Andrea Facskó

University of Szeged, Algyő, Csongrád, Hungary

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Publications (33)71.77 Total impact

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    ABSTRACT: Autophagy and apoptosis function as important early cellular defense mechanisms in infections and other diseases. The outcome of an infection is determined by a complex interplay between the pathogenic microorganism and these intracellular pathways. To better understand the cytopathogenicity of Herpes simplex virus types 1 and 2 (HSV-1 and -2), we studied the effect of these viruses on the autophagic and apoptotic processes in the SIRC corneal cell line. Infection with the KOS strain of HSV-1 and a wild-type strain of HSV-2 enhanced autophagosome formation, triggered cytoplasmic acidification, increased LC3B lipidation and elevated the ratio of apoptotic cells. The autophagy inhibitor bafilomycin A1 triggered a significant increase in the apoptotic responses of HSV-1- and HSV-2-infected cells. Thus, both HSV types affect autophagy and apoptosis in a coordinated fashion, and autophagy plays cytoprotective role in HSV-infected cells via antagonizing apoptosis. Together these data implicate autophagy in the pathogenic mechanism of herpetic keratitis.
    Journal of Biosciences 07/2014; 39:1-10. · 1.76 Impact Factor
  • Acta ophthalmologica 07/2014; · 2.44 Impact Factor
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    ABSTRACT: Purpose. To investigate the osmotic water permeability of lacrimal gland (LG) duct epithelium by means of calculation of filtration permeability and to investigate LG ductal fluid secretion. Methods. Experiments were performed on isolated rabbit LG duct segments maintained in short term culture. Osmotically determined fluid movement or fluid secretion into the closed intraluminal space of cultured LG interlobular ducts was analyzed using video microscopic technique. Results. The end of the LG ducts sealed after overnight incubation forming a closed luminal space. For the calculation of osmotic water permeability, ducts were initially perfused with isotonic HEPES-buffered solution, and then with hypotonic HEPES-buffered solution. Filtration permeability was calculated from the initial slope of the relative volume increase. Secretory responses to carbachol or to forskolin stimulation were also investigated. Forskolin stimulation resulted in a rapid and sustained secretory response in both solutions. Forskolin-stimulated fluid secretion was completely inhibited by bumetanide both in HEPES-buffered and in HCO3-/CO2- buffered solutions, suggesting the central role of Na+-K+-2Cl- cotransporter type 1 (NKCC1). Administration of carbachol initiated a rapid but short secretory response in both HEPES buffered and in HCO3-/CO2 buffered solutions. Atropine completely abolished the carbachol-evoked fluid secretion. Conclusions. New method was introduced to investigate LG duct function. Water permeability of rabbit LG duct epithelium was measured by calculating filtration permeability. Fluid secretion of LG duct cells induced by carbachol or forskolin was also demonstrated. These results provide calculated values of lacrimal duct osmotic permeability and direct experimental evidence of LG duct fluid secretion.
    Acta ophthalmologica 06/2014; · 2.44 Impact Factor
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    ABSTRACT: Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.
    BioMed research international. 01/2014; 2014:768026.
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    ABSTRACT: Introduction: Bardet-Biedl syndrome is characterised by retinal dystrophy, polydactily, obesity and slow mental development. Aim: The aim of the authors was to present ophthalmologic signs and symptoms of the syndrome. Method: Between 1980 and 2010, 4 children with Bardet-Biedl syndrome were evaluated at the Department of Ophthalmology, University of Szeged, Szeged, Hungary. Their age at the first visit was between 1 and 10 years. Basic ophthalmological and electrophysiological evaluation, as well as orthoptic examinations were performed. Results: In two cases the electroretinographic curves were subnormal, and in two cases the electroretinographic curves showed no elevation. In the 4 children abnormal electroretinographic curves appeared at the ages of 1, 5, 10, and 18 years. Pigmentary changes on the periphery of the retina were detected in two cases. Conclusions: The different signs and symptoms of Bardet-Biedl syndrome may manifest at different ages. Electrophysiological changes failed to correlate with retinal alterations is these patients. Orv. Hetil., 2013, 154(52), 2071-2077.
