Novel ageing-biomarker discovery using data-intensive technologies.

Ageing is accompanied by many visible characteristics. Other biological and physiological markers are also well-described e.g. loss of circulating sex hormones and increased inflammatory cytokines. Biomarkers for healthy ageing studies are presently predicated on existing knowledge of ageing traits. The increasing availability of data-intensive methods enables deep-analysis of biological samples for novel biomarkers. We have adopted two discrete approaches in MARK-AGE Work Package 7 for biomarker discovery; (1) microarray analyses and/or proteomics in cell systems e.g. endothelial progenitor cells or T cell ageing including a stress model; and (2) investigation of cellular material and plasma directly from tightly-defined proband subsets of different ages using proteomic, transcriptomic and miR array. The first approach provided longitudinal insight into endothelial progenitor and T cell ageing. This review describes the strategy and use of hypothesis-free, data-intensive approaches to explore cellular proteins, miR, mRNA and plasma proteins as healthy ageing biomarkers, using ageing models and directly within samples from adults of different ages. It considers the challenges associated with integrating multiple models and pilot studies as rational biomarkers for a large cohort study. From this approach, a number of high-throughput methods were developed to evaluate novel, putative biomarkers of ageing in the MARK-AGE cohort.

[Comparative evaluation of blood flow velocity and pulsation curve in the posterior ciliary arteries supplying the choroid and the anterior part of the optic nerve]. / Porównawcza ocena predkosci przeplywu krwi i krzywej pulsacji w tetnicach rzeskowych tylnych zaopatrujqcych naczyniówke i przedniq czesc nerwu wzrokowego.

The speed of the blood-flow and the indexes of pulsation in posterior ciliary arteries supplying the choroid and the anterior optic nerve segment were evaluated in 30 healthy persons (60 eyes) aged 20-60 years with intraocular pressure values of 15-20 mm Hg and in 60 persons with primary glaucoma (120 eyes) aged 22-76 years. The investigations were carried out by the method of Doppler focused pulsating ultrasonography, with an 8.0 MHz probe; the instrument used was the TC-2-64 produced by EME (Germany). It was established that the main speed of the blood-flow in the choroid vessels in healthy people is higher than in the arteries supplying the anterior segment of the optic nerve. These speeds are respectively: 15.13 +/- 4.3 cm/s and 12.03 +/- 3.0 cm/s. The difference is statistically significant. The index of pulsation in the posterior ciliary arteries of both vascular systems does not differ in a statistically significant way and amounts respectively: 0.68 +/- 0.13 and 0.71 +/- 0.11. In patients with glaucoma it comes much earlier to a decrease of the speed of the blood-flow and to an increase of the indexes of pulsation together with a raise of the IOP in the system of the choroidal posterior ciliary arteries than in the anterior segment of the visual system.

[Acute insufficiency of the ophthalmic artery during occlusion of the internal carotid artery]. / Ostra niewydolnosc tetnicy ocznej w przebiegu niedroznosci tetnicy szyjnej wewnetrznej.

The authors present a case of a patients aged 41 years in whom the acute insufficiency of the ophthalmic artery was the first and single sign of an internal carotid occlusion. Doppler's pulsating focused ultrasonography showed to be an indispensable method which rendered possible a prompt diagnosis. Besides--this methods enables us to evaluate the dynamics of changes--the regeneration of the ciliary circulation with a compensatory perfusion of blood in some branches of the posterior ciliary arteries, the creation of collateral circulation from the ipsilateral external carotid artery through the ophthalmic artery with a reverse direction of perfusion in its extent and creation of a collateral circulation from the contralateral internal carotid through the anterior cerebral artery.

[Ciliary circulation in glaucoma complicated by diabetes mellitus]. / Krazenie rzeskowe w jaskrze skojarzonej z cukrzyca.

The speed of blood perfusion and the pulsation curve in ciliary arteries was checked by the method of Doppler's pulsating focused ultrasonography in 30 patients aged 46-78 years treated for glaucoma and diabetes. The data obtained were compared with analogical data in nondiabetic patients with glaucoma. It was established that the increase of the intraocular pressure caused a larger and earlier impairment of the regulating mechanism of the ciliary microcirculation in diabetic patients with glaucoma in comparison with the group of glaucomatous patients without diabetes. Particularly high values of pulsation indexes for ciliary arteries were observed in eyes with glaucoma and with diabetic changes rated as the fifth group of diabetic changes.

[Evaluation of blood perfusion velocity in the ophthalmic artery of glaucoma patients]. / Ocena predkosci przeplywu krwi w tetnicy ocznej u chorych z jaskra.

