recently developed NEG cartridge, that is part of a modular pump under development for neutral beam injectors. The cartridge is composed of six stacks of ZAO® porous sintered NEG disks and a heater. It was tested under hydrogen loads relevant for neutral beam injectors, namely, at constant pressure or constant flow, such that the hydrogen pressure was in the range of 20 mPa-40 mPa. The result of the sorption test was reproduced by a three dimensional flow simulation in molecular regime to determine the actual pumping speed, the effective sticking coefficient, and the uniformity of the gas load on the various NEG disks. The procedure developed and the results obtained provide the basic understanding for interpreting the large-scale tests on the modular pump, consisting of 34 of these cartridges.

Simulation of the gas density distribution in the accelerator of the ELISE test facility.

In multiaperture electrostatic accelerators of negative ion sources, the plasma discharge is sustained by injecting gas in the plasma source, in a dynamic equilibrium with the gas flowing out through the accelerator. In this work, we present a three-dimensional numerical simulation of the gas flow inside the accelerator system of the large negative ion source ELISE at Max-Planck-Institut für Plasmaphysik Garching. ELISE has 640 apertures per electrode and lateral gaps between the electrode support structures that also contribute to the total gas conductance. Assuming molecular regime, we estimated the gas conductance, the gas density profile along the path of the ion beams from upstream of the plasma grid to downstream of the ground grid, and the transverse nonuniformities in the accelerator. The simulation included the most relevant geometrical features, while the results are compared to analytical results.

Two siblings affected by Netherton/Comèl syndrome. Diagnostic pathology and description of a new SPINK5 variant.

Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the SPINK5 gene encompassing three main clinical findings: 1) ichthyosiform dermatitis and/or ichthyosis linearis circumflexa, 2) hair shaft defects with peculiar "trichorrhexis invaginata" (bamboo pole hair) findings, 3) atopic dermatitis. We describe two siblings affected by Netherton/Comèl syndrome who were referred to our Center for Genodermatosis. A diagnostic pathway and the description of a new SPINK5 variant has been determined for these two patients. A novel genetic mutation has been found.

135La as an Auger-electron emitter for targeted internal radiotherapy.

135La has favorable nuclear and chemical properties for Auger-based targeted internal radiotherapy. Here we present detailed investigations of the production, emissions, and dosimetry related to 135La therapy. 135La was produced by 16.5 MeV proton irradiation of metallic natBa on a medical cyclotron, and was isolated and purified by trap-and-release on weak cation-exchange resin. The average production rate was 407 ± 19 MBq µA-1 (saturation activity), and the radionuclidic purity was 98% at 20 h post irradiation. Chemical separation recovered > 98 % of the 135La with an effective molar activity of 70 ± 20 GBq µmol-1. To better assess cellular and organ dosimetry of this nuclide, we have calculated the x-ray and Auger emission spectra using a Monte Carlo model accounting for effects of multiple vacancies during the Auger cascade. The generated Auger spectrum was used to calculate cellular S-factors. 135La was produced with high specific activity, reactivity, radionuclidic purity, and yield. The emission spectrum and the dosimetry are favorable for internal radionuclide therapy.

New prospective in treatment of Parkinson's disease: studies on permeation of ropinirole through buccal mucosa.

The aptitude of ropinirole to permeate the buccal tissue was tested using porcine mucosa mounted on Franz-type diffusion cells as ex vivo model. Drug permeation was also evaluated in presence of various penetration enhancers and in iontophoretic conditions. Ropinirole, widely used in treatment of motor fluctuations of Parkinson's disease, passes the buccal mucosa. Flux and permeability coefficient values suggested that the membrane does not appear a limiting step to the drug absorption. Nevertheless, an initial lag time is observed but the input rate can be modulated by permeation enhancement using limonene or by application of electric fields. Absorption improvement was accompanied by the important reduction of the lag time; at once the time required to reach the steady state plasma concentration was drastically decreased. On the basis of these results we could assume that clinical application of ropinirole by buccal delivery is feasible.

An intriguing case of Prurigo pigmentosa in a Sicilian young patient.

Prurito pigmentosa is an inflammatory disease mainly reported by Japanese dermatologists. We report a case of Prurigo pigmentosa observed in a Sicilian young patient affected by intellectual disability. In the past, we had already observed and reported some cases of Prurigo pigmentosa in patients living in Sicily. The differential diagnosis, the treatment of the disease, the role of chronic intake of psychodrugs and the possible relation to G6PD deficiency of this patient are pointed out.

