Ruthenium(III) complexes entrapped in liposomes with enhanced cytotoxic and anti-metastatic properties

Metal-based anticancer drugs are pivotal in the fight against cancer pathologies. Since 1978 cis-platin was licensed for medical treatment of a wide number of tumor pathologies(1). However its chemiotherapic use is strongly limited by many and severe side effects and acquired tumor resistance. Since these limitations could be overcome by other metal complexes, in the last thirty years ruthenium compounds have been tested showing a remarkable antitumoral and antimetastatic activity associated with a lower toxicity. A hexacoordinate Ru(III) complex (NAMI-A) is currently undergoing advanced clinical evaluation (2). All data indicate that NAMI-A acts as a pro-drug, but the integrity of ruthenium complexes is essential to store the cytotoxic activity. In this scenario the condition of administration of ruthenium drugs are crucial to exploit their anticancer activity (3). In the last years innovative strategies have been produced to vehicle ruthenium ions in tumor cells like aggregates. This study aims to incorporate the ruthenium complexes in the inner aqueous compartment of liposomes and to test biological properties of two NAMI-A like pyridine derivatives. Specifically, we have investigated the pyridine derivatives of the sodium-compensated analogue of NAMI-A, Na[trans-RuCl4(pyridine)(DMSO)] (NAMI-Pyr) and Na[trans-RuCl4(Pytri)(DMSO)] (NAMI-Pytri). In thelatter complex the pyridine ligand is functionalized with a sugar moiety so as to increase biocompatibility and the ability to cross the cell membrane. The stability of the complexes was studied and compared in solution at different pH following UV-VIS spectra. Lipid formulations based on Egg PC were prepared adding Cholesterol, DSPE-PEG2000 joining molar ratio 57/38 /5% w/w respectively in MeOH/CHCl3 (50/50 v/v) mixture and hydrated with 0.9% w/w of NaCl. This composition was selected to reproduce analog supramolecular aggregates in clinical use to vehicle doxorubicin (Doxil). Ruthenium complexes were loaded into liposomes using the passive equilibration loading method. Full drug containing liposomes were structurally characterized by dynamic light scattering (DLS) measurements. Data indicate the formation of stable aggregates with size and shape in the right range for in vivo applications. The amount of encapsulated ruthenium complexes was quantified by means of ICP-AES. Stability and drug release properties of ruthenium containing liposomes were confirmed in buffer. The growth inhibitory effects of both liposomal and free complexes drug were tested on prostate cancer cells (PC3). Preliminary results show high cytotoxic effect of ruthenium complexes delivered by supramolecular aggregates with respect to free complexes drug

Reverse engineering of mandible and prosthetic framework: Effect of titanium implants in conjunction with titanium milled full arch bridge prostheses on the biomechanics of the mandible.

This study aimed at investigating the effects of titanium implants and different configurations of full-arch prostheses on the biomechanics of edentulous mandibles. Reverse engineered, composite, anisotropic, edentulous mandibles made of a poly(methylmethacrylate) core and a glass fibre reinforced outer shell were rapid prototyped and instrumented with strain gauges. Brånemark implants RP platforms in conjunction with titanium Procera one-piece or two-piece bridges were used to simulate oral rehabilitations. A lateral load through the gonion regions was used to test the biomechanical effects of the rehabilitations. In addition, strains due to misfit of the one-piece titanium bridge were compared to those produced by one-piece cast gold bridges. Milled titanium bridges had a better fit than cast gold bridges. The stress distribution in mandibular bone rehabilitated with a one-piece bridge was more perturbed than that observed with a two-piece bridge. In particular the former induced a stress concentration and stress shielding in the molar and symphysis regions, while for the latter design these stresses were strongly reduced. In conclusion, prosthetic frameworks changed the biomechanics of the mandible as a result of both their design and manufacturing technology

Coronary Artery By-Pass Grafting in Patient With Paroxysmal Nocturnal Hemoglobinuria (Case Report)

Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell disease that presents with haemolytic anaemia, thrombosis and bone marrow failure. We report a case of a 51-year-old male with a history of PNH in treatment with Eculizumab admitted to our Hospital for acute chest pain and dyspnoea. The diagnosis was a triple vessel disease and patient was scheduled for coronary artery bypass grafting surgery. To balance the risk between thrombosis and bleeding in this particular clinical setting, we decided to use thromboelastography (TEG) as point of care solution and we used the R parameter as the target of our anticoagulant therapy. The R parameter between 11 and 14 sec can be used as a target value to balance the risk; in addition, there was no evidence of acute hemolysis during the surgery and supplemental dose of Eculizumab was administered in order to minimize any potential exacerbation of intravascular hemolysis

Аортокоронарное шунтирование у пациента с пароксизмальной ночной гемоглобинурией (клиническое наблюдение)

Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell disease that presents with haemolytic anaemia, thrombosis and bone marrow failure. We report a case of a 51-year-old male with a history of PNH in treatment with Eculizumab admitted to our Hospital for acute chest pain and dyspnoea. The diagnosis was a triple vessel disease and patient was scheduled for coronary artery bypass grafting surgery. To balance the risk between thrombosis and bleeding in this particular clinical setting, we decided to use thromboelastography (TEG) as point of care solution and we used the R parameter as the target of our anticoagulant therapy. The R parameter between 11 and 14 sec can be used as a target value to balance the risk; in addition, there was no evidence of acute hemolysis during the surgery and supplemental dose of Eculizumab was administered in order to minimize any potential exacerbation of intravascular hemolysis.Пароксизмальная ночная гемоглобинурия (ПНГ) — клональное заболевание гемопоэтических стволовых клеток, которое проявляется гемолитической анемией, тромбозами и недостаточностью функции костного мозга. Пациент мужского пола 51 года с ПНГ в анамнезе, по поводу которой он получал лечение экулизумабом, поступил в больницу с жалобами на острую боль в грудной клетке и одышку. Поставили диагноз трехсосудистого поражения коронарного русла, по поводу чего запланировали проведение аортокоронарного шунтирования. Для того, чтобы избежать развития как тромбоза, так и кровотечения, в данном сложном клиническом случае, решили провести пациенту тромбоэластографическое исследование и использовать параметр R в качестве целевого при проведении антикоагулянтной терапии. При поддержании значений данного параметра в рамках 11-14 сек можно достичь оптимального баланса между риском тромбоза и кровотечения. Кроме того, во время оперативного вмешательства не наблюдали острого гемолиза, а для уменьшения риска развития внутрисосудистого гемолиза дополнительно назначили экулизумаб

The Impact of Long-Term Exposure to Space Environment on Adult Mammalian Organisms: A Study on Mouse Thyroid and Testis

Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis

Gli Ottomani e il bagno turco: il ḥammām nel Seyāḥatnāme di Evliyā Çelebi

Verso la metà del XVII secolo, il famoso viaggiatore ottomano Evliyā Çelebi (1611- ca. 1685), dopo aver trascorso circa 40 anni viaggiando in lungo e largo in tutto l’Impero ottomano compilò una lunga opera in dieci volumi nota come Seyāḥatnāme (Libro dei viaggi). Tra le molteplici osservazioni e descrizioni raccolte in quest’opera numerosi sono i riferimenti agli edifici pubblici presenti nelle varie località che Evliyā Çelebi aveva visitato. Una edificio che il viaggiatore immancabilmente descrive è il ḥammām. Nonostante tutti i limiti che il Seyāḥatnāme può avere come fonte storica, il modo in cui Evliyā Çelebi descrive i ‘bagni turchi’ offre una prospettiva interna e senz’altro meno nota su questa istituzione e più in generale sulla società ottomana della metà del XVII secolo

Shafak, Elif

A biographical profile of the Turkish writer Elif Shafak containing an outline of her major works

Nazlı Eray

A biographical profile of the Turkish writer Nazlı Eray containing an outline of her major works