Joanna Harazny - Academia.edu (original) (raw)

Papers by Joanna Harazny

Acta Biochimica Polonica, 2019

Ubiquitin-specific peptidase 18 (USP18) is a multifunctional protein and its roles are still bein... more Ubiquitin-specific peptidase 18 (USP18) is a multifunctional protein and its roles are still being investigated. This enzyme removes ubiquitin-like molecules from their substrates and the only known interferon-stimulated gene 15 (ISG15) specific protease. Apart from its enzymatic function, it also inhibits interferon type I and III signalling pathways. USP18 is known to regulate multiple processes, such as: cell cycle, cell signalling and response to viral and bacterial infections. Moreover, it contributes to the development of several autoimmune diseases and carcinogenesis, and recently was described as a cardiac remodelling inhibitor. This review summarizes the current knowledge on USP18 functions, highlighting its contribution to the development of heart failure, given the fact that this disease’s etiology is now considered to be inflammatory in nature.

Background Subclinical damage to both the small and large vessels may contribute to the developme... more Background Subclinical damage to both the small and large vessels may contribute to the development and progression of cardiovascular disease. Scanning laser Doppler flowmetry (SLDF), an established method used to measure retinal microcirculation, has been successfully applied in hypertensive and post-stroke patients. To the best of our knowledge, no previous studies have assessed the impact of type 1 diabetes and its duration on retinal arteriole structure denoted by wall-to-lumen ratio (WLR) and retinal capillary flow (RCF). MethodsRetinal microcirculation was assessed in 158 patients with type 1 diabetes and 38 age-matched healthy controls. The diabetics were divided into 3 groups: group A with diabetes duration <12 months, group B with diabetes duration between 1 and 10 years, and group C >10 years of diabetes. Retinal capillary structure and perfusion were evaluated using a Heidelberg retina flowmeter and automatically analyzed with full-field perfusion imaging. Diabetes ...

Scientific Reports, 2020

Spectral-domain optical coherence tomography (SD-OCT) represents a reliable tool for retinal laye... more Spectral-domain optical coherence tomography (SD-OCT) represents a reliable tool for retinal layer volume and thickness measurement. The aim of this study was to evaluate retinal changes indicating neurodegenerative processes in patients with end-stage renal disease (ESRD) compared to healthy controls. This was a cross-sectional, single-center study comprising 32 ESRD patients and 38 controls. Sectoral retinal nerve fiber layer (RNFL) thickness and retinal layer volumes were obtained by SD-OCT. Age- and gender-adjusted retinal layer volumes such as total retinal volume (p = 0.037), ganglion cell layer volume (GCL, p = 0.003), ganglion cell layer – inner plexiform layer volume (GCL-IPL, p = 0.005) and inner retinal layer volume (IRL, p = 0.042) of the right eye were lower in ESRD patients. Inner plexiform layer volume of both eyes (IPL, right eye: p = 0.017; left eye: 0.044) was reduced, as was RNFL thickness in the temporal superior sector (right eye: p = 0.016). A subgroup analysis...

Nephrology Dialysis Transplantation, May 1, 2018

Polycystic liver disease(PLD) is one of the complications of autosomal dominant polycystic kidney... more Polycystic liver disease(PLD) is one of the complications of autosomal dominant polycystic kidney disease(ADPKD). Severity of these complications are varies. Total liver volume is increasing after patients reached end stage of renal disease, causing abdominal compression, portal hypertension, liver cyst infection, liver dysfunction. The aim of this study is to find out the correlations between liver volume and clinical characteristics. METHODS: Cross-sectional study was conducted. Total liver volume(TLV) and total kidney volume(TKV) were calculated in a cohort of 152 outpatients with ADPKD in our hospital by using 3 dimensional calculated program from computed tomography and evaluated according to clinical and laboratory data. RESULTS: Among the study cohort, median age was 53 year old, male predominant(n¼90). Median serum creatinine level was 1.03mg/dL, median TLV was 1639cm 3 , median TKV was 1495cm 3. Hemodialysis was conducted in nine patients. Esophageal varix was found in five patients by endoscopy. There was no correlation between TLV and TKV. From univariate linear regression analysis, low level of hemoglobin, platelet count, serum albumin, calcium, choline esterase, existence of esophageal varix, not taking tolvaptan, high level of aspartate aminotransferase, C-related protein, urine protein excretion were significantly corelate to TLV. But multivariate analysis reveals that only varix associated with TLV(p<0.01). CONCLUSIONS: Clinical factors related to liver, especially varix, were associated to TLV in ADPKD. There was no co-relation between renal factors and TLV.

