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Brodska H.,Institute of Clinical Biochemistry and Laboratory Diagnostics | Malickova K.,Institute of Clinical Biochemistry and Laboratory Diagnostics | Valenta J.,Charles University | Fabio A.,University of Pittsburgh | Drabek T.,University of Pittsburgh
Scandinavian Journal of Clinical and Laboratory Investigation | Year: 2013

Objective. Multiple biomarkers are used to assess sepsis severity and prognosis. Increased levels of the soluble receptor for advanced glycation end products (sRAGE) were previously observed in sepsis but also in end-organ injury without sepsis. We evaluated associations between sRAGE and (i) 28-day mortality, (ii) sepsis severity, and (iii) individual organ failure. Traditional biomarkers procalcitonin (PCT), C-reactive protein (CRP) and lactate served as controls. Methods. sRAGE, PCT, CRP, and lactate levels were observed on days 1 (D1) and 3 (D3) in 54 septic patients. We also assessed the correlation between the biomarkers and acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and acute heart failure. Results. There were 38 survivors and 16 non-survivors. On D1, non-survivors had higher sRAGE levels than survivors (p = 0.027). On D3, sRAGE further increased only in non-survivors (p < 0.0001) but remained unchanged in survivors. Unadjusted odds ratio (OR) for 28-day mortality was 8.2 (95% CI: 1.02-60.64) for sRAGE, p = 0.048. Receiver operating characteristic analysis determined strong correlation with outcome on D3 (AUC = 0.906, p < 0.001), superior to other studied biomarkers. sRAGE correlated with sepsis severity (p < 0.00001). sRAGE showed a significant positive correlation with PCT and CRP on D3. In patients without ARDS, sRAGE was significantly higher in non-survivors (p < 0.0001) on D3. Conclusion. Increased sRAGE was associated with 28-day mortality in patients with sepsis, and was superior compared to PCT, CRP and lactate. sRAGE correlated with sepsis severity. sRAGE was increased in patients with individual organ failure. sRAGE could be used as an early biomarker in prognostication of outcome in septic patients. © 2013 Informa Healthcare. Source


Zeman M.,Charles University | Jachymova M.,Institute of Clinical Biochemistry and Laboratory Diagnostics | Jirak R.,Charles University | Vecka M.,Charles University | And 3 more authors.
Folia Biologica | Year: 2010

The prevalence of metabolic syndrome as well as the occurrence of depressive disorder, which are both connected with increased risk of diabetes mellitus type 2 and cardiovascular diseases, is continually increasing worldwide. These disorders are interconnected at various levels; the genetic one seems to be promising. Contribution of genetic factors to the aetiopathogenesis of depressive disorder weighs within the range 40-50 %, whereas the genetic background for the manifestation of metabolic syndrome is more complicated. In this pilot study, we investigated the incidence of polymorphisms in several genes supposed to play a role in the development of both depressive disorder and metabolic syndrome such as brain-derived neurotrophic factor, methylenetetrahydrofolate reductase, tyrosine hydroxylase, and endothelial nitric oxide synthase. The entire group consisted of 42 patients with depressive disorder, 57 probands with metabolic syndrome and 41 control individuals. We found that genotype Met/Met of the Val66Met polymorphism of the brain-derived neurotrophic factor gene was positively associated with depressive disorder (P < 0.05), but we were not able to find any significant associations of both the depressive disorder and metabolic syndrome with the remaining polymorphisms studied (methylenetetrahydrofolate reductase 677CT, methylenetetrahydrofolate reductase 1298AC, endothelial nitric oxide synthase Glu298Asp, and tyrosine hydroxylase). Source


Dvoankova B.,Charles University | Szabo P.,Charles University | Lacina L.,Charles University | Gal P.,Charles University | And 10 more authors.
Cells Tissues Organs | Year: 2011

