An Assessment of Selected Molecular and Biochemical Markers of the Folate Pathway as Potential Risk Factors for Fetal Trisomy 21 during the First Trimester of Pregnancy in the Polish Population.

Are the maternal gene variants MTHFR: c.665C>T, MTHFR: c.1286A>C, MTR: c.2756A>G, MTRR: c.66A>G, RFC1: c.80C>T and TCN2: c.776G>C and blood markers of the folate pathway important factors in assessing the risk of fetal trisomy 21 (fetal-T21)? Twenty pregnant women with a high risk and twenty with a low risk of fetal-T21 underwent prenatal examination. Selected gene variants and folate pathway markers and pregnancy-associated plasma protein A (PAPP-A) and free ß-subunit of human chorionic gonadotropin ß (free-ß-hCG) multiple of the medians (MoMs) were determined. The distributions of the alternative alleles and genotypes of the gene variants did not differ between the studied groups. There was no relationship between PAPP-A and ß-hCG MoM values and the presence of allele alternative genotype variants. The occurrence of alternative variants of the selected genes and concentrations of most of the studied folate pathway markers may not play a crucial role in the risk of fetal-T21 in pregnant women. However, the relationships between erythrocyte folate concentrations and the occurrence of alternative variants: c.665C>T MTHFR and c.776G>C TCN2, as well as the methylmalonic acid concentration and the occurrence of alternative variant c.776G>C TCN2 in pregnant women with fetal-T21, encourage further research. So far, of the biochemical markers, maternal PAPP-A and ß-hCG MoM values remain independent risk factors for fetal-T21.

Can redox imbalance predict abnormal foetal development?

OBJECTIVES: Based on the current state of knowledge, elevated levels of oxidative stress markers may be considered as risk factors for pregnancy complications. The aim of the research was to assess the correlation between selected oxidative stress biomarkers with the occurrence of foetal chromosomal aberration and congenital malformations. MATERIAL AND METHODS: This retrospective research lasted for two years. The purpose was to determine serum levels of selected oxidative stress markers, including total protein (TP), glutathione (GSH), S-nitrosothiols (RSNO), nitric oxide (NO), trolox equivalent antioxidant capacity (TEAC) and glutathione S-transferase (GST) at 11-13 + 6 gestational weeks in 38 women with confirmed foetal developmental abnormalities and in 34 healthy pregnancies in order to assess their utility as predictors of abnormal foetal development. RESULTS: Serum concentrations of TP (56.90 ± 5.30 vs 69.1 ± 15.30 mg/mL), TEAC (4.93 ± 0.82 vs 5.64 ± 0.74 µM/mL) and GST (15.94 ± 4.52 vs 21.72 ± 6.81 nM/min/mg) were statistically significantly (p < 0.05) lower in the group of patients with developmental abnormalities in the fetus, whereas GSH levels (6.43 ± 1.24 vs 4.98 ± 1.88 nM/mg) were significantly higher, compared to the group of healthy fetuses. There were no differences in the concentration of these markers between chromosomal aberrations and fetal dysmorphia in subjects. A significant difference in odds ratio obtained for GSH (OR = 0.57, 95% CL: 0.40-0.80) indicates that its higher concentration can relate to reduced risk of developmental abnormalities, whereas odds ratio for TP (OR=1.11, 95% CL: 1.04-1.17), TEAC (OR = 3.54, 95% CL: 1.56-8.05) and GST (OR = 1.18, 95% CL: 1.03-1.17) indicate that their elevation may increase the risk of developmental abnormalities CONCLUSIONS: Elevated levels of TP, GST, TEAC and low GSH level may be relevant to predict congenital defects.

Assessment of endothelial progenitor cells, VEGF-A and SDF-1α in Hodgkin's lymphoma.