Medicina, 2019

Background and Objectives: Salmonellosis is a major foodborne bacterial infection throughout the ... more Background and Objectives: Salmonellosis is a major foodborne bacterial infection throughout the world. Epidemiological surveillance is one of the key factors to reduce the number of infections caused by this pathogen in both humans and animals. The first outcome measure was the prevalence of non-typhoid Salmonella (NTS) infections between 2000 and 2017 among the population of the predominantly agricultural and touristic Polish region of Warmia and Masuria (WaM). The second outcome measure was the comparison of the NTS hospitalization rate of all registered NTS cases, an investigation of the monthly reports of infections, and the exploration of the annual minimal and maximal NTS infection number in WaM in the above-mentioned time period. The last outcome was a comparison of the prevalence of NTS infections in the region and in its administrative districts by considering both rural and urban municipalities three years before and three years after the accession of Poland into the Euro...

Journal of Hypertension, 2018

improved by 34% (34.8% vs 52.8%), treatment by 64% (11.1% vs 30.9%), control by 98% (0.2% vs 10.1... more improved by 34% (34.8% vs 52.8%), treatment by 64% (11.1% vs 30.9%), control by 98% (0.2% vs 10.1%) and control rates in treated hypertensives by 96.3% (1.2% vs 32.1%) in 2015. Compared to 1998-2000, mean systolic blood pressure lowered 16.7mmHg (144.4 vs 127.7mmHg) and diastolic blood pressure lowered 13.2mmHg (89.6 vs 76.4mmHg) in 2015. Conclusion: Introduction of standard simple algorithm into primary care setting could improve the hypertension treatment and control rates in resource restricted region, whereas further efforts should be coordinated. In addition, secular trends should also be kept in mind.

Artery Research, 2015

The study of vascular adaptation to extreme conditions, and in particular to hypoxia, represents ... more The study of vascular adaptation to extreme conditions, and in particular to hypoxia, represents a unique opportunity in cardiovascular physiology, with relevant translational implications. First, it has crucial clinical consequences for about 140 million people worldwide living at high altitude and chronically exposed to hypobaric hypoxia. Second, an increasing number of lowlanders are exposed to high altitude for recreational or working purposes, including aged, diseased individuals: in these cases, hypoxia could be a trigger for acute cardiovascular events. Finally, hypoxia plays a major role in the pathogenesis of many diseases and chronic conditions, as respiratory (i.e. chronic obstructive pulmonary disease and obstructive sleep apnea syndrome) and cardiovascular disorders (i.e. heart failure, ischemic heart disease and cerebrovascular disease). Thus, results from field studies at high altitude might be important for a deeper understanding of their pathophysiology. This review is aimed at summarizing the main findings in the field of chronic and acute vascular adaptation to hypoxia, focusing on the role of nitric oxide (NO) and endothelial function, as well as large artery behavior.

Diabetologie und Stoffwechsel, 2014

In type-2 diabetes early vascular changes (among others) are hyperperfusion in the retinal circul... more In type-2 diabetes early vascular changes (among others) are hyperperfusion in the retinal circulation (like in the kidney) and increased pulse wave reflection leading to increased aortic pressure. We analyzed whether the DPP4-inhibitor saxagliptin reverses early vascular and haemodynamic changes in type-2 diabetes. In this double-blind randomized controlled clinical cross-over trial 42 patients with type-2 diabetes (age 60.3, 13 were females, BMI 30.6 kg/m2, mean duration of diabetes 4 years, HbA1c 7.0%, blood pressure 132/79 mmHg) were consecutively [PB1] included and randomized to placebo or saxagliptin 5 mg for 6 weeks each. Retinal capillary flow (RCF) was assessed at baseline and after flickerlight exposure (as a vasodilatory test) by scanning laser Doppler flowmetry. Central (aortic) systolic blood pressure (SBP), central pulse pressure (PP), augmentation index and pulse wave velocity were determined with the SphygmoCor device. Following treatment with saxagliptin (as opposed to placebo) saxagliptin effected a better glycemic control, a reduced retinal capillary flow (p=0.033) and, in parallel, reduced central systolic augmentation and pulse pressure (see table). In accordance, Flicker light induced increment of RCF (indicative of vasodilatory capacity of the retinal circulation) was numerically 2-fold greater, although not significant.

