Prevalence, clinical characteristics and echocardiography parameters of non-resistant, resistant and refractory hypertension in Chinese.

OBJECTIVES: Refractory and resistant hypertension is defined as hypertension that is uncontrolled despite the use of multiple antihypertensives. The aim of the present study is to evaluate the prevalence, both in young and elderly, and the pattern of left ventricular hypertrophy (LVH) in South-Eastern Chinese patients with refractory, resistant and non-resistant hypertension. METHODS: A total of 1455 patients (age 60.3 ± 13.9, male 55.7%) with essential hypertension were recruited. Refractory hypertension was defined as uncontrolled blood pressure (systolic/diastolic, ≥140/90 mm Hg) on ≥5 antihypertensive drug classes. Resistant hypertension was defined as uncontrolled blood pressure (systolic/diastolic, ≥140/90 mm Hg) on 3 or <140/90 mm Hg on ≥4 antihypertensive classes. RESULTS: Among the total population, 1273 (87.4%) patients were considered non-resistant hypertension; 170 (11.7%) with resistant hypertension and 12 (0.8%) with refractory hypertension. The prevalence of the three groups of hypertension were similar between patients age <60 or ≥60. Patients with refractory hypertension had the most dilated LV dimension, greatest left ventricular mass index and highest prevalence of diastolic dysfunction than patients with resistant and non-resistant hypertension. In particular, all patients with refractory hypertension had either concentric or eccentric LVH. CONCLUSIONS: In South-Eastern Chinese patients, the prevalence of refractory and resistant hypertension was 0.8% and 11.7%, respectively. Furthermore, no difference was observed in the hypertensive patterns between patients age <60 and ≥60. Importantly, patients with refractory hypertension had the worst LV remodeling with all suffering from either concentric or eccentric hypertrophy.

Targeted delivery of GDNF through the blood-brain barrier by MRI-guided focused ultrasound.

Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), are promising therapeutic agents for neurodegenerative diseases. However, the application of GDNF to treat these diseases effectively is limited because the blood-brain barrier (BBB) prevents the local delivery of macromolecular therapeutic agents from entering the central nervous system (CNS). Focused ultrasound combined with microbubbles (MBs) using appropriate parameters has been previously demonstrated to be able to open the BBB locally and noninvasively. This study investigated the targeted delivery of GDNF MBs through the BBB by magnetic resonance imaging (MRI)-guided focused ultrasound. Evans Blue extravasation and histological examination were used to determine the optimum focused ultrasound parameters. Enzyme-linked immunosorbent assay was performed to verify the effects of GDNF bound on MBs using a biotin-avidin bridging chemistry method to promote GDNF delivery into the brain. The results showed that GDNF can be delivered locally and noninvasively into the CNS through the BBB using MRI-guided focused ultrasound combined with MBs under optimum parameters. MBs that bind GDNF combined with MRI-guided focused ultrasound may be an effective way of delivering neurotrophic factors directly into the CNS. The method described herein provides a potential means of treating patients with CNS diseases.

Treatment of atherosclerosis by transplantation of bone endothelial progenitor cells over-expressed paraoxonase-1 gene by recombinant adeno-associated virus in rat.

Endothelial dysfunction/loss is a key event in the development of vascular diseases, including native atherosclerosis (AS). Recent studies have shown that endothelial progenitor cells (EPCs) have the ability to repair endothelial cells that have been lost or damaged following AS. As a result, the therapy of transplanting EPCs is a promising option for the treatment of AS. However, the therapeutic effect on AS with only EPCs transplantation has not been satisfactory. The upregulation of those genes, which prevent the progress of AS in EPCs, is a novel therapeutic strategy for AS. Because it can reduce macrophage foam cell formation and protect endothelial cells from the oxidation of low-density lipoprotein (ox-LDL), paraoxonase-1 (PON1) gene is a candidate for gene therapy in AS. In this study, a recombinant adeno-associated virus (rAAV) vector carrying the human paraoxonase-1 (hPON1) gene (rAAV-PON1) was constructed, and endothelial progenitor cells (EPCs) transfected with rAAV-PON1 were transplanted into the atherosclerosis model of Sprague-Dawley rats (SD rats). The results of doppler ultrasound and histological analysis showed that the group transplanted with the hPON1 gene-transfected EPCs was superior to the group transplanted only with the EPCs and was also better than the group with hPON1 gene injection alone. The results indicated that rAAV-mediated hPON1 gene-transfected EPCs is a potentially valuable new tool in the treatment of atherosclerosis.