On the role of specific drug binding in modelling arterial eluting stents

In this paper we consider drug binding in the arterial wall following delivery by a drug-eluting stent. Whilst it is now generally accepted that a non-linear saturable reversible binding model is required to properly describe the binding process, the precise form of the binding model varies between authors. Our particular interest in this manuscript is in assessing to what extent modelling specific and non-specific binding in the arterial wall as separate phases is important. We study this issue by extending a recently developed coupled model of drug release and arterial tissue distribution, and comparing simulated profiles of drug concentration and drug mass in each phase within the arterial tissue

Capillary filling using Lattice Boltzmann Equations: the case of multi-phase flows

We present a systematic study of capillary filling for multi-phase flows by using mesoscopic lattice Boltzmann models describing a diffusive interface moving at a given contact angle with respect to the walls. We compare the numerical results at changing the density ratio between liquid and gas phases and the ratio between the typical size of the capillary and the interface width. It is shown that numerical results yield quantitative agreement with the Washburn law when both ratios are large, i.e. as the hydrodynamic limit of a infinitely thin interface is approached. We also show that in the initial stage of the filling process, transient behaviour induced by inertial effects and ``vena contracta'' mechanisms, may induce significant departure from the Washburn law. Both effects are under control in our lattice Boltzmann equation and in good agreement with the phenomenology of capillary filling

Modelling wall shear stress in small arteries using LBM and FVM

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.In this study a finite-volume discretisation of a Lattice Boltzmann equation over unstructured grids is presented. The new scheme is based on the idea of placing the unknown fields at the nodes of the mesh and evolve them based on the fluxes crossing the surfaces of the corresponding control volumes. The method, named unstructured Lattice Boltzmann equation (ULBE) is compared with the classical finite volume method (FVM) and is applied here to the problem of blood flow over the endothelium in small arteries. The study shows a significant variation and a high sensitivity of wall shear stress to the endothelium corrugation degree

Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma

\ua9 2024 Author(s).Osteosarcoma (OS) is a rare form of primary bone cancer, impacting approximately 3.4 7 106 individuals worldwide each year, primarily afflicting children. Given the limitations of existing cancer therapies, the emergence of nanotheranostic platforms has generated considerable research interest in recent decades. These platforms seamlessly integrate therapeutic potential of drug compounds with the diagnostic capabilities of imaging probes within a single construct. This innovation has opened avenues for enhanced drug delivery to targeted sites while concurrently enabling real-time monitoring of the vehicle\u27s trajectory. In this study, we developed a nanotheranostic system employing the layer-by-layer (LbL) technique on a core containing doxorubicin (DOXO) and in-house synthesized carbon quantum dots. By utilizing chitosan and chondroitin sulfate as polyelectrolytes, we constructed a multilayered coating to encapsulate DOXO and docetaxel, achieving a coordinated co-delivery of both drugs. The LbL-functionalized nanoparticles exhibited an approximate size of 150 nm, manifesting a predominantly uniform and spherical morphology, with an encapsulation efficiency of 48% for both drugs. The presence of seven layers in these systems facilitated controlled drug release over time, as evidenced by in vitro release tests. Finally, the impact of the LbL-functionalized nanoparticles was evaluated on U2OS and Saos-2 osteosarcoma cells. The synergistic effect of the two drugs was found to be crucial in inducing cell death, particularly in Saos-2 cells treated with nanoparticles at concentrations higher than 10 μg/ml. Transmission electron microscopy analysis confirmed the internalization of the nanoparticles into both cell types through endocytic mechanisms, revealing an underlying mechanism of necrosis-induced cell death

Effects of Orthogonal Rotating Electric Fields on Electrospinning Process

Electrospinning is a nanotechnology process whereby an external electric field is used to accelerate and stretch a charged polymer jet, so as to produce fibers with nanoscale diameters. In quest of a further reduction in the cross section of electrified jets hence of a better control on the morphology of the resulting electrospun fibers, we explore the effects of an external rotating electric field orthogonal to the jet direction. Through extensive particle simulations, it is shown that by a proper tuning of the electric field amplitude and frequency, a reduction of up to a $30 \%$ in the aforementioned radius can be obtained, thereby opening new perspectives in the design of future ultra-thin electrospun fibres. Applications can be envisaged in the fields of nanophotonic components as well as for designing new and improved filtration materials.Comment: 22 pages, 8 figure

reduced models for blood flow in curved vessels

Flow in curved pipes has been intensively investigated and applications to arterial o w are relevant both in physiological and pathological conditions. A comprehensive survey of the work devel- oped over almost one century from experimental and modelling point of view is carried out. Despite its complex nature, the 3D curved o w can be modeled, under reasonable assumptions, accounting only for 2, or even 1, geometrical dimensions. A couple of dieren t reduced models are presented and discussed here. Results of numerical simulations demonstrate the role of curvature in the formation of the secondary o w patterns and in the asymmetry of wall shear stresses. Both the above features can have important haemodynamical eects and clinical diagnostic velocimeters should be equipped with correction algorithms for the measurement bias induced by vessel curvature

