Joanna Siódmiak

Engrailed-2 protein as a potential urinary prostate cancer biomarker: a comparison study before and after digital rectal examination.

This study was designed to compare and evaluate the presence of engrailed-2 (EN2) protein in urine collected before and after prostate massage as a diagnostic marker for prostate cancer (PCa). We analysed and compared 76 urine samples (38 before and 38 after prostate massage) from the benign group (BPH) and 66 urine samples (33 before and 33 after prostate massage) from patients with PCa confirmed by prostate biopsy. EN2 levels from the PCa and men with BPH (age range 50–82) were related to the tumour stage, Gleason score and prostate-specific antigen. EN2 levels were determined by enzyme-linked immunosorbent assay in urine. The median EN2 levels in urine after prostate massage were significantly different from those determined in urine before prostate massage (1.25 ng/ml in the PCa group and 0.34 ng/ml in the BPH). The mean EN2 levels in PCa patients were 3.76-fold higher than those in non-PCa patients after prostate massage. The distinct influence of prostate massage on EN2 levels was found to be related to the Gleason score and tumour stage. EN2 may be considered a marker of PCa with certain limitations, such as those related to tumour staging. The specificity and sensitivity of the protocol are highly dependent on prostate massage.

25-Hydroxyvitamin D, biomarkers of eosinophilic inflammation, and airway remodeling in children with newly diagnosed untreated asthma.

BACKGROUND Low 25-hydroxyvitamin D (25[OH]D) and asthma development may be related to airway remodeling and eosinophilia. Periostin is proposed as a key molecule that links remodeling and eosinophilic inflammation. OBJECTIVE We evaluated the association of 25(OH)D concentration with periostin, peripheral blood eosinophil counts, and immunoglobulin E (IgE) in children with newly diagnosed asthma. METHODS The study included 150 children: 110 with atopic asthma and 40 constituted a reference group. Fasting blood was collected for cell counts and serum for measurements of 25(OH)D, periostin, IgE, and C-reactive protein (CRP) concentrations. RESULTS Significantly lower 25(OH)D, elevated IgE concentrations, and eosinophil counts were found in children with asthma compared with the reference group (p = 0.0001). A lower forced expiratory volume in the first second of expiration percentage predicted value was associated with a lower 25(OH)D value in children with asthma. The bronchodilator reversibility was inversely related to serum 25(OH)D concentrations (R = -0.45, p = 0.029). The children with asthma and with a 25(OH)D deficient concentration (≤20 ng/mL) had higher concentrations of periostin (p = 0.035) and CRP (p = 0.01) than those with a sufficient 25(OH)D concentration (≥30 ng/L). Additional analysis revealed statistically significant differences (p = 0.013) when comparing periostin concentrations between subjects with a 25(OH)D deficient concentration (≤20 ng/mL) and subjects who did not have a deficient concentration (>20 ng/mL). In individuals with asthma, a 25(OH)D concentration of <30 ng/mL had no impact on eosinophilia, whereas IgE concentrations were associated with increased eosinophils, and the effect of periostin on eosinophilia was small although significant. Multivariate regression, including 25(OH)D concentration, CRP level, eosinophil counts, and sex, accounted for 7% of periostin variation in subjects with asthma. CONCLUSION In newly diagnosed pediatric asthma, 25(OH)D concentrations revealed a small although significant association with periostin levels but no effect on eosinophilia. A low vitamin D concentration may increase airway remodeling induced by inflammatory mediators, but further clinical studies aimed to explain the causal link between vitamin D insufficiency and asthma are needed.BACKGROUND Low 25-hydroxyvitamin D (25[OH]D) and asthma development may be related to airway remodeling and eosinophilia. Periostin is proposed as a key molecule that links remodeling and eosinophilic inflammation. OBJECTIVE We evaluated the association of 25(OH)D concentration with periostin, peripheral blood eosinophil counts, and immunoglobulin E (IgE) in children with newly diagnosed asthma. METHODS The study included 150 children: 110 with atopic asthma and 40 constituted a reference group. Fasting blood was collected for cell counts and serum for measurements of 25(OH)D, periostin, IgE, and C-reactive protein (CRP) concentrations. RESULTS Significantly lower 25(OH)D, elevated IgE concentrations, and eosinophil counts were found in children with asthma compared with the reference group (p = 0.0001). A lower forced expiratory volume in the first second of expiration percentage predicted value was associated with a lower 25(OH)D value in children with asthma. The bronchodilator reversibility was inversely related to serum 25(OH)D concentrations (R = -0.45, p = 0.029). The children with asthma and with a 25(OH)D deficient concentration (≤20 ng/mL) had higher concentrations of periostin (p = 0.035) and CRP (p = 0.01) than those with a sufficient 25(OH)D concentration (≥30 ng/L). Additional analysis revealed statistically significant differences (p = 0.013) when comparing periostin concentrations between subjects with a 25(OH)D deficient concentration (≤20 ng/mL) and subjects who did not have a deficient concentration (>20 ng/mL). In individuals with asthma, a 25(OH)D concentration of <30 ng/mL had no impact on eosinophilia, whereas IgE concentrations were associated with increased eosinophils, and the effect of periostin on eosinophilia was small although significant. Multivariate regression, including 25(OH)D concentration, CRP level, eosinophil counts, and sex, accounted for 7% of periostin variation in subjects with asthma. CONCLUSION In newly diagnosed pediatric asthma, 25(OH)D concentrations revealed a small although significant association with periostin levels but no effect on eosinophilia. A low vitamin D concentration may increase airway remodeling induced by inflammatory mediators, but further clinical studies aimed to explain the causal link between vitamin D insufficiency and asthma are needed.

