Plasma and Peritoneal Fluid Annexin A2 Levels in Patients with Endometriosis.

Introduction: Endometriosis is an inflammatory-related reproductive age disease characterized by the presence of endometrial cells outside the uterine cavity. Current laboratory practice does not provide specific markers for detecting and assessing the advancement of endometriosis in either plasma or peritoneal fluid. The severity of disease is assessed in stages from I to IV based on the results of laparoscopic inspection. The protein annexin A2 (ANXA2) has been reported to be associated with inflammatory processes. Aim of the Study: The study aimed to investigate and compare ANXA2 protein concentration using the ELISA method in plasma and peritoneal fluid in a group of women with endometriosis compared to controls. Materials and Methods: Biological material was collected during a multicenter, cross-sectional study, which was conducted at eight departments during elective laparoscopy from 53 women with and 40 women without endometriosis. Patients were divided by endometriosis stage and infertility status, and then compared with subgroups. Analysis included the Chi-square test for categorical variables, Mann-Whitney U-test and two-sided Wilcoxon rank-sum test for continuous variables. Results: Women with endometriosis had significantly elevated plasma ANXA2 levels compared to women without endometriosis (mean concentrations 28.69 vs 19.61 ng/L, p=0.01). Differences in peritoneal fluid ANXA2 levels were statistically insignificant (mean concentrations of 23.7 vs 22.97 ng/L, p=0.06). Plasma concentrations in patients with stage III and IV endometriosis were significantly higher compared to controls (mean concentrations of 24.19 vs 19.71 ng/L, p=0.03). No such differences were observed in plasma when comparing stages I-II vs III-IV, and stages I-II vs controls (mean concentrations of 33.82 vs 24.19 ng/L, p=0.72 and 33.82 vs 19.71 ng/L, p=0.12, respectively). Comparison of samples from patients with or without infertility, primary or secondary infertility, endometriosis with or without infertility, and non-endometriosis with or without infertility showed no significant differences in the plasma nor in the peritoneal fluid concentrations. Conclusion: ANXA2 is possibly involved in the pathogenesis of endometriosis, especially in advanced stages. Due to the limited group of tested samples, further studies are needed to confirm its role.

An Array SPRi Biosensor for the Determination on PARP-1 in Blood Plasma.

A biosensor was developed for the quantification of poly(ADP-ribose) polymerase-1 (PARP-1) in body fluids. An antibody specific for PARP-1 was placed on a chip with cysteamine (linker) and a gold layer. This biosensor has a linear response range (10-1000 pg∙mL-1) under appropriate pH conditions and with an antibody ligand concentration of 5 ng∙mL-1. Plasma samples were diluted with PBS buffer in appropriate quantities so that they fell within the linear range of the calibration curve. The biosensor exhibited suitable precision and accuracy, and good recovery (at levels from 95% to 105%). The method was validated by means of PARP-1 determinations in plasma samples from patients with endometriosis and a control group, using surface plasmon resonance imaging (SPRi) biosensors and an enzyme-linked immunosorbent assay (ELISA) test. The Spearman correlation coefficient was close to 1. PARP-1 may be a marker providing information about pathological changes in the body during endometriosis.

Plasma and Peritoneal Poly (ADP-Ribose) Polymerase Levels in Patients with Endometriosis.

The evidence of poly (ADP-ribose) polymerase (PARP) association with the immune response could be coherent with the immunological theory of endometriosis and suggests the possibility of a new research direction. The aim of the study was to evaluate the levels of PARP in plasma and peritoneal fluid of patients with and without endometriosis. It was a multicenter, cross-sectional study. Plasma and peritoneal fluid samples were collected from patients with and without endometriosis during planned laparoscopic procedures in eight clinical centers. In total, 84 samples of plasma and 84 samples of the peritoneal fluid were included in the final analyses. Double-antibody sandwich enzyme-linked immunosorbent assay was performed in order to assess levels of PARP in collected samples. No statistically significant differences regarding the detected levels of PARP in plasma and peritoneal fluid comparing patients with and without endometriosis were observed. Patients with a history of infertility had significantly higher plasma PARP concentrations (p = 0.04). We have not observed the potential role of PARP concentration levels in plasma nor peritoneal fluid as an endometriosis biomarker. We have determined an association between a higher plasma PARP concentration and a history of infertility.