Raising awareness of non-hodgkin lymphoma in HIV-infected adolescents: Report of 2 cases in the HAART era

Human immunodeficiency virus (HIV) chronically infected patients are at increased risk of developing non-Hodgkin lymphoma compared with the general population. Highly active antiretroviral therapy has had a dramatic effect on the natural history of HIV infection, reducing the incidence of acquired immunodeficiency syndrome-related non-Hodgkin lymphoma and improving overall survival. However, problems related to adherence to treatment, frequently experienced during adolescence, may increase the risk of acquired immunodeficiency syndrome-related cancers. Optimizing highly active antiretroviral therapy and monitoring noncompliant patients with persisting HIV replication should be considered by physicians who take care of these patients. We herein report 2 cases of relapsed/progressive Burkitt lymphoma in HIV vertically infected adolescents

Rapamycin promotes autophagy cell death of Kaposi’s sarcoma cells through P75NTR activation

The mammalian target of rapamycin inhibitor (mTOR-I) Rapamycin, a drug widely used in kidney transplantation, exerts important anti-cancer effects, particularly in Kaposi's Sarcoma (KS), through several biological interactions. In this in vivo and in vitro study, we explored whether the activation of the autophagic pathway through the low-affinity receptor for nerve growth factor, p75NTR, may have a pivotal role in the anti-cancer effect exerted by Rapamycin in S. Our Kimmunohistochemistry results revealed a significant hyper-activation of the autophagic pathway in KS lesions. In vitro experiments on KS cell lines showed that Rapamycin exposure reduced cell viability by increasing the autophagic process, in the absence of apoptosis, through the transcriptional activation of p75NTR via EGR1. Interestingly, p75NTR gene silencing prevented the increase of the autophagic process and the reduction of cell viability. Moreover, p75NTR activation promoted the upregulation of phosphatase and tensin homolog (PTEN), a tumour suppressor that modulates the PI3K/Akt/mTOR pathway. In conclusion, our in vitro data demonstrated, for the first time, that in Kaposi's sarcoma, autophagy triggered by Rapamycin through p75NTR represented a major mechanism by which mTOR inhibitors may induce tumour regression. Additionally, it suggested that p75NTR protein analysis could be proposed as a new potential biomarker to predict response to Rapamycin in kidney transplant recipients affected by Kaposi's sarcoma

CD40 cross-linking induces migration of renal tumor cell through nuclear factor of activated T cells (NFAT) activation

CD40 crosslinking plays an important role in regulating cell migration, adhesion and proliferation in renal cell carcinoma (RCC). CD40/CD40L interaction on RCC cells activates different intracellular pathways but the molecular mechanisms leading to cell scattering are not yet clearly defined. Aim of our study was to investigate the main intracellular pathways activated by CD40 ligation and their specific involvement in RCC cell migration. CD40 ligation increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH (2)-terminal kinase (JNK) and p38 MAPK. Furthermore, CD40 crosslinking activated different transcriptional factors on RCC cell lines: AP-1, NFkB and some members of the Nuclear Factor of Activated T cells (NFAT) family. Interestingly, the specific inhibition of NFAT factors by cyclosporine A, completely blocked RCC cell motility induced by CD40 ligation. In tumor tissue, we observed a higher expression of NFAT factors and in particular an increased activation and nuclear migration of NFATc4 on RCC tumor tissues belonging to patients that developed metastases when compared to those who did not. Moreover, CD40-CD40L interaction induced a cytoskeleton reorganization and increased the expression of integrin β1 on RCC cell lines, and this effect was reversed by cyclosporine A and NFAT inhibition. These data suggest that CD40 ligation induces the activation of different intracellular signaling pathways, in particular the NFATs factors, that could represent a potential therapeutic target in the setting of patients with metastatic RCC