Karowicz-Bilińska A

Indices of oxidative stress in pregnancy with fetal growth restriction

Intrauterine fetal growth restriction (IUGR), the main cause of premature delivery and fetal mortality, has been suggested to involve oxidative stress. We found elevated values of indices of oxidative stress in the blood serum of pregnant women with IUGR: increased levels of malondialdehyde and 4-hydroxyalkenals, decreased activity of α-1-antitrypsin and decreased total antioxidant capacity of the serum, with respect to healthy pregnancy. Twenty day treatment with 3 g of l-arginine and 75 mg of acetylsalicylic acid daily resulted in a decrease of the level of lipid peroxidation products and augmentation of α-1-antitrypsin activity. This study confirms the occurrence of oxidative stress in IUGR and demonstrates the beneficial effect of arginine/acetylsalicylic acid therapy in reducing oxidative stress in IUGR.

Ultrasound evaluation of intrauterine growth restriction therapy by a nitric oxide donor (L-arginine)

Objective: There are numerous methods available of treating intrauterine growth restriction but their results are still not satisfactory. Currently, we are conducting a research project whose main aim is based on the use of the nitric oxide (NO) donor L-arginine in growth restriction therapy. The main aim of this study was the ultrasound evaluation of the efficacy of this therapy based on biometric measurements (the estimated fetal weight) compared with the estimated weight of newborn children. Study design: The investigated group comprised two randomly chosen groups of pregnant women with ultrasound-diagnosed intrauterine growth restriction (biometry < 10th centile for gestation age): 78 patients were treated by L-arginine 3 g daily orally for 20 days; and 30 patients, not treated, acted as the control group. Results: The ultrasound estimation of fetal weight at the start and at the end of the treatment showed a mean increase of 642 g (SE 90 g) using the Shepard method, and 648 g (SE 94 g) using the Hadlock method, respectively. By comparison, within the control group a mean value increase of 395 g (SE 77 g) was found, using the Shepard method, and 404 g (SE 82 g) using the Hadlock method, respectively. There was a significant statistical difference when comparing the estimated fetal weight increase in both methods: p = 0.008 for the Shepard calculation and p = 0.012 for the Hadlock calculation. The weight of the newborn infants was also evaluated: in the treated group the mean value was 2823 g (SE 85 g) and in the untreated group the mean value was 2495 g (SE 147 g). There was a significant (p = 0.027) difference, showing a positive effect of the treatment on the weight of newborns. In the treated group the percentage of growth-retarded newborns was 29% while in the untreated group it was 73%. A significant difference has been found (p < 0.01) between both of the groups of newborns. Conclusions: The ultrasound evaluation of the estimated fetal weight and the birth weight of the newborns showed an improvement: there was an acceleration of fetal development in the L-arginine-treated group of pregnant women as compared with the untreated group. The ultrasound evaluation of the estimated fetal weight is a good diagnostic tool, properly monitoring the efficacy of the L-arginine treatment of the growth-retarded fetuses.

The antioxidant properties of carnitine in vitro

Many of the effects of carnitine are ascribed to its antioxidant properties. The aim of this study was to evaluate the antioxidant properties of carnitine in vitro. Carnitine was found to decolorize ABTS•+, and to protect fluorescein against bleaching induced by AAPH-derived peroxyl radicals and peroxynitrite, thiol groups against oxidation induced by hydrogen peroxide, peroxyl radicals, hypochlorite and peroxynitrite, and erythrocytes against hemolysis induced by peroxyl radicals and hypochlorite. These results show that carnitine has a direct antioxidant action against physiologically relevant oxidants.

Changes of markers of oxidative stress during menstrual cycle.

Abstract The levels of urinary hydrogen peroxide and thiobarbituric acid reactive substances have been compared during the menstrual cycle of 12 regularly menstruating women. Higher level of both indices of oxidative stress (normalized with respect to creatinine content) were found in the luteal phase of the cycle. These results give further evidence for the usefulness of urinary hydrogen peroxide and thiobarbituric acid reactive substances as potential biomarkers of oxidative stress and for the antioxidant action of estrogens.

