Rafał Rzepka

Isoprostanes 8-iPF2α-III: risk markers of premature rupture of fetal membranes?

Aims: Isoprostanes may serve as sensitive and specific markers of in vivo oxidative stress intensity. We wanted to determine, whether or not isoprostane concentration may be considered as a risk marker of premature rupture of fetal membranes (PROM). Methods: On the basis of the presence of PROM and gestational maturity, a total of 128 patients were divided into: (1) preterm PROM (pPROM) group; (2) PROM at term group; (3) control preterm (C1) group and (4) control at term (C2) group. The concentrations of 8-iPF2α-III were determined using the enzyme-linked immunosorbent assay method. Results: The mean free isoprostane concentrations, examined in amniotic fluid and maternal plasma in the PROM at term patients were significantly higher than in C2 individuals (p < 0.01). The mean concentrations of free 8-iPF2α-III measured in blood plasma from women in the C1 group were significantly lower than in patients from the pPROM, PROM at term and C2 groups (p < 0.001, p < 0.00001 and p < 0.00001, respectively). Conclusion: The measurement of free isoprostane concentration in maternal plasma and amniotic fluid may be considered as a laboratory marker of a PROM-risk pregnancy.

A Common Profile of Disordered Angiogenic Factor Production and the Exacerbation of Inflammation in Early Preeclampsia, Late Preeclampsia, and Intrauterine Growth Restriction

Preeclampsia and intrauterine growth restriction are two separate disease entities that, according to numerous reports, share the same pathogenesis. In both, angiogenesis disorders and generalized inflammation are the dominant symptoms. In this study, we hypothesized that both diseases demonstrate the same profile in early preeclampsia, late preeclampsia, and intrauterine growth restriction patients, with the only difference being the degree of exacerbation of lesions. One hundred sixty-seven patients were enrolled in the study and divided into four groups: early preeclampsia, late preeclampsia, and intrauterine growth restriction groups, and one control group. Concentrations of the angiogenesis and inflammatory markers soluble fms-like tyrosine kinase receptor 1, placental growth factor, high-sensitivity C-reactive protein, and interleukin-6 were determined, and the behavior of these markers and correlations among them were studied. Higher concentrations of soluble fms-like tyrosine kinase receptor 1, high-sensitivity C-reactive protein, and interleukin-6 and a lower concentration of placental growth factor were observed in the study groups compared with the control group. No differences in concentrations of the studied markers were found among the study groups but significant correlations were observed. The higher values for the angiogenesis and inflammatory markers both in preeclampsia patients and patients with intrauterine growth restriction of placental origin compared with the control group suggest the existence of the same underlying disorders in the development of these pathologies. The observed mutual correlations for disordered angiogenesis and inflammatory markers are suggestive of a mutual relationship between these processes in the development of pathologies evolving secondary to placental ischemia. The same lesion profile was observed for both preeclampsia and ‘placental’ intrauterine growth restriction patients, which could be used in developing common diagnostic criteria for pregnant patients.

On the Significance of New Biochemical Markers for the Diagnosis of Premature Labour

Preterm labour is defined as a birth taking place between 22nd and 37th weeks of gestation. Despite numerous studies on the aetiology and pathogenesis of preterm labour, its very cause still remains unclear. The importance of the cytokines and acute inflammation in preterm labour aetiology is nowadays well-proven. However, chronic inflammation as an element of the pathogenesis of premature labour is still unclear. This paper presents a literature review on the damage-associated molecular patterns (DAMPs), receptors for advanced glycation end products (RAGE), negative soluble isoforms of RAGE, chemokine-stromal cell-derived factor-1 (SDF-1) and one of the adipokines, resistin, in the pathogenesis of preterm labour. We conclude that the chronic inflammatory response can play a much more important role in the pathogenesis of preterm delivery than the acute one.