Molecular characterization of Fusarium oxysporum f. melongenae by ISSR and RAPD markers on eggplant.

Fusarium oxysporum f. melongenae is a major soil-borne pathogen of eggplant (Solanum melongena). ISSR and RAPD markers were used to characterize Fusarium oxysporum f. melongenae isolates collected from eggplant fields in southern Turkey. Those isolates were not pathogenic to tomato. Pathogens were identified by their morphology, and their identity was confirmed by PCR amplification using the specific primer PF02-3. The isolates were classified into groups on the basis of ISSR and RAPD fingerprints, which showed a level of genetic specificity and diversity not previously identified in Fusarium oxysporum f. melongenae, suggesting that genetic differences are related to the pathogen in the Mediterranean region. The primers selected to characterize Fusarium oxysporum f. melongenae may be used to determine genetic differences and pathogen virulence. This study is the first to characterize eggplant F. oxysporum species using ISSR and RAPD.

Synthesis and in vitro studies on a potential dopamine prodrug.

Dopamine delivery to the central nervous system (CNS) undergoes the permeability limitations of blood-brain barrier (BBB) which is a selective interface that excludes most water-soluble molecules from entering the brain. Neutral amino acids permeate the BBB by specific transport systems. Condensation of dopamine with neutral amino acids could afford potential prodrugs able to interact with the BBB endogenous transporters and easily enter the brain. The synthesis and characterization of the dopamine derivative 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (7) is described. The chemical and enzymatic stability of 7 was evaluated. The molecular weight (300 Da) and Log Papp (0.76) indicated that the physico-chemical characteristics of compound 7 are adequate to cross biological membranes. Compound 7 was enzymatically cleaved to free dopamine in rat brain homogenate (t1/2 = 460 min). In human plasma, the t1/2 of 7 was estimated comparable to that reported for L-DOPA. In view of a possible oral administration of 7, studies of its chemical behavior under conditions simulating those of the gastrointestinal tract showed that no dopamine production occurred; furthermore, 7 is able to permeate through a simulated intestinal mucosal membrane. The collected data suggest that compound 7 could beconsidered a very valuable candidate for subsequent in vivo evaluation.

Carbamazepine transbuccal delivery: the histo-morphological features of reconstituted human oral epithelium and buccal porcine mucosae in the transmucosal permeation.

Transbuccal drug delivery is an attractive way of administration since several well-known advantages are provided, especially with respect to peroral management. Carbamazepine (CBZ) is an anticonvulsant which is useful in controlling neuropathic pain, and it is currently administered by peroral route, although its absorption and bioavailability is limited due to various factors. The oral cavity could be an interesting site for transbuccal CBZ delivery due to two properties: slow administration of constant low drug doses and less dose-related side effects. However, in transbuccal absorption a major limitation could be the low permeability of the mucosa which results in low drug bioavailability; thus the aptitude of the drug to penetrate the buccal mucosa has to be assessed by using tissue models resembling human normal mucosa. In our experience, CBZ well permeates mucosal membranes. In order to assess the efficacy of CBZ transbuccal delivery and to verify the reliability of these tissues in permeability testing before and after the passage of CBZ, the histo-morphological features of reconstituted human oral (RHO) epithelium (E) and buccal porcine mucosae were investigated. Significant histological changes due to CBZ passage were observed both in RHO-E and porcine mucosa. The main findings detected in RHO samples were cellular swellings with a signet ring-like appearance, nuclear swelling, prominent nucleoli lined against the nuclear membrane and the presence of keratohyalin granules. The most striking finding regarding porcine buccal mucosa was a cytoplasmic vacuolization, mainly involving the basal layer.

Transbuccal tablets of carbamazepine: formulation, release and absorption pattern.

