SummaryCysteinyl leukotrienes (i.e. LTC4, LTD4), produced by activated leukocytes or by transcellular metabolism may act at different levels on vascular smooth muscle cells (VSMC) during inflammatory processes or atherosclerosis. We studied the effect of LTC4, LTD4, and LTE4 on the in vitro proliferation of rat VSMC, measured by [3H]-thymidine incorporation and cell count. LTD4 had a stronger stimulatory effect on [3H]-thymidine incorporation than LTC4, whereas LTE4 was inactive. The effect of LTD4 on [3H]-thymidine incorporation was dose-dependent, with the maximal activity at 10−6 M. The stimulatory activity of LTD4 was inhibited in a dose-dependent manner by MK-571, a specific LTD4 receptor antagonist. In addition, MK-571 (1 mg/kg/day) given for at least 1 day after injury in a model of balloon catheter injury of rat carotid artery, provided effective inhibition of myointimal VSMC proliferation, with a 58% reduction of 5-bromo-2’-deoxyuridine (BrdU) uptake in the neointima and 69% reduction of neointimal thickening. Our data support the importance of inflammatory mechanisms in the pathogenesis of atherosclerosis and suggest a possible role for cysteinyl leukotrienes, specifically LTD4, in the control of VSMC proliferation.

Hypertrophic Cardiomyopathy (HCM) is a pathological condition characterized by an abnormal thickening of the myocardium. When affecting the medio-basal portion of the septum, it is named Hypertrophic Obstructive Cardiomyopathy (HOCM) because it induces a flow obstruction in the left ventricular outflow tract. In any type of HCM, the myocardial function can become compromised, possibly resulting in cardiac death. In this study, we investigated with computational analysis the hemodynamics of patients with different types of HCM. The aim was quantifying the effects of this pathology on the intraventricular blood flow and pressure gradients, and providing information potentially useful to guide the indication and the modality of the surgical treatment (septal myectomy). We employed an image-based computational approach, integrating fluid dynamics simulations with geometric and functional data, reconstructed from standard cardiac cine-MRI acquisitions. We showed that with our approach we can better understand the patho-physiological behavior of intraventricular blood flow dynamics due to the abnormal morphological and functional aspect of the left ventricle. The main results of our investigation are: (a) a detailed patient-specific analysis of the blood velocity, pressure and stress distribution associated to HCM; (b) a computation-based classification of patients affected by HCM that can complement the current clinical guidelines for the diagnosis and treatment of HOCM.

The vascular microenvironment is the scale at which microvascular transport, interstitial tissue properties and cell metabolism interact. The vascular microenvironment has been widely studied by means of quantitative approaches, including multi‐physics mathematical models as it is a central system for the pathophysiology of many diseases, such as cancer. The microvascular architecture is a key factor for fluid balance and mass transfer in the vascular microenvironment, together with the physical parameters characterizing the vascular wall and the interstitial tissue. The scientific literature of this field has witnessed a long debate about which factor of this multifaceted system is the most relevant. The purpose of this work is to combine the interpretative power of an advanced multi‐physics model of the vascular microenvironment with state of the art and robust sensitivity analysis methods, in order to determine the factors that most significantly impact quantities of interest, related in particular to cancer treatment. We are particularly interested in comparing the factors related to the microvascular architecture with the ones affecting the physics of microvascular transport. Ultimately, this work will provide further insight into how the vascular microenvironment affects cancer therapies, such as chemotherapy, radiotherapy or immunotherapy.

We report on experiments aimed at the assessment of a new method for cell marking. This method combines superparamagnetic particles, commonly used for cell separation, linked to monoclonal antibodies, and biomagnetic instrumentation featuring an extremely high magnetic field sensitivity. The final goal of the method is to locate and estimate specific cell populations in the human body. In this experiment, quantitative features of the method are evaluated in vitro with lymphocytes and carcinoma cells. Comparison between estimation and direct counting of cells is quite satisfactory and motivates further development of the technique.

Hypertrophic Cardiomyopathy (HCM) is a pathological condition characterized by an abnormal thickening of the myocardium. When it affects the medio-basal portion of the septum, it is named Hypertrophic Obstructive Cardiomyopathy because it induces a flow obstruction in the left ventricle outflow tract, which may compromise the cardiac function and possibly lead to cardiac death. In this work, we investigate the hemodynamics of different HCM patients by means of computational hemodynamics, aiming at quantifying the effects of this pathology on blood flow and pressure gradients and thus providing clinical indications that may help diagnosis and the design of surgical treatment (septal myectomy). To this aim, we employ an enhanced version of an image-based computational pipeline proposed in a previous work, integrating fluid dynamics simulations with geometrical and functional data reconstructed from standard cine-MRI acquisitions. Blood flow is modelled as an incompressible Newtonian fluid, The corresponding Navier-Stokes equations are solved in a moving domain obtained from cine-MRI, whereas the valve leaflets are accounted for by a resistive method.