520 research outputs found

    HELP-based matrices for stimuli-responsive controlled release of bioactive compounds

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    Direct delivery of bioactive substances to the sites of injury represents a key issue for therapies based on regenerative medicine and tissue repair [1]. Protein derived hydrogels represent an interesting system for this purpose because they possess several features that make them suitable to this purpose. A method for preparation of hydrogel matrices based on Human Elastin-like Polypeptide (HELP) has been set up [2]. HELPs are a family of elastin-like recombinant biopolymers modeled after the most regularly repeated domain in human tropoelastin, retaining peculiar properties as self-assembling and thermoresponsive behavior [3]. In this study we assayed two elastolytic activities from different sources to test their potential to specifically degrade the HELP matrix

    The Ferroxidase Hephaestin in Lung Cancer: Pathological Significance and Prognostic Value

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    Hephaestin (HEPH) belongs to a group of exocytoplasmic ferroxidases which contribute to cellular iron homeostasis by favouring its export. Down-regulation of HEPH expression, possibly by stimulating cell proliferation due to an increase in iron availability, has shown to correlate with poor survival in breast cancer. The lung is particularly sensitive to iron-induced oxidative stress, given the high oxygen tension present, however, HEPH distribution in lung cancer and its influence on prognosis have not been investigated yet. In this study we explored the prognostic value of HEPH and its expression pattern in the most prevalent histotypes of lung cancers, namely lung adenocarcinoma and lung squamous cell carcinoma. In silico analyses, based on UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier plotter bioinformatics, revealed a significant correlation between higher levels of HEPH expression and favorable prognosis, in both cancer histotypes. Moreover, TIMER web platform showed a statistically significant association between HEPH expression and cell elements belonging to the tumor microenvironment identified as endothelial cells and a subpopulation of cancer-associated fibroblasts, further confirmed by double immunohistochemical labeling with cell type specific markers. Taken together, these data shed a light on the complex mechanisms of local iron handling lung cancer can exploit to support tumorigenesis

    Asbestos Fibers Enhance the TMEM16A Channel Activity in Xenopus Oocytes

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    Background: The interaction of asbestos fibers with target cell membranes is still poorly investigated. Here, we detected and characterized an enhancement of chloride conductance in Xenopus oocyte cell membranes induced by exposure to crocidolite (Croc) asbestos fibers. Methods: A two-microelectrode voltage clamp technique was used to test the effect of Croc fiber suspensions on outward chloride currents evoked by step membrane depolarization. Calcium imaging experiments were also performed to investigate the variation of 'resting' oocyte [Ca2+]i following asbestos exposure. Results: The increase in chloride current after asbestos treatment, was sensitive to [Ca2+]e, and to specific blockers of TMEM16A Ca2+-activated chloride channels, MONNA and Ani9. Furthermore, asbestos treatment elevated the 'resting' [Ca2+]i likelihood by increasing the cell membrane permeability to Ca2 in favor of a tonic activation of TMEME16A channels. Western blot analysis confirmed that TMEME16A protein was endogenously present in the oocyte cell membrane and absorbed by Croc. Conclusion: the TMEM16A channels endogenously expressed by Xenopus oocytes are targets for asbestos fibers and represent a powerful tool for asbestos-membrane interaction studies. Interestingly, TMEM16A channels are highly expressed in many types of tumors, including some asbestos-related cancers, suggesting them, for the first time, as a possible early target of crocidolite-mediated tumorigenic effects on target cell membranes

    Closing the knowledge gap on the composition of the asbestos bodies

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    Asbestos bodies (AB) form in the lungs as a result of a biomineralization process initiated by the alveolar macrophages in the attempt to remove asbestos. During this process, organic and inorganic material deposit on the foreign fibers forming a Fe-rich coating. The AB start to form in months, thus quickly becoming the actual interface between asbestos and the lung tissue. Therefore, revealing their composition, and, in particular, the chemical form of Fe, which is the major component of the AB, is essential to assess their possible role in the pathogenesis of asbestos-related diseases. In this work we report the result of the first x-ray diffraction measurements performed on single AB embedded in the lung tissue samples of former asbestos plant workers. The combination with x-ray absorption spectroscopy data allowed to unambiguously reveal that Fe is present in the AB in the form of two Fe-oxy(hydroxides): ferrihydrite and goethite. The presence of goethite, which can be explained in terms of the transformation of ferrihydrite (a metastable phase) due to the acidic conditions induced by the alveolar macrophages in their attempt to phagocytose the fibers, has toxicological implications that are discussed in the paper

    Deep subcutaneous application of poly-L-lactic acid as a filler for facial lipoatrophy in HIV-infected patients