    Orvosi Hetilap 12/2013; 154(52):2071-7.
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    ABSTRACT: : The release of different cytokines and mediators in tears of patients with keratoconus (KC) wearing contact lenses (CLs) may contribute to the pathology of KC. : Cohort study was established in patients with KC wearing rigid gas permeable (RGP) CL (group I), patients with ametropia wearing silicone hydrogel (Si-Hi) CL (group II) and ametropic patients wearing RGP CL (group III). : Our findings indicate that before CL wear, the release of epidermal growth factor (EGF) and tissue-type plasminogen activator (t-PA) was attenuated, whereas matrix metalloproteinase (MMP)-9, interleukin (IL)-6, chemokine (C-C motif) ligand 5 (CCL5), IL-13, and plasminogen activator inhibitor (PAI)-1 were enhanced in KC compared with ametropes. An increasing linear trend over time was found for MMP-9, EGF, and CXCL8 in KC and MMP-9, MMP-13, IL-6, and CXCL8 in group III. Significant differences were observed in the linear trend over time between groups I and III for MMP-13 and tissue inhibitor of metalloproteinases (TIMP)-1; between groups I and II for MMP-9 and CXCL8; and between groups III and II for MMP-9, CXCL8, and MMP-13. In KC, the release of MMP-9 at week 6 and nerve growth factor (NGF) at 10 min was higher, but NGF at week 2 was lower than that in group II. The release of MMP-13 and NGF at week 2 and 6 were lower in the KC group as compared with group III, and similarly, with IL-6 and CXCL8 at week 2 and PAI at all time points. : Contact lens wear can influence the levels and dynamics of various mediators in the tears of patients with KC that might have an impact on the progression of the disease.
    Eye & contact lens 03/2013; 39(2):147-52.
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    ABSTRACT: Recent reports of retinal stem cells being present in several locations of the adult eye have sparked great hopes that they may be used to treat the millions of people worldwide who suffer from blindness as a result of retinal disease or injury. A population of proliferative cells derived from the ciliary body epithelium (CE) has been considered one of the prime stem cell candidates, and as such they have received much attention in recent years. However, the true nature of these cells in the adult human eye has still not been fully elucidated, and the stem cell claim has become increasingly controversial in light of new and conflicting reports. In this paper, we will try to answer the question of whether the available evidence is strong enough for the research community to conclude that the adult human CE indeed harbors stem cells.
    BioMed research international. 01/2013; 2013:531579.
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    ABSTRACT: Characterization of the cell surface marker phenotype of ex vivo cultured cells growing out of human fibrovascular epiretinal membranes (fvERMs) from proliferative diabetic retinopathy (PDR) can give insight into their function in immunity, angiogenesis, and retinal detachment. FvERMs from uneventful vitrectomies due to PDR were cultured adherently ex vivo. Surface marker analysis, release of immunity- and angiogenesis-pathway-related factors upon TNF α activation and measurement of the intracellular calcium dynamics upon mechano-stimulation using fluorescent dye Fura-2 were all performed. FvERMs formed proliferating cell monolayers when cultured ex vivo, which were negative for endothelial cell markers (CD31, VEGFR2), partially positive for hematopoietic- (CD34, CD47) and mesenchymal stem cell markers (CD73, CD90/Thy-1, and PDGFR β ), and negative for CD105. CD146/MCAM and CD166/ALCAM, previously unreported in cells from fvERMs, were also expressed. Secretion of 11 angiogenesis-related factors (DPPIV/CD26, EG-VEGF/PK1, ET-1, IGFBP-2 and 3, IL-8/CXCL8, MCP-1/CCL2, MMP-9, PTX3/TSG-14, Serpin E1/PAI-1, Serpin F1/PEDF, TIMP-1, and TSP-1) were detected upon TNF α activation of fvERM cells. Mechano-stimulation of these cells induced intracellular calcium propagation representing functional viability and role of these cells in tractional retinal detachment, thus serving as a model for studying tractional forces present in fvERMs in PDR ex vivo.