Recently, there is great interest in vasculogenesis, a process of the formation of new blood vessels from progenitor cells or angioblasts, in the pathogenesis of cancer. To the best of our knowledge, the evaluation of endothelial progenitor cells (EPCs) in Hodgkin's lymphoma has not yet been reported. The aim of the present study was to assess the number of EPCs and selected cytokines, such as vascular endothelial growth factor (VEGF-A) and stromal cell-derived factor (SDF-1α) involved in vasculogenesis in Hodgkin's lymphoma patients. The study was conducted in a group of 42 patients with Hodgkin's lymphoma (eight patients with relapsed Hodgkin's lymphoma and 34 patients before the first treatment) and 30 healthy controls. The number of EPCs defined as CD31(+), CD34(+), CD45(-), CD133(+) was analysed on FacsCalibur flow cytometer and the concentration of VEGF-A and SDF-1α was assessed by ELISA. The study showed that there was a significantly higher EPCs number and VEGF-A concentration in the blood of Hodgkin's lymphoma patients compared to healthy individuals (8.20 vs. 0.55 cells/µl; P < 0.000001; 85.10 vs. 25.33 pg/ml, P = 0.000017; respectively). Detailed analysis revealed that there was elevated EPCs number in both study subgroups as compared to the control group. However, there was no difference in VEGF concentration between recurrent Hodgkin's lymphoma patients and the control group. A significant positive correlation was found between the number of EPCs and VEGF-A concentration (R = 0.31, P = 0.047). Significantly higher EPCs number combined with increased VEGF-A concentration, found in Hodgkin's lymphoma patients before the first treatment, suggest stimulation of new blood vessels formation, which may in turn contribute to tumour growth and metastasis in these patients.

In vitro evaluation of electrochemically bioactivated Ti6Al4V 3D porous scaffolds.

Triply periodic minimal surfaces (TPMS) are known for their advanced mechanical properties and are wrinkle-free with a smooth local topology. These surfaces provide suitable conditions for cell attachment and proliferation. In this study, the in vitro osteoinductive and antibacterial properties of scaffolds with different minimal pore diameters and architectures were investigated. For the first time, scaffolds with TPMS architecture were treated electrochemically by plasma electrolytic oxidation (PEO) with and without silver nanoparticles (AgNPs) to enhance the surface bioactivity. It was found that the scaffold architecture had a greater impact on the osteoblast cell activity than the pore size. Through control of the architecture type, the collagen production by osteoblast cells increased by 18.9% and by 43.0% in the case of additional surface PEO bioactivation. The manufactured scaffolds demonstrated an extremely low quasi-elastic modulus (comparable with trabecular and cortical bone), which was 5-10 times lower than that of bulk titanium (6.4-11.4 GPa vs 100-105 GPa). The AgNPs provided antibacterial properties against both gram-positive and gram-negative bacteria and had no significant impact on the osteoblast cell growth. Complex experimental results show the in vitro effectiveness of the PEO-modified TPMS architecture, which could positively impact the clinical applications of porous bioactive implants.

Key Properties of a Bioactive Ag-SiO2/TiO2 Coating on NiTi Shape Memory Alloy as Necessary at the Development of a New Class of Biomedical Materials.

Recent years have seen the dynamic development of methods for functionalizing the surface of implants using biomaterials that can mimic the physical and mechanical nature of native tissue, prevent the formation of bacterial biofilm, promote osteoconduction, and have the ability to sustain cell proliferation. One of the concepts for achieving this goal, which is presented in this work, is to functionalize the surface of NiTi shape memory alloy by an atypical glass-like nanocomposite that consists of SiO2-TiO2 with silver nanoparticles. However, determining the potential medical uses of bio(nano)coating prepared in this way requires an analysis of its surface roughness, tribology, or wettability, especially in the context of the commonly used reference coat-forming hydroxyapatite (HAp). According to our results, the surface roughness ranged between (112 ± 3) nm (Ag-SiO2)-(141 ± 5) nm (HAp), the water contact angle was in the range (74.8 ± 1.6)° (Ag-SiO2)-(70.6 ± 1.2)° (HAp), while the surface free energy was in the range of 45.4 mJ/m2 (Ag-SiO2)-46.8 mJ/m2 (HAp). The adhesive force and friction coefficient were determined to be 1.04 (Ag-SiO2)-1.14 (HAp) and 0.247 ± 0.012 (Ag-SiO2) and 0.397 ± 0.034 (HAp), respectively. The chemical data showed that the release of the metal, mainly Ni from the covered NiTi substrate or Ag from Ag-SiO2 coating had a negligible effect. It was revealed that the NiTi alloy that was coated with Ag-SiO2 did not favor the formation of E. coli or S. aureus biofilm compared to the HAp-coated alloy. Moreover, both approaches to surface functionalization indicated good viability of the normal human dermal fibroblast and osteoblast cells and confirmed the high osteoconductive features of the biomaterial. The similarities of both types of coat-forming materials indicate an excellent potential of the silver-silica composite as a new material for the functionalization of the surface of a biomaterial and the development of a new type of functionalized implants.

