Low placental angiotensin-converting enzyme expression is related to fetal small for gestational age but not to metabolic control in type 1 diabetic pregnancies.

The maternal renin-angiotensin system is involved in blood pressure control and plays a crucial role in fetoplacental nutrition. Pre-gestational type 1 diabetes (PGDM) leads to serious pregnancy complications. We thus performed a longitudinal study to analyse the association of maternal angiotensin-converting enzyme (ACE) serum levels and placental mRNA expression with fetal newborns gestational weight in type 1 diabetes mellitus (T1DM) women. We recruited 65 singleton pregnant women with T1DM. Placental mRNA ACE gene expression was examined using quantitative real-time PCR. Serum ACE levels were measured in the first, second and third trimesters of pregnancy by ELISA commercial kits. Placental expression of ACE mRNA was significantly lower in small for gestational age (SGA) than appropriate for gestational age (AGA) and large for gestational age (LGA) mothers (0.55±0.06 vs 0.78±0.06 and 0.85±0.07 respectively, p=0.003). In the SGA group, the mRNA expression of ACE positively correlated with maternal body mass index (BMI) in the third trimester (r=0.49; p=0.04). In all study groups maternal ACE level was significantly higher in the third trimester (mean 139.91±SD 69.64) compared to the first and second trimesters of pregnancy (13.57±4.32 and 15.69±15.92 respectively). Our data suggest that lower placental ACE gene mRNA expression may have a vital role in the etiology of SGA babies.

The role of genetic factors in the pathogenesis of neonatal intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) affects 15-20% of babies born before 32 weeks of pregnancy. Besides gestational age (below 32 weeks) there are a number of IVH risk factors. Increasing attention is being paid to genetic factors in the development of IVH. The authors discuss genetic factors (mutations of coagulation factors, gene polymorphisms in pro-inflammatory cytokines, mutation of type IV collagen gene, polymorphisms of genes responsible for the regulation of systemic blood pressure and cerebral blood flows) whose involvement in IVH pathogenesis has been confirmed in the highest number of reports and for which being a carrier plays an important role in their pathophysiology. The role of genetic factors in IVH remains unclear. Further analysis of the role of genetic factors in the pathophysiology of IVH will make it possible to determine the group of newborns who are specifically at risk of developing IVH in the perinatal period.

Placental vascular endothelial growth factor expression in pregnancies complicated by type 1 diabetes.

UNLABELLED: Type 1 diabetes mellitus (T1DM) is still associated with increased risk of severe maternal and foetal complications but their pathomechanism remains unclear. OBJECTIVES: we investigated the possible role of placental vascular endothelial growth factor (VEGF) and VEGF single nucleotide polymorphisms (SNP) in foetal development in T1DM pregnancies. Sixty seven pregnant women with T1DM and singleton pregnancy were enrolled into the study. Results demonstrated higher expression of placental VEGF in women who delivered neonates with birth weight (NBW)>4000g. No such correlation was found in the overall T1DM group and in women who delivered appropriate for gestational age (AGA) and small for gestational age (SGA) newborns. We also demonstrated a significant correlation between 3(rd) trimester mean blood glucose, HbA1C and placental VEGF. No such correlation was found for the 1(st) and 2(nd) trimesters. Top placental VEGF expression and placental mass were found in women who delivered large for gestational age (LGA) newborns. We also found a statistically significant difference in homozygous and heterozygous frequency variants of VEGF SNPs in study groups. We conclude that the increased placental VEGF together with impaired metabolic control may have a role in stimulating foetal overgrowth in T1DM pregnancy.

The effect of standardized Echinacea purpurea extract on rat cytochrome P450 expression level.

