Validation of a Cleanroom Compliant Sonication-Based Decellularization Technique: A New Concept in Nerve Allograft Production

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze–thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique.     

OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

The Novel Organic Cation Transporter, OCTN1, is the first member of the OCTN subfamily; it belongs to the wider Solute Carrier family SLC22, which counts many members including cation and anion organic transporters. The tertiary structure has not been resolved for any cation organic transporter. The functional role of OCNT1 is still not well assessed despite the many functional studies so far conducted. The lack of a definitive identification of OCTN1 function can be attributed to the different experimental systems and methodologies adopted for studying each of the proposed ligands. Apart from the contradictory data, the international scientific community agrees on a role of OCTN1 in protecting cells and tissues from oxidative and/or inflammatory damage. Moreover, the involvement of this transporter in drug interactions and delivery has been well clarified, even though the exact profile of the transported/interacting molecules is still somehow confusing. Therefore, OCTN1 continues to be a hot topic in terms of its functional role and structure. This review focuses on the most recent advances on OCTN1 in terms of functional aspects, physiological roles, substrate specificity, drug interactions, tissue expression, and relationships with pathology.     

Be radioactive beam production at CIRCE and its utilization in basic and applied physics

A pure ⁷Be beam with an energy E = 1-8 MeV is available for nuclear and applied physics at the 3 MV Pelletron tandem accelerator CIRCE in Caserta. The beam is produced using an offline technique. Typical analyzed beam intensities are about 2 ppA, using cathodes with an activity of the order of 200 MBq. The ⁷Be implantation has been used for both fundamental nuclear physics and applied physics. In particular, different metals have been implanted with ⁷Be in order to study the influence of the chemical composition and of the number of quasi-free electrons of the host material on the ⁷Be half-life. In the field of applied physics, the ⁷Be implantation turns out to be very interesting for wear measurement. In fact, in this case ⁷Be is used as a depth-sensitive tracer. The continuous detection of the sample activity during the wear allows a high sensitivity measurement of wearing speed. The ⁷Be beam production at CIRCE, the implantation procedure and the results obtained from the ⁷Be half-life measurements and the wear characterization of implanted steel samples are described.     

Toxic metals (Hg, Cd, and Pb) in fishery products imported into Italy: suitability for human consumption

Mercury, cadmium, and lead concentrations were determined in various fishery products (fishes, cephalopod molluscs, and crustaceans) imported into Italy from many European and non-European coastal countries. Considerable differences were found in the concentrations of these metals among the products tested. The highest mean Hg concentration was found in fishes (0.21 μg g(-1) wet weight), whereas cephalopods had the highest mean Cd concentration (0.35 μg g(-1) wet weight). Swordfish (0.80 μg g(-1) wet weight), longtail tuna (0.53 μg g(-1) wet weight), and thornback ray (0.52 μg g(-1) wet weight) had the highest concentrations of Hg, whereas maximum Cd concentrations were found in samples of common cuttlefish (0.85 μg g(-1) wet weight) and common octopus (0.64 μg g(-1) wet weight). The majority of the samples analyzed were in compliance with European Union legislation, except for a few cases. The calculated mean weekly intakes of Hg, Cd, and Pb through consumption of the fishery products tested were all below the legislated respective provisional tolerable weekly intakes. In general, the samples analyzed were considered safe to eat with regard to the metal concentrations found and the allowable intakes based on legislation. Nevertheless, the consumption of some species may be of significant importance for consumer health.     

Nanoindentation Characterization of Submicro- and Nano-Sized Liquid-Phase-Sintered SiC Ceramics

Submicro- and nano-sized liquid-phase-sintered SiC ceramics were mechanically tested by nanoindentation in the peak load range 5–400 mN. The submicro-sized sample showed a marked indentation size effect which the nano-sized samples did not exhibit. The relevance of indentation depth with respect to the microstructural scale has been outlined. In the investigated grain-size range, the hardness dependence on the grain size could be described by a load-dependent inverse Hall–Petch relation. Young's modulus was less microstructure- and load-dependent. Because of the very fine microstructure, the nano-sized SiC materials gave lower elastic values than the submicro-sized SiC ceramic.     

