Correlation of Vitreous Vascular Endothelial Growth Factor and Uric Acid Concentration Using Optical Coherence Tomography in Diabetic Macular Edema

Purpose. We investigated two factors linked to diabetic macular edema (DME), vitreous and serum levels of vascular endothelial growth factor (VEGF) and uric acid (UA) in patients with DME, and compared the results with changes in optical coherence tomography (OCT) and visual acuity (VA). Methods. A prospective study of 29 eyes, 16 cystoid DME and nonproliferative diabetic retinopathy (DR) and 13 nondiabetic controls. Biochemical analysis of vitreous and serum samples was performed and OCT scans were graded according to central retinal thickness (CRT), cube volume (CV), cube average thickness (CAT), and serous retinal detachment (SRD). Results. In DME group, intravitreal concentrations of VEGF (p<0.001), UA (p=0.038), and total protein (p<0.001) were significantly higher than in control group. In DME subjects, intravitreal UA correlated significantly with intravitreal VEGF (ƍ = 0.559, p=0.03) but not with total vitreous protein and serum UA. Increased intravitreal VEGF in DME group correlated with increase in CV (ƍ = 0.515/p=0.041). None of the OCT parameters correlated with the VA. Conclusions. The results suggest that the CV might be assessor of anti-VEGF therapy efficacy. Second, apart from VEGF, the role of UA in the pathogenesis and progression of DR should be considered

Produkty pokrocile glykace a produkty pokrocile oxidace proteinu a jejich klinicky vyznam.

Pathogenesis of many diseases and their complications is connected with oxidative and carbonyl stress. Advanced glycation end products (AGEs) and advanced oxidation protein products (AOPP) are two outstanding markers of these mechanisms. The aim of the thesis was to introduce a method for determination of AGEs and AOPP and their studying in diabetology and nephrology. ELISA method for AGE-assessment was tested in our laboratory. Even repeated glycation, immunization and purification didn't result in suitable antiserum. This method is very discutable and its use for AGE-determination is becoming obsolent. A spectrofluorimetric method for AGE-determination was introduced and gel permeation chromatography with fluorescent detection was used for characterisation of fluorescent substances. AOPP were determined with a spectrophotometric method. AGEs and AOPP were examined in patients with type 1 and 2 diabetes mellitus, in hemodialyzed patients with and without diabetes mellitus, in hemodialyzed patients during dialysis, and in healthy subjects for comparison. Our studies show a useful application for determination of glycoxidation parameters -AGEs and AOPP - in the course of chronic diseases and their complications in patients with diabetes mellitus and chronic renal failure.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Placental growth factor, pregnancy-associated plasma protein-A, soluble receptor for advanced glycation end products, extracellular newly identified receptor for receptor for advanced glycation end products binding protein and high mobility group box 1 levels in patients with acute kidney injury: a cross sectional study