Plasma and Peritoneal Fluid ZEB Levels in Patients with Endometriosis and Infertility.

Zinc finger E-box-binding homeobox 1 (ZEB1) and zinc finger E-box-binding homeobox 2 (ZEB2) are transcription factors that regulate epithelial−mesenchymal transformation (EMT). The aim of this study was to compare levels of ZEB1 and ZEB2 in the peritoneal fluid and plasma between patients with and without endometriosis in order to assess their utility in the diagnostic process. Plasma and peritoneal fluid samples were collected from 50 patients with and 48 without endometriosis during planned surgical procedures in eight clinical centers. Quantitative ZEB1 and ZEB2 levels analyses were performed using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in ZEB1 levels in any of the subanalyses nor any differences regarding ZEB2 levels between patients with and without endometriosis. Plasma ZEB2 levels were significantly higher among patients with infertility compared to fertile women (16.07 ± 12.70 ng/L vs. 12.07 ± 11.92 ng/L; p < 0.04). Both ZEB1 and ZEB2 do not seem to have a significant value in the initial diagnosis of endometriosis as a single marker. The differences in ZEB2 plasma levels between patients with and without infertility indicate the possibility of EMT dysregulation in the pathogenesis of adverse fertility outcomes.

Factors Influencing Longevity of Humoral Response to SARS-CoV-2 Vaccination in Patients with End Stage Kidney Disease Receiving Renal Replacement Therapy.

COVID-19 has severely affected the population of patients with end stage renal disease. Current data have proved a two-dose vaccination schedule against SARS-CoV-2 to be effective among dialyzed patients. There are limited data on the longevity and modulating factors of humoral response after vaccination. We performed a prospective longitudinal cohort study to determine longevity of the humoral response after SARS-CoV-2 vaccine. The study included 191 adult patients on hemodialysis and peritoneal dialysis. All participants had been vaccinated with three doses, either with BNT162b2 (Pfizer-BioNTech) (n = 109) or mRNA-1273 (Moderna) (n = 82). Anti-spike protein receptor-binding domain antibodies (anti-S IgG) were assessed using SARS-CoV-2 (RBD) IgG ELISA EIA-6150 IVD assay at baseline, on the 21st day and 43rd day, before a booster dose and two weeks thereafter. We found that before vaccination, 37.7% of the cohort had anti-S IgG titres concordant with seroconversion. After two-dose vaccination, seroconversion occurred in 97% of patients. The booster dose evoked a ~12-fold increase in antibody level. Obesity increased more than two-fold the odds for a decrease in anti-S IgG. Previous COVID-19 infection enhanced longevity of the humoral response following vaccination. In patients with previous COVID-19 infection, the BNT162b2 vaccine was associated with a higher odds of anti-S IgG waning compared to the mRNA-1273 vaccine. In conclusion, we report that obesity predisposes patients to protective antibody waning, hybrid immunity enhances odds for higher anti-S IgG concentrations and vaccine efficacy may be influenced by previous SARS-CoV-2 infection. The results might provide a rationale for vaccination protocol design.

The Role of Cadherin 12 (CDH12) in the Peritoneal Fluid among Patients with Endometriosis and Endometriosis-Related Infertility.

Cadherin 12 (CDH 12) can play a role in the pathogenesis of endometriosis. The aim of this study was to compare the levels of cadherin 12 in the peritoneal fluid between women with and without endometriosis. This was a multicenter cross-sectional study. Eighty-two patients undergoing laparoscopic procedures were enrolled in the study. Cadherin 12 concentrations were determined using the enzyme-linked immunosorbent assay. The level of statistical significance was set at p < 0.05. No differences in cadherin 12 concentrations between patients with and without endometriosis were observed (p = 0.4). Subgroup analyses showed that CDH 12 concentrations were significantly higher in patients with infertility or primary infertility and endometriosis in comparison with patients without endometriosis and without infertility or primary infertility (p = 0.02) and also higher in patients with stage I or II endometriosis and infertility or primary infertility than in patients without endometriosis and infertility or primary infertility (p = 0.03, p = 0.048, respectively). In total, CDH 12 levels were significantly higher in patients diagnosed with infertility or primary infertility (p = 0.0092, p = 0.009, respectively) than in fertile women. Cadherin 12 can possibly play a role in the pathogenesis of infertility, both in women with and without endometriosis.