Increased number of endothelial progenitor cells in the blood of patients with psoriasis vulgaris.

Introduction: Psoriasis vulgaris (PsV) is a common dermatosis characterized by excessive activation of neovascularization. Latest research has shown that endothelial progenitor cells (EPCs) are a crucial factor involved in the repair of endothelial injury and formation of new blood vessels, in a process termed postnatal vasculogenesis. However, the exact mechanism of creating psoriatic skin patches and the involvement of EPCs in this process remains unknown. Aim: To evaluate the number of EPCs in the blood of patients with PsV, characterized by the expression of specific cell surface markers, including CD45-, CD31+, CD34+ and CD133+. Material and methods: A total of 49 patients suffering from PsV and 40 healthy volunteers were enrolled in the study. The number of EPCs in each of the volunteers' whole blood samples was measured with a FACSCalibur flow cytometer using monoclonal antibodies directed against antigens specific for EPCs. Results: The number of EPCs was significantly higher in patients with psoriasis compared with the controls (p = 0.0007) and inversely correlated with disease severity assessed by PASI score (R = -0.2935, p = 0.0407). Statistical analysis did not show significant relations between the count of EPCs and age, body mass index, gender, disease duration, blood pressure, extent of itching, severity and frequency of pruritus, presence of bruises, vitamin D supplementation and smoking habit. Conclusions: The results of our studies indicate that patients with psoriasis showed an increased mobilization of EPCs compared with healthy individuals which correlated negatively with disease severity.

Formation of a Bacteriostatic Surface on ZrNb Alloy via Anodization in a Solution Containing Cu Nanoparticles.

High strength, excellent corrosion resistance, high biocompatibility, osseointegration ability, and low bacteria adhesion are critical properties of metal implants. Additionally, the implant surface plays a critical role as the cell and bacteria host, and the development of a simultaneously antibacterial and biocompatible implant is still a crucial challenge. Copper nanoparticles (CuNPs) could be a promising alternative to silver in antibacterial surface engineering due to low cell toxicity. In our study, we assessed the biocompatibility and antibacterial properties of a PEO (plasma electrolytic oxidation) coating incorporated with CuNPs (Cu nanoparticles). The structural and chemical parameters of the CuNP and PEO coating were studied with TEM/SEM (Transmission Electron Microscopy/Scanning Electron Microscopy), EDX (Energy-Dispersive X-ray Dpectroscopy), and XRD (X-ray Diffraction) methods. Cell toxicity and bacteria adhesion tests were used to prove the surface safety and antibacterial properties. We can conclude that PEO on a ZrNb alloy in Ca-P solution with CuNPs formed a stable ceramic layer incorporated with Cu nanoparticles. The new surface provided better osteoblast adhesion in all time-points compared with the nontreated metal and showed medium grade antibacterial activities. PEO at 450 V provided better antibacterial properties that are recommended for further investigation.

Endothelial Progenitor Cells as a Marker of Vascular Damage But not a Predictor in Acute Microangiopathy-Associated Stroke.

