Agnieszka Seremak-Mrozikiewicz

The significance of -786T > C polymorphism of endothelial NO synthase (eNOS) gene in severe preeclampsia.

Objective. Preeclampsia (PE) is believed to be induced by endothelial cell dysfunction in placenta. Highly polymorphic endothelial nitric oxide synthase (eNOS) activity belongs to the factors significantly influencing vaso-motor tone in placenta and PE susceptibility. The aim of this study was to evaluate prevalence of −786T/C polymorphism of eNOS gene in the groups of women with mild and severe PE. Study design. The study was performed in the group of 218 preeclamptic (including 136 with severe PE) and of 400 normotensive healthy women delivered normally after a healthy gestation. The eNOS −786T/C polymorphism was determined using PCR/RFLP assay. Additionally, detailed correlation between eNOS genotypes and clinical/laboratory data in the PE group has been analyzed. Results. The higher frequency of mutated homozygous CC genotypes (17.4% vs. 11.5% in controls, OR 1.62, n.s.) and of C alleles (allelic frequency 44.1 vs. 36.6%; OR 1.36, p = 0.012) in the group of PE has been determined. Furthermore, in the group of severe PE the overrepresentation of mutated CC genotypes (23.5% vs. 11.5%, OR 2.37, p = 0.0014) and mutated C alleles (47.8 vs. 36.6%, OR 1.58, p = 0.0016) has been found. Conclusions. The presence of mutated homozygous CC genotype and C allele of −786T/C polymorphism of eNOS gene influences the higher susceptibility to develop severe PE development.

1166C mutation of angiotensin II type 1 receptor gene is correlated with umbilical blood flow velocimetry in women with preeclampsia

OBJECTIVE To ascertain the frequency of polymorphic variants of the gene coding for angiotensin II type 1 receptor (AT1) and its correlation with umbilical artery (UA) blood flow velocity in a group of women with preeclampsia (PE). STUDY DESIGN AT1 polymorphism, pulsatility index (PI) in UA, and perinatal outcome in 47 women with PE and in 113 healthy pregnant women were investigated. Investigation of AT1 receptor genotypes was performed by PCR/RFLP assays. PI value has been measured by Doppler velocimetry technique. RESULTS The overrepresentation of CC homozygotic genotype in PE group (6.4% vs. 2.7%) and the overrepresentation of mutated C allele in the PE group were observed (28.7% vs. 23.0%). Analyzing PI index we observed statistically significant differences between PE and control groups. Comparing PI values in PE group between genotypes: AA vs. AC + CC statistically significant differences (p < 0.05) have been observed. CONCLUSIONS Observed overrepresentation of mutated C allele of the AT1 gene was correlated with increased blood flow in umbilical artery in women with preeclampsia. Doppler velocimetry might be a useful tool for indication in the high-risk group with overrepresentation of C alleles.

Fetal and maternal Doppler velocimetry and cytokines in high-risk pregnancy

Abstract Objective: Fetal hypoxia and preterm delivery are reported to be strongly associated with brain damage and neurodevelopmental delay. Doppler signs of fetal brain sparing have been described during chronic hypoxia, but whether they are related to brain damage is unknown. The aim of this study was to evaluate if markers of tissue injury, i.e., tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are related to signs of increased perinatal vascular impedance and/or fetal brain sparing in high-risk pregnancies. Study design: TNF-α and IL-6 levels were evaluated in maternal blood serum of 67 high-risk pregnancies. Serum samples were taken at the time of umbilical, middle cerebral artery and uterine artery Doppler velocimetry examination. The values for TNF-α and IL-6 were correlated with reference median values obtained with gestational age in the form of a Z-score. Results: TNF-α levels showed values within the normal range in only four cases. IL-6 values were found normal in 14 cases. The Z-score for mean middle cerebral artery pulsatility index (PI) showed a significant correlation to TNF-α and IL-6 levels, P<0.0001 and P<0.003, respectively. This might suggest a strong correlation between signs of fetal brain sparing and increased maternal serum TNF-α and IL-6 levels. Abnormal uterine artery PI and the presence of a “notch” were also highly significantly related to TNF-α and IL-6 levels, which were nearly two-fold higher compared to normal uterine artery blood flow and the absence of a “notch”. Abnormal cerebro/placental ratios showed significant correlations to TNF-α and IL-6 levels. Conclusion: The present results suggest a strong correlation between levels of TNF-α and IL-6 not only for signs of fetal brain sparing, but also for uteroplacental blood flow. This finding supports the role of tissue injury in cases of fetal brain sparing, but whether this is a reflection of brain damage or secondary to placental pathology needs further evaluation.