Alpha-methylacyl-CoA racemase and hepsin as urinary prostate cancer markers

Background Because of the numerous limitations of prostate-specific antigen (PSA), α-methylacyl-CoA racemase (AMACR) and hepsin have recently been suggested as potential biomarkers in prostate cancer (PC). This report presents a comparison study of the presence of AMACR and hepsin in urine collected before and after digital rectal examination (DRE) as a previously suggested diagnostic marker for PC. Methods Seventy-six urine samples (38 before and 38 after prostate massage) from patients with benign prostate hyperplasia (BPH) and 66 urine samples (33 before and 33 after prostate massage) from patients with PC were analyzed. PC was confirmed by prostate biopsy. Urinary levels of AMACR and hepsin were determined by ELISA and related to the tumor stage, Gleason score and PSA level. Results AMACR and hepsin levels in urine collected after prostate massage were higher only in the PC group. There were no correlations between AMACR levels, hepsin levels, tumor stage and Gleason score. AMACR and hepsin did not differentiate between BPH and PC with better true positive and false negative rates than serum PSA. Conclusions AMACR and hepsin were unable to diagnose PC with better true positive and false negative rates than PSA. An additional procedure combined with other markers should be applied for the reliable diagnosis of PC.

Serum 25(OH)D status and lipid profile in children with newly diagnosed asthma

Background. The problem of the influence of hyperlipidemia on asthma was addressed several years ago. Systematic review and meta-analysis performed in the pediatric population on the association between vitamin D status and lipid profile components revealed discordant results and indicated that higher serum 25(OH)D is related to a more favorable lipid profile. Objective. We aimed to elucidate whether there was an association between vitamin D status and lipid profile components and apolipoprotein B in a sample of children with newly diagnosed atopic asthma. Methods. The study included 150 children aged 2–12 years. Atopic asthma was diagnosed in 110 children; 40 children constituted a reference group. Fasting blood was collected to measure 25(OH)D total, lipid profile and apolipoprotein B concentrations. Results. Children with asthma had significantly lower 25(OH)D (p < 0.0001) but similar lipid and apolipoprotein B concentrations. The proportions of hypercholesterolemia, hypertriglyceridemia and increased apoB concentrations were similar in both groups. HDL-C concentrations in asthmatic 25(OH)D-deficient children were higher compared with the children with sufficient levels (p = 0.05). ApoB concentration was lower in 25(OH)D-deficient compared with vitamin D sufficient asthmatics (p = 0.0008). Correlations between 25(OH)D concentration and lipids and apoB in asthmatics revealed gender differences. An inverse relationships between vitamin D and total cholesterol and HDL-C (R= –0.39, p < 0.05; R= –0.475, p < 0.001) were found in girls. In boys vitamin D correlated with LDL-C and apoB (R = 0.376, R = 0.498; p < 0.001). Conclusion. In children with asthma lower 25(OH)D had more favorable gender-dependent effect on the lipid profile. The association of serum 25(OH)D and lipid levels in children with asthma remains for further studies.