BACKGROUND: The aim of the study was to assess the number of endothelial progenitor cells (EPCs) in patients with acute stroke due to cerebral microangiopathy and evaluate whether there is a relationship between their number and clinical status, radiological findings, risk factors, selected biochemical parameters, and prognosis, both in ischemic and hemorrhagic stroke. METHODS: In total, 66 patients with lacunar ischemic stroke, 38 patients with typical location hemorrhagic stroke, and 22 subjects from the control group without acute cerebrovascular incidents were included in the prospective observational study. The number of EPCs was determined in serum on the first and eighth day after stroke onset using flow cytometry and identified with the immune-phenotype classification determinant (CD)45-, CD34+, CD133+. RESULTS: We demonstrated a significantly higher number of EPCs on the first day of stroke compared to the control group (med. 17.75 cells/µL (0-488 cells/µL) vs. 5.24 cells/µL (0-95 cells/µL); p = 0.0006). We did not find a relationship between the number of EPCs in the acute phase of stroke and the biochemical parameters, vascular risk factors, or clinical condition. In females, the higher number of EPCs on the first day of stroke is related to a favorable functional outcome on the eighth day after the stroke onset compared to males (p = 0.0355). We found that a higher volume of the hemorrhagic focus on the first day was correlated with a lower number of EPCs on the first day (correlation coefficient (R) = -0.3378, p = 0.0471), and a higher number of EPCs on the first day of the hemorrhagic stroke was correlated with a lower degree of regression of the hemorrhagic focus (R = -0.3896, p = 0.0367). CONCLUSION: The study showed that endothelial progenitor cells are an early marker in acute microangiopathy-associated stroke regardless of etiology and may affect the radiological findings in hemorrhagic stroke. Nevertheless, their prognostic value remains doubtful in stroke patients.

Electrochemical modification of the Ti-15Mo alloy surface in solutions containing ZnO and Zn3(PO4)2 particles.

This paper reports on the plasma electrolytic oxidation (PEO) of titanium alloy Ti-15Mo in baths containing zinc to obtain biomaterials with bacteriostatic and antibacterial properties. The Ti-15Mo surface was oxidised in a 0.1 M Ca(H2PO2)2 bath containing zinc compound particles: ZnO or Zn3(PO4)2. During the PEO process, the applied voltage was 300 V, and the current density was 150 mA∙cm-2. The surface morphology, roughness and wettability were determined. It has been noted that both roughness and wettability of Ti-15Mo alloy surface increased after PEO. EDX and XPS chemical composition analysis was carried out, and Raman spectroscopy was also performed indicating that Zn has been successfully incorporated into oxide layer. To investigate the antibacterial properties of the PEO oxide coatings, microbial tests were carried out. The bacterial adhesion test was performed using four different bacterial strains: reference Staphylococcus aureus (ATCC 25923), clinical Staphylococcus aureus (MRSA 1030), reference Staphylococcus epidermidis (ATCC 700296) and clinical Staphylococcus epidermidis (15560). Performed zinc-containing oxide coatings did not indicate the bacteria growth inducing effect. Additionally, the cytocompatibility of the formed oxide layers was characterised by MG-63 osteoblast-like live/dead tests. The surface bioactivity and cytocompatibility increased after the PEO process. The zinc was successfully incorporated into the titanium oxide layer. Based on the obtained results of the studies, it can be claimed that zinc-containing PEO layers can be an interesting course of bacteriostatic titanium biomaterials development.

Antibacterial and cytocompatible coatings based on poly(adipic anhydride) for a Ti alloy surface.

This paper describes a formation of hybrid coatings on a Ti-2Ta-3Zr-36Nb surface. This is accomplished by plasma electrolytic oxidation and a dip-coating technique with poly(adipic anhydride) ((C6H8O3)n) that is loaded with drugs: amoxicillin (C16H19N3O5S), cefazolin (C14H14N8O4S3) or vancomycin (C66H75Cl2N9O24 · xHCl). The characteristic microstructure of the polymer was evaluated using scanning electron microscopy and confocal microscopy. Depending on the surface treatment, the surface roughness varied (between 1.53 µm and 2.06 µm), and the wettability was change with the over of time. X-ray photoelectron spectroscopy analysis showed that the oxide layer did not affect the polymer layer or loaded drugs. However, the drugs lose their stability in a phosphate-buffered saline solution after 6.5 h of exposure, and its decrease was greater than 7% (HPLC analysis). The stability, drug release and concentration of the drug loaded into the material were precisely analyzed by high-performance liquid chromatography. The results correlated with the degradation of the polymer in which the addition of drugs caused the percent of degraded polymer to be between 35.5% and 49.4% after 1 h of material immersion, depending on the mass of the loaded drug and various biological responses that were obtained. However, all of the coatings were cytocompatible with MG-63 osteoblast-like cells. The drug concentrations released from the coatings were sufficient to inhibit adhesion of reference and clinical bacterial strains (S. aureus). The coatings with amoxicillin showed the best results in the bacterial inhibition zone, whereas coatings with cefazolin inhibited adhesion of the above bacteria on the surface.