PLOS ONE, 2016

In diabetes mellitus type 2, capillary rarefaction plays a pivotal role in the pathogenesis of en... more In diabetes mellitus type 2, capillary rarefaction plays a pivotal role in the pathogenesis of end-organ damage. We investigated retinal capillary density in patients with early disease. Methods This cross-sectional study compares retinal capillary rarefaction determined by intercapillary distance (ICD) and capillary area (CapA), measured non-invasively and in vivo by scanning laser Doppler flowmetry, in 73 patients with type 2 diabetes, 55 healthy controls and 134 individuals with hypertension stage 1 or 2. Results In diabetic patients, ICD was greater (23.2±5.5 vs 20.2±4.2, p = 0.013) and CapA smaller (1592±595 vs 1821±652, p = 0.019) than in healthy controls after adjustment for differences in cardiovascular risk factors between the groups. Compared to hypertensive patients, diabetic individuals showed no difference in ICD (23.1±5.8, p = 0.781) and CapA (1556±649, p = 0.768). Conclusion In the early stage of diabetes type 2, patients showed capillary rarefaction compared to healthy individuals.

Stroke; a journal of cerebral circulation, 2004

Arterial hypertension constitutes a central factor in the pathogenesis of stroke. We examined end... more Arterial hypertension constitutes a central factor in the pathogenesis of stroke. We examined endothelial function of the retinal vasculature as a model of the cerebral circulation. Thirty-eight young subjects (19 hypertensive and 19 normotensive) were treated with the AT1-receptor blocker candesartan cilexetil and placebo, each over 7 days. Retinal capillary flow and blood flow velocity in the central retinal artery were assessed with scanning laser Doppler flowmetry and pulsed Doppler ultrasound, respectively. N(G)-monomethyl-L-arginine (L-NMMA) was infused to inhibit nitric oxide (NO) synthesis. Diffuse luminance flicker was applied to stimulate NO release. In normotensive subjects, L-NMMA decreased retinal capillary flow by 8.2%+/-13% (P<0.05) and flickering light increased mean blood flow velocity in the central retinal artery by 19%+/-29% (P<0.01). In contrast, no significant change to these provocative tests was seen in hypertensive subjects. Treatment with candesartan ...

Laser Scanning: Update 1, 2001

Purpose: to image functionally perfused retinal vessels and to assess quantitatively the intercap... more Purpose: to image functionally perfused retinal vessels and to assess quantitatively the intercapillary space of the retinal microvasculature. Method: The base of functional imaging and the quantitative assessment of the retinal vasculature is the two-dimensional map of the retina encoded by the laser Doppler frequency shift. By Scanning Laser Doppler Flowmetry (HRF. Heidelberg Engineering) the laser Doppler frequency shift of 16.384 retinal sites (256 pixels × 64 lines, spatial resolution 10 mum) of a retinal area of 2.7 × 0.7 mm was gained. The image processing was performed by a recently described algorithm (AFFPIA). Using the data of the laser Doppler frequency shift of every retinal site, a color-coded retinal image was established showing perfused vessels and capillaries. By automatic pattern analysis of this image vessels and capillaries were identified and segmented. Based on this image the distances in [µm] of every retinal site to the next vessel or capillary were calculated ("distance to next capillary"). The functional imaging of the retinal perfusion was demonstrated in (1) normal retina, (2) retinal arterial occlusion, and (3) proliferative retinopathy. Intraobserver reliability of the quantitative assessment of the parameter "distance to next capillary" was estimated by measuring 10 eyes of 10 subjects at 5 different days by one observer. Interobserver reliability of the quantitative assessment was evaluated by analysing 10 perfusion maps by 5 different operators. In 93 eyes of 71 normal subjects (mean age 40.4 µ 15 years) the juxtapapillary retina was quantitatively evaluated. Results: Qualitative evaluation: The functional images of the retinal perfusion of eyes with normal retina, with retinal arterial occlusion, and with proliferative retinopathy corresponded well with the fluorescein angiography. Perfused vessels and capillaries became visible in a high local resolution. Quantititative assessment: The coefficient of reliability of the introobserver and interobserver reproducibility of the parameter "mean distance to next capillary" was 0.74, and 0.95, respectively. The quantitative assessment of the perfusion showed that the major part of the retinal sites (>700%) had distances to the next capillary lower than 30 µm 46% of the retinal area had distances to the next capillary from 0-20 lµm 26% of the retina had distances from 20-30 µm, 12% of the retina had distances from 30-40 µm 7% of the retina had distances from 40-50 µm, 4% of the retina had distances from 50-60 µm, and 4% of the retinal sites showed distances to the next capillary greater than 60 mum. The mean distance to the next capillary or vessel was calculated with 21 ± 6.5 µm. Conclusion: By non-invasive Scanning Laser Doppler Flowmetry in combination with adequate software it is possible to perform a functional imaging of the retinal vasculature and to measure all index for the functional density of retinal capillaries and vessels.