Response to “The Putative Role of Vitamin D in Essential Hypertension: Stepping Into the Light?”

To the Editor: In their letter, “The Putative Role of Vitamin D in Essential Hypertension: Stepping Into the Light?,” Gkaliagkousi et al. seem to question the use of traditional circulating biomarkers such as soluble intercellular adhesion molecule (sICAM), C-reactive protein (CRP), and homocysteine (Hcy) for the evaluation of endothelial dysfunction. They point out the latest position statement1 and recent European Society of Hypertension guidelines2 as a source of information on methods for the evaluation of endothelial dysfunction. It is obvious, however, that guidelines do not explicitly define which biomarkers should be used, and the position statement presents different methods for evaluating endothelial function, including the measurement of biomarkers we used,3 with the special focus on emerging biomarkers. We strongly disagree with Gkaliagkousi et al.’s criticism because we measured the circulating biomarkers that are widely and commonly used by others as determinants of endothelial dysfunction.4–6 Serum biomarkers of the endothelial origin reflect endothelial function; higher levels are thought to mirror the endothelial activation or damage.4 It has been reported that activated endothelial cells show enhanced expression and release of cell-surface adhesion molecules. sICAM-1 concentration correlates with its cell expression and was confirmed recently to be a sensitive marker of inflammatory vascular activation in hypertensive adolescents.7 Within the past 10 years the association between CRP and other inflammatory markers (including s-ICAM-1, Hcy) with prehypertension, hypertension, and arterial stiffness has been demonstrated.5 CRP is not only a biomarker of inflammation but, as recently unraveled,6 also actively and directly participates in the development of the endothelial dysfunction, which stands in stark contrast to the criticism of Dr Gkaliagkousi. Besides an array of traditional biomarkers, several modern but expensive methods may be used to assess the endothelial status: imaging methods and measurement of endothelial progenitor cells, circulating endothelial cells, and endothelial-derived microparticles (EMPs).1 Interestingly, a recent study8 demonstrated that sICAM-1 correlated significantly with EMPs measured by flow cytometry, which unequivocally substantiates its use as a surrogate marker of endothelial dysfunction. The emerging evidence suggests that blood EMPs may serve as both specific markers and contributors to pathology; however, their accurate quantification is a substantial challenge. EMPs and ECPs (endothelial progenitor cells) may be attractive biomarkers, but their measurement by multicolor flow cytometry or proteomic analysis by mass spectrometry is not widely available. Furthermore, progress in standardization of measurement of the emerging biomarkers is crucial to establish their clinical interest for the assessment of endothelial dysfunction. In the recent European Society of Hypertension guidelines, the term “BP variability” obviously refers to visit-tovisit blood pressure variability or blood pressure variability assessed by ambulatory blood pressure measurement. The mathematical definition of “variation” describes a function that relates the values of one variable to those of other variables, and in this sense we assessed variables of significance for the prediction of systolic blood pressure variation that was adjusted for possible confounders. In fact, both terms “variation” and “variability” are used interchangeably, which does not necessarily have to be correct because the R2 value explains the variability in the statistics. 25-Hydroxyvitamin D might mediate various biological effects, and it regulates physiological functions such as the expression of adhesion molecules and endothelium-dependent vasoconstriction. The endothelial dysfunction was associated with 25(OH) D deficiency; moreover, 25(OH)D deficiency was propounded to promote endothelial dysfunction. We presented potential mechanisms relating to the role of 25(OH)D and its influence on the endothelial dysfunction in hypertension. The putative causal relationships remain to be elucidated.