BACKGROUND: Placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A), soluble receptor for advanced glycation end products (sRAGE), extracellular newly identified receptor for RAGE binding protein (EN-RAGE) and high mobility group box 1 (HMGB-1) are novel biomarkers in chronic kidney disease (CKD). However, their clinical significance in acute kidney injury (AKI) is unknown. The aim of this cross-sectional study was to determine whether selected biomarkers are changed in AKI patients. METHODS: Serum PlGF, PAPP-A, sRAGE, EN-RAGE and HMGB-1 levels were assessed in 40 patients with AKI, 42 CKD 5 patients, 31 haemodialysis patients (HD) and 39 age-matched healthy controls. RESULTS: PAPP-A was elevated in AKI (20.6 ± 16.9 mIU/L) compared with controls (9.1 ± 2.3 mIU/L, p < 0.001). PlGF was not increased in AKI (11.7 ± 7.4 pg/mL) versus controls (8.5 ± 2.4 pg/mL, n.s.), as well as sRAGE was not elevated in AKI (2400 ± 1400 pg/mL) compared with controls (1760 ± 730 pg/mL, n.s), but was lower compared with CKD 5 (3200 ± 1500 pg/mL, p < 0.05); EN-RAGE was elevated in AKI 480 ± 450 ng/mL in comparison with controls (60 ± 62 ng/mL), CKD 5 (190 ± 120 ng/mL), and HD (120 ± 100 ng/mL), all p < 0.001. Similarly, HMGB-1 was increased in AKI (5.8 ± 7.5 ng/mL) versus controls (1.7 ± 1.4 ng/mL), CKD 5 (3.2 ± 3.1 ng/mL) and HD (2.5 ±2.1 ng/mL), all p < 0.001. In AKI group, in multivariate regression analysis: PAPP–A levels were associated with transferrin (p <0.001), negatively with albumin (p < 0.01) and prealbumin (p < 0.05); PlGF levels were associated with C - reactive protein (p < 0.001). EN-RAGE levels were associated with ferritin (p < 0.01) and orosomucoid (p = 0.02), and HMGB-1 levels with leukocyte count (p < 0.01) and negatively with proteinuria (p = 0.02). CONCLUSIONS: In AKI patients, PAPP-A, EN-RAGE and HMGB1 are elevated, but sRAGE and PlGF are not increased. Whereas PAPP-A correlates with markers of nutrition; PlGF, EN-RAGE and HMGB-1 are related to inflammatory parameters

Levels and avidities of antiphosphatidylethanolamine antibodies in patients with thrombotic events and immunologically-mediated diseases

Aims. Antiphosphatidylethanolamine antibodies (aPE) represent one type of antiphospholipid antibody (aPL) directed against the neutral phospholipids - phosphatidylethanolamines. The aim of this study was to evaluate levels and avidities of aPE in several groups of patients and compare them with conventional aPLs. Methods. aPE were analysed in a cohort consisting of 68 hospitalized patients. The other cohort comprised 22 patients with immunologically-mediated diseases. The control group consisted of 20 healthy persons. ELISA methods were used for determination of aPL. Avidities of aPE were tested by modified ELISA with urea as a chaotropic agent. Results. aPE IgG/IgM were significantly higher in the group of patients with venous thromboembolism than those with non-thrombotic internal disorders (P=0.02 for both Ig classes). aPE IgG/IgM elevated above cut-off values were found in 10.8% of patients with venous thromboembolism and as a single aPL in 6.5%. Levels of aPE IgG higher than our limit (&gt;6 U/mL) were detected in 29% of patients with immunologically-mediated diseases with other positive aPL. Low-, intermediate- and high-avidity aPE IgG were found in patients of both cohorts. The avidities of aPE IgG differed from those of anticardiolipin antibodies IgG. Neither aPE IgG levels nor avidity dynamics significantly changed during follow-up. Conclusion. aPE may be related to venous thromboembolism and may be part of the repertoire of aPL in immunologically-mediated diseases. There are patients with thrombosis negative for conventional aPL but positive for aPE. aPE IgG may have different avidities

Vitamin D Binding Protein Is Not Involved in Vitamin D Deficiency in Patients with Chronic Kidney Disease

Objective. This study was designed to evaluate vitamin D status with separate determination of 25-OH D2 and 25-OH D3 and its relationship to vitamin D binding protein (VDBP) in patients with chronic kidney disease (CKD) and long-term haemodialysis patients (HD). Methods. 45 CKD patients, 103 HD patients, and 25 controls (C) were included. Plasma vitamin D concentrations were determined using chromatography and VDBP in serum and urine in CKD using enzyme immunoassay. Results. Plasma vitamin D levels were lower in CKD (30.16 ± 16.74 ng/mL) and HD (18.85 ± 15.85 ng/mL) versus C (48.72 ± 18.35 ng/mL), P<0.0001. 25-OH D3 was the dominant form of vitamin D. Serum VDBP was higher in CKD (273.2 ± 93.8 ug/mL) versus C (222 ± 87.6 ug/mL) and HD (213.8 ± 70.9 ug/mL), P=0.0003. Vitamin D/VDBP ratio was the highest in C and the lowest in HD; however, there was no correlation between vitamin D and VDBP. Urinary concentration of VDBP in CKD (0.25 ± 0.13 ug/mL) correlated with proteinuria (r=0.43, P=0.003). Conclusions. Plasma levels of vitamin D are decreased in CKD patients and especially in HD patients. 25-OH D3 was the major form of vitamin D. Despite urinary losses of VDBP, CKD patients had higher serum VDBP concentrations, indicating compensatory enhanced production. Vitamin D binding protein is not involved in vitamin D deficiency

