The role of the cystectomy and minimally invasive surgery in the complex patient with bladder cancer

L'abstract è presente nell'allegato / the abstract is in the attachmen

The Foreign Corrupt Practices act and Corporate Charity: Rethinking the Regulations

American companies bring U.S. innovation and capital to all corners of the globe. The U.S. corporate presence abroad is seen not only in oil rigs and factories, but also in corporate development projects and humanitarian relief efforts

Electron-transfer-induced reductive dealkoxylation of alkyl aryl ethers. III. Reductive cleavage of methoxy-substituted <i>N</i>,<i>N</i>-dimethylanilines (<i>N</i>,<i>N</i>-dimethylanisidines)

The reactivity of the three isomeric methoxy-substituted N,N-dimethylanilines (N,N-dimethylanisidines) and of N,N-dimethyl-2,6-dimethoxyaniline in the reduction with alkali metals in aprotic solvents was investigated. N,N-Dimethyl-p-methoxyaniline was found to be unreactive, while the other substrates underwent exclusive cleavage of carbon-oxygen bond(s), with the following order of reactivity: 2,6-dimethoxy > o-methoxy > m-methoxy > p-methoxy. Both the relative reactivity and the regioselectivity of cleavage (demethoxylation vs. demethylation) was found to parallel closely that of the corresponding di- and trimethoxysubstituted substrates. These results suggest that intermediates with different electron distribution or even different intermediates are involved in the reductive cleavage of aryl-oxygen and arylnitrogen bonds

Regressivity reducing VAT reforms

A concern about a more extensive use of the Value Added Tax (VAT) in national tax systems often arises both from its impact on aggregate consumption and its alleged regressivity over income. Yet, the empirical evidence on this latter issue is still narrow mainly due to the lack of joint data on income and expenditures with enough detail to account for commodity-specific tax rates. After discussing relevant problems in the measurement of VAT incidence over current income – which are likely to cause severe upward bias in the estimated regressivity – the paper aixsms at analysing the distributional implications of different VAT structures. In a framework of marginal tax reforms, relying on the concept of Gini elasticity (Yitzhaki, 1983), a general methodology is proposed to analyse and improve the distributional profile of VAT over income. Using a static microsimulation model (EGaLiTe), the methodology is applied on a comprehensive dataset of expenditures and incomes obtained by a statistical matching of two different sources representative of the Italian population. It is shown that an alternative allocation of goods among existing rates could mitigate the regressive profile of the tax over income, and that a properly designed two-rate setting could even improve the distributional outcome compared with the current setting. Finally, behavioural responses to tax-driven price changes are also simulated in order to assess the potential impact of the proposed reforms on aggregate expenditures

Freeze-thawing of liposomes: investigation of cryoprotectants for freeze-drying

Liposomes are phospholipid membranes widely used for drug delivery in biomedical applications. They can retain, protect and deliver macromolecules to target tissues and then control the release of their cargoes. To exploit this function, the liposomal membrane integrity is crucial to avoid undesired leakage of cargoes. In this work, the influence of low temperature storing conditions on the stability of liposomes is investigated for further delivery applications

Comparative Studies of Different Preservation Methods and Relative Freeze-Drying Formulations for Extracellular Vesicle Pharmaceutical Applications

Extracellular vesicles (EVs) have been studied for years for their role as effectors and mediators of cell-to-cell communication and their potential application to develop new and increasingly performing nanotechnological systems for the diagnosis and/or treatment of many diseases. Given all the EVs applications as just isolated, functionalized, or even engineered cellular-derived pharmaceuticals, the standardization of reliable and reproducible methods for their preservation is urgently needed. In this study, we isolated EVs from a healthy blood cell line, B lymphocytes, and compared the effectiveness of different storage methods and relative freeze-drying formulations to preserve some of the most important EVs’ key features, i.e., concentration, mean size, protein content, and surface antigen’s expression. To develop a preservation method that minimally affects the EVs’ integrity and functionality, we applied the freeze-drying process in combination with different excipients. Since EVs are isolated not only from body fluids but also from culture media conditioned by the cells growing there, we decided to test both the effects of the traditional pharmaceutical excipient and of biological media to develop EVs solidified products with desirable appearance and performance properties. Results showed that some of the tested excipients, i.e., sugars in combination with dextran and glycine, successfully maintained the stability and integrity of EVs upon lyophilization. In addition, to evaluate the preservation of the EVs’ biological activity, we assessed the cytotoxicity and internalization ability of the reconstituted EVs in healthy (B lymphocytes) and tumoral (Burkitt’s lymphoma) cells. Reconstituted EVs demonstrated toxicity only toward the cancerous cells, opening new therapeutic opportunities for the oncological field. Furthermore, our study showed how some biological or cellular-conditioned fluids, commonly used in the field of cell cultures, can act not only as cryoprotectants but also as active pharmaceutical ingredients, significantly tuning the therapeutic effect of EVs, even increasing their cellular internalization