Retina, 2004

Background: To date, no satisfactory therapy has become available for patients with acute central... more Background: To date, no satisfactory therapy has become available for patients with acute central retinal artery occlusion (CRAO) or branch retinal artery occlusion (BRAO). Enhanced external counterpulsation (EECP) is a new noninvasive procedure that increases perfusion of inner organs. In the current study, the authors measured the impact of EECP on reperfusion in ischemic retinal tissue. Methods: In a prospective, randomized study, 20 patients with CRAO or BRAO were included. Ten patients were given hemodilution therapy and 2 hours of EECP, and 10 patients were given regular hemodilution therapy only. Quantification of changes in retinal perfusion was carried out by means of scanning laser Doppler flowmetry (in arbitrary units). Results: Enhanced external counterpulsation caused no observable adverse events. A significant increase in perfusion occurred immediately after EECP in the ischemic retinal areas (57 Ϯ 19 arbitrary units versus 99 Ϯ 14 arbitrary units). In contrast, no change was measured in the group not treated with EECP (83 Ϯ 19 arbitrary units versus 89 Ϯ 44 arbitrary units). Forty-eight hours later, a significant increase in perfusion could be shown in the ischemic retina of both groups, and no significant difference of perfusion was found between the two groups any longer. Conclusion: The current study suggests that EECP could be a clinically useful and safe procedure in patients with CRAO or BRAO to accelerate recovery of perfusion in ischemic retinal areas.

Ophthalmology, 1997

The authors quantified the relationship between ocular pulse pressures and retinal vessel velocit... more The authors quantified the relationship between ocular pulse pressures and retinal vessel velocities. Method: The blood velocity in the ophthalmic artery (OA), the central retinal vein (CRV), and artery (CRA) was measured by pulsed Doppler sonography (4-Mhz probe). The pulse curve of the intraocular pressure (lOP) was evaluated by pneumotonometry. With multichannel data acquisition and storage software, the velocity pulse curve of the OA, the CRV and CRA, the lOP-pulse curve, the arterial blood pressure, and the electrocardiogram were recorded simultaneously in real-time mode. The relationships between the pulse curves of the blood velocity in the OA, the CRV and CRA, and the lOP were calculated off-line. The onset time, the time of half maximum, and the time to the maximum of the pulse curves were evaluated. A relative retinal venous outflow resistance index (R') was calculated by R' = ~IOP/~Vcrv' We examined 23 eyes of 23 healthy subjects. The mean age of the group was 46 ± 16 years. Results: In all eyes, the outflow in the CRV was pulsatile and ran in synchrony with the lOP pulsation. The CRV velocity-and lOP-pulse curve showed a significant mean delay of 0.024 second compared with the CRA and OA velocity-pulse curve. The relative resistance index R' for venous outflow was 1.0 ± 0.44 mmHg/cm/seconds. Conclusion: In all eyes, the authors found a significant linear relationship between the blood velocity in the CRV and the lOP pulsation. The CRV velocity-and lOP-pulse curve were significantly delayed compared with the CRA and OA velocity-pulse curve.