Effects of hemodialysis on serum fetuin-A levels

Fetuin-A is a calcification inhibitor, negative acute phase response marker and cardiovascular mortality predictor in hemodialysis patients. Low levels of fetuin-A are associated with malnutrition, inflammation, decreased bone mass density, low-turnover bone and use of high calcium concentration dialysate. Hemodialysis procedure (HD) has been shown to decrease fetuin-A levels by 20%, probably due to HD-induced inflammation or acute changes in calcium metabolism. The aim of our study was to investigate effects of HD on serum fetuin-A levels. Forty clinically and hemodynamically stable hemodialysis patients (21 females, 68 (38-85) years) underwent routine bicarbonate hemodialysis or hemodiafiltration with polysulfone dialyzer. On consecutive HD dialysis solution with different calcium concentration with/without citric acid was used to assess influence of calcium shifts and parathyroid activity on fetuin-A changes during HD. All other parameters of HD were kept constant. Serum fetuin-A, calcium, phosphorus, iPTH, CRP and other biochemical parameters were measured before and after each HD. Our data show that predialysis serum fetuin-A levels have positive correlation with iPTH levels (p<0.05) and tendency to decrease with higher CRP levels. There was no change in fetuin-A levels during HD: 206 (167.1; 231.9) ug/ml before and 208.9 (170.3; 246.3) ug/ml after HD; respectively. When corrected for haemoconcentration, decrease in fetuin-A was only 2.8% (p<0.05). There was also no difference between effect of hemodialysis and hemodia-filtration procedure. The use of different calcium dialysate concentrations had distinct effect on iPTH levels during and after HD, however, we observed no associated changes in fetuin-A levels. The use of dialysate solution with citric acid had no effect on fetuin-A levels. In conclusion, standard bicarbonate HD with polysulfone dialyser and ultrapure dialysate induces only minor changes in fetuin-A and no changes in hsCRP levels. iPTH levels correlate positively with predialysis fetuin-A, but distinct acute changes in iPTH secretion induced by different dialysate calcium concentrations have no effect on serum fetuin-A levels after a single HD

CSF Markers of Oxidative Stress Are Associated with Brain Atrophy and Iron Accumulation in a 2-Year Longitudinal Cohort of Early MS

In this prospective longitudinal study, we quantified regional brain volume and susceptibility changes during the first two years after the diagnosis of multiple sclerosis (MS) and identified their association with cerebrospinal fluid (CSF) markers at baseline. Seventy patients underwent MRI (T1 and susceptibility weighted images processed to quantitative susceptibility maps, QSM) with neurological examination at the diagnosis and after two years. In CSF obtained at baseline, the levels of oxidative stress, products of lipid peroxidation, and neurofilaments light chain (NfL) were determined. Brain volumetry and QSM were compared with a group of 58 healthy controls. In MS patients, regional atrophy was identified in the striatum, thalamus, and substantia nigra. Magnetic susceptibility increased in the striatum, globus pallidus, and dentate and decreased in the thalamus. Compared to controls, MS patients developed greater atrophy of the thalamus, and a greater increase in susceptibility in the caudate, putamen, globus pallidus and a decrease in the thalamus. Of the multiple calculated correlations, only the decrease in brain parenchymal fraction, total white matter, and thalamic volume in MS patients negatively correlated with increased NfL in CSF. Additionally, negative correlation was found between QSM value in the substantia nigra and peroxiredoxin-2, and QSM value in the dentate and lipid peroxidation levels