The Optimal Treatment of Thyroid Gland Function Disturbances During Pregnancy

Thyroid disorders are quite a common health problem in pregnant women, thus adequate treatment in this period is very important in order to decrease maternal and fetal morbidity. The prevalence of hyperthyroidism is estimated to be present in approximately 0.2-0.4% of all pregnancies and the most common is Graves disease. Untreated hyperthyroidism is connected with disturbed fertilisation, recurrent miscarriages, preeclampsia development, hypotrophy of the fetus, and haemorrhage in the postpartum period. Hypothyroidism is found in pregnant women in 0.3-0.7% of all cases. Uncontrolled hypothyroidism in pregnancy can lead to preterm birth, low birth weight and mental retardation. The goal of the treatment of both hypo- and hyperthyroidism is to reach a stable euthyroid state by applying thyroid hormones or antithyroid drugs, respectively. It seems that well-controlled management of thyroid diseases does not pose any problem for pregnancy. However, the most important is to avoid any neurological abnormalities in the fetus in hyperthyroid women resulting from antithyroid drugs exposure. Moreover, it is also crucial to abstain from subclinical hypothyroidism and hypothyroxinaemia in the mother and its effect on the fetuss development which merits exact screening and intense monitoring. In this paper we described the complex pharmacology of the drugs that are used in pregnant women suffering from thyroid disorders, considering the clinical application, practical recommendation, and side effects in pregnancy and lactation. This systematic analysis could contribute some pharmacological knowledge which will be helpful in the clinical management of thyroid disorders during pregnancy.

Influence of the Melissa officinalis Leaf Extract on Long-Term Memory in Scopolamine Animal Model with Assessment of Mechanism of Action

Melissa officinalis (MO, English: lemon balm, Lamiaceae), one of the oldest and still most popular aromatic medicinal plants, is used in phytomedicine for the prevention and treatment of nervous disturbances. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 50% ethanol extract of MO leaves (200 mg/kg, p.o.) compared with rosmarinic acid (RA, 10 mg/kg, p.o.) and huperzine A (HU, 0.5 mg/kg, p.o.) on behavioral and cognitive responses in scopolamine-induced rats. The results were linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex of rats. In our study, MO and HU, but not RA, showed an improvement in long-term memory. The results were in line with mRNA levels, since MO produced a decrease of AChE mRNA level by 52% in the cortex and caused a strong significant inhibition of BACE1 mRNA transcription (64% in the frontal cortex; 50% in the hippocampus). However, the extract produced only an insignificant inhibition of AChE activity in the frontal cortex. The mechanisms of MO action are probably more complicated, since its role as a modulator of beta-secretase activity should be taken into consideration.

Screening of Trace Elements in Hair of the Female Population with Different Types of Cancers in Wielkopolska Region of Poland

Background. Cancer constitutes a major health problem worldwide. Thus, search for reliable and practical markers of the disease process remains the key issue of the diagnostic process. Objectives. The study aims at linking the trace element status of an organism, assessed by hair analysis, with the occurrence of cancer diseases. Material and Methods. Hair samples were collected from 299 patients with cancer diseases confirmed by a histopathological test and from 100 controls. Cancer patients were divided into three groups, depending on cancer type: hormone-dependent cancer, cancer of the alimentary tract, and cancer with high glycolytic activity. Mineral element analysis of hair was performed using an atomic emission spectrophotometer with inductively coupled plasma (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). Results. Statistically significantly lower concentrations of selenium, zinc, copper, germanium and boron, iron, and magnesium were observed in the three groups of cancer patients. Disturbance in the axis glucose-insulin and changes in concentrations of heavy metals and toxic elements were also noted. Conclusions. It seems safe to conclude that our results confirmed usefulness of hair element analysis in screening tests for the assessment of the biomarker of various cancer diseases in a female population.

The importance of MTHFR, MTR, MTRR and CSE expression levels in Caucasian women with preeclampsia.

OBJECTIVE Preeclampsia (PE) is a major cause of maternal and perinatal mortality and morbidity. The studies suggest that both polymorphisms and changes of expression in genes encoding enzymes involved in the methionine and homocysteine metabolism (MHM), such as methylenetetrahydrofolate, reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR) and cystathionine gamma-lyase (CSE), could play a role in the development of hypertension during pregnancy. The aim of the study was to determine the expression level of MTHFR, MTR, MTRR and CSE genes in the development of PE in Caucasian women. STUDY DESIGN The control group consisted of 74 healthy pregnant women and 90 patients with diagnosed pre-eclampsia. Total RNA was isolated from placenta and the mRNA level of examined genes was to determine using real-time PCR. RESULTS The expression level of MTHFR gene showed no statistically significant difference in the study group as compared to the control group. An increase of mRNA levels for MTR and CTH was observed by 124.7% (p<0.0001) and 26.6% (p>0.05), respectively. However, a decrease of placental expression was noted for MTRR by 50% in preeclamptic women as compared to control group (p<0.0001). CONCLUSIONS Our findings suggest that the elevated RNA expression of MTR in placenta of preeclamptic patients is probably results of a potential compensation mechanism of the MHM while elevated CSE expression indicates that homocysteine may be eliminated through the alternate transsulfuration pathway.

Improvement in Long-Term Memory following Chronic Administration of Eryngium planum Root Extract in Scopolamine Model: Behavioral and Molecular Study.