Assessment of interleukin-6, interleukin-8 and interleukin-18 count in the serum of IUGR newborns

Abstract Aim: Aim of this study was to assess concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) in the serum of newborns with diagnosed intrauterine growth restriction (IUGR) in comparison to concentrations in serum of newborns with weight appropriate for gestational age (AGA). Materials: Research was conducted at the Lodz Medical University Clinic of Neonatology during 2010–2011. Surveyed group consisted of 50 hypotrophic full-term infants of single pregnancies (average weight: 2329 ± 287 g); control group, enclosing 50 infants AGA (average weight: 3544 ± 2161 g). Both groups received average Apgar score of 9 points. Concentrations of analysed cytokines were marked between 4–6 hours after birth. The enzyme-linked immunosorbent assay (ELISA) test was used to determine interleukins concentrations. Study was prospective. Statistics on the data were conducted with the Kolmogorov–Smirnov test. Significance level: p < 0.05. Results: Concentrations of IL-6 and IL-18 were elevated in the IUGR group in a statistically significant manner in comparison to the control group. Conclusions: An elevated level of IL-6 and IL-18 in the IUGR group, comparing to control group, signifies the existence of inflammation in the process of developing IUGR, therefore, screening tests estimating levels of interleukins as IL-6 and IL-18 might be clinically useful in predicting the occurrence of IUGR and help preventing it.

Evaluation of soluble concentration Fas and Fas ligand in maternal and cord blood 3rd trimester of pregnancy

OBJECTIVES The the study was to estimate the concentrations of antiapoptotic sFas and pro-apoptotic FasL in the serum of pregnant women in the third trimester of pregnancy and in the cord blood serum of neonates from vein and arteries separately. The correlation could be crucial for evaluation of apoptosis process intensity in placenta and the role of fetal blood circulation system on distribution of sFas and FasL. MATERIAL AND METHODS The study group consisted of 28 pregnant women in physiological pregnancy, between 38- 41 weeks. Vein blood was taken from maternal elbow vein and umbilical cord, separately from vein and arteries. The research was done by sets for sFas and FasL from R&D Systems Elisa kit. RESULTS In arterial and vein cord blood there were much more lower concentrations of sFas than in maternal blood-arterial cord blood 3351.78 pg/mL, vein cord blood 3351.78 pg/mL versus maternal blood 5769.62 pg/mL (p < 0.001). No differ-ence was found in sFas concentrations between cord arterial and vein blood sera. Statistical difference was found between mean concentration of Fas ligand in maternal blood serum (71.36 pg/mL) and arterial cord blood serum (164.57 pg/mL) p < 0.05 (p = 0.001). Cord arterial blood serum showed much higher concentrations of FasL than maternal blood serum. No difference was found between cord arterial and vein blood sera concentrations of FasL: 164.57 pg/mL vs. 170.00 pg/mL (p = 0.701). CONCLUSIONS Obtained results suggest no influence of sFas and FasL production on fetal organism apoptosis. Lowering of sFas concentration in fetal blood could mean the increase of apoptosis in fetal organism compared to maternal. Higher concentration of FasL in cord blood than in mothers suggests higher apoptosis intensification in fetal circulation and no influence of blood flow across placenta on its concentration.

[Evaluation of the expression of selected pro- and anti-apoptotic factors in syncytiotrophoblasts of human placenta and changes observed after vitamin supplementation].

AIM The main aim of the study was to estimate expression of Bcl-2 and Bax proteins in syncytiotrophoblast in placenta obtained from pregnancies complicated by hypertension and to compare results with group supplemented by antioxidants. MATERIAL AND METHOD The study was performed in High Risk Department of Medical University Lodz. 3 groups of pregnant women were compared: I-pregnancy complicated by hypertension, II pregnancy complicated by hypertension treated by oral administration of antioxidants--vitamin C and vitamin E.III-rd group consisted of healthy women. After delivery incision from central part of placenta was taken on obtained slides due to immunohistochemical reactions the character intensity surface affected by reaction and expression of two proteins involved into process of apoptosis was measured- anti-apoptotic Bcl-2 and pro-apoptotic Bax. In every slide ten of random choosen fields were evaluated in 200x zoom using semi-quantative method. RESULTS Highest value of Bcl-2 character was found in I-st group, the lowest in III-rd group- healthy women. The lowest intensity surface affected and expression of the reaction was found in II group- treated by antioxidants. The highest value of Bax reaction character and intensity was found in III group comparing to others. The lowest mean surface of syncytiotrophoblast affected by Bax reaction was found in II group. In III-rd group expression of reaction was higher than in both other groups. CONCLUSIONS In the base of Bcl-2 reaction in syncytiotrophoblast no influence of antioxidants supplementation on apoptosis process that occurs by this path was found. Antioxidants supplementation decrease Bax activity in syncytiotrophoblast, that suggests restriction of apoptosis process despite of changes connected to hypertension.