Assessment of Peritoneal Membrane Arteriolar Structure in Conjunction with Traditional Cardiovascular System Evaluation in Chronic Kidney Disease (CKD) Stage 5 Patients

Background/Aims: Cardiovascular complications are responsible for increased mortality and morbidity in chronic kidney disease (CKD) patients. Functional and structural changes of peritoneal membrane are reported in CKD patients both on conservative treatment and on renal replacement therapy (RRT). The aim of the study was to assess the structure of peritoneal membrane small arteries (precapillary arterioles) in diabetic and non-diabetic CKD stage 5 patients before initiation of peritoneal dialysis (PD) and evaluate its relationship with heart and large arteries abnormalities and with selected biochemical parameters. Methods: Evaluation of 42 CKD stage 5 patients before starting PD. Diabetic (n=26) and non-diabetic (n=16) patients were compared. Peritoneal membrane samples were taken during Tenckhoff catheter insertion. Histopathological evaluation of peritoneal precapillary arterioles (arteriolar evaluation) with measurement of wall thickness (WT) and calculation of lumen/vessel (L/V) ratio was performed in each patients. Echocardiography, intima media thickness (IMT), pulse wave velocity (PWV), ambulatory blood pressure monitoring (ABPM) and biochemical parameters assessment: serum albumin (SA), total cholesterol (TCH), hemoglobin (Hgb), parathormone (PTH), serum calcium (Ca), serum phosphorus (P), transferrin saturation (TSAT%), C-reactive protein (CRP) were performed in each participant. Results: There were no statistically significant differences in peritoneal membrane arteriolar indices – wall thickness (WT) and L/V ratio between investigated groups. There was statistically significant higher PWV value in diabetic patients. There were no statistically significant differences in echocardiographic indices, IMT, laboratory data in analyzed groups. There were some linear correlations between: PWV vs IMT (R=0,84; p=0,0006); PWV vs PP (R=0,58; p=0,03) in non-diabetic and linear correlation between: PWV vs age (R=0,75; p=0,02); WT vs DP (R=-0,93; p=0,001); WT vs DBP ( R=0,64; p=0,04) in diabetic group. Conclusion: Peritoneal membrane arteriolar damage seems to be an integrated part of cardiovascular system damage in CKD stage 5 patients.

Thyroid-stimulating hormone within low-normal range is related to imbalance of bone remodeling in euthyroid postmenopausal women with osteoporotic fractures

Introduction. Data relating to thyroid-stimulating hormone (TSH) and risk of fractures are limited, and the effect of TSH within the normal range on bone mineral density (BMD) and bone remodelling is controversial. We aimed to evaluate whether variations across TSH concentration within the normal range are associated with bone metabolism expressed by bone remodeling markers in euthyroid postmenopausal women with osteoporotic fractures. Material and methods. The study group consisted of 60 elderly women admitted to the hospital due to nonvertebral osteoporotic fractures of which 57 were diagnosed as euthyroid. In all serum fT4, and TSH, P1NP (a bone formation marker) and CTX (a bone resorption marker) were measured. Results. The majority of fractures occurred at the lower TSH tertile (0.14–2.19 mIU/L). Most of the patients (70%) in this tertile had TSH value below 1 mIU/L. There was a clear tendency towards lower P1NP in the first TSH tertile (p = 0.056 and p = 0.057) whereas most CTX values tended to be higher than the median concentration in the whole group. A significant positive correlation between TSH and P1NP was observed (r = 0.32; p = 0.01). TSH within the normal range and CTX explained 25% of the variability of P1NP in euthyroid women with osteoporotic fractures. Conclusions. In elderly euthyroid women low-normal TSH level seems to be associated with the imbalance between bone resorption and formation. Diminished bone formation may predispose to increased risk of nonvertebral fractures. Bone marker testing in subjects with low-normal TSH may add new value in the assessment of fracture risk.