    BioMed research international. 01/2013; 2013:492376.
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    ABSTRACT: Purpose Besides bone marrow, mesenchymal stem cells (MSCs) can be separated from various tissues including the cornea. We investigated whether human corneal stroma-derived cells resemble MSCs and if they can be grown in animal-materials free medium containing human serum as the only supplement.Methods Human cornea stromal cells were isolated from cadavers after removal of the epithelial and endothelial layers (approved by the Hungarian Regional Ethical Committee). The cells were grown in DMEM containing human serum as the only supplement. Immunophenotyping with MSC markers, integrins/cell-adhesion-, endothelial- and hematopoietic markers was carried out by FACS analysis. Standard manufacturer protocols were used for differentiating the cells into fat, cartilage or bone.Results Cells isolated from human corneal stroma grew as monolayers in vitro and could be maintained in culture for more than 10 passages (n=6). They expressed the most important markers for MSCs (CD73, CD90, CD105, CD44, CD147, PDGFRb) and were negative for the hematopoietic markers CD34, CD45, HLA-DR, CD69 and CD133. High per cent of the cells expressed the pluripotency markers CD117, C-kit and CD47, but not the endothelial cell markers CD31, CD105/V-CAM, VEGFR2. One of the hallmarks of human MSCs being capable to differentiate towards adipocytes, chondrocytes and osteocytes could also be demonstrated.Conclusion Our results indicate the presence of MSC-like cells in the human corneal stroma, which can be grown in human serum-containing medium. This opens the door for studying human keratopathies, as well as corneal tissue engineering and cell-based therapies.
    Acta ophthalmologica 09/2011; 89(s248). · 2.44 Impact Factor
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    ABSTRACT: The transient receptor potential vanilloid 1 (TRPV1) plays a role in the activation of sensory neurons by various painful stimuli and is a therapeutic target. However, functional TRPV1 that affect microvascular diameter are also expressed in peripheral arteries and we attempted to characterize this receptor. Sensory TRPV1 activation was measured in rats by use of an eye wiping assay. Arteriolar TRPV1-mediated smooth muscle specific responses (arteriolar diameter, changes in intracellular Ca(2+)) were determined in isolated, pressurized skeletal muscle arterioles obtained from the rat and wild-type or TRPV1(-/-) mice and in canine isolated smooth muscle cells. The vascular pharmacology of the TRPV1 agonists (potency, efficacy, kinetics of action and receptor desensitization) was determined in rat isolated skeletal muscle arteries. Capsaicin evoked a constrictor response in isolated arteries similar to that mediated by noradrenaline, this was absent in arteries from TRPV1 knockout mice and competitively inhibited by TRPV1 antagonist AMG9810. Capsaicin increased intracellular Ca(2+) in the arteriolar wall and in isolated smooth muscle cells. The TRPV1 agonists evoked similar vascular constrictions (MSK-195 and JYL-79) or were without effect (resiniferatoxin and JYL-273), although all increased the number of responses (sensory activation) in the eye wiping assay. Maximal doses of all agonists induced complete desensitization (tachyphylaxis) of arteriolar TRPV1 (with the exception of capsaicin). Responses to the partial agonist JYL-1511 suggested 10% TRPV1 activation is sufficient to evoke vascular tachyphylaxis without sensory activation. Arteriolar TRPV1 have different pharmacological properties from those located on sensory neurons in the rat.