High-Temperature Resistant Composites in the AlN–SiC–MoSi2 System

Two fully dense composites containing AlN, SiC, and MoSi₂ in different amounts were produced by hot pressing. Young modulus, hardness, electrical conductivity, and thermal expansion coefficient were measured at room temperature. Strength and toughness were evaluated up to 1300°C in air. According to statistical analysis, the temperature has little or no effect on high-temperature fracture behavior of the composites. These electroconductive materials are suitable for thermomechanical applications at high temperature, the strength being about 600 MPa at 1300°C.     

Edge Chipping Resistance of Alumina/Zirconia Laminates

The edge chipping test was used to measure the fracture resistance of alumina/alumina‐zirconia laminated structures. Tailored, symmetrical laminated structures were prepared with a variety of layer thickness. The laminates had a significantly greater edge chipping resistance. Laminates with thin layers were just as effective in impeding edge chips as laminates with thick layers.     

On the formation of blisters in annealed hydrogenated a-Si layers

Differently hydrogenated radio frequency-sputtered a-Si layers have been studied by infrared (IR) spectroscopy as a function of the annealing time at 350°C with the aim to get a deeper understanding of the origin of blisters previously observed by us in a-Si/a-Ge multilayers prepared under the same conditions as the ones applied to the present a-Si layers. The H content varied between 10.8 and 17.6 at.% as measured by elastic recoil detection analysis. IR spectroscopy showed that the concentration of the clustered (Si-H)_n groups and of the (Si-H₂)_n (n ≥ 1) polymers increased at the expense of the Si-H mono-hydrides with increasing annealing time, suggesting that there is a corresponding increase of the volume of micro-voids whose walls are assumed from literature to be decorated by the clustered mono-hydride groups and polymers. At the same time, an increase in the size of surface blisters was observed. Also, with increasing annealing time, the total concentration of bonded H of any type decreases, indicating that H is partially released from its bonds to Si. It is argued that the H released from the (Si-H)_n complexes and polymers at the microvoid surfaces form molecular H₂ inside the voids, whose size increases upon annealing because of the thermal expansion of the H₂ gas, eventually producing plastic surface deformation in the shape of blisters.     

Advanced Pyrrolidine-Carbamate Self-Immolative Spacer with Tertiary Amine Handle Induces Superfast Cyclative Drug Release

Amine-carbamate self-immolative (SI) spacers represent practical and versatile tools in targeted prodrugs, but their slow degradation mechanism limits drug activation at the site of disease. We engineered a pyrrolidine-carbamate SI spacer with a tertiary amine handle which strongly accelerates the spacer cyclization to give a bicyclic urea and the free hydroxy groups of either cytotoxic (Camptothecin) or immunostimulatory (Resiquimod) drugs. In silico conformational analysis and pK_a calculations suggest a plausible mechanism for the superior efficacy of the advanced SI spacer compared to state-of-art analogues.     

Developing pyrrole-derived antimycobacterial agents: a rational lead optimization approach

Tuberculosis (TB) represents a never-ending challenge toward which research efforts are needed. Drug resistance is the key problem that scientists in the field need to fight. The development of new drugs endowed with novel modes of action against different biological targets is of extreme importance; these new agents should also exhibit lower toxicity compared with the anti-TB drugs currently available. Furthermore, new drugs should be inexpensive since most of the TB-infected population lives in developing nations. In the last few years, numerous researchers have focused their attention on TB, leading to the discovery of some interesting compounds. Among these, the pyrrole-derived compounds we developed can be considered very promising antimycobacterial agents. Aided by molecular modeling studies, we synthesized numerous compounds characterized by the same 1,5-diarylpyrrole scaffold and elucidated very interesting antitubercular/antimycobacterial properties. Some compounds identified are extremely promising and represent a step towards the design of novel lead structures in the fight against TB. Our efforts to this end are reviewed here.