The Northern Finland Birth Cohort Eye Study: Design and baseline characteristics.

BACKGROUND: To describe the rationale and design of the Northern Finland Birth Cohort (NFBC) Eye Study. METHODS: The NFBC Eye Study is a randomised prospective cohort study. The original NFBC study population consists of 12058 subjects born in the region of Lapland and the Province of Oulu. A postal questionnaire covering extensively the medical and socioeconomical background was sent to the 10300 subjects of the NFBC alive and residing in Finland. For the NFBC eye study the subjects were randomised to the screening group (50%) and the control group (50%). The screening protocol includes the following tests: automated and manifest refraction, best corrected visual acuity, central corneal thickness, intraocular pressure, Humphrey 24-2 perimetry, stereoscopic optic nerve head (ONH) and retinal nerve fibre layer (RNFL) photography and imaging with Scanning Laser Ophthalmoscopy (HRT), Scanning Laser Polarimetry (GDx) and Optical Coherence Tomography (OCT).Two ophthalmologists evaluate the ONH and RNFL photographs and the visual fields independently. All suspected glaucoma cases are re-evaluated by two independent glaucoma experts. HRT, GDx and OCT findings are assessed separately. In the future, both groups (100%) will be examined. The effectiveness and the cost-effectiveness of glaucoma screening will be calculated. The response rate of the questionnaire was 67% (n = 6855) and 871 randomised subjects had undergone the eye screening protocol by the end of April 2013. DISCUSSION: The trial is designed to address the following questions: what is the best combination of diagnostic tests for detecting glaucoma in an unscreened population, what are the benefits and disadvantages of the screening to the individual and the society and is glaucoma screening both effective and cost-effective. The prevalence, incidence and risk factors of glaucoma and other eye diseases will be evaluated, as well as their impact on quality of life.

Adrenomedullin modulates hemodynamic and cardiac effects of angiotensin II in conscious rats.

We examined whether adrenomedullin, a vasoactive peptide expressed in the heart, modulates the increase in blood pressure, changes in systolic and diastolic function, and left ventricular hypertrophy produced by long-term administration of ANG II or norepinephrine in rats. Subcutaneous administration of adrenomedullin (1.5 microg.kg(-1).h(-1)) for 1 wk inhibited the ANG II-induced (33.3 microg.kg(-1).h(-1) sc) increase in mean arterial pressure by 67% (P < 0.001) but had no effect of norepinephrine-induced (300 microg.kg(-1).h(-1) sc) hypertension. Adrenomedullin enhanced the ANG II-induced improvement in systolic function, resulting in a further 9% increase (P < 0.01) in the left ventricular ejection fraction and 19% increase (P < 0.05) in the left ventricular fractional shortening measured by echocardiography, meanwhile norepinephrine-induced changes in systolic function were remained unaffected. Adrenomedullin had no effect on ANG II- or norepinephrine-induced left ventricular hypertrophy or expression of hypertrophy-associated genes, including contractile protein and natriuretic peptide genes. The present study shows that adrenomedullin selectively suppressed the increase in blood pressure and augmented the improvement of systolic function induced by ANG II. Because adrenomedullin had no effects on ANG II- and norepinephrine-induced left ventricular hypertrophy, circulating adrenomedullin appears to act mainly as a regulator of vascular tone and cardiac function.

Mechanisms regulating adrenomedullin gene expression in the left ventricle: role of mechanical load.

Adrenomedullin (AM) may function as an autocrine and/or paracrine factor in the heart, but the exact mechanisms regulating cardiac AM gene expression are unknown. The aim of the present study was to characterize the role of mechanical load in regulating gene expression of AM by using two hypertensive rat strains as experimental models. Acute pressure overload was produced by arginine(8)-vasopressin (AVP, 0.05 microg/kg/min, i.v.) infusion in conscious spontaneously hypertensive rats (SHR) and double transgenic rats (dTGR) harboring both the human renin and angiotensinogen genes and in their respective normotensive strains. A significant increase in left ventricular AM mRNA levels was seen in the left ventricles of all rat strains, the increase being augmented in hypertensive strains. Direct left ventricular wall stretch in isolated, perfused rat heart preparation also activated AM gene expression. However, stretching of cultured neonatal ventricular myocytes resulted in inhibition of AM gene expression, and stretch also blocked hypoxia-induced increase in AM gene expression. The present study shows that cardiac AM gene expression is upregulated in response to pressure overload and that this upregulation may be mediated via cell types other than cardiac myocytes.