    British Journal of Pharmacology 08/2011; 165(6):1801-12. · 5.07 Impact Factor
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    ABSTRACT: The role of platelets in the development of atherosclerosis and obesity-related prothrombotic state is still under investigation. In this cross-sectional cohort study, we measured the levels of different platelet activation markers and evaluated their relationship with carotid intima-media thickness (IMT) along with other atherosclerotic risk factors in obese patients with or without atherosclerotic co-morbidities. We enrolled 154 obese patients, including 98 with either hypertension, type 2 diabetes mellitus or dyslipidaemia, 56 without these co-morbidities and 62 age- and sex-matched healthy controls. Platelet P-selectin expression and the number of platelet-derived microparticles (PMPs) were measured by flow cytometry; soluble P-selectin levels were analysed by ELISA and Thr715Pro P-selectin polymorphism was determined by PCR-RFLP. Carotid IMT was examined by ultrasonography. The levels of platelet activation parameters were significantly elevated in all obese subjects with increased carotid IMT compared to healthy controls. There was no effect of Thr715Pro genotype on soluble P-selectin levels in obese individuals contrary to normal subjects. Significant and positive association was revealed between carotid IMT and platelet P-selectin (p<0.0001), soluble P-selectin (p=0.039) and PMP (p=0.0001) levels. After adjusting for multiple variables, independent association was found between soluble P-selectin and fibrinogen (p=0.007), PMP levels and body mass index (p<0.0001) as well as platelet P-selectin and carotid IMT (p=0.012) plus plasminogen activator inhibitor-1 (p=0.009). In conclusion, P-selectin and PMP levels showed positive associations with abnormal carotid IMT and other risk factors in obesity suggesting a critical role of enhanced platelet reactivity in atherosclerotic wall alteration.
    Thrombosis and Haemostasis 08/2011; 106(4):683-92. · 6.09 Impact Factor
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    ABSTRACT: To identify changing trends in indications for corneal transplantation in Debrecen, Hungary over the past 64 years. Retrospective study, at the Department of Ophthalmology, University of Debrecen, Hungary. Four thousand seven hundred and seventy-eight patients who underwent keratoplasty. The analysis was based on medical charts, surgical descriptions and eye bank records. Keratoplasty indications between January 1946 and December 2009. For an easier overview, the 64-year interval was divided into seven time periods (1946-1955, I; 1956-1965, II; 1966-1975, III; 1976-1985, IV; 1986-1995, V; 1996-2005, VI; 2006-2009, VII). Over the 64 years, clinical indications for keratoplasty were corneal scarring (24.9%), regraft (18.6%), keratoconus (18.6%), pseudophakic/aphakic corneal oedema (12%), stromal corneal dystrophies (6%), non-infectious keratitis (4.7%), chemical injuries (3.3%), corneal degenerations (3%), mechanical trauma (1.7%), infectious keratitis (1.4%), endothelial corneal dystrophies (1.3%) and others (4.5%). During periods I-IV, corneal scarring was the most common indication for corneal transplantation. In period V, corneal ectasia became the leading clinical indication. Regraft was the most frequent indication in period VI. In the most recent years, an emerging tendency in pseudophakic/aphakic corneal oedema as the indication for keratoplasty was observed. In Hungary, the number of grafts has increased greatly in the past 64 years, the transplantation rates are similar to those of industrial countries. Indications for corneal transplantation have changed considerably over the last half decade from corneal scarring to corneal ectasia, regraft and pseudophakic/aphakic corneal oedema.
    Clinical and Experimental Ophthalmology 08/2011; 39(6):520-5. · 1.96 Impact Factor
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    ABSTRACT: The identification of cells with properties of retinal progenitor cells (RPCs) in the adult human ciliary margin (CM) prompted a number of studies of their proliferative and differentiation potential. One of the remaining challenges is to find a feasible method of isolating RPCs from the patient's eye. In the human CM, only the iris pigment epithelium (IPE) is easily obtained by a minimally invasive procedure. In the light of recent studies questioning the existence of RPCs in the adult mammalian CM, we wanted to assess the potential of the adult human IPE as source of RPCs. The IPE were isolated from peripheral iridectomies during glaucoma surgery, and IPE and ciliary body (CB) epithelium were also isolated from post-mortem tissue. Cells were cultivated in sphere-promoting conditions or as monolayers. Whole-tissue samples, undifferentiated and differentiated cells were studied by immunocytochemistry, RT-PCR and transmission electron microscopy. The adult human IPE, like the CB, expressed markers of RPCs such as Pax6, Sox2 and Nestin in vivo. Both sphere-promoting and monolayer cultures preserved this phenotype. However, both IPE/CB cultures expressed markers of differentiated epithelial cells such as Claudin, microphtalmia-associated transcription factor (MITF) and Cytokeratin-19. Ultrastructurally, IPE spheres displayed epithelial-like junctions and contained mature melanosomes. After induced differentiation, IPE-derived cells showed only partial neuronal differentiation expressing β-III-tubulin, Map-2 and Rhodopsin, whereas no mature glial markers were found. Proliferative cells with some properties of RPCs can be isolated from the adult human IPE by peripheral iridectomies. Yet, many cells retain properties of differentiated epithelial cells and lack central properties of somatic stem cells.