The Key Role of Hepcidin-25 in Anemia in Multiple Myeloma Patients with Renal Impairment.

Background and objectives: Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron turnover: serum soluble transferrin receptor (sTfR) and hepcidin-25 in patients at various stages of MM in relation with markers of anemia, iron status, inflammation, renal impairment and burden of the disease and as predictors of mortality. Materials and methods: Seventy-three MM patients (six with smoldering and 67 with symptomatic disease) were recruited and observed for up to 27 months. Control group included 21 healthy individuals. Serum sTfR and hepcidin were measured with immunoenzymatic assays. Results: MM patients with and without anemia had higher sTFR compared to controls, while only anemic patients had higher hepcidin-25. Both hepcidin-25 and sTfR were higher in anemic than non-anemic patients. Higher hepcidin-25 (but not sTfR) was associated with increasing MM advancement (from smoldering to International Staging System stage III disease) and with poor response to MM treatment, which was accompanied by lower blood hemoglobin and increased anisocytosis. Neither serum hepcidin-25 nor sTfR were correlated with markers of renal impairment. Hepcidin-25 predicted blood hemoglobin in MM patients independently of other predictors, including markers of renal impairment, inflammation and MM burden. Moreover, both blood hemoglobin and serum hepcidin-25 were independently associated with patients' 2-year survival. Conclusions: Our results suggest that hepcidin-25 is involved in anemia in MM and its concentrations are not affected by kidney impairment. Moreover, serum hepcidin-25 may be an early predictor of survival in this disease, independent of hemoglobin concentration. It should be further evaluated whether including hepcidin improves the early diagnosis of anemia in MM.

Renal Impairment Detectors: IGFBP-7 and NGAL as Tubular Injury Markers in Multiple Myeloma Patients.

Background and Objectives: Urine insulin-like growth factor-binding protein 7 (IGFBP-7), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and neutrophil gelatinase-associated lipocalin (NGAL) monomer are novel tubular kidney injury biomarkers. In multiple myeloma (MM), immunoglobulin free light chains (FLCs) play an integral role in renal impairment. This study aimed to investigate the correlation between new biomarkers and acclaimed parameters of renal failure, MM stage, and prognosis. Materials and Methods: The examined parameters included: urinary and serum cystatin-C, IGFBP-7, and TIMP-2, and urinary NGAL monomer in 124 enrolled patients. Results: Urinary and serum IGFBP-7 and urinary NGAL were higher among patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and positively correlated with urine light chains. Serum and urine IGFBP-7 and urine NGAL were greater among patients with a higher disease stage. In the whole study group, urinary concentrations of the studied markers were positively correlated with each other. In multiple linear regression, urinary IGFBP-7 and NGAL were associated with lower eGFR, independently of other urinary markers. Conclusions: Urinary IGFBP-7 and NGAL monomer may be useful markers of tubular renal damage in patients with MM. Biomarker-based diagnostics may contribute to earlier treatment that may improve renal outcomes and life expectancy in MM.

Serum sirtuin 1 is independently associated with intact PTH among patients with chronic kidney disease.