Maternal endothelial damage as a disorder shared by early preeclampsia, late preeclampsia and intrauterine growth restriction

Abstract Introduction: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are separate disease entities that have frequently been reported as sharing the same pathogenesis. In both of them, angiogenesis disorders and generalized endothelial damage with an accompanying inflammation are the dominant symptoms. In this study, we attempted to prove that both these processes demonstrate the same profile in early PE, late PE and IUGR patients, while the only difference is in the degree of exacerbation of the lesions. Patients, materials and methods: In 167 patients divided into four groups, three of those with early PE, late PE and IUGR and one control group, fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), high sensitive c-reactive protein (hsCRP) and fibronectin were determined. The behavior of these parameters in each of the groups was studied, and correlations between them were sought for. Results: Higher concentrations of sFlt-1, hsCRP and fibronectin and a lower concentration of PlGF were found in the study groups compared to the control group. Significant correlations were observed between the factors concerned. Conclusions: The higher values of disordered angiogenesis markers, endothelial damage markers and inflammatory markers both in the PE and the intrauterine growth restriction (IUGR) groups suggest the existence of shared disorders in the development of these pathologies. The correlations between disordered angiogenesis markers and endothelial damage markers argue in favor of a mutual relationship between these two processes in the development of pathologies evolving as secondary to placental ischemia. The results obtained confirm that the lesion profiles are the same in both PE and IUGR patients, which can be utilized in developing common diagnostic criteria.

Maternal plasma lipopolysaccharide binding protein (LBP) concentrations in pregnancy complicated by preterm premature rupture of membranes.

OBJECTIVES To compare maternal plasma LBP concentrations in pregnancies complicated by preterm premature rupture of membranes (pPROM), and PROM at term, with their levels in uncomplicated pregnancy, and to determine whether LBP concentrations are of value in the diagnosis of subclinical intra-amniotic infection (IAI) in the prediction of the length of the pPROM-to-delivery interval, and in the prediction of neonatal congenital infection. STUDY DESIGN Thirty-one patients with pPROM, 35 with PROM at term, 33 healthy women at preterm gestation and 35 healthy women at term were included. In the pPROM group, analysis of maternal plasma LBP concentrations with reference to leukocytosis, C-reactive protein, vaginal fluid culture, neonatal infection and pPROM-to-delivery interval was carried out. RESULTS LBP concentrations in the four studied groups were comparable. Although in 58.1% of pPROM cases at least one laboratory parameter of infection was observed, the only difference concerned the subgroup with CRP above 10mg/L, in which LBP concentrations were higher. Comparison of LBP concentrations in patients delivered within 24 and 72h of pPROM and after these times showed no differences, or between patients who gave birth to newborns with and without congenital infection. The predictive values of these measurements were poor. CONCLUSION The predictive value of maternal LBP determinations in the diagnostics of pPROM cases suspected of IAI is unsatisfactory. LBP measurements performed shortly after pPROM, are not of value either in the prediction of newborns infection, or in the prognosis of latency period duration.

The Activity of Erythrocyte Sodium-Proton Exchanger in Women with Pregnancy- Induced Hypertension

Background: Hypertension that develops after 20 gestational weeks and is defined as pregnancy-induced hypertension (PIH). The main cause of PIH is vasoconstriction and the thickening of vascular media, which decreases vascular capacity and increases peripheral resistance. One of the theories postulated to explain this phenomenon is that a transmembrane sodium transport disorder causes an increase in intracellular sodium concentration. In the latest literature, special attention is paid to the role of the increased intracellular sodium concentration in the pathogenesis of essential hypertension (EH). One of the best documented phenotypes for EH is the increased activity of the sodium-proton exchanger (NHE). The aim of this study was to assess if increased NHE activity could be the mechanism responsible for the development of PIH. Subjects and methods: The study included 30 women: 10 pregnant women with PIH after gestational week 30, 10 women with physiological pregnancy after 30 gestational weeks, and 10 healthy non-pregnant women. NHE activity was determined according to Orlov’s method as amiloride-sensitive H+ efflux from acid-loaded cells. Results: The NHE activity in the group of women with PIH was significantly higher than that in women with physiological pregnancy: 10.09 ± 1.65 vs. 6.81 ± 2.3 mmol/L RBC/h (p < 0.049) and in the group of non-pregnant women: 10.09 ± 1.65 vs. 7.56 ± 1.66 mmol/L RBC/h (p < 0.029). Erythrocyte NHE activity did not differ in the group of women with physiological pregnancy and in the group of non-pregnant women. Conclusion: These results seem to suggest that erythrocyte NHE activity is elevated in PIH pregnancies.

Do the physiological aging of the placenta and the changes in angiogenesis marker sFlt-1 and PlGF concentrations predispose patients to late-onset preeclampsia?