Mid-trimester ultrasound parameters for predicting birth weight in low risk pregnancies vs high-risk pregnancies complicated with pre-gestational diabetes mellitus.

OBJECTIVES: The aim of the study was to assess the utility of mid-trimester ultrasound parameters in predicting birth weight in low-risk pregnancy and high-risk pregnancy complicated with pregestational diabetes mellitus. MATERIAL AND METHODS: A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division. We also checked uterine artery blood flow parameters. RESULTS: There is a correlation between the birth weight and ultrasound-ascertained parameters, including those characterising uterine artery blood flow and foetal biometry [abdominal circumference (AC), femoral length (FL), biparietal dimension (BPD)].The biparietal dimension (BPD), head circumference (HC) abdominal circumference (AC) and pre-existing diabetes are the ultrasound predictors of LGA. The presence of an early-diastolic uterine artery blood flow waveform notching, as well as the uterine artery pulsatility index (UAPI), femoral length (FL) and hypertension in pregnancy are the ultrasound predictors of SGA. In the subset of women with pre-gestational diabetes (PGDM), there is a negative correlation between the birth weight and the uterine artery pulsatility index and early-diastolic uterine artery blood flow waveform notching. In women with pre-gestational diabetes mellitus (PGDM), femoral length (FL) is a significant predictor of LGA and in case of SGA significant predictors are uterine artery pulsatility index, artery blood flow waveform notching and femoral length (FL). CONCLUSIONS: Midtrimester ultrasound parameters with confirmed usefulness in the prediction of birth weight in low-risk pregnancy and high-risk pregnancy complicated with pregestational diabetes mellitus include: uterine artery PI, early-diastolic uterine artery blood flow waveform notching and foetal biometry.

Inhibitors of the blood coagulation process in patients with essential thrombocythemia.

: The aim of the study was to assess the activity of protein C, protein S and tissue factor pathway inhibitor in relation to the risk factors for thrombotic complications in patients with essential thrombocythemia.The study group consisted of 45 newly diagnosed patients with essential thrombocythemia. Protein S activity was determined by chromogenic method. Activities of protein C and tissue factor pathway inhibitor (TFPI) were determined using ELISAs.Significantly lower protein C and protein S activity but higher TFPI activity were found in patients with ET in comparison with the control group. TFPI activity was higher in women as compared to men, and in patients over 60 years of age compared with patients below 60 years of age. TFPI activity was higher in patients with leukocytes count at least 11 g/l than in patients with leukocytes count below 11 g/l and the difference almost reached statistical significance. Significantly lower protein C activity was found in patients with the JAK2V617F mutation, in comparison with essential thrombocythemia patients JAK2V617F (-).The reduced protein C and protein S activity may be one of the pathogenic factors of increased prothrombotic state in essential thrombocythemia patients. The decreased protein C activity in patients with the JAK2 V617F mutation seems to confirm the significant role of this mutation in the pathogenesis of thrombotic complications in essential thrombocythemia patients. Significantly increased TFPI activity in essential thrombocythemia patients above 60 years of age and with leukocyte count above 11 g/l expresses the activation of the compensatory mechanism for increased prothrombotic activity.

The significance of maternal blood pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (ß-hCG) levels for the risk assessment of fetal trisomy 18 during the first prenatal testing between 11 and 13+6 weeks of pregnancy.