BACKGROUND: Sirtuin 1 is involved in the pathogenesis of age-related diseases. PURPOSE: The aim of the study was to assess the clinical and diagnostic value of serum sirtuin 1 concentration in patients with CKD. PATIENTS AND METHODS: The serum sirtuin 1 level was evaluated using ELISA kit in 100 CKD patients stratified for five stages and in a control group of 24 healthy volunteers. RESULTS: Serum sirtuin 1 concentration was higher in the CKD group compared with the control group (p<0.05). Sirtuin 1 correlated with conventional CKD biomarkers and eGFR equations, intact parathyroid hormone (iPTH) and age (all p<0.05). Statins, AT1 receptor antagonists and ß-blockers use were associated with decreased sirtuin concentration (p<0.05). Sirtuin 1 was able to distinguish CKD from control group with high sensitivity and specificity (93% and 87%, respectively; AUC=0.954). Surprisingly, after adjustment only iPTH concentration was an independent predictor of sirtuin 1 level. CONCLUSION: The association between sirtuin 1, eGFR equations and iPTH indicates its possible usefulness as a kidney function marker. In terms of iPTH being the only independent predictor of circulating sirtuin 1 it can be considered as an indirect cardiovascular risk biomarker regardless of renal function and provide additional information for patient management. Alternatively, sirtuin 1 is recognized as protective against vascular disease, and we demonstrated a positive correlation with iPTH, which may be related to accumulation of (7-84)-PTH having opposite biological effects to full-length PTH. Further studies are needed to explore the interplay between sirtuin 1, PTH and CKD-related vascular calcification as well as to assess its prognostic value in observational studies.

Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

Transgelin is a 22-kDa protein involved in cytoskeletal organization and expressed in smooth muscle tissue. According to animal studies, it is a potential mediator of kidney injury and fibrosis, and moreover, its role in tumorigenesis is emerging in a variety of cancers. The study included 126 ambulatory patients with multiple myeloma (MM). Serum transgelin-2 concentrations were measured by enzyme-linked immunoassay. We evaluated associations between baseline transgelin and kidney function (serum creatinine, estimated glomerular filtration rate-eGFR, urinary markers of tubular injury: cystatin-C, neutrophil gelatinase associated lipocalin-NGAL monomer, cell cycle arrest biomarkers IGFBP-7 and TIMP-2) and markers of MM burden. Baseline serum transgelin was also evaluated as a predictor of kidney function after a follow-up of 27 months from the start of the study. Significant correlations were detected between serum transgelin-2 and serum creatinine (R = 0.29; p = 0.001) and eGFR (R = -0.25; p = 0.007). Transgelin significantly correlated with serum free light chains lambda (R = 0.18; p = 0.047) and serum periostin (R = -0.22; p = 0.013), after exclusion of smoldering MM patients. Patients with decreasing eGFR had higher transgelin levels (median 106.6 versus 83.9 ng/mL), although the difference was marginally significant (p = 0.05). However, baseline transgelin positively correlated with serum creatinine after the follow-up period (R = 0.37; p < 0.001) and negatively correlated with eGFR after the follow-up period (R = -0.33; p < 0.001). Moreover, higher baseline serum transgelin (beta = -0.11 ± 0.05; p = 0.032) significantly predicted lower eGFR values after the follow-up period, irrespective of baseline eGFR and follow-up duration. Our study shows for the first time that elevated serum transgelin is negatively associated with glomerular filtration in MM and predicts a decline in renal function over long-term follow-up.

Vitamin D deficiency and anemia is highly prevalent and dependent on the etiology of heart failure: A pilot study.

BACKGROUND: Anemia and vitamin D deficiency are common factors in chronic heart failure (CHF). The aim of this study was to assess vitamin D levels as well as its binding protein and anemia in relation to a cause of CHF: coronary heart disease, valvular disease and cardiomyopathy. METHODS: One hundred and sixteen consecutive patients (36 females and 80 males) with CHF were admitted for percutaneous coronary interventions (PCI). Hemoglobin concentration, serum creatinine, B-type natriuretic peptide (BNP), 25-hydroxyvitamin D [25(OH)D] and its binding protein-VDBP were measured. RESULTS: The prevalence of anemia was 22%. BNP was the highest in the group with coronary artery disease. Ejection fraction was the lowest in cardiomyopathy group. 25(OH)D was lowest in valvular disease group, significantly lower than in the coronary artery group. A similar pattern of change showed vitamin D binding protein. The prevalence of vitamin D deficiency (level below 20 ng/mL) in the whole group was 95%, in 49% of the patients 25(OH)D was below 10 ng/mL. In univariate analysis 25(OH)D correlated with hemoglobin, red blood cell count, hematocrit, mean corpuscular volume and BNP in patients with CHF in the whole group. In multiple regression analysis, predictors of 25(OH)D were estimated, glomerular filtration rate, BNP and valvular disease. CONCLUSIONS: 25(OH)D deficiency is common in CHF patients. Valvular disease is associated the most severe vitamin D deficiency and worsened kidney function. A higher prevalence of anemia in CHF due to coronary heart disease may be associated with wider use of angiotensin converting enzyme inhibitors and acetylsalicylic acid. Heart and kidney function are predictors of 25(OH)D level in the patients of this study.