Abstract Objective: Aging of the placenta is associated with natural processes that impair its functions. The processes are related to both oxidative stress exacerbation and the occurrence of higher concentrations of disordered angiogenesis markers. Both these types of processes are known to play roles in the development of preeclampsia. We attempted to show that natural ageing of the placenta can be one of the cofactors contributing to the development of late-onset preeclampsia. Patients, materials and methods: 159 pregnant patients were divided into four groups: Two of preeclampsia patients and two of patients with physiological pregnancies, depending on the gestational age. For each group, disordered angiogenesis markers sFlt-1 and PlGF before and after 34 weeks of gestation and in particular stages of gestation were analyzed. Results: Lower PlGF and sFlt-1/PlGF ratio values were found in cases of late-onset preeclampsia. In physiological pregnancies, sFlt-1 values were observed to increase and PlGF values to decrease with gestational age. An association was shown to exist between disordered angiogenesis markers and gestational age both in preeclampsia and physiological pregnancies. Conclusions: (1) Analyses of disordered angiogenesis markers in early- and late-onset preeclampsia patients and patients with physiological pregnancies allow for a suggestion that natural “ageing of the placenta” and placental hypoperfusion lesions exacerbating with the advancing gestational age are some of the causes of late-onset preeclampsia. (2) Cases of early-onset preeclampsia are associated with more severe changes of disordered angiogenesis marker concentrations, which may be indicative of a more considerable impairment of placental perfusion in such patients. (3) In the course of the physiological pregnancy, there is a gradual increase in sFlt-1 and decrease in PlGF, which implies an elevated angiogenesis disorder that progresses with the gestational age.

Development of a focal segmental glomerulosclerosis after pregnancy complicated by preeclampsia: case report and review of literature

Abstract The global incidence of preeclampsia has been estimated at 3–5% of all pregnancies. It is the main cause of morbidity and mortality among pregnant women and their fetuses worldwide. In preeclampsia, the incorporation of cytotrofoblast into the spiral arteries is incomplete. Changed placenta releases into the mother’s circulation soluble VEGF receptor-1 (sFlt-1) which causes many disorders including kidney damage. VEGF is produced by glomerular podocytes and is necessary for their normal function. The damage of podocytes leads to a glomerulosclerosis development. The damage of the critical number of podocytes contributes to the development of focal segmental glomerulosclerosis – kind of glomerulonephritis. We present a case of woman who as a result of preeclampsia developed focal segmental glomerulosclerosis manifested as nephritic syndrome. We describe a mechanism for the development of such changes in glomeruli in the course of preeclampsia.

Soluble and Endogenous Secretory Receptors for Advanced Glycation End Products in Threatened Preterm Labor and Preterm Premature Rupture of Fetal Membranes

The aim of the study was to compare sRAGE and esRAGE plasma levels in pregnant women with (A) threatened premature labor (n = 41), (B) preterm premature rupture of membranes (n = 49), and (C) preterm rupture of membranes at term (n = 48). The relationship between these and classic intrauterine infection markers and the latent time from symptoms up to delivery depending on RAGEs concentration were investigated. In groups A and B, a positive correlation was found between plasma sRAGE and latent time (r = 0,422; p = 0,001; r = 0,413, p = 0,004, resp.). High prognostic values were found in both groups for plasma sRAGE concentration and the latent time from symptoms up to delivery. Groups B and C presented higher levels of esRAGE than group A (526,315 ± 129,453 pg/mL and 576,212 ± 136,237 pg/mL versus 485,918 ± 133,127 pg/mL, p< 0,05). The conclusion is that sRAGE concentration can be a favorable prognostic factor in the presence of symptoms of threatened premature labor. Higher esRAGE plasma level in case of the rupture of membranes in mature and premature pregnancy suggests its participation in fetal membranes destruction.

Successful pregnancy in the patient with Fanconi‐Bickel syndrome undergoing daily hemodialysis

Successful Pregnancy in the Patient With Fanconi-Bickel Syndrome Undergoing Daily Hemodialysis Karolina Kędzierska, Sebastian Kwiatkowski, Andrzej Torb e,* Mal-gorzata Marchelek-Myśliwiec, Oliwia Marcinkiewicz, Katarzyna Bobrek-Lesiakowska, Edyta Gol-embiewska, Ewa Kwiatkowska, RafalRzepka, Kazimierz Ciechanowski, Ryszard Czajka, and Ren e Santer Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland Department of Obstetrics and Gynecology, Pomeranian Medical University, Szczecin, Poland Department of Children Diseases, University Hospital of Hamburg, Hamburg, Germany