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    Introduction: Facial lipoatrophy is a crucial problem of HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Poly-L-lactic acid (PLA), provided as New-Fill(R)/Sculptra(TM), is known as one possible treatment option. In 2004 PLA was approved by the FDA as Sculptra(TM) for the treatment of lipoatrophy of the face in HIV-infected patients. While the first trials demonstrated relevant efficacy, this was to some extent linked to unwanted effects. As the depth of injection was considered relevant in this context, the application modalities of the preparation were changed. The preparation was to be injected more deeply into subcutaneous tissue, after increased dilution. Material and Methods: To test this approach we performed a pilot study following the new recommendations in 14 patients. Results: While the efficacy turned out to be about the same, tolerability was markedly improved. The increase in facial dermal thickness was particularly obvious in those patients who had suffered from lipoatrophy for a comparatively small period of time. Conclusion: With the new recommendations to dilute PLA powder and to inject it into the deeper subcutaneous tissue nodule formation is a minor problem. However, good treatment results can only be achieved if lipoatrophy is not too intense; treatment intervals should be about 2 - 3 weeks. Copyright (C) 2005 S. Karger AG, Basel

    Performance evaluation of a commercial protective coating through field-exposure tests on three stone substrates

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    In the last decades, there have been several studies on Cultural Heritage regarding the performance of protective and consolidating coatings for the prevention of decay. A coating must have several characteristics such as efficiency, breathability, and must be durable and reversible. In this research work, the performance of a commercial protective product (Fosbuild FBLE 200) was evaluated. This coating is composed of a TiO2 nanopowder dispersed in an aqueous solution of an acrylic polymer. The product, which exhibits depolluting, antimicrobial, water-repellent and self-cleaning properties, has been applied on three different lithotypes: Carrara marble, Noto stone, and Comiso stone. Field-exposure tests were carried out in two different outdoor environments (Catania and Palermo) in order to assess its suitability. Promising results were obtained for the Carrara marble after one year of exposure; however, a decrease in effectiveness was observed at the end of the second year

    Derivative expansion of quadratic operators in a general 't Hooft gauge

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    A derivative expansion technique is developed to compute functional determinants of quadratic operators, non diagonal in spacetime indices. This kind of operators arise in general 't Hooft gauge fixed Lagrangians. Elaborate applications of the developed derivative expansion are presented.Comment: 40 pages, to appear in Phys. Rev.

    Clinical and instrumental assessment of herniated discs after nucleoplasty: A preliminary study

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    Background and Aim: The therapy for low back pain boasts different approaches; one of these is nucleoplasty. We wanted to assess the effectiveness of nucleoplasty both by clinical response both by MR imaging evaluation, including even extrusions larger than one third of the spinal canal. Methods: Fifty-seven patients were treated with nucleoplasty in our hospital, 11 of these patients accepted both clinical and MRI evaluation after six months from treatment. The clinical evaluation was performed with Visual Analogue Scale (VAS) of pain, scored before and after the procedure. MRI evaluation consisted of analysing some imaging parameters of disc protrusions before and after the treatment. Results: In 10 out of 11 (91%) patients, VAS was reduced and only 1 out of 11 (9%) had the same pain after procedure. The mean of decrease of VAS score was 64%. In our population 8/11 (72%) patients had a herniation larger than 1/3 of the sagittal diameter of spinal canal and 100% of them had an improvement with a mean VAS reduction value of 75%. With MRI evaluation, the mean percentage of expulsion before and after treatment was respectively 40% and 34%. The expulsion decreased in 7/13 discs, remained equal in 4/13, and increased in 2/13 discs. Among the 9 larger protrusions, 3 didn\u2019t change, 6 reduced with a decrease mean value of 13%. Other MRI parameters didn\u2019t change significantly. Conclusions: Our preliminary experience supports the success of coblation on pain relief, aiming to show progressively that this treatment is suitable even in case of great extrusions, which are generally treated only with surgical approach. It\u2019s not clear the usefulness of MRI control yet, even if in most of cases we could have found a certain reduction of expulsion degree

    Inicio de pubertad y caracteres reproductivos en toritos Braford del nordeste argentino

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    El presente estudio tuvo como objetivo determinar la edad de inicio de pubertad en toritos Braford 3/8, por medio de la evaluación del semen, junto a mediciones de circunferencia escrotal y características zoométricas. Para tal fin, durante 120 días se trabajó con 34 animales, que fueron identificados por medio de caravana y destetados el 1° de marzo del año 2010, entre los 6 y 8 meses de edad. Los toritos fueron mantenidos a campo con pasturas implantadas, con amplio predominio de avena (Avena sativa), trébol blanco (Trifolium repens) y alfalfa (Medicago sativa), además de la administración de alimento balanceado a razón del 1 al 2% de su peso vivo. En forma seriada, cada 14 días a partir del mes de junio, se evaluaron parámetros como circunferencia escrotal, consistencia testicular (por palpación bimanual), altura a la cruz y al sacro, así como perímetro torácico y peso corporal individual. El semen extraído por medio de un electroeyaculador fue evaluado macro y microscópicamente. Se concluye que, en promedio, los toritos alcanzan la pubertad a la edad de 13,1 meses, con un peso promedio de 333 kg y una circunferencia escrotal de 27,5 cm.
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