Evaluating the Relationship of GDF-15 with Clinical Characteristics, Cardinal Features, and Survival in Multiple Myeloma.

Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-ß superfamily, participates in processes associated with myeloma development and its end-organ complications. It plays a significant role in both physiological and abnormal erythropoiesis and regulates iron homeostasis through modulation of hepcidin. It is abnormally secreted in marrow stromal cells of patients with multiple myeloma (MM), which may reflect the tumor microenvironment. We analyzed the associations of serum GDF-15 with clinical characteristics of 73 MM patients (including asymptomatic MM) and the laboratory indices of renal function, anemia, and inflammation. Baseline serum GDF-15 was studied as the predictor of two-year survival. We defined five clinically relevant subgroups of patients (symptomatic MM only, patients with and without remission, patients on chemotherapy, and without treatment). Increased GDF-15 concentrations were associated with more advanced MM stage, anemia, renal impairment (lower glomerular filtration and higher markers of tubular injury), and inflammation. Most of the results were confirmed in the subgroup analysis. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin were associated with GDF-15 independently of other variables. In the studied MM patients, GDF-15 did not significantly predict survival (p = 0.06). Our results suggest that serum GDF-15 reflects myeloma burden and shares a relationship with several markers of prognostic significance, as well as major manifestations.

New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies.

* Correspondence: kasiajanda@op [...].

The Serum Concentration of Anti-Aging Proteins, Sirtuin1 and αKlotho in Patients with End-Stage Kidney Disease on Maintenance Hemodialysis.

INTRODUCTION: Sirtuin1 (SIRT1) acts as an anti-aging protein due to anti-apoptotic, anti-oxidative and anti-inflammatory effect and is implicated in several diseases including diabetes or cardiovascular problems. SIRT1 renal overexpression indicates oxidative stress. Similarly, αKlotho was primarily exposed as anti-aging factor. It is primary produced in kidney. It's deficiency is associated with progression of chronic kidney disease and heart disorders. PURPOSE: The aim of the study was to assess the serum concentration of sirtuin1 and αKlotho in hemodialysis (HD) patients compared to healthy volunteers in regard to age, blood pressure control, residual kidney function (RKF), diabetes, cardiovascular disease, dialysis vintage and type of dialyzer. PATIENTS AND METHODS: The serum level of SIRT1 and αKlotho was evaluated using ELISA tests in 103 HD patients, median age 67 years and in 21 volunteers. Blood pressure, RRF, echocardiography and dialysis parameters were assessed. HD group was divided according to the presence/absence of RKF. RESULTS: The serum SIRT1 level was higher (28.4 vs 2.71ng/mL, p<0.0001) and αKlotho was lower (433.9 vs 756.6pg/mL, p<0.0001) in HD then in control group. αKlotho was lower in those without RKF (387.2 vs 486.2pg/mL, p=0.028). SIRT1 positively correlated with hemodialysis vintage. αKlotho negatively correlated with left ventricular posterior wall thickness. There was no significant relationship between SIRT1 and αKlotho level and age, blood pressure control, type of dialyzer, Kt/V and diabetes. Multivariate analysis revealed association of SIRT1 with ejection fraction (B -0.72; p=0.32). CONCLUSION: Elevated SIRT1 and lower αKlotho concentration are associated with impaired kidney function. The decrease in levels of αKlotho may also indicate heart hypertrophy in hemodialysis patients. The role of anti-aging proteins, particularly SIRT1 as biomarkers/predictors of oxidative stress, inflammation and cardiovascular diseases need further examination.

Prognostic value of midregional proadrenomedullin in critically ill patients.

