Anticancer Applications of Nanostructured Silica-Based Materials Functionalized with Titanocene Derivatives: Induction of Cell Death Mechanism through TNFR1 Modulation

A series of cytotoxic titanocene derivatives have been immobilized onto nanostructured silica-based materials using two different synthetic routes, namely, (i) a simple grafting protocol via protonolysis of the Ti-Cl bond; and (ii) a tethering method by elimination of ethanol using triethoxysilyl moieties of thiolato ligands attached to titanium. The resulting nanostructured systems have been characterized by different techniques such as XRD, XRF, DR-UV, BET, SEM, and TEM, observing the incorporation of the titanocene derivatives onto the nanostructured silica and slight changes in the textural features of the materials after functionalization with the metallodrugs. A complete biological study has been carried out using the synthesized materials exhibiting moderate cytotoxicity in vitro against three human hepatic carcinoma (HepG2, SK-Hep-1, Hep3B) and three human colon carcinomas (DLD-1, HT-29, COLO320) and very low cytotoxicity against normal cell lines. In addition, the cells' metabolic activity was modified by a 24-h exposure in a dose-dependent manner. Despite not having a significant effect on TNFα or the proinflammatory interleukin 1α secretion, the materials strongly modulated tumor necrosis factor (TNF) signaling, even at sub-cytotoxic concentrations. This is achieved mainly by upregulation of the TNFR1 receptor production, something which has not previously been observed for these systems.We gratefully acknowledge financial support from FEDER and the Ministerio de Economía y Competitividad, Spain (grant no. CTQ2015-66164-R) and the Romanian UEFISCDI Exploratory Research Project PN-III-P4-ID-PCE-2016-0870, IMPRESS.We would also like to thank Universidad Rey Juan Carlos and Banco de Santander for supporting our Research Group of Excellence QUINANOAP. Finally, we thank D. Pérez for valuable discussion and S. Carralero and C. Forcé for their assistance with solid-state NMR experiments

Farmacia

The aim of the present study was to evaluate the pharmaceutical market of analgesic medicines in Romania during 2011 - 2015. A retrospective descriptive analysis was conducted on sales data provided by IQVIA (formerly IMS Health). Data corresponded to the volume of analgesic sales in hospital and retail pharmacies, split up in units and value (EUR), in prescription only (POM) and over-the-counter (OTC) medication and by region. Data was estimated to cover 95% of the Romanian market. From 2011 to 2015, the analgesic pharmaceutical market increased by 18.7% in value and by 6.1% in units. It was mainly assured by the retail distribution channel (95%), both for OTC and POM. The highest sales (6.3 units/capita, 12.3 EUR/capita) were found for the capital, Bucharest, while the lowest for counties of the North-East region of Romania (3.5 units/capita, 6.0 EUR/capita). In the context of an increasing analgesic market, programs that promote rational use of these medicines should be a priority at present for the Romanian healthcare system

EVALUATION OF CAROTID CALCIFICATIONS IN AMBULATORY DIALYSIS PATIENTS

Vascular calcification and atherosclerosis are commonly associated with chronic terminal kidney disease (BCRT). The aim of the present study was to evaluate ultrasound the prevalence of calcifications and carotid plaques in BCRT patients treated with hemodialysis (HD), and to investigate the potential risk factors. The current observational-prospective study included 203 patients with BCRT, monitored for 48.5 ± 19.0 months and treated by hemodialysis in Arad county. The main etiologies for BCRT were chronic glomerulonephritis in 32% of cases and diabetes in 22% of cases. 43.84% of patients had a mean carotid IMT value ≥ 0.9. Carotid vascular calcification was found in 175 patients (86.20%), most calcifications being located at the level of the carotid bifurcation on the posterior wall. 105 carotid plaques have determined stenosis of the vessel's diameter. The total number of carotid plaques and plaques as well as the average value of carotid IMT were associated with age. Vascular calcifications were directly associated with the presence of diabetes. A linear association relation between vascular calcifications and carotid plaques was found, the correlation coefficient being equal to 0.73. Cardiovascular mortality was most strongly associated with the total number of carotid calcifications. Ultrasound remains the only readily available technique, capable of highlighting the non-calcified plaque. Highlighting the vascular calcifications and the intuition of the pathophysiological mechanisms that contribute to their appearance may be factors influencing the therapeutic behavior applied to dialysis patients