Britta Frederiksen-Møller

Urinary Plasmin Activates Collecting Duct ENaC Current in Preeclampsia

In nephrotic syndrome, plasminogen is aberrantly filtered from plasma to the urinary space and activated along the tubular system. In vitro, plasmin increases ENaC current by proteolytic cleavage of the &ggr;-subunit. It was hypothesized that preeclampsia is associated with plasmin-dependent ability of tubular fluid to activate ENaC. Urine was sampled from 16 preeclamptic (PE) patients and 17 normotensive pregnant women (Ctrl). Urine was analyzed for plasmin(ogen), creatinine, albumin, aldosterone, Na+, K+, proteolytic activity, and for its effect on inward current in cortical collecting duct cells (M1 cells) by whole-cell patch clamp. In PE, urine plasmin(ogen): creatinine ratio was elevated 40-fold (geometric mean, 160 versus 4 µg/g; P<0.0001) and urine aldosterone: creatinine ratio was suppressed to 25% of Ctrl (geometric mean, 27 versus 109 µg/g; P<0.001). A significant negative correlation was found in PE between urinary plasmin(ogen) and aldosterone (P<0.05). In PE, proteolytic activity was detected at 90 to 75 kD by gelatin zymography in 14 of 16 patients and confirmed by serine protease assay. Immunoblotting showed active plasmin in PE urine. Whole-cell inward current increased in M1 cells on exposure to urine from PE (173±21%; n=6; P<0.001). The increase in current was abolished by amiloride (2 &mgr;mol/L; P<0.001), &agr;2-antiplasmin (1 &mgr;mol/L; P<0.001), and heat denaturation (P<0.001). Preeclampsia is associated with urinary excretion of plasmin(ogen) and plasmin-dependent activation of ENaC by urine. Proteolytic activation of ENaC by plasmin may contribute to Na+ retention and hypertension in preeclampsia.

Prostasin and matriptase (ST14) in placenta from preeclamptic and healthy pregnant women.

Objective: Preeclampsia is characterized by disturbed placentation, hypertension, proteinuria, and suppression of plasma renin, angiotensin II, and aldosterone. Regulated activity of tissue serine proteases, prostasin, and matriptase is necessary for normal placental development in mice. Prostasin activates the renal epithelial sodium channel. We hypothesized that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomerular barrier. Methods: In a cross-sectional study, 20 healthy pregnant women and 20 patients suspected of preeclampsia were included. Plasma and urine was obtained before delivery, and placental biopsies were taken immediately after delivery (mean gestational age: control 39 and preeclampsia 38 weeks). Results: Patients with preeclampsia displayed lower levels of aldosterone in plasma and in spot urine normalized for creatinine (P = 0.0001). Prostasin, matriptase, hepatocyte growth factor activator inhibitor type 1 (HAI-1) and 2, and nexin-1 mRNA abundances were not different in placental tissue between groups. Prostasin mRNA in placenta correlated directly with nexin-1 and HAI-1 mRNA, but not with matriptase mRNA. Plasma prostasin and placental homogenate prostasin and nexin-1 protein levels did not differ between groups. Activated, arginine 614 (Arg614)-cleaved matriptase was not detectable in placentas. Western blotting showed significant elevated levels of prostasin in urine from preeclamptic patients that correlated with urine albumin. Placenta and plasma prostasin did not correlate to aldosterone or placental weight. Conclusion: Preeclampsia is not associated with altered prostasin in placenta or plasma at term, but with increased prostasin in urine. An impact of prostasin–matriptase on placental development is likely to be at the level of activity and not protein abundance.

Second Nordic Congress on Obesity in Gynecology and Obstetrics (NOCOGO)

About 200 experts, researchers and clinicians attended the 3-day 2nd Nordic Congress on Obesity in Gynecology and Obstetrics (NOCOGO) held at Hindsgavl Conference Center in Middelfart, Denmark, from 27 to 29 August 2015. Speakers and delegates attended from 20 different countries, mainly from the Nordic region, but also from the UK, Australia, Belgium, Netherlands, Germany, Austria, the USA, China and Egypt. The primary aim of the NOCOGO conference was to assemble experts in obstetrics and gynecology and related areas with an interest in obesity to provide an update on research, to discuss current knowledge as well as knowledge gaps, and to explore the evidence so that we could adjust our clinical approach to obese patients and their offspring. This is also relevant for future generations. The focus of NOCOGO was on the epidemiology of obesity globally and its influence on the pre-conceptional environment, on lifestyle interventions during pregnancy, challenges in communicating with obese women within the field of obstetrics and gynecology, on pre-gestational counseling, reproductive medicine, antenatal care, parturition, perinatal medicine, and polycystic ovarian syndrome (PCOS). Obesity from the perspective of anesthetists and neonatologists was also presented. The presentations were followed by discussions as well as “walk and talk” sessions

First Nordic Conference on Obesity in Gynecology and Obstetrics (NOCOGO)

“The only way to keep your health is to eat what you don’t want, drink what you don’t like, and do what you’d rather not.” Mark Twain. The First Nordic Conference on Obesity in Gynecology and Obstetrics (NOCOGO) took place in Billund, Denmark between 22 and 24 October 2012. The goal of the meeting was to encourage attendance and interaction between obstetricians, gynecologists, nurses and midwives with regard to obesity, because of its worsening global nature. The University of Southern Denmark has a special interest and expertise in this area and the members of the organizing and scientific committees were from the university and/or Odense University Hospital. Financial support for the Conference was provided solely by the Region of South Denmark. Approximately 200 delegates and speakers attended from 11 countries, mainly the Nordic countries but also from Australia, Belgium, Dominica, Israel, Spain, UK, and the USA. Plenary lectures

Long-term infant subcutaneous retention of a fragment of fetal scalp electrode following caesarean section

The authors present the case of an uncommon yet potentially fatal complication after the use of a scalp electrode for intrapartum fetal heart rate monitoring. A 25-year-old nulliparous woman in spontaneous term labour had a fetal scalp electrode applied and subsequently required an emergency cesarean section. After discharge home, the mother noticed a swelling on her baby’s head, where the scalp electrode had been attached. Healthcare providers neglected the mother’s repeated concerns about the nature of the swelling. Seven months later, a metal spiral was expelled from the baby’s head which appeared to be a broken part of the scalp electrode. The remaining metal was removed with no further signs or complications. We are aware of only a few similar cases which have been reported in the published literature.