One hundred and ten examination were performed in 71 patients with primary glaucoma aged 21-81 years (217 eyes). The blood perfusion speed in the ophthalmic artery was measured in each patient by the ultrasonographic pulsating Doppler's method with a probe of a 2.0 MHz frequency by means of a TC-2-64 apparatus of EME production. The ophthalmic artery was examined by transorbital technique according to Spencer and Whisler on a 40-50 mm depth. The examined orbits were divided into 4 groups in dependence of the grade of the optic nerve atrophy. A lowering of over 50 per cent of the blood speed (below 10 cm/s) was found in 10.6 per cent of the eyes. Optic atrophy of the 3d and 4th grade was revealed in 70 p.c. of these eyes; the intraocular pressure remained in normal limits.

[Comparative evaluation of blood flow in posterior ciliary arteries in patients with glaucoma after surgical and pharmacological treatment]. / Porównawcza ocena przeplywu krwi w tetnicach rzeskowych tylnych u chorych z jaskra po leczeniu operacyjnym i farmakologicznym.

The perfusion of blood and pulsation curve in the posterior ciliary arteries in glaucomatous patients was evaluated before and after surgical and pharmacological treatment by Doppler's focused pulsating ultrasonographic method by means of a TC-2-64 apparatus with a probe of 8 MHz frequency. Twenty two patients were treated only conservatively, 27 by a surgical intervention. Before the installation of the treatment the intraocular pressure was higher than 35 mm Hg (averagely), the perfusion velocity was lowered and the indexes of pulsation elevated. After surgery the IOP was lowered--averagely beneath 15 mm Hg, the velocity of blood perfusion and pulsation indexes showed normal values in all the operated persons. After pharmacological treatment the IOP lowered but its mean value persisted in the 20-22 mm Hg range. Only in patients with early glaucomatous changes the blood perfusion remained normal with the intraocular pressure around 20 mm Hg. Instead in patients with advanced glaucomatous changes the velocity of the blood perfusion and the pulsation indexes showed pathological values with the IOP around 20 mm Hg.

[Correlation of blood flow in the posterior ciliary arteries with visual field changes and the appearance of the optic disc in patients with primary glaucoma]. / Korelacja przeplywu krwi w tetnicach rzeskowych tylnych ze zmianami w polu widzenia i wygladzie tarczy nerwu wzrokowego u chorych z jaskra pierwotna.

The velocity of blood perfusion and pulsation curve in posterior ciliary arteries was evaluated in 180 patients (476 eyes) with primary glaucoma, aged 22 to 81 years. The investigations were carried out by Doppler's focused pulsating ultrasonographic method with probes of 2 and 8 MHz frequency connected with a TC-2-64 apparatus (made by EME of German Federal Republic). The blood perfusion in the posterior ciliary arteries was compared with the changes in the visual field, in the aspect of the optic disc in patients with primary glaucoma and various levels of the IOP. In patients with primary glaucoma and advanced fundus changes (of 2-nd and 3-rd grade) the mechanisms of regulation of the ciliary circulation were normally functioning for quite a long time. In the period of breaking down of the mechanisms the changes in the visual field came into being.

[Evaluation of methods for reproducing doppler pulsating focused ultrasonography]. / Ocena powtarzalnosci metody ultrasonografii dopplerowskiej pulsacyjnej zogniskowanej.

In 53 patients treated for primary glaucoma the authors performed 2 examinations of blood perfusion in the posterior ciliary arteries during 2 following days. The patients had been examined in the period of a normalized IOP. The difference in the IOP between the first and second examination did not exceed 3.3 mm Hg and the difference in the mean general blood pressure--10 mm Hg. The blood perfusion in the posterior ciliary arteries was checked by Doppler's pulsating focused ultrasonography, by means of a TC-2-64 apparatus with a probe of 8.0 MHz frequency. The velocity of the blood perfusion, the pulsating index and the transmission of pulsation were evaluated. The differences between respective parameters characterizing the blood perfusion in the posterior ciliary arteries between the first and second examination were statistically insignificant, on the importance level of 0.01.

[Evaluation of blood flow velocity and pulsation curve in the posterior ciliary arteries in glaucoma]. / Ocena predkosci przeplywu krwi i krzywej pulsacji w tetnicach rzeskowych tylnych w jaskrze.

One hundred and thirty two examinations (253 eyes) were performed in 78 patients with primary glaucoma, 21-81 years of age. The blood speed and pulsation curve in the posterior ciliary arteries were evaluated by the ultrasonographic pulsating focused Doppler's method with a probe of 8 MHz frequency, connected to the TC-2-64 apparatus of EME production in eyes with a various grade of the optic nerve lesion and by various values of the IOP. It was shown that in eyes with early glaucomatous changes of the optic nerve the correct perfusion in the ciliary circulation is secured in the presence of a rise of the IOP up to 34 mm Hg. Instead in eyes with an advanced optic atrophy a normal perfusion in the ciliary arteries persists only when the IOP is lower than 15 mm Hg.