INTRODUCTION: Scoring systems can be used to predict the risk of mortality and outcomes in critically ill patients. Acute kidney injury (AKI) is one of the strongest factors negatively influencing patient outcomes. Midregional proadrenomedullin (MR­proADM) shows promising results as an outcome predictor in patients with sepsis. OBJECTIVES: We aimed to evaluate the value of MR­proADM in incident AKI and mortality prognostication among patients admitted to the intensive care unit (ICU) in comparison with commonly used scoring systems. PATIENTS AND METHODS: Our study included a single­center cohort of 77 patients admitted to the ICU. Plasma MR­proADM levels were measured within 24 h of admission. The Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scores were used as a reference. The primary endpoints were incident AKI and in­hospital mortality. RESULTS: Patients who died during hospitalization period had a higher MR­proADM concentrations as compared with patients who survived (2592.5 pg/ml vs 995.3 pg/ml; P <0.001). The levels of MR­proADM correlated positively with the APACHE II or SOFA score (r = 0.3; P = 0.004 and r = 0.3; P = 0.008, respectively). In the receiver operating characteristics analysis, MR­proADM concentration was superior to both scoring systems (P = 0.002 and P = 0.001, respectively). In univariate logistic regression, MR­proADM was associated with in­hospital mortality (odds ratio [OR], 1.22; 95% CI, 1.11-1.35 per 100 pg/ml increase of MR­proADM) and after adjusting for multiple variables remained an independent predictor of death (OR, 1.35; 95% CI, 1.22-1.49 per 100 pg/ml increase of MR­proADM). MR­proADM was not useful in predicting incident AKI. CONCLUSIONS: MR­proADM can be applied in clinical practice as a prognostic tool for mortality but not incident AKI in the general ICU population with at least similar accuracy as APACHE II and SOFA scores.

Hepcidin - Potential biomarker of contrast-induced acute kidney injury in patients undergoing percutaneous coronary interventions.

PURPOSE: Contrast-induced acute kidney injury (CI-AKI) is a common and potentially serious complication of percutaneous coronary interventions (PCI). In this study, we tested the hypothesis whether serum and urinary hepcidin could represent early biomarkers of CI-AKI in patients with normal serum creatinine undergoing PCI. In addition, we assessed serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, eGFR and serum creatinine in these patients. METHODS: Serum and urinary hepcidin and NGAL, serum cystatin C, were evaluated before, and after 2, 4, 8, 24 and 48 h after PCI using commercially available kits. Serum creatinine was assessed before, 24 and 48 h after PCI. RESULTS: We found a significant rise in serum hepcidin as early as after 4 and 8 h when compared to the baseline values. Serum NGAL increased after 2, 4 and 8 h, and in urinary NGAL after 4, 8 and 24 h after PCI. We found a significant fall in urinary hepcidin after 8 and 24 h after PCI. Serum cystatin C increased significantly 8 h after PCI, reaching peak 24 h after PCI and then decreased after 48 h. The prevalence of CI-AKI was 8%. Urine hepcidin was significantly lower 8 and 24 h after PCI in patients with CI-AKI, while serum and urine NGAL were significantly higher in patients with CI-AKI. CONCLUSIONS: Our findings suggest that serum hepcidin might be an early predictive biomarker of ruling out CI-AKI after PCI, thereby contributing to early patient risk stratification. However, our data needs to be validated in large cohorts with various stages of CKD.

Effects of Enoxaparin on Intravascular Sclerostin Release in Healthy Men.