Biomarkers of bone cell activity in children and adolescents with newly diagnosed, untreated acute lymphoblastic leukemia

Introduction. Controversial data on disturbances in mineral homeostasis and bone mass were reported in children with diagnosed untreated acute lymphoblastic leukemia (ALL). Early detection of bone metabolism abnormalities is important for monitoring the effect of therapy on the skeleton. The purpose of this study was to evaluate bone metabolism in children and adolescents with newly diagnosed acute lymphoblastic leukemia by assessing biomarkers of bone cell activity. Materials and methods. Propeptide of type 1 procollagen (P1NP) and osteocalcin (OC) as bone formation markers and C-terminal telopeptide of type 1 collagen (CTX) and tartrate resistant acid phosphatase 5b (TRAP 5b) as resorption markers were determined in 22 Caucasian children and adolescents (12 boys 4–21 years, 10 girls 4–16 years) with newly diagnosed, untreated ALL and in 22 age- and gender-matched controls. Results. Bone formation, in particular, and bone resorption were significantly reduced in ALL children and adolescents compared with controls (Me P1NP 51.9 vs. 433.4 μ g/L and OC 16.1 vs. 80.5 μ g/L; p < 0.0001; Me CTX 0.454 vs. 1.225 μ g/L and TRAP 5b 2.8 vs. 5.6 U/L; p < 0.001). P1NP positively correlated with OC (r = 0.56; p = 0.01) and CTX correlated with TRAP 5b (r = 0.54; p = 0.02) in children and adolescents with ALL. Median P1NP and OC concentrations in ALL children (4–9 years) were dramatically reduced compared with the healthy ones (10-fold and 9-fold respectively), whereas in adolescents with ALL (10–21 years) both bone formation markers were reduced in a lesser degree in comparison with the healthy adolescents. Conclusions. Acute lymphoblastic leukemia influences bone metabolism which is strongly related to the age of onset. More significant disturbances in bone turnover, particularly in bone formation (suppression of collagen synthesis), are observed in children with untreated ALL in comparison with adolescents with ALL.

The fructose tolerance test in patients with chronic kidney disease and metabolic syndrome in comparison to healthy controls

BackgroundFructose acutely raises serum uric acid in normal subjects, but the effect in subjects with metabolic syndrome or subjects with chronic kidney disease is unknown. The aim of the study was to evaluate changes in serum uric acid during the fructose tolerance test in patients with chronic kidney disease, metabolic syndrome with comparison to healthy controls.MethodsStudies were performed in 36 subjects with obesity (body mass index >30) and metabolic syndrome, 14 patients with stage 3 chronic kidney disease, and 25 healthy volunteers. The fructose tolerance test was performed in each patient. The change in serum uric acid during the fructose challenge was correlated with baseline ambulatory blood pressure, serum uric acid, metabolic, and inflammatory markers, and target organ injury including carotid intima media thickness and renal resistive index (determined by Doppler).ResultsAbsolute serum uric acid values were highest in the chronic kidney disease group, followed by the metabolic syndrome and then healthy controls. Similar increases in serum uric acid in response to the fructose tolerance test was observed in all three groups, but the greatest percent rise was observed in healthy controls compared to the other two groups. No significant association was shown between the relative rise in uric acid and clinical or inflammatory parameters associated with kidney disease (albuminuria, eGFR) or metabolic syndrome.ConclusionsSubjects with chronic kidney disease and metabolic syndrome have higher absolute uric acid values following a fructose tolerance test, but show a relatively smaller percent increase in serum uric acid. Changes in serum uric acid during the fructose tolerance test did not correlate with changes in metabolic parameters, inflammatory mediators or with target organ injury. These studies suggest that acute changes in serum uric acid in response to fructose do not predict the metabolic phenotype or presence of inflammatory mediators in subjects with obesity, metabolic syndrome or chronic kidney disease.Trial registrationThe study was registered in ClinicalTrials.gov. Identifier : NCT01332526. www.register.clinicaltrials.gov/01332526