Journal of Neurology, Neurosurgery & Psychiatry, 2003

Journal of Hypertension, 2004

Background: Arterial hypertension is the major risk factor for stroke. In Patients with known man... more Background: Arterial hypertension is the major risk factor for stroke. In Patients with known manifestation of hypertensive disease we examined nitric oxide activity in vivo of the retinal vasculature considered as a model of cerebral vasculature. Methods: In an open pilot study 20 elderly patients with arterial hypertension were treated additionally with the AT1-blocker Valsartan (160 mg o.d.) for 8 days. All participants were males, non-smokers, non-diabetics and had no treatment with ACE-inhibitors or other AT1blockers. Perfusion of the central retinal artery and retinal capillary flow was measured before and after treatment. The perfusion of the central retinal artery was assessed with pulsed wave Doppler sonography at rest and during flicker light stimulation which is known to stimulate nitric oxide release. Retinal capillary flow was assessed with scanning laser Doppler flowmetry at rest and following infusion of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endothelial NO synthase. Results: At rest perfusion of the central retinal artery and retinal capillary flow were similar before and after treatment with Valsartan. The mean blood flow velocity increased in response to flicker light (pϽ0.001), but this response was similar before and after treatment (⌬17 Ϯ33% vs. ⌬27 Ϯ 38 % n.s.). Increase in retinal capillary flow after L-NMMA was not changed by treatment (⌬ 4.7 Ϯ 22 % before and ⌬4.5 Ϯ23 % after valsartan, n.s.). The response of retinal capillary flow to L-NMMA depended on the serum LDL cholesterol level of the subjects. The group with LDL above average (Ͼ136 mg/dl) tended to have an increased response to L-NMMA after Valsartan treatment compared to before treatment ([Delta13 Ϯ 26 %vs. ⌬0.4Ϯ17 % pϭ0.08) and the change of L-NMMA induced vasoconstiction in the high LDL group before and after treatment differed from that observed in the low LDL group (⌬ Ϫ13 Ϯ 20% vs. ⌬12 Ϯ16% pϭ0.01). Blood pressure was not a confounding determinant since in the high and low LDL group the change in blood pressure in response to L-NMMA was similar before and after treatment (⌬ 2.4 Ϯ 8.4 mmHg vs. ⌬ Ϫ2.1 Ϯ 5.8 mmHg pϭ0.2). Conclusion: Our pilot study suggests that Valsartan improves the basal NO-availability in the retinal capillary bed taken as a mirror of cerebral circulation in hypertensive patients with high LDL.

$Research paper thumbnail of Retinal Microcirculation Correlates With Ocular Wall Thickness, Axial Eye Length, and Refraction in Glaucoma Patients$

Journal of Glaucoma, 2001

To examine the correlations of refraction, axial eye length, and posterior eye wall thickness wit... more To examine the correlations of refraction, axial eye length, and posterior eye wall thickness with retinal microcirculation. Patients and Methods: In a prospective study, 25 patients with primary open-angle glaucoma, 12 patients with ocular hypertension, and 12 healthy subjects were examined; only one eye of each participant was considered in the analysis. Posterior eye wall thickness and axial eye length were measured with standardized A-scan ultrasonography. Retinal microcirculation temporal to the optic disc was determined by a scanning laser Doppler flowmeter using automatic full-field perfusion image analyzer software. Results: In glaucoma patients, temporal retinal mean flow exhibited significant correlation to the eye wall thickness (r ‫ס‬ 0.470, P ‫ס‬ 0.042), axial eye length (r ‫ס‬ −0.570, P ‫ס‬ 0.011), and refraction of the eye (r ‫ס‬ 0.520, P ‫ס‬ 0.022). In glaucomatous eyes, the temporal retinal mean flow was significantly lower than in healthy subjects or in ocular hypertensive patients (P ‫ס‬ 0.01). Conclusions: Myopic eyes have longer axial eye length and thinner ocular wall than emmetropic eyes. In glaucoma patients, the longer the axial eye length and the thinner the ocular wall, the more reduced the retinal microcirculation. The reduced microcirculation found in myopic glaucomatous eyes might contribute to the development of glaucomatous damage in these eyes.