Tranbsuccal drug administration is an attractive method, as it has several advantages especially with respect to peroral delivery. Here we report: i) the aptitude of carbamazepine (CBZ) to penetrate porcine buccal mucosa and reconstituted human oral (RHO) epithelium; ii) three different tablet formulations for transbuccal administration; iii) the drug release rate from tablets. CBZ permeation through the buccal mucosa was investigated by using two different bi-compartmental open models: Franz cells for porcine buccal mucosa and Transwell diffusion cells system for RHO epithelium. Results, expressed as drug flux (Js) and permeability coefficients (Kp), indicated that CBZ well penetrates the membrane and arrives in the acceptor phase. Js and Kp resulted 7x10(-2) mg/cm2h and 0.23 cm/h for in vitro experiments and 1.81 x 10(-2) mg/cm2h and 4.57 x 10(-2) cm/h for ex vivo experiments. The flux is extensively affected by the membrane thickness. The CBZ release from three different formulations of tablets, prepared with loaded microspheres, loaded matrices, and conventional compressed physical mixture of components was studied. Using the new formulated "non-conventional" tablets prolonged drug release was obtained. Loaded matrix tablets discharged CBZ faster than microsphere tablets (17% and 12% in about 2.5 h respectively). Results indicate the possibility of administering CBZ on buccal mucosa.

Zygotic and nucellar embryo survival following dehydration and cryopreservation of citrus intact seeds.

A cryopreservation procedure by dehydration and direct immersion in liquid nitrogen was developed for seeds of four polyembryonic Citrus species, and the sexual or nucellar origin of the recovered seedlings was investigated. Seeds of three species could be desiccated in a sterile air flow to 16 percent (C. sinensis) or 10 percent (C. aurantium and C. limon) moisture content with a negligible reduction in germination levels. Differently, the germinability of C. deliciosa seeds dropped to 50 percent after drying to 15 percent moisture content. Following dehydration treatments, a reduction in the average number of seedlings per germinated seed was always observed. However, all four species benefited from desiccation in terms of protection during immersion in liquid nitrogen, with C. sinensis and C. aurantium showing the greatest survival (93 percent germination) after cryopreservation. The Inter-Simple Sequence Repeat analysis of seedlings recovered from cryopreserved seeds showed that the dehydration/cryopreservation procedure promotes the germination of zygotic embryos and reduces the number of apomictic seedlings per seed.

Indirect digital images: limit of image compression for diagnosis in endodontics.

AIM: To analyse the impact of the loss of information that results from the compression of a file containing a radiographic image. METHODOLOGY: Fourteen intraoral radiographs were digitized employing an AGFA ARCUS II scanner at an optical resolution of 300 ppi and with a grey scale of 8 bytes. The images were stored in Tagged Image File Format (TIFF). The files were compressed with no information loss with the WinZip 8.0 program. Compression with information loss was performed using the Photoshop 5.0 program (Adobe Systems Inc., San José, CA. USA) and the Joint Photograph Expert (Group (JPEG) format. Each of the images was compressed to one of the 11 qualities available (10-0). An expert performed the qualitative analysis. The quantitative analysis involved digital subtraction with each of the JPEG images to yield a new image using Photoshop 5.). The histograms of grey values were submitted to statistical analysis. The mean and standard deviation were calculated for each image. RESULTS: The data revealed that a JPEG lossy compression, six times smaller than the original TIFF, is compatible with diagnostic applications. CONCLUSIONS: The compression ratio calculated as the quotient between the file sizes and the standard deviation of the values corresponding to the image that resulted from digital subtraction may be employed to assess the outcome of the compression process and guarantee adequate quality.

Eruptive syringomas with calcium deposits in a young woman with Down's syndrome.

Eruptive syringomas are uncommon in the general population. We describe here an 18-year-old female, affected by Down's syndrome, who presented with an abrupt eruption of small skin-colored or reddish papules on the face, neck and limbs. Light microscopy allowed us to diagnose syringomas, whereas the study of the ultrastructural features revealed calcium deposits in many lumina and also in the mitochondria. This observation confirms the hypothesis that the syringeal structure plays a role in the pathogenesis of calcinosis cutis.

Friction melanosis, friction amyloidosis, macular amyloidosis, towel melanosis: many names for the same clinical entity.

Macular or friction amyloidosis is a cutaneous entity characterized by a brownish pigmentation distributed on the skin over bony regions of the trunk and limbs after the use, for many years, of a nylon towel or scrub brush to clean the skin. Electron microscopy is necessary for the diagnosis of this dermatosis and reveals deposits of amyloid in the papillary dermis. This condition is relatively unknown in Western countries. In this report, we describe 24 Italian patients affected by friction amyloidosis which was caused by the use of cotton towels, horse-hair gloves or artificial and rough sponges to clean their skin.