It is claimed that application of botanical supplements or herbal medicinal products with synthetic drugs that are cytochrome P450 enzymes substrates may induce significant herb-drug interactions and may alter pharmacotherapy. Echinacea preparations are one of the best selling products in the Europe and their medicinal use is still increasing but data about interactions of Echinacea extract with CYP enzymes are limited. In this study, we have investigated potential influence of standardized Echinacea purpurea extract containing 3.7% polyphenolic compounds on the mRNA expression level of major CYP450 enzymes using animal model. Total RNA was isolated from the rat liver tissue according to the manufacturer's protocol. Complementary DNA was synthesized from a mature mRNA template using reverse transcription. The level of mRNA expression in liver was analyzed by real-time quantitative PCR using specific target primers for CYP450 genes. In this study, it was demonstrated a significant increase of rat CYP2D1 and CYP1A1 expression level by 40% (p = 0.007) and 80% (p = 0.01), respectively. A weak inductory effect of the extract was observed for CYP1A2 by 16% (p > 0.05) compared with the control group. The levels of rat CYP3A1 and CYP3A2 mRNA were reduced by 41% (p < 0.05) and 25% (p = 0.001), respectively. A weak inhibitory effect was observed for CYP2D2 by 15% (p = 0.008) and CYP2C6 by 18% (p = 0.004) after long application of the Echinacea ethanolic extract. CYP2D2 and CYP2C6 activities were also inhibited by extract but in a lesser degree than CYP3A1 activity. Moreover, very little or no inhibition was noted for CYP2E1 both after 3 and 10 days of treatment. Our in vivo data indicate that the Echinacea ethanolic extract can potently inhibit the expression of CYP3A1/2 and can also induce of CYP1A1, CYP2D1. These findings suggest that Echinacea extract may influence the P450-mediated metabolism of different drugs and may initiate chemical carcinogenesis by activation of some compounds to their carcinogenic metabolites.

Leptin gene, leptin gene polymorphisms and body weight in pregnant women with diabetes mellitus type I.

UNLABELLED: There have been several genetic causes of obesity discussed by past authors, among others leptin, that have provided information regarding signaling pathways in energy expenditure in humans. Genetic variants of the leptin gene and its receptor may influence body weight. AIM: To investigate the role of the leptin gene's polymorphism promotion region (2548 G/A) and the leptin gene receptor polymorphism (668 A/G) and its associations with body weight in pregnant women with type 1 diabetes (PGDM-1). METHODS: 78 PGDM-1 were qualified to the study group (SG) which was divided into normal and over-weight individuals according to BMI criteria. The control group (CG) consisted of first trimester healthy pregnant women with normal body weight. Genetic variants of the leptin gene and its receptor were analyzed using PCR-RFLP assays. Within the SG, the following metabolic parameters were estimated: MBG, HbA1C, insulin dose, LDL, HDL, T-CHOL, creatinine, creatinine clearance and blood pressure. RESULTS: There was a trend found among the majority of homozygous A and G variants in LEP -2548 G/A and LEPR 668 A/G in over-weight and obese individuals in comparison to normal-weight subjects (CG). There were no specific differences found in selected first trimester metabolic parameters in relation to patients' genotypes.

The significance of C3435T point mutation of the MDR1 gene in endometrial cancer.

The P-glycoprotein (P-gp) plays an important role in carcinogen distribution and is connected with cell differentiation and apoptotic processes leading to carcinogenesis. Interindividual differences in P-gp activity could modulate susceptibility to cancer development. The MDR1 gene, coding for P-gp, is highly polymorphic and some mutations modulate P-gp activity. Recently, association between the MDR1 C3435T polymorphism and the cancer susceptibility was shown. We have hypothesized that MDR1 polymorphism could influence endometrial cancer susceptibility. We have matched 198 women with endometrial cancer and 198 controls. An additional group of 488 healthy volunteers was investigated. The MDR1 C3435T polymorphism was tested by LightCycler assay. The distribution of MDR1 3435 genotypes was significantly different between cases and controls (P = 0.006). Genotypes containing at least one 3435T allele were statistically significant more frequent in the endometrial cancer group (86.8% vs 75.2%, OR 2.18, P = 0.004). Our observation suggests that MDR1 C3435T polymorphism is correlated with endometrial cancer susceptibility.

[Polymorphism of gene angiotensin converting enzyme in pregnancy induced hypertension]. / Polimorfizm genu kodujacego konwertaze angiotensyny i w nadcisnieniu indukowanym ciaza.

In the recent years genetic background of pregnancy induced hypertension (PIH) are intensively investigated. Genetically determined differences in activity of renin-angiotensin system (RAS) are of importance to hypertension susceptibility. The insertion/deletion (I/D) polymorphism of angiotensin I converting enzyme (ACE) was suggested to play an important role in the aetiology of idiopathic hypertension. We have tested if this polymorphism could be associated with PIH. ACE polymorphism was investigated in 87 pregnant women with PIH and in 110 healthy pregnant women (control group). Investigation was performed by polymerase chain reaction (PCR). We have amplified genomic DNA excteracted by phenol-chloroform method from blood leucocytes. We have detected overrepresentation of the I allele in the PIH group (47.2% and 41.4% in PIH and controls, respectively). ACE genotype frequency in control group was in agreement with expected values, according to Hardy-Weinberg law, but in the PIH group the obtained values were different from expected. This observation confirmed the possible role of I allele in aetiology of PIH, and we believe that continuation of this investigation is necessary.