Eryngium planum L. (EP) is as a rare medicinal plant with a lot of potentials as pharmaceutical crops. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 70% ethanol extract of EP roots (200 mg/kg, p.o.) on behavioral and cognitive responses in Wistar rats linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex. On the last day of experiment, 30 min after the last dose of EP or Huperzine A (HU), scopolamine (SC) was given at a dose of 0.5 mg/kg b.w. intraperitoneally. The results of a passive avoidance test showed an improvement in long-term memory produced by the EP extract in both scopolamine-induced rats and control group. EP caused an insignificant inhibition of AChE and BuChE activities in the frontal cortex and the hippocampus. EP decreased mRNA AChE, BuChE, and BACE-1 levels, especially in the cortex. Our results suggest that the EP extract led to the improvement of the long-term memory in rats coupled with total saponin content. The mechanism of EP action is probably complicated, since HPLC-MS analysis showed 64 chemical compounds (phenolics, saponins) in the extract of EP roots.

Evaluation of anti-inflammatory and analgesic activities of extracts from herb of Chelidonium majus L.

The aim of the study was to evaluate analgesic activity (“hot plate” test), anti-inflammatory activity (carrageenan-induced paw edema) and locomotor activity in rats under the influence of three fractions of Chelidonium majus herb extract: full water extract (FWE), protein enriched fraction (PEF), and non-protein fraction (NPF). Effects of the fractions on the level of chosen cytokines and their mRNA levels were also assessed using lipopolysaccharide (LPS) administration as a proinflammatory cue. All fractions and diclofenac did not affect the locomotor activity of rats in comparison with the control group. FWE and PEF three hours after administration showed statistically significant analgesic activities comparable to morphine (p < 0.05). A slight reduction in rat paw edema was observed after three (comparable with diclofenac) and six hours in the NPF group. FWE revealed a statistically significant pro-inflammatory effect after three hours in comparison with the control group. Peripheral IL-1 and IL-4 cytokine concentrations were reduced under FWE and NPF, PEF fractions. The combination of FWE, PEF and NPF together with LPS showed only the effects of LPS. We suggest that protein enriched fraction (PEF) produced centrally mediated (morphine-like) analgesic action, whereas the anti-inflammatory potential was shown only after LPS-induced inflammation. The precise mechanisms involved in the production of anti-nociceptive and anti-inflammatory responses of studied fractions are not completely understood, but they may be caused rather by the presence of protein more than alkaloids-enriched fraction. This fraction of the extract could be used as an alternative therapy for the prevention of inflammatory-related diseases in the future, but further studies are needed.

The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women

OBJECTIVE The aim of the study was assessment of a possible relationship between the polymorphisms of the candidate genes participating in the etiology of some neurological and psychiatric disorders and the risk of depression in perimenopausal and postmenopausal women. METHODS A total of 167 (54 perimenopausal and 113 postmenopausal) Caucasian women from western Poland, aged 42-67, were recruited as the patient group in the study because of depressive symptoms, and another 321 healthy women (102 perimenopausal and 219 postmenopausal) served as the controls. All study participants were evaluated for climacteric and depressive disorders according to the Kupperman index and Hamilton rating scale for depression (HRSD), respectively. The following candidate genes were selected for the study: 5HTR2A, 5HTR1B, 5HTR2C, TPH1, TPH2, MAOA, COMT, NET, GABRB1, ESR1, MTHFR, MTR and MTHFD1. In each group the frequencies of the polymorphisms were determined using PCR-RFLP analysis. RESULTS After correcting for Bonferroni multiple tests, we found associations between the MAOA c.1460C>T (SNP 1137070), COMT c.472G>A (SNP 4680), MTHFR c.677C>T (SNP 1801133) and ESR1 454(-351) A>G (SNP 9340799) polymorphisms to mild and moderate depressive symptoms in menopausal women. In the perimenopausal and postmenopausal women, genotype association of the MAOA c.1460 CT and c.1460 CT+TT (OR=1.83; pcorr=0.009 and OR=1.85; pcorr=0.003, resp.), and of the MTHFR c.677 TT and c.677 CT+TT (OR=3.52; pcorr=0.00009 and OR=2.06; pcorr=0.0006, resp.), as well as of the COMT c.472 GA and COMT c.472 GA+AA genotypes (OR=2.23; pcorr=0.03 and OR=2.17; pcorr=0.027, resp.) in the postmenopausal women revealed significantly higher frequencies of these variants in depressed female patients than in controls, whereas the ESR1 454(-351) AG and 454(-351) AG+GG genotypes were associated with lower risk of depression in postmenopausal women (OR=0.48; pcorr=0.012, and OR=0.52; pcorr=0.015, resp.). CONCLUSIONS Our study substantiates the involvement of the MAOA and MTHFR polymorphisms in climacteric depression and offers evidence that the COMT and ESR1 genes may also play a role in the susceptibility to depressive mood in postmenopausal women.