OBJECTIVE: The aim of the study was to evaluate the significance of the maternal blood level of pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (ß-hCG), to estimate the risk of fetal trisomy 18 and their correlation with the assessment of nuchal translucency (NT) during the first prenatal testing. MATERIAL AND METHODS: Examinations of 93 pregnant women between 11 and 13+6 weeks of pregnancy were conducted, which included determination of ß-hCG and PAPP-A concentrations in the maternal serum and ultrasound assessment of fetal nuchal translucency. Concentrations of biochemical parameters were expressed as multiples of median (MoM) for the appropriate gestational age. The risk assessment of trisomy 18 was analyzed using Astraia software. Pregnant women with a high (≥ 1:300) risk of trisomy 18 were offered a genetic amniocentesis with an examination of fetal karyotype. Twenty cases were healthy and 23 with trisomy 18. RESULTS: PAPP-A and ß-hCG MoM values < 0.3 were found in 61% cases of fetal trisomy 18. In 26% of cases, PAPP-A and ß-hCG MoM values < 0.2 were NT-independent risk factors for trisomy 18. There were no significant differences between groups with normal fetal karyotype (40%) and trisomy 18 (35%) in PAPP-A and ß-hCG MoM 0.2-0.5 range. CONCLUSIONS: Maternal free ß-hCG MoM was found to change parallelly to fetal NT widening in case of trisomy 18 diagnosis. Maternal ß-hCG and PAPP-A MoM results presented less then 0.2 might be used independently of NT widening in fetus for trisomy 18 risk evaluation. Above 0.2 for PAPP-A and ß-hCG MoMs, fetal NT measurement was an requirment.

Diurnal variations in tissue factor and tissue factor pathway inhibitor concentrations in relation to on-treatment platelet reactivity: an analysis of patients with acute myocardial infarction.

The aim of the study was to evaluate diurnal changes of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) concentrations in relation to on-treatment platelet reactivity. The study group included 51 patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention and dual antiplatelet therapy. TF and TFPI concentrations were assessed using enzyme-linked immunosorbent assay kits. We found a significant increase of TF concentration in clopidogrel-resistant, but not clopidogrel-sensitive, patients at 10.00 a.m. (410.66 pg/mL) in comparison with 6.00 a.m. (250.99 pg/mL), 14.00 p.m. (255.12 pg/mL) and 19.00 p.m. (267.58 pg/mL). Moreover, TF concentration at 10.00 a.m. was 30% higher in clopidogrel-resistant than clopidogrel-sensitive patients (p = .043). We failed to demonstrate diurnal variation in TFPI concentration in clopidogrel-resistant patients. However, TFPI concentration in clopidogrel-sensitive patients was significantly higher at 10.00 a.m. as compared with other sampling points (p < .05). We observed a marked elevation in TF concentration at 10.00 a.m. only in aspirin-resistant patients and a significant increase in TFPI concentration at 10 a.m. only in aspirin-sensitive patients. Our findings suggest the presence of diurnal variations in TF and TFPI concentrations in AMI patients, with the highest thrombotic risk in patients with high on-treatment platelet reactivity in the midmorning.

Low Pre-Treatment Count of Circulating Endothelial Progenitors as a Prognostic Biomarker of the High Risk of Breast Cancer Recurrence.

Neoangiogenesis is mediated by circulating bone marrow-derived endothelial progenitors (circulating EPCs). The aim of the study was the quantification of circulating EPCs from the peripheral blood mononuclear cells of invasive breast cancer (IBrC) patients by flow cytometry, before and after cancer adjuvant treatment. A total of 88 stage IA-IIB primary IBrC patients were enrolled prospectively. Circulating EPCs with the immune-phenotype CD45-CD34+CD133+CD31+ were assessed. Treatment significantly reduced the number of EPCs/µL in the general IBrC cohort. However, there was a relevant elevation in the number of circulating EPCs after nine months of adjuvant treatment in the group of patients aged ≥ 55 years, of T2 clinical type, with nodal involvement (N1) and Ki67 expression > 15%. Follow-up revealed a significantly higher incidence of disease relapse in breast cancer patients with low pre-treatment circulating EPCs levels compared with those with a high baseline circulating EPCs count. The receiver-operating characteristic curve identified a tumour diameter of 2.1 cm as the best cut-off value to discriminate between disease-relapse subjects and non-relapse disease cases. Our study strongly indicates that, next to tumour diameter and Ki67 expression, circulating bone marrow-derived EPCs may serve as useful markers for predicting therapeutic outcomes as well as a future prognosis.