[Analysis of interleukin-6 serum concentration in trophoblastic tumors prognosis]. / Wartosc kliniczna analizy stezen interleukiny-6 u kobiet chorych na rozrosty i nowotwory trofoblastu.

OBJECTIVES: Our purpose was to estimate the prognosis based on Il-6 concentration in cases of trophoblastic tumors. MATERIALS AND METHODS: The study population was 65 women suffering from hydatiform mola or choriocarcinoma. We divided them into two groups: 30 patients who required only operative management and 35 patients who required operative procedures and additional chemotherapy. The observation period was 6 months. Blood samples were collected every 4 weeks. Concentration of Il-6 was measured in ELISA assay. RESULTS: The serum Il-6 concentration was significantly higher in cases of trophoblastic diseases than in the group of healthy women and higher in patients who required chemotherapy after operation (451.0 +/- 88.5 pg/ml), than in patients treated only surgically (257.1 +/- 77.1 pg/ml). CONCLUSIONS: Patients with hydatiform mola and choriocarcinoma reveal higher concentration of Il-6 than healthy women. It is associated with disease prognosis and allows to determine at the time of establishing a diagnosis, whether a patient can be treated only surgically or requires an additional chemotherapy.

[Gestational hypertension (GH) and a1166c polymorphism of angiotensin II type 1 receptor]. / Nadcisnienie ciazowe (GH) a polimorfizm A1166C receptora typu 1 angiotensyny II (AT1).

INTRODUCTION: Recent studies have suggested an association between genetic background of renin-angiotensin system (RAS) and the pathogenesis of pregnancy induced hypertension (PIH). However, the role of the gene coding for angiotensin II receptor (AT1) polymorphism in PIH is not fully understood, thus the aim of the present study was to determine the frequency of A1166C mutation in women with gestational hypertension (GH) and to establish the role of this polymorphism on the susceptibility to the PIH development. PATIENTS & METHODS: We have analysed 88 women with PIH and 113 healthy pregnant women as a controls. Genomic DNA was extracted from leucocytes using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). RESULTS: We have detected overrepresentation of mutated homozygous genotypes in the PIH group (11.4% in the PIH versus 2.7% in the controls). Homozygous wild-type genotypes were underrepresented in the PIH group (48.9% in PIH and 56.6% in controls). The frequency of heterozygotes was similar in both groups. Statistically significant overrepresentation of allele with mutation in the PIH group (31.3% in the women with PIH, and 23.0% in the controls) (O.R. = 1.5, p = 0.04) was observed. CONCLUSION: We suggest that presence of A1166C mutation is a risk factor for the development of PIH.

[Cesarean section for the second twin during the course of delivering twins]. / Ciecie cesarskie na drugim plodzie w przebiegu porodu ciazy blizniaczej.

We have analysed 6 cases of twin pregnancies with vertex presentation of the first foetus. In this cases after delivery of the first twin by vaginal route caesarean, section was made. Caesarean section of the second twin was made because of: transversal presentation with fetal distress syndrom (four cases), umbilical cord drop (one case), and premature placenta ablation (one case). We have determined acid base balance and Apgar score. We have noted worse results for the second twin, independently too of the time between deliveries both twins. Caesarean section of the second twin is the rarely clinical situation, but in motivated situation is accepted and reasonable solution.

[Triplet gestation--analysis of pregnancy course, delivery and neonatal outcome, based on personal material]. / Ciaza trojacza--analiza przebiegu ciazy, porodu, stanu noworodków, na podstawie materialu wlasnego.

UNLABELLED: Triplet gestation appears in 0.1-0.3% of all pregnancies and it is high risk pregnancy for mother and foetus. It appears more frequently in Afroamerican women, rarely in Japan women. In multifetal pregnancy early prenatal diagnosis and management are very important. AIM: Analysing course of pregnancy, way of delivery, condition of newborns, influence of environmental factors, and concomitant diseases in triplets gestation. MATERIAL: 30 women treated between 1989-1998, in Division of Perinatology, University of Medical Sciences in Poznan, Poland. RESULTS: 21 pregnancies were ended by caesarean section, 9 by vaginal delivery. Apgar score for II and III foetus decreases significantly. pH value of umbilical artery was without significant differences. CONCLUSIONS: Almost all triplets have ended preterm. Route of delivery of triplets have to be considered individually. Environment factors could play an important role in multifetal pregnancy.