Evaluation of anatomical and histopathological changes in target organs of cattle slaughtered in Sardinia as a result of the illegal use of growth hormones. Preliminary results

Within the bovine specie, illegal use of anabolic agents can be grouped into four categories: beta-agonists, thyrostatics, glucocorticoids, sexual steroids. These substances, further their anabolic effect, cause morphological changes in target organs which can be evidenced by anatomical and histopathological testing. Such investigations are extremely important to screen and to detect in advance groups of animals in risk-breeding

Cytotoxicity and Thermal Characterization Assessment of Excipients for the Development of Innovative Lyophilized Formulations for Oncological Applications

Freeze-drying, also known as lyophilization, significantly improves the storage, stability, shelf life, and clinical translation of biopharmaceuticals. On the downside, this process faces complex challenges, i.e., the presence of freezing and drying stresses for the active compounds, the uniformity and consistency of the final products, and the efficiency and safety of the reconstituted lyophilized formulations. All these requirements can be addressed by adding specific excipients that can protect and stabilize the active ingredient during lyophilization, assisting in the formation of solid structures without interfering with the biological and/or pharmaceutical action of the reconstituted products. However, these excipients, generally considered safe and inert, could play an active role in the formulation interacting with the biological cellular machinery and promoting toxicity. Any side effects should be carefully identified and characterized to better tune any treatments in terms of concentrations and administration times. In this work, various concentrations in the range of 1 to 100 mg/mL of cellobiose, lactose, sucrose, trehalose, isoleucine, glycine, methionine, dextran, mannitol, and (2-hydroxypropyl)-β-cyclodextrin were evaluated in terms of their ability to create uniform and solid lyophilized structures. The freeze-dried products were then reconstituted in the appropriate cell culture media to assess their in vitro cytotoxicity on both a healthy cell line (B-lymphocytes) and their tumoral lymphoid counterpart (Daudi). Results showed that at 10 mg/mL, all the excipients demonstrated suitable lyophilized solid structures and high tolerability by both cell lines, while dextran was the only excipient well-tolerated also up to 100 mg/mL. An interesting result was shown for methionine, which even at 10 mg/mL, selectively affected the viability of the cancerous cell line only, opening future perspectives for antitumoral applications

Tailoring dry microparticles for pulmonary drug delivery: ultrasonic spray freeze-drying with mannitol and salbutamol sulphate

Spray freeze-drying has emerged as a valid alternative to traditional spray drying to produce therapeutic dry microparticles. In particular, the spherical shape and high porosity of spray freeze-dried microparticles make them suitable for pulmonary drug delivery through dry powder inhalers. However, an appropriate particle size and fine particle fraction are required to guarantee lung deposition. This study used ultrasonic spray freeze-drying to generate dry microparticles composed of mannitol either alone or added with the bronchodilator salbutamol sulphate. The influence of the solid concentration and the feed flow rate on the particle size, morphology, surface area, porosity, and crystallinity was investigated. Growing particle size was observed, increasing the concentration and feed flow rate. Similarly, the addition of the drug led to a larger particle size and surface area. The in vitro simulation of drug deposition highlighted the dependence of the aerodynamic properties on the solid concentration and feed flow rate. Due to the lower density and particle geometric size, the highest fine particle fraction (26%) and smallest mass median aerodynamic diameter (4.4 μm) were reached at the lowest solid concentration and feed flow rate

Tailoring Dry Microparticles for Pulmonary Drug Delivery: Ultrasonic Spray Freeze-Drying with Mannitol and Salbutamol Sulphate

Spray freeze-drying has emerged as a viable alternative to traditional spray drying for manufacturing therapeutic dry microparticles. These microparticles exhibit spherical shapes and high porosity, making them ideal for pulmonary drug delivery via dry powder inhalers. However, achieving the right particle size and fine particle fraction is crucial for effective lung deposition. This study employed ultrasonic spray freeze-drying to produce dry microparticles composed of mannitol, either alone or in combination with the bronchodilator salbutamol sulfate. The investigation explored the impact of solid concentration and feed flow rate on particle size, morphology, surface area, porosity, and crystallinity. Increasing the solid concentration and feed flow rate resulted in larger particle sizes. Additionally, the inclusion of the drug led to greater particle size and increased surface area. In vitro drug deposition simulations underscored the influence of solid concentration and feed flow rate on aerodynamic properties. The lowest solid concentration and feed flow rate yielded the highest fine particle fraction and the smallest mass median aerodynamic diameter, owing to lower particle density and smaller geometric size