Serum homocysteine and vitamin B12 levels in women with gestational diabetes mellitus.

OBJECTIVES: Gestational diabetes mellitus (GDM) is described as a glucose intolerance of variable severity which begun or was firstly recognized during gravidity. Two major metabolic disorders, insulin resistance and ß-cell dysfunction, currently play major role in pathogenesis of GDM. Our intention was to investigate total serum homocysteine and vitamin B12 levels in pregnant women with GDM and non-diabetic gravid women. MATERIAL AND METHODS: Serum homocysteine and vitamin B12 levels were prospectively measured in a total of 79 pregnant women, 60 of whom were diagnosed with GDM, and 19 of whom were healthy controls. Serum homocysteine levels were analyzed by ELISA. Vitamin B12 concentrations were determined by chemiluminescent immunoassay, and lipids were determined enzymatically. RESULTS: GDM and control groups did not differ in terms of the serum homocysteine levels (median 7.24 vs 7.97 umol/L, respectively, p = 0.15). Nor did we find any association between serum homocysteine levels and BMI (r = 0.06, p = 0.55, respectively). There was no correlation between serum homocysteine and fasting serum glucose (r = 0.3, p = 0.8, respectively). There was no relationship between serum homocysteine concentrations and glycosylated hemoglobin (HgbA1c) levels (r = 0.06, p = 0.67, respectively). Serum vitamin B12 concentrations did not differ between the GDM and control groups (median 286 vs 262 pg/mL, respectively, p = 0.17). We found that levels of Vitamin B12 correlated inversely with fasting serum glucose concentrations (r = -0.44, p = 0.0009). Vitamin B12 concentrations increased along with LDL (r = 0.27, p = 0.043) and HDL (r = 0.38, p = 0.004) levels, however were inversely correlated with serum triglycerides (r = -0.34, p = 0.009). CONCLUSIONS: GDM patients with low Vitamin B12 values tend to have higher fasting serum glucose and altered lipid profiles (high triglycerides, low HDL and LDL). In women with GDM, serum homocysteine levels are not associated with HbA1c level, fasting glycemia, or BMI.

Maternal factors, ultrasound and placental function parameters in early pregnancy as predictors of birth weight in low-risk populations and among patients with pre-gestational diabetes.

OBJECTIVES: The aim of our work was to assess the usefulness of maternal factors, ultrasound and placental function parameters during early pregnancy as predictors of birth weight in populations of healthy pregnant women and women suffering from pregestational diabetes. MATERIAL AND METHODS: A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division. We also checked uterine artery blood flow parameters. During the first trimester consultation, all patients were surveyed and the following data were collected: age, BMI, reproductive history, comorbidities and smoking. We also collected blood samples and assessed PlGF, PAPP-A, and BhCG levels. RESULTS: Our study showed that newborn birth weight negatively correlated with mother's age, her diastolic blood pressure, PI of her uterine arteries and BhCG protein levels. Moreover, birth weight directly correlated with PlGF and PAPPA-A protein levels, and maternal early-pregnancy BMI. CONCLUSIONS: LGA diagnosis in the first trimester of pregnancy allows for selection and modification of some risk factors and closer monitoring of endangered fetuses throughout the pregnancy, with emphasis on the perinatal period. Parameters with confirmed usefulness in the prediction of birth weight in the first trimester included: maternal age, BMI, blood pressure, PAPP-A, BhCG and PlGF levels, fetal CRL and uterine artery PI.

The clinical usefulness of biochemical (free ß-hCg, PaPP-a) and ultrasound (nuchal translucency) parameters in prenatal screening of trisomy 21 in the first trimester of pregnancy.