    Acta ophthalmologica 07/2011; 89(8):e635-44. · 2.44 Impact Factor
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    ABSTRACT: To report a detailed spectroscopic analysis of explanted hydrophilic acrylic intraocular lenses (IOLs) that were removed because of postoperative opacification of the lens optic. Thirteen Hydroview H60M (Bausch & Lomb Surgical) IOLs were explanted from 13 different patients on average 56 months after phacoemulsification and IOL implantation. All patients had decreased visual acuity because of a fine granularity of the optical surface of the IOLs. The surface was investigated by gross, microscopic, histochemical and scanning electron microscopic analysis, and the elemental composition of the opacified IOLs was determined by X-ray fluorescence spectroscopy (XRF). The spectrograms were compared to three different originally packed and never-implanted hydrophilic acrylic IOLs. Light and scanning electron microscopy of the optical surface of explanted IOLs revealed multiple fine granular deposits varying in size and shape that were positive for alizarin red. XRF confirmed that the explanted IOLs contained not only the previously reported calcium and phosphorous (calcium apatite), chlorine, silicone, sodium, aluminum and magnesium but also iron, sulfur, potassium as well as lesser amounts of iodine, zinc, strontium and yttrium. This is the first spectroscopic analysis determining the content of more than 10 elements of explanted and originally packed never-implanted hydrophilic acrylic IOLs. The possible origin of the different elements obtained from the spectrograms and their implications are discussed.
    Acta ophthalmologica 03/2011; 89(2):e161-6. · 2.44 Impact Factor
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    ABSTRACT: Failure of retinal pigment epithelial (RPE) cells and macrophages to engulf different dying cells in the retina may result in accumulation of debris and development of age-related macular degeneration (AMD). The dynamics and influence of different treatments on this clearance process can be studied in vitro using human ARPE-19 cells and macrophages as phagocytes modelling dry and wet type of AMD, respectively. Death through extracellular matrix detachment using polyHEMA-coated surfaces (anoikis) and UV irradiation (apoptosis) was induced in ARPE-19 cells. Two-coloured phagocytic assays were performed to quantify the amount of dying cells phagocytes engulfed (flow cytometry) and for visualization (fluorescent and scanning electron microscopy). The effect of phosphatidylserine inhibition with recombinant annexin-V and glucocorticoid (triamcinolone) treatment on the phagocytic process was tested. The clearance of anoikic and apoptotic cells by nondying ARPE-19 cells over 8 hr of co-incubation increased over time (at 8 hr, over 53% and 35% of the phagocytes contained engulfed dying cells, respectively). The human macrophages engulfed the anoikic and apoptotic ARPE-19 cells with seven and four times lower capacity, respectively. Phosphatidylserine appearance on the dying cells did not affect, but triamcinolone treatment enhanced the phagocytosis of the dying cells by macrophages. ARPE-19 cells are more efficient in clearing anoikic than UV-induced apoptotic cells. Macrophages are less efficient in the clearance process than ARPE-19 cells. The present model can be used for studying both dry and wet type of AMD in vitro and for testing different pharmacological aspects affecting this disease.
    Acta ophthalmologica 02/2011; 89(1):e30-4. · 2.44 Impact Factor
  • Szemészet 01/2011; 148:129-133.