Members of the galectin family of endogenous lectins are potent adhesion/growth-regulatory effectors. Their multifunctionality opens possibilities for their use in bioapplications. We studied whether human galectins induce the conversion of human dermal fibroblasts into myofibroblasts (MFBs) and the production of a bioactive extracellular matrix scaffold is suitable for cell culture. Testing a panel of galectins of all three subgroups, including natural and engineered variants, we detected activity for the proto-type galectin-1 and galectin-7, the chimera-type galectin-3 and the tandem-repeat-type galectin-4. The activity of galectin-1 required the integrity of the carbohydrate recognition domain. It was independent of the presence of TGF-β1, but it yielded an additive effect. The resulting MFBs, relevant, for example, for tumor progression, generated a matrix scaffold rich in fibronectin and galectin-1 that supported keratinocyte culture without feeder cells. Of note, keratinocytes cultured on this substratum presented a stem-like cell phenotype with small size and keratin-19 expression. In vivo in rats, galectin-1 had a positive effect on skin wound closure 21 days after surgery. In conclusion, we describe the differential potential of certain human galectins to induce the conversion of dermal fibroblasts into MFBs and the generation of a bioactive cell culture substratum. © 2011 S. Karger AG, Basel. Source


Pedersen N.,Copenhagen University | Lenicek M.,Institute of Clinical Biochemistry and Laboratory Diagnostics | Elkjaer M.,Copenhagen University | Bortlik M.,Charles University | And 6 more authors.
European Journal of Gastroenterology and Hepatology | Year: 2010

Background: Infliximab dependency in children with Crohn's disease (CD) has recently been described and found to be associated with a decreased surgery rate. AIM: To assess infliximab dependency of adult CD patients, evaluate the impact on surgery, and search for possible clinical and genetic predictors. Methods: Two hundred and forty-five CD patients treated with infliximab were included from Danish and Czech Crohn Colitis Database (1999-2006). Infliximab response was assessed as immediate outcome, 1 month after infliximab start: complete, partial, and no response. Three months outcome, after last intended infusion: prolonged response (maintenance of complete/partial response), infliximab dependency (relapse requiring repeated infusions to regain complete/partial response or need of infliximab >12 months to sustain response). Results: Forty-seven percent obtained prolonged response, 29% were infliximab dependent and 24% nonresponders. The cumulative probability of surgery 40 months after infliximab start was 20% in prolonged responders, 23% in infliximab-dependent patients and 76% in nonresponders (P<0.001). The cumulative probability of surgery at 40 months in patients on maintenance versus on demand regime was 33 and 31%, respectively (P=0.63). No relevant clinical or genetic predictors were identified. Conxlusion: The infliximab dependency response seems to be equivalent to the prolonged response in adult CD patients when comparing surgery rates. Copyright © Lippincott Williams & Wilkins. Source


Habara P.,Institute of Clinical Biochemistry and Laboratory Diagnostics | Habara P.,Institute of Immunology and Microbiology | Mareckova H.,Institute of Immunology and Microbiology | Malickova K.,Institute of Clinical Biochemistry and Laboratory Diagnostics | Zima T.,Institute of Clinical Biochemistry and Laboratory Diagnostics
Folia Biologica (Czech Republic) | Year: 2012

Glomerulonephritides together create a heterogenic group of supposedly immunologically mediated diseases of glomeruli. They still belong among the most frequent causes of chronic renal failure. Detection of podocytes in urine might serve as an important marker of glomerulonephritides activity. The aim of this study was to develop a novel flow cytometric method for the detection of podocyte fragments and podocytes in urine and assess its possible use in clinical practice. We placed emphasis on the improvement of pre-analytic phase. To suppress the autofluorescence of the background, blocking solutions and magnetic separation were used. An additional surface marker CD10 (nephrilysin) was used together with routinely used podocalyxin (PCX) in order to achieve better identification of podocytes. Based on the surface marker expression, three different element types were identified in the urine samples: PCX+/CD10+ elements (EL) (supposedly podocytes), PCX-/CD10+ EL (supposedly parietal epithelial cells) and PCX+ EL. We examined a total of 36 patients who underwent renal biopsy (non-glomerular nephropathy, MGN, FSGS, IgAN, AAV and MPGN) and 27 healthy controls. Negative results were found in non-glomerular nephropathy and in MGN. In patients with FSGS and IgAN, the levels of urine elements were slightly increased. The highest levels of all elements were found in AAV and MPGN. Our first results suggest that flow cytometric detection may distinguish between glomerular and nonglomerular diseases and that the levels of urine elements might correlate with the degree of glomerular destruction. Source

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