OBJECTIVES: The aim of the study was to analyze the correlation of multiples of the normal median of PAPP-A, free ß-hCG levels and nuchal translucency values in prenatal, first trimester screening of trisomy 21 in pregnant women. MATERIAL AND METHODS: 251 pregnant women underwent antenatal screening at 11-13+6 weeks of pregnancy which was composed of the measurement of free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein (PAPP-A) levels in the maternal serum and an ultrasound assessment of nuchal translucency (NT). The pregnant women with a high risk of trisomy 21 (≥ 1:300) were given amniocentesis to verify fetal defects. There were 217 cases of normal fetal karyotype and 34 cases of trisomy 21. PAPP-A, ß-hCGMoM and NT values were analyzed for the predefined ranges. RESULTS: 85% cases of trisomy 21 had elevated free ß-hCGMoM (> 1.5) and only 53% of these had a PAPP-AMoM result below 0.5 (p < 0.05). Analysis of NT in selected ranges of ß-hCG (> 1.5) and PAPP-AMoM (< 0.05), which are typical for Down Syndrome values, showed that not all fetuses with Down Syndrome presented with an increased NT. Respectively 44.15% and 26.5% of fetuses presented with increased NT. Characteristic for trisomy 21, a correlation with all 1st trimester screening tests' parameters occurred in only 23.5% of cases. In 53% of cases the results were atypical. CONCLUSIONS: The PAPP-A and ß-hCG values in the selected MoM ranges did not shown a correlation to the NT measurement, therefore they are independent factors in the diagnosis of trisomy 21. Simultaneous biochemical and ultrasound testing is an indispensable condition for prenatal diagnosis of trisomy 21 in the 1st trimester of pregnancy.

Activation of TF-Dependent Blood Coagulation Pathway and VEGF-A in Patients with Essential Thrombocythemia.

Background and objectives: Recent studies suggest that a vascular endothelial growth factor (VEGF-A) may be involved in the thrombotic process by stimulating the expression of tissue factor in vascular endothelial cells. Tissue factor (TF) can also stimulate the transcription of the gene encoding VEGF-A. The relationship between coagulation and angiogenesis in myeloproliferative neoplasms is not fully understood. The aim of this study was to evaluate the concentration of TF in relation to VEGF-A in the blood of patients with essential thrombocythemia (ET). Patients and methods: The study group consisted of 130, newly diagnosed patients with ET (mean age 61 years). The control group consisted of 35 healthy volunteers (mean age 51 years). Concentrations of VEGF-A, TF, and tissue factor pathway inhibitor (TFPI) were analysed using immunoenzymatic methods. TF and TFPI activities were performed using chromogenic assays. Results: The median concentration of TF Ag was 3-fold higher and the TF activity was more than 15-fold higher in ET patients than in normal individuals. There were no statistically significant differences in the TFPI concentration and activity between groups. VEGF-A was significantly increased in patients with ET (p < 0.000001). Analysis of correlations revealed a positive correlation between VEGF-A and TF Ag as well as a positive correlation between VEGF-A and TFPI activity. Conclusions: The simultaneous increase of TF concentration and activity, VEGF-A in the blood of patients with ET, as well as a positive correlation between the concentration of TF and VEGF-A demonstrates the coexistence of TF-dependent coagulation and activation of angiogenesis.

Selected Parameters of Angiogenesis and the JAK2, CALR, and MPL Mutations in Patients With Essential Thrombocythemia.

The aim of the study was to evaluate selected angiogenic factors in patients with essential thrombocythemia (ET) depending on JAK2V617F, calreticulin gene (CALR) and myeloproliferative leukemia virus oncogene (MPL) mutations. Sixty ET patients and 20 healthy volunteers were enrolled in the study. The following tests were performed: vascular endothelial growth factor- A (VEGF-A), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1),soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), platelet-derived growth factor( PDGF-BB), and stromal-derived factor-1α (SDF-1α). We observed an increased PDGF-BB level in patients with ET compared to the controls. Patients with CALR mutation had significantly higher concentration of PDGF-BB and lower concentration of SDF-1α than patients with JAK2V617F mutation. High concentration of PDGF-BB and low concentration of SDF-1α in patients with CALR(+) ET may indicate a contribution of these chemokines in disturbed Ca2+ metabolism in platelets.