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    ABSTRACT: The goal of this study was to investigate the importance of the vascular angiotensin convertase enzyme (ACE) in coronary artery bypass graft surgery (CABG) patients. Vascular tissue (distal saphenous vein [n= 163] and/or radial artery [n= 120] segments) and blood samples were collected from CABG patients (n= 81). We studied (i) the potency of angiotensin I (AngI) and angiotensin II (AngII) to evoke vascular contractions; (ii) vascular and plasma ACE concentrations; and (iii) ACE genotype of the patients enrolled. The ratio of the potencies (EC(50) ) of AngII and AngI was significantly lower in radial artery compared to the saphenous vein (0.17 ± 0.03 nM and 0.51 ± 0.14 nM, respectively, P= 0.003), suggesting a 3-fold more effective AngI conversion in saphenous vein samples. Angiotensin constrictions were inhibited with telmisartan and captopril in both saphenous veins and radial arteries. Vascular ACE expression was significantly higher in saphenous vein compared to radial artery (9.7 ± 1.0 ng/mg and 5.3 ± 0.7 ng/mg, respectively, P= 0.01). Serum but no tissue ACE concentration was determined by ACE insertion/deletion polymorphism. Accordingly, no relation was found between serum and tissue ACE expression. ACE-inhibitor therapy targeting tissue located ACE may be beneficial to patients with saphenous vein grafts after CABG surgery.
    Cardiovascular Therapeutics 11/2010; 30(3):136-44. · 2.85 Impact Factor
  • Inflammatory Bowel Diseases 10/2010; 16(10):1637-9. · 5.12 Impact Factor
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    ABSTRACT: As blood coagulation factor XIII (FXIII) is of high importance in wound healing, we determined the concentrations of FXIII A and B subunits (FXIII-A and FXIII-B) and their complex (FXIII-A(2)B(2)) in normal tears and in tears from patients undergoing penetrating keratoplasty (PKP). FXIII complex and subunit concentrations were measured by highly sensitive chemiluminescent ELISAs in tears from 60 healthy volunteers and from 31 patients undergoing corneal transplantation. In non-stimulated tears from healthy volunteers, low but consistent amounts of FXIII-A and FXIII-B (medians: 2.13 μg/L and 7.22 μg/L, respectively) were measured, mostly in non-complexed form. Following stimulation of tear secretion FXIII levels moderately decreased, but if normalized to protein concentration they did not change. One day after PKP FXIII levels became highly elevated, then gradually decreased, but even on day 7 significantly exceeded pre-surgery values. The elevation of tear FXIII levels was significantly higher in PKP patients who later developed neovascularization of donor cornea. FXIII subunits are low concentration components of normal tear. The striking elevation of FXIII subunit and FXIII-A(2)B(2) concentrations after PKP suggests the involvement of FXIII in corneal wound healing. Perioperatively measured high FXIII levels in tears seem to represent a risk of neovascularization.
    Clinica chimica acta; international journal of clinical chemistry 10/2010; 412(3-4):271-6. · 2.54 Impact Factor
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    ABSTRACT: A 25-year-old woman who developed transient neurological abnormalities after scuba diving is reported. The subsequent day she experienced transient left-side monocular blindness. Arterial ocular occlusion in apparently healthy young women is unusual, and a search for the cause of this devastating vascular event is mandatory. Occlusion of the left branch retinal artery, total occlusion of the left internal carotid artery, and a petrous apex epidermoid were found, together with a shortened prothrombin time (INR: 0.73), a slightly elevated serum cholesterol level (6.1 mmol/l) and combined thrombophilia (elevated FVIIIC plus type 2 sticky platelet syndrome). This case underlines the complex mechanism of thromboembolic diseases, and the importance of the acquired trigger (in the present case scuba diving) in addition to the long-term anatomical and biochemical risk factors.
    Pathophysiology of Haemostasis and Thrombosis 03/2010; 36(6):311-4. · 2.23 Impact Factor

Publication Stats

155 Citations
71.77 Total Impact Points

Institutions

  • 2013–2014
    • University of Szeged
      • Ophthalmology Department
      Algyő, Csongrád, Hungary
  • 2003–2013
    • University of Debrecen
      • Department of Ophthalmology
      Debreczyn, Hajdú-Bihar, Hungary