Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung

Aqueous humor enhances the proliferation of rat retinal precursor cells in culture, and this effect is partially reproduced by ascorbic acid.

Aqueous humor has been shown to influence the proliferation of various ocular cell types, but the effect on immature retinal cells is not known. Here, the effect of pig aqueous humor on the proliferation of rat retinal precursor cells (RPCs) was investigated. RPCs were prepared from embryonic day 19 Sprague-Dawley rats and cultured in the presence or absence of aqueous humor from healthy pigs along with a medium consisting of Dulbecco's modified Eagle's medium: Ham's F-12 medium, N2 supplement, and epidermal growth factor. Proliferation was quantified by [H-3] thymidine incorporation under different treatment conditions, and any associated morphological changes were noted. Potential active components of porcine aqueous humor were partially characterized by gel filtration chromatography, and the effect on RPC proliferation was determined. Results showed that adding 20% aqueous humor increased [H-3] thymidine incorporation by as much as 317%, as compared with controls. Aqueous supplementation also increased both the number and size of RPC spherical aggregates ("spheres") over the first 4 days, consistent with increased proliferative activity. Using gel filtration and the in vitro proliferation assay, the growth- promoting activity of aqueous humor was localized to two different molecular mass ranges, namely, around 30 kDa and less than 1 kDa. Ascorbic acid was present in the lower molecular mass fraction, and use of this molecule reproduced some, but not all, of the proliferative activity present in aqueous humor. These results highlight the potential role of soluble factors present in the cellular microenvironment with respect to modulation of endogenous progenitor cell activity.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000242696200018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Cell & Tissue EngineeringBiotechnology & Applied MicrobiologyOncologyCell BiologyHematologySCI(E)10ARTICLE122766-27752

Vitreous humor and albumin augment the proliferation of cultured retinal precursor cells.

Intravitreal injection is an important delivery route for studies involving the transplantation of various types of precursor cells to the retina; however, the effect on these cells of exposure to the vitreous microenvironment has not been specifically investigated. Here vitreous humor was evaluated for the potential to influence the proliferation of rat retinal precursor cells in vitro. Cells were isolated at embryonic day 19 and plated in standard proliferation medium in the presence or absence of fluid expressed from porcine vitreous humor. Cellular proliferation at different concentrations of vitreous fluid supplementation was quantified by using a 3 H-thymidine incorporation assay. Active components of vitreous fluid were partially characterized by gel filtration chromatography (GFC) and UV spectral analysis. The effect of each vitreous fraction on proliferation was determined as well. Results showed that addition of 20% vitreous fluid to primary rat retinal cultures significantly increased 3 H-thymidine incorporation compared with growth medium without vitreous supplementation. A vitreous fraction showing growth-promoting activity was localized to a molecular mass range < 1000 Da, consistent with ascorbic acid. Ascorbic acid was confirmed in vitreous fluid by UV spectral analysis. Growth-augmenting activity was present in higher molecular mass vitreous fractions, consistent with protein components. Albumin, the major protein in vitreous fluid, was found to augment proliferation. Because vitreous-associated augmentation of retinal precursor proliferation remains an epidermal growth factor-dependent phenomenon, the proliferative status of transplanted cells in the vitreous cavity is likely determined by a combination of factors. (c) 2008 Wiley-Liss, Inc.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000263079300020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701NeurosciencesSCI(E)3ARTICLE2495-5028

High Intensity Aerobic exercise training and Immune cell Mobilization in patients with lung cancer (HI AIM):a randomized controlled trial

BACKGROUND: The increasing role of exercise training in cancer care is built on evidence that exercise can reduce side effects of treatment, improve physical functioning and quality of life. We and others have shown in mouse tumor models, that exercise leads to an adrenalin-mediated increased influx of T and NK cells into the tumor, altering the tumor microenvironment (TME) and leading to reduced tumor growth. These data suggest that exercise could improve immune responses against cancer cells by increase immune cell infiltration to the tumor and potentially having an impact on disease progression. Additionally, there are data to suggest that infiltration of T and NK cells into the TME is correlates with response to immune checkpoint inhibitors in patients. We have therefore initiated the clinical trial HI AIM, to investigate if high intensity exercise can mobilize and increase infiltration of immune cells in the TME in patients with lung cancer. METHODS: HI AIM (NCT04263467) is a randomized controlled trial (70 patients, 1:1) for patients with non-small cell lung cancer. Patients in the treatment arm, receive an exercise-intervention consisting of supervised and group-based exercise training, comprising primarily intermediate to high intensity interval training three times per week over 6 weeks. All patients will also receive standard oncological treatments; checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Blood samples and biopsies (ultrasound guided), harvested before, during and after the 6-week training program, will form basis for immunological measurements of an array of immune cells and markers. Primary outcome is circulating NK cells. Secondary outcome is other circulating immune cells, infiltration of immune cells in tumor, inflammatory markers, aerobic capacity measured by VO(2) max test, physical activity levels and quality of life measured by questionnaires, and clinical outcomes. DISCUSSION: To our knowledge, HI AIM is the first project to combine supervised and monitored exercise in patients with lung cancer, with rigorous analyses of immune and cancer cell markers over the course of the trial. Data from the trial can potentially support exercise as a tool to mobilize cells of the immune system, which in turn could potentiate the effect of immunotherapy. TRIAL REGISTRATION: The study was prospectively registered at ClinicalTrials.gov on February 10(th) 2020, ID: NCT04263467. https://clinicaltrials.gov/ct2/show/NCT0426346