Investigative Opthalmology & Visual Science, 2009

PURPOSE. There is evidence that generalized retinal arteriolar narrowing, which can be measured b... more PURPOSE. There is evidence that generalized retinal arteriolar narrowing, which can be measured by the arteriole-to-venule ratio (AVR) of retinal vessels, predicts cerebrovascular events. The wall-to-lumen ratio (WLR) and wall cross-sectional area (WCSA) of retinal arterioles reflect structural arteriolar parameters. The primary objective was to test the association between WLR and AVR in a distinct cohort of patients with cerebrovascular damage. METHODS. In this cross-sectional study, 23 patients (57.5 Ϯ 9.4 years) with acute transitory ischemic attack or lacunar cerebral infarct were compared with two age-matched control groups: 83 subjects with essential hypertension (53.7 Ϯ 5.5 years) and 16 normotensive subjects (52.2 Ϯ 8.3 years). Retinal arteriolar parameters (WLR, WTH, and WCSA) were assessed in vivo with scanning laser Doppler flowmetry (SLDF). AVR and a qualitative evaluation of retinal vessels were obtained from digital retinal color photographs. The intima-media thickness (IMT) of the carotid artery was measured. RESULTS. WLR (0.44 Ϯ 0.1 vs. 0.34 Ϯ 0.1 vs. 0.30 Ϯ 0.1, P Ͻ 0.001) and carotid IMT (P Ͻ 0.05) were significantly greater in the cerebrovascular event group compared with normotensive subjects. WLR and WCSA were significantly higher in the cerebrovascular event group compared with subjects with mild arterial hypertension. AVR was similar in all three study groups (0.75 Ϯ 0.07 vs. 0.74 Ϯ 0.07 vs. 0.78 Ϯ 0.1, P ϭ 0.18). CONCLUSIONS. The increase in WLR and WCSA of retinal arterioles, as well as in IMT in patients with cerebrovascular damage suggests vascular hypertrophy in the microvascular and macrovascular bed. The lack of association between AVR of retinal vessels and WLR of retinal arterioles may point to different stages of cerebrovascular disease and/or different pathophysiological changes in the arteriolar wall.

Hypertension, 2012

We hypothesized that the increase of retinal capillary blood flow (RCF) to flicker light exposure... more We hypothesized that the increase of retinal capillary blood flow (RCF) to flicker light exposure is impaired in subjects with arterial hypertension. In 146 nondiabetic untreated male subjects with (n=50) or without (n=96) arterial hypertension, RCF was measured before and after flicker light exposure noninvasively and in vivo using scanning laser Doppler flowmetry. In addition, in a subgroup of 28 subjects, the change of RCF to flicker light exposure was again assessed during parallel infusion of nitric oxide synthase inhibitor N-monomethyl- l -arginine (L-NMMA). The increase of RCF to flicker light exposure was lower in patients with untreated hypertension compared with normotensive subjects when expressed in absolute terms (7.69±54 versus 27.2±44 AU; P adjusted=0.013) or percent changes (2.95±14 versus 8.33±12%; P adjusted=0.023). Systolic (β=−0.216; P =0.023) but not diastolic blood pressure (β=−0.117; P =0.243) or mean arterial pressure (β=−0.178; P =0.073) was negatively relat...

Hypertension, 2007

Arterial hypertension is a major risk factor for stroke, and retinal vessels can be regarded as a... more Arterial hypertension is a major risk factor for stroke, and retinal vessels can be regarded as a mirror of the cerebral vasculature. Whether vascular remodeling of retinal arterioles with ageing and hypertension plays a role in cerebrovascular risk stratification has not yet been adequately addressed. In study 1, retinal arteriolar structure was assessed in 182 normotensive volunteers and 117 patients with essential hypertension. In study 2, we compared retinal arteriolar structure among 74 normotensive volunteers, 47 patients with treated essential hypertension, and 18 subjects with a history of a cerebrovascular event. Retinal arteriolar structure was assessed using scanning laser Doppler flowmetry and automatic full-field perfusion imaging analysis. In study 1, wall:lumen ratio of retinal arterioles revealed a significant correlation with age ( r =0.198; P =0.001). In study 2, wall:lumen ratio was highest in patients with a history of a cerebrovascular event compared with treate...