Reduced methylation of the thromboxane synthase gene is correlated with its increased vascular expression in preeclampsia

Preeclampsia is characterized by increased thromboxane and decreased prostacyclin levels, which predate symptoms, and can explain some of the clinical manifestations of preeclampsia, including hypertension and thrombosis. In this study, we examined DNA methylation of the promoter region of the thromboxane synthase gene (TBXAS1) and the expression of thromboxane synthase in systemic blood vessels of normal pregnant and preeclamptic women. Thromboxane synthase is responsible for the synthesis of thromboxane A(2), a potent vasoconstrictor and activator of platelets. We also examined the effect of experimentally induced DNA hypomethylation on the expression of thromboxane synthase in a neutrophil-like cell line (HL-60 cells) and in cultured vascular smooth muscle and endothelial cells. We found that DNA methylation of the TBXAS1 promoter was decreased and thromboxane synthase expression was increased in omental arteries of preeclamptic women as compared with normal pregnant women. Increased thromboxane synthase expression was observed in vascular smooth muscles cells, endothelial cells, and infiltrating neutrophils. Experimentally induced DNA hypomethylation only increased expression of thromboxane synthase in the neutrophil-like cell line, whereas tumor necrosis factor-α, a neutrophil product, increased its expression in cultured vascular smooth muscle cells. Our study suggests that epigenetic mechanisms and release of tumor necrosis factor-α by infiltrating neutrophils could contribute to the increased expression of thromboxane synthase in maternal systemic blood vessels, contributing to the hypertension and coagulation abnormalities associated with preeclampsia.     

Distribution of aerosols in murine obliterative bronchiolitis lungs by fluorescent imaging

ABSTRACT Background: Obliterative bronchiolitis (OB) is a major obstacle to the success of lung transplantation and is also a serious complication of hematopoietic stem cell transplant. It has few therapeutic options and respiratory delivery of potential therapeutic drugs is hindered by the narrowed and occluded airways. Methods: OB was induced in mice using an established protocol and lung function was assessed by plethysmograph. Mice were exposed to four different aerosols of aluminum phthalocyanine tetrasulfonic acid (AlPCS) that ranged in concentration and median particle size distribution (0.2-4.0?μm). The fluorescent intensity and number of pixels were measured for the trachea and lobes at two different compressional thicknesses. With analysis of the fluorescent intensity, the concentration and attenuation coefficient were estimated for each lobe and the trachea as well as individual pixels. The latter allowed generation of images reflective of the concentration. Results: Lungs/trachea from OB mice had lower deposition, which correlated with lung function measurements, and apparent greater variability in the intensity compared to controls. The estimated lung volumes measured by plethysmograph were not different between the OB group and controls; however, total inflational lung capacity was reduced in OB mice. Conclusions: Despite the variability in disease induction, there is a clear link between aerosol deposition and lung function, which was revealed by fluorescent imaging. The modulation of aerosol deposition in lungs with restrictive airway disease underscores the importance of tailoring aerosolization to optimize drug delivery.     

Participatory and persuasive telehealth

Technological advances in telehealth systems are primarily focused on sensing and monitoring. However, these systems are limited in that they only rely on sensors and medical devices to obtain vital signs. New research and development are urgently needed to offer more effective and meaningful interactions between patients, medical professionals and other individuals around the patients. Social networking with Web 2.0 technologies and methods can meet these demands, and help to develop a more complete view of the patient. Also many people, including the elderly, may be resistant to change, which can reduce the efficacy of telehealth systems. Persuasive technology and mechanisms are urgently needed to counter this resistance and promote healthy lifestyles. In this paper, we propose the participatory and persuasive telehealth system as a solution for these two limitations. By integrating connected health solutions with social networking and adding persuasive influence, we increase the chances for effective interventions and behavior alterations.