Risultati terapeutici della luto-balneoterapia alle Terme di Casciana nella psoriasi

Come specialisti in affezioni a carico dell’apparato cutaneo, ci troviamo non di rado a dover sospendere, per alcuni pazienti affetti da psoriasi, le terapie in atto, sia per scarsa rispondenza, sia per un necessario periodo di riposo farmacologico (wash out), sia per comparsa di effetti collaterali. La sola alternativa non farmacologica oggi disponibile è quella di inviare i soggetti ad un ciclo di cure termali a Comano (Trento), unica stazione termale realmente in grado di trattare pazienti psoriasici. Il costo per il Servizio Sanitario Regionale e l’impegno per il paziente, costretto ad allontanarsi da casa per almeno due settimane, non ci sembrano parametri da sottovalutare. Riteniamo per questo che sia più che giustificato il tentativo di creare alle Terme di Casciana (Pisa) un secondo polo nazionale indirizzato al trattamento del dermo-paziente. Il nostro non è un tentativo ipotetico, poiché i risultati sperimentali attenuti con altre indagini confermano la validità dell’ipotesi. Oltre a un abbattimento dei costi per la terapia può essere aggiunto il vantaggio che la Toscana può divenire un polo di attrazione per tutti quei soggetti che ora trovano in Comano l’unico sito di riferimento

Iron Oxide Nanoconstructs for the Ablation Therapy in Diseased Tissues: Systemic Analysis and Rational Design

A plethora of magnetic nanoparticles has been developed and investigated under different alternating magnetic fields (AMF) for the hyperthermic treatment of malignant tissues. Yet, clinical applications of magnetic hyperthermia are sporadic, mostly due to the low energy conversion efficiency of the metallic nanoparticles and the high tissue concentrations required. In this work the hyperthermic performance of commercially available formulations of superparamagnetic iron oxide nanoparticles (SPIOs) are studied. These nanoparticles are operated under a broad range of AMF conditions. Using a computational model for heat transport in a biological tissue, the minimum requirements for local hyperthermia (Ttissue > 42°C) and thermal ablation (Ttissue > 50°C) are derived in terms of particles concentrations, operating AMF conditions and blood perfusion. The resulting maps can be used to rationally design hyperthermic treatments and identifying the proper route of administration – systemic versus intratumor injection – depending on the magnetic and biodistribution properties of the nanoparticles. Moreover, Iron oxide nanoparticles (IOs) are intrinsically theranostic agents that could be used for magnetic resonance imaging (MRI) and local hyperthermia or tissue thermal ablation. Yet, effective hyperthermia and high MR contrast have not been achieved with the same nanoparticle. In the attempt to optimize and fully employ their potentiality in a single particle formulation, magnetic nanoconstructs are obtained by confining multiple, nanocubes within a polymeric (deoxy-chitosan) matrix. The resulting nanoconstructs – Magnetic NanoFlakes (MNFs) – exhibit a hydrodynamic diameter of 156 ± 3.6 nm, with a polydispersity index of about 0.2, and are stable in PBS up to 7 days. Upon exposure to an alternating magnetic fields they provide a specific absorption rate (SAR) about 60-fold than the single Nanocubes alone. The same nanoconstructs provide a remarkably high transversal relaxivity of 500 (mM s)-1, comparable with the hghest values avaiable in the current literature. Moreover, MNFs in phisiological relevant flow conditions shown potentials in magnetic targetted using an external static magnet. The MNFs represent a first step towards the realization of nanoconstructs with superior relaxometric and ablation properties for more effective theranostics

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE-/-Mice via Nanoformulated Lipid-Methotrexate Conjugates

