In overloaded heart the cardiomyocytes adapt to increased mechanical and neurohumoral stress by activation of hypertrophic program, resulting in morphological changes of individual cells and specific changes in gene expression. Accumulating evidence suggests an important role for the zinc finger transcription factor GATA-4 in hypertrophic agonist-induced cardiac hypertrophy. However, its role in stretch-induced cardiomyocyte hypertrophy is not known. We employed an in vitro mechanical stretch model of cultured cardiomyocytes and used rat B-type natriuretic peptide promoter as stretch-sensitive reporter gene. Stretch transiently increased GATA-4 DNA binding activity and transcript levels, which was followed by increases in the expression of B-type natriuretic peptide as well as atrial natriuretic peptide and skeletal ␣-actin genes. The stretch inducibility mapped primarily to the proximal 520 bp of the B-type natriuretic peptide promoter. Mutational studies showed that the tandem GATA consensus sites of the proximal promoter in combination with an Nkx-2.5 binding element are critical for stretch-activated B-type natriuretic peptide transcription. Inhibition of GATA-4 protein production by adenovirus-mediated transfer of GATA-4 antisense cDNA blocked stretch-induced increases in B-type natriuretic peptide transcript levels and the sarcomere reorganization. The proportion of myocytes with assembled sarcomeres in control adenovirus-infected cultures increased from 14 to 59% in response to stretch, whereas the values for GATA-4 antisense-treated cells were 6 and 13%, respectively. These results show that activation of GATA-4, in cooperation with a factor binding on Nkx-2.5 binding element, is essential for mechanical stretchinduced cardiomyocyte hypertrophy.

Background-The signaling cascades responsible for the activation of transcription factors in the hypertrophic growth of cardiac myocytes during hemodynamic overload are largely unknown. Several of the genes upregulated in the hypertrophied heart, including B-type natriuretic peptide (BNP) gene, are controlled by the cardiac-restricted zinc finger transcription factor GATA4. Methods and Results-An in vivo model of intravenous administration of arginine 8 -vasopressin (AVP) for up to 4 hours in conscious normotensive rats was used to study the signaling mechanisms for GATA activation in response to pressure overload. Gel mobility shift assays were used to analyze the trans-acting factors that interact with the GATA motifs of the BNP promoter. AVP-induced increase in mean arterial pressure was followed by a significant increase in the BNP and c-fos mRNA levels in both the endocardial and epicardial layers of the left ventricle, whereas GATA4 and GATA6 mRNA levels remained unchanged. Pressure overload within 15 to 60 minutes produced an increase in left ventricular BNP GATA4 but not GATA5 and GATA6 binding activity, and at 30 minutes a 2.2-fold increase (PϽ0.001) in GATA4 binding was noted. The mixed endothelin-1 ET A /ET B receptor antagonist bosentan but not the angiotensin II type 1 receptor antagonist losartan completely inhibited the pressure overload-induced increase in left ventricular BNP GATA4 binding activity. Bosentan alone had no statistically significant effect on GATA4 binding activity of the left ventricle in conscious animals. Conclusions-ET-

CNS-related symptoms and inflammation in the CSF are common in acute NE. Genetic properties of the host may predispose to CNS involvement. It does seem that pituitary injury and subsequent hormonal insufficiency may complicate the recovery.

ABSTRACT.Purpose: Diabetic retinopathy (DR) is the most common complication of diabetes and needs to be diagnosed early to prevent severe sight-threatening retinopathy. Digital photography with telemedicine connections is a novel way to deliver cost-effective, accessible screening to remote areas. Screening for DR in a mobile eye examination unit (EyeMo) is compared to traditional service models (i.e. local municipal services or a commercial service provider). The quality of images, delays from screening to treatment, the stage of DR, coverage of screening and the rate of visual impairment due to DR are evaluated. Methods: EyeMo utilizes telemedicine technology. The electronic databases of the hospital and information from the Finnish Register of Visual Impairment were used to determine delays and the rate of visual impairment. Results: Fourteen thousand eight hundred and sixty-six fundus photographs were taken in EyeMo in 2007-2011. Coverage reached 78% of potential clients. No DR was detected in 43%, mild background retinopathy in 23%, moderate or severe background retinopathy in 31% and proliferative retinopathy in 3% of the evaluations. The quality of images was higher (p < 0.01) and delays shorter (p < 0.01) in EyeMo as compared to traditional service models. The rate of visual impairment due to DR decreased by 86% in the area covered by EyeMo, and the change compared favourably to the situation in the entire Finland (p < 0.0005). Conclusion: EyeMo is a feasible model of telemedicine application for screening of DR. Effective screening and timely access to care may indeed have influenced the reduced rate of visual damage.

Ocular symptoms and disturbances are common in acute NE, and the symmetry of the ocular changes reflects the systemic nature of the disease. A decrease in IOP and myopic shift mainly due to thickening of the lens are evident in acute disease. The myopic shift only partially explains the visual disturbances supporting the possible multifactorial origin of the ocular findings in patients with NE.