Sclerostin (Scl) is implicated in vascular calcification and angiogenesis and localizes within vasculature. Its molecule incorporates a heparin-binding site that implies also binding to endothelial glycocalyx. We preliminary tested whether intravenous (IV) low-molecular-weight heparin enoxaparin can stimulate intravascular release of this calcification inhibitor in humans. Sixteen male volunteers were injected with a bolus of 1 mg/kg body weight of enoxaparin. After 10 minutes, plasma immunoreactive Scl levels increased uniformly by a mean of 184% versus baseline level of 0.56 ± 0.17 ng/mL ( P = .0004). Plasma Scl levels were found still elevated after 2 and 6 hours (with a median of 20.9% and 8.69%, respectively) and became normal after 24 hours. The percentage of increase (Δ) in plasma Scl after 10 minutes was directly correlated with enoxaparin dose per kg/m2 of body mass index (ρ = 0.587, P = .017) and strongly inversely correlated with the preinjection Scl levels (ρ = -0.747, P = .0008). A robust negative association between the ΔScl increase after 10 minutes and the ΔScl decrease after 2 hours versus 10 minutes was observed (ρ = -0.835, P < .0001). Complementary in vitro spiking experiment showed no effects of enoxaparin addition and whole blood incubation on plasma Scl levels when measured with the immunoassay. This study shows that enoxaparin has a stimulating effect on the intravascular release of calcification inhibitor Scl in healthy men. This novel pharmacological action of the popular anticoagulant drug seems important in cardiovascular medicine.

Angiogenic factor screening in women with mild preeclampsia - New and significant proteins in plasma.

INTRODUCTION: The aim of this study was to analyse a panel of 60 angiogenic factors (pro-angiogenic and antiangiogenic) in the plasma of women with mild preeclampsia. MATERIALS AND METHODS: We recruited 21 women between 25 and 40 weeks gestation with diagnosed mild preeclampsia into the study group and 27 healthy women with uncomplicated pregnancies of corresponding gestational age to that of the study to the control group. We used a quantitative protein macroarray method that allowed for analysis of 60 angiogenic proteins per sample simultaneously. RESULTS: We showed a statistically significant increase in the concentration of 8 proteins, interferon gamma (IFN-γ), interleukin 6 (IL-6), leukaemia inhibitory factor (LIF), heparin-binding EGF-like growth factor (HB-EGF), hepatocyte growth factor (HGF), C-X-C motif chemokine 10 (IP-10), leptin and platelet-derived growth factor BB (PDGF-BB), as well as a significant decrease in the concentration of 3 proteins, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and follistatin, in the plasma of women with preeclampsia. CONCLUSION: Based on our findings, it seems that protein factors may play an important role in the pathogenesis of preeclampsia, and there are many proteins that have not been studied in PE to date. There are no previous studies assessing the LIF, follistatin, HGF, HB-EGF and PDGF-BB concentrations in the plasma of women with PE; therefore, our obtained results indicate that these proteins are new factors that can play an important role in the pathomechanisms of PE.

Endocan Concentration in Patients With Primary Hypertension.

Inflammation and endothelial dysfunction may play an important role in the multifactorial pathogenesis of hypertension. Endocan is also thought to play a role in cell adhesion and inflammatory disorders. The aim of the study was to compare endocan concentrations in patients with primary hypertension and healthy volunteers. There were 104 patients with hypertension (study group) and 21 healthy volunteers (control group). The correlation between endocan, catecholamines, and blood pressure control in patients with primary hypertension and the control group was analyzed. The median endocan concentration in the study group (2.03 ng/mL) was significantly higher than in the control group (1.09 ng/mL, P = .0001). Endocan concentration was correlated positively with renalase ( r = .2, P = .047) and norepinephrine ( r = .25, P = .02). Negative correlation was observed between endocan and body mass index ( r = -.25, P = .016) and leukocyte count ( r = -.36, P = .0004). The present study reports higher plasma endocan concentration in patients with treated, well-controlled primary hypertension compared with healthy volunteers. The higher endocan concentration in the study group may reflect endothelial dysfunction in this population.

Zonulin, inflammation and iron status in patients with early stages of chronic kidney disease.

BACKGROUND/AIMS: Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters. METHODS: Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study. Zonulin, hepcidin-25, soluble transferrin receptor, interleukin-6 and high-sensitivity C-reactive protein were measured using commercially available assays. RESULTS: Zonulin was significantly lower among patients with CKD in comparison with healthy volunteers. There were no statistically significant differences in zonulin concentration between patients with and without inflammation. Zonulin was significantly correlated with hepcidin only in patients with inflammation. Zonulin was neither related to iron nor related to ferritin. CONCLUSIONS: Zonulin cannot be considered as an inflammatory marker in CKD. It does not play a role in the disturbances of iron metabolism in CKD. Its physiological role remains to be elucidated.