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In the process of toxic accumulation of Amyloid-beta (Aβ) peptides in plaques, problems may arise in the exchange of nutrients across the blood–brain barrier (BBB) level and impaired brain clearance. These plaques are associated with the progression of Alzheimer's disease (AD). A four-compartmental model to describe the alteration of Aβ transport across BBB level and its accumulation in the brain is presented here. Furthermore, potential target mechanisms of therapy, to counteract the disease progression, are investigated using an'in silico' approach. A sensitivity analysis is presented to show the most important parameters on which to act in order to potentially bring pathological conditions back to non-pathological ones. [ABSTRACT FROM AUTHOR]

We developed a mathematical model of monochorionic twin pregnancies to simulate both the normal gestation and the Twin-Twin Transfusion Syndrome (TTTS), a disease in which the interplacental anastomose create a flow imbalance, causing one of the twin to receive too much blood and liquids, becoming hypertensive and polyhydramnios (the Recipient) and the other to become hypotensive and oligohydramnios (the Donor). This syndrome, if untreated, leads almost certainly to death one or both twins. We propose a compartment model to simulate the flows between the placenta and the fetuses and the accumulation of the amniotic fluid in the sacs. The aim of our work is to provide a simple but realistic model of the twins-mother system and to stress it by simulating the pathological cases and the related treatments, i.e. aminioreduction (elimination of the excess liquid in the recipient sac), laser therapy (removal of all the anastomoses) and other possible innovative therapies impacting on pressure and flow parameters. [ABSTRACT FROM AUTHOR]

Summary: We argue that volumetric growth dynamics of a solid cancer depend on the tumor system’s overall surface extension. While this at first may seem evident, to our knowledge, so far no theoretical argument has been presented explaining this relationship explicitly. In here, we therefore develop a conceptual framework based on the so-called ‘universal scaling law’ and then support our conjecture through evaluation with experimental data. Our concept suggests not only that cancer tissue invasion operates with relatively few and thin branches of mobile cells but also that this overall tumor surface expansion, and the diffusion of nutrients that it enables, can nourish the tumor prior to the impact of neovascularization. [Copyright &y& Elsevier]

Summary: Both the lack of nutrient supply and rising mechanical stress exerted by the microenvironment appear to be able to cause discrepancies between the actual, observed tumor mass and that predicted by West et al.’s [A general model for ontogenetic growth. Nature 2001;413:628–31] universal growth model. Using our previously developed model we hypothesize here, that (1) solid tumor growth and cell invasion are linked, not only qualitatively but also quantitatively, that (2) the onset of invasion marks the time point when the tumor’s cell density reaches a compaction maximum, and that (3) tumor cell invasion, reduction of mechanical confinement and angiogenesis can all contribute to an increase in the actual tumor mass m towards the level m W predicted by West et al.’s universal growth curve. These novel insights contribute to our understanding of tumorigenesis and thus may have important implications not only for experimental cancer research but also be of value for clinical purposes such as for predictions of tumor growth dynamics and treatment impact. [Copyright &y& Elsevier]

Vancomycin (Vm) currently represents the gold standard against methicillin-resistant Staphylococcus aureus (MRSA) infections. However, it is associated with low oral bioavailability, formulation stability issues, and severe side effects upon systemic administration. These drawbacks could be overcome by Vm topical administration if properly encapsulated in a nanocarrier. Intriguingly, nanobubbles (NBs) are responsive to physical external stimuli such as ultrasound (US), promoting drug delivery. In this work, perfluoropentane (PFP)-cored NBs were loaded with Vm by coupling to the outer dextran sulfate shell. Vm-loaded NBs (VmLNBs) displayed ∼300 nm sizes, anionic surfaces and good drug encapsulation efficiency. In vitro, VmLNBs showed prolonged drug release kinetics, not accompanied by cytotoxicity on human keratinocytes. Interestingly, VmLNBs were generally more effective than Vm alone in MRSA killing, with VmLNB antibacterial activity being more sustained over time as a result of prolonged drug release profile. Besides, VmLNBs were not internalized by staphylococci , opposite to Vm solution. Further US association promoted drug delivery from VmLNBs through an in vitro model of porcine skin. Taken together, these results support the hypothesis that proper Vm encapsulation in US-responsive NBs might be a promising strategy for the topical treatment of MRSA wound infections. [ABSTRACT FROM AUTHOR]

The aim of the study described here was to quantitatively assess thermal and mechanical effects of therapeutic ultrasound (US) by sonicating a joint-mimicking phantom, made of muscle-equivalent material, using clinical US equipment. The phantom contains two bone disks simulating a deep joint (treated at 1 MHz) and a superficial joint (3 MHz). Thermal probes were inserted in fixed positions. To test the mechanical (cavitational) effects, we used a latex balloon filled with oxygen-loaded nanobubbles; the dimensions of the oxygen-loaded nanobubbles were determined before and after sonication. Significant increases in temperature (up to 17°C) with fixed field using continuous waves were detected both in front of and behind the bones, depending on the US mode (continuous wave vs. pulsed wave) and on the treatment modality (fixed vs. massage). We found no significant differences in mechanical effects. Although limited by the in vitro design (no blood perfusion, no metabolic compensation), the results can be used to guide operators in their choice of the best US treatment modality for a specific joint. [ABSTRACT FROM AUTHOR]

Abstract: Doppler indices are widely used to assess normal versus pathologic haemodynamics. In obstetrics, the assessment of abnormal values in some critical compartments, such as the umbilical arteries (UA), may be crucial in the clinical management of growth-restricted foetuses. It was recently proposed that the UA should be sampled in their perivesical portion (PVC), i.e., where they surround the foetal urinary bladder. However, measurements at this site could be biased by the degree of curvature of the vessel due to bladder filling. We investigated this possibility in vivo and in vitro, i.e., measurements on rubber tubes at different radii of curvature Rc. There was significant dependence of the Doppler indices A/B and PI on the vessel curvature and insonation angle; in fact, we recorded errors of about 25% when Rc was 10 times larger than the radius of the vessel and about 100% when Rc was five times larger than the radius of the vessel. Therefore, measurements of the UA at the PVC site should only be performed when the foetal bladder is empty. (E-mail: caterina.guiot@unito.it) [Copyright &y& Elsevier]

Abstract: Ultrasound (US) energy combined with gas-filled microbubbles has been used for several years in medical imaging. This study investigated the ability of oxygen-loaded chitosan bubbles to exchange oxygen in the presence or in the absence of US. Oxygen delivery is enhanced by sonication and both frequency and time duration of US affected the exchange kinetics. [Copyright &y& Elsevier]