Macrophage inflammation and maturation into foam cells, following the engulfment of oxidized low-density lipoproteins (oxLDL), are major hallmarks in the onset and progression of atherosclerosis. Yet, chronic treatments with anti-inflammatory agents, such as methotrexate (MTX), failed to modulate disease progression, possibly for the limited drug bioavailability and plaque deposition. Here, MTX-lipid conjugates, based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), were integrated in the structure of spherical polymeric nanoparticles (MTX-SPNs) or intercalated in the lipid bilayer of liposomes (MTX-LIP). Although, both nanoparticles were colloidally stable with an average diameter of ∼200 nm, MTX-LIP exhibited a higher encapsulation efficiency (>70%) and slower release rate (∼50% at 10 h) compared to MTX-SPN. In primary bone marrow derived macrophages (BMDMs), MTX-LIP modulated the transcellular transport of oxLDL more efficiently than free MTX mostly by inducing a 2-fold overexpression of ABCA1 (regulating oxLDL efflux), while the effect on CD36 and SRA-1 (regulating oxLDL influx) was minimal. Furthermore, in BMDMs, MTX-LIP showed a stronger anti-inflammatory activity than free MTX, reducing the expression of IL-1β by 3-fold, IL-6 by 2-fold, and also moderately of TNF-α. In 28 days high-fat-diet-fed apoE-/- mice, MTX-LIP reduced the mean plaque area by 2-fold and the hematic amounts of RANTES by half as compared to free MTX. These results would suggest that the nanoenhanced delivery to vascular plaques of the anti-inflammatory DSPE-MTX conjugate could effectively modulate the disease progression by halting monocytes' maturation and recruitment already at the onset of atherosclerosis

Dynamic markers based on blood perfusion fluctuations for selecting skin melanocytic lesions for biopsy

Skin malignant melanoma is a highly angiogenic cancer, necessitating early diagnosis for positive prognosis. The current diagnostic standard of biopsy and histological examination inevitably leads to many unnecessary invasive excisions. Here, we propose a non-invasive method of identification of melanoma based on blood flow dynamics. We consider a wide frequency range from 0.005 – 2 Hz associated with both local vascular regulation and effects of cardiac pulsation. Combining uniquely the power of oscillations associated with individual physiological processes we obtain a marker which distinguishes between melanoma and atypical nevi with sensitivity of 100% and specificity of 90.9%. The method reveals valuable functional information about the melanoma microenvironment. It also provides the means for simple, accurate, in vivo distinction between malignant melanoma and atypical nevi, and may lead to a substantial reduction in the number of biopsies currently undertaken

Targeting Inflammation With Nanosized Drug Delivery Platforms in Cardiovascular Diseases: Immune Cell Modulation in Atherosclerosis

Atherosclerosis (AS) is a disorder of large and medium-sized arteries; it consists in the formation of lipid-rich plaques in the intima and inner media, whose pathophysiology is mostly driven by inflammation. Currently available interventions and therapies for treating atherosclerosis are not always completely effective; side effects associated with treatments, mainly caused by immunodepression for anti-inflammatory molecules, limit the systemic administration of these and other drugs. Given the high degree of freedom in the design of nanoconstructs, in the last decades researchers have put high effort in the development of nanoparticles (NPs) formulations specifically designed for either drug delivery, visualization of atherosclerotic plaques, or possibly the combination of both these and other functionalities. Here we will present the state of the art of these subjects, the knowledge of which is necessary to rationally address the use of NPs for prevention, diagnosis, and/or treatment of AS. We will analyse the work that has been done on: (a) understanding the role of the immune system and inflammation in cardiovascular diseases, (b) the pathological and biochemical principles in atherosclerotic plaque formation, (c) the latest advances in the use of NPs for the recognition and treatment of cardiovascular diseases, (d) the cellular and animal models useful to study the interactions of NPs with the immune system cells

A review on the heat and mass transfer phenomena in nanofluid coolants with special focus on automotive applications

Engineered suspensions of nanosized particles (nanofluids) are characterized by superior thermal properties. Due to the increasing need for ultrahigh performance cooling in many industries, nanofluids have been widely investigated as next-generation coolants. However, the multiscale nature of nanofluids implies nontrivial relations between their design characteristics and the resulting thermo-physical properties, which are far from being fully understood. This pronounced sensitivity is the main reason for some contradictory results among both experimental evidence and theoretical considerations presented in the literature. In this Review, the role of fundamental heat and mass transfer mechanisms governing thermo-physical properties of nanofluids is assessed, from both experimental and theoretical point of view. Starting from the characteristic nanoscale transport phenomena occurring at the particle-fluid interface, a comprehensive review of the influence of geometrical (particle shape, size and volume concentration), physical (temperature) and chemical (particle material, pH and surfactant concentration in the base fluid) parameters on the nanofluid properties was carried out. Particular focus was devoted to highlight the advantages of using nanofluids as coolants for automotive heat exchangers, and a number of design guidelines was suggested for balancing thermal conductivity and viscosity enhancement in nanofluids. This Review may contribute to a more rational design of the thermo-physical properties of particle suspensions, therefore easing the translation of nanofluid technology from small-scale research laboratories to large-scale industrial applications