Designermoleküle hemmen die Semaphorin 3F Wirkung in vitro, haben aber keinen Einfluss auf den Verlauf der experimentellen Arthritis.

Im Verlauf der rheumatoiden Arthritis kommt es zu einem Rückzug sympathischer Nervenfasern aus dem Entzündungsgebiet, der über Semaphorin 3F vermittelt wird. Das Fehlen des Sympathikus führt zu einem Ungleichgewicht der proinflammatorischen und antiinflammatorischen Faktoren zugunsten der Entzündung. In dieser Arbeit wurden Substanzen entwickelt, die den durch Semaphorin 3F am Neuropilin-2/ Plexin A2 vermittelten Rückzug der Nervenfasern verhindern, und so zu einer Verbesserung des Verlaufs der rheumatoiden Arthritis führen können. Es wurden sechs verschiedene Substanzen gefunden die in einem in vitro Modell den Rückzug effektiv hemmen. Diese Moleküle hatten allerdings keinen Einfluss auf den Verlauf der experimnetellen Arthritis im Mausmodell

Effects of a Lifestyle Intervention in Routine Care on Short- and Long-Term Maternal Weight Retention and Breastfeeding Behavior—12 Months Follow-up of the Cluster-Randomized GeliS Trial

Postpartum weight retention (PPWR) is associated with an increased risk for maternal obesity and is discussed to be influenced by breastfeeding. The objective was to evaluate the effect of a lifestyle intervention delivered three times during pregnancy and once in the postpartum period on PPWR and on maternal breastfeeding behavior. In total, 1998 participants of the cluster-randomized “healthy living in pregnancy” (GeliS) trial were followed up until the 12th month postpartum (T2pp). Data were collected using maternity records and questionnaires. Data on breastfeeding behavior were collected at T2pp. At T2pp, mean PPWR was lower in women receiving counseling (IV) compared to the control group (C) (−0.2 ± 4.8 kg vs. 0.6 ± 5.2 kg), but there was no significant evidence of between-group differences (adjusted p = 0.123). In the IV, women lost more weight from delivery until T2pp compared to the C (adjusted p = 0.008) and showed a slightly higher rate of exclusive breastfeeding (IV: 87.4%; C: 84.4%; adjusted p < 0.001). In conclusion, we found evidence for slight improvements of maternal postpartum weight characteristics and the rate of exclusive breastfeeding in women receiving a lifestyle intervention embedded in routine care, although the clinical meaning of these findings is unclear

Effects of a lifestyle intervention during pregnancy to prevent excessive gestational weight gain in routine care – the cluster-randomised GeliS trial

Abstract Background Excessive gestational weight gain (GWG) leads to obstetric complications, maternal postpartum weight retention and an increased risk of offspring obesity. The GeliS study examines the effect of a lifestyle intervention during pregnancy on the proportion of women with excessive GWG and pregnancy and obstetric complications, as well as the long-term risk of maternal and infant obesity. Methods The GeliS study is a cluster-randomised multicentre controlled trial including 2286 women with a pre-pregnancy BMI between 18.5 and 40.0 kg/m2 recruited from gynaecological and midwifery practices prior to the end of the 12th week of gestation in five Bavarian regions. In the intervention regions, four lifestyle counselling sessions covering a balanced healthy diet, regular physical activity and self-monitoring of weight gain were performed by trained healthcare providers alongside routine pre- and postnatal practice visits. In the control regions, leaflets with general recommendations for a healthy lifestyle during pregnancy were provided. Results The intervention did not result in a significant reduction of women showing excessive GWG (adjusted OR 0.95, 95% CI 0.66–1.38, p = 0.789), with 45.1% and 45.7% of women in the intervention and control groups, respectively, gaining weight above the Institute of Medicine recommendations. Gestational diabetes mellitus was diagnosed in 10.8% and 11.1% of women in the intervention and control groups, respectively (p = 0.622). Mean birth weight and length were slightly lower in the intervention group (3313 ± 536 g vs. 3363 ± 498 g, p = 0.020; 51.1 ± 2.7 cm vs. 51.6 ± 2.5 cm, p = 0.001). Conclusion In the setting of routine prenatal care, lifestyle advice given by trained healthcare providers was not successful in limiting GWG and pregnancy complications. Nevertheless, the potential long-term effects of the intervention remain to be assessed. Trial registration NCT01958307, ClinicalTrials.gov, retrospectively registered October 9, 2013

Sympathetic nerve repulsion inhibited by designer molecules in vitro and role in experimental arthritis

Aims: In rheumatoid arthritis and collagen type II arthritis (CIA), sympathetic nerve fibers get lost in inflamed tissue. The process is probably induced by nerve repellent factors like semaphorin 3F (SEMA3F). Repulsion of sympathetic nerve fibers in inflamed tissue has proinflammatory effects due to the loss of anti-inflammatory neurotransmitters. We hypothesized that design molecules like antibodies and specific peptides that inhibit nerve fiber repulsion can ameliorate CIA. Materials and methods: Two blocking antibodies were used and four blocking peptides were generated using the phage display technique with the targets of SEMA3F and plexin-A2. All blocking molecules were tested in vitro using a sympathetic neurite outgrowth assay. CIA was induced by collagen type II in mice. Key findings: In the neurite outgrowth assay, the two antibodies against plexin-A2 and neuropilin-2 as well as the four blocking peptides - two SEMA3F analogous peptides (WLFQRDPGDR, QATVKWLFQRDPGDRR) and two plexin A2 analogous peptides (DSSDQFSFDYELEQN, DSSIQFFSFEKDKERI) - were able to block sympathetic nerve fiber repulsion in vitro (at 150-600 nmol/1). Administration of the two antibodies prophylactically on day 4 after immunization did not change clinical CIA. Similarly, using the top candidate antibody to plexin-A2 after CIA onset (mild score of 4 points, maximum = 52 points), did not ameliorate CIA. The tested blocking peptides were not recovered in peripheral blood after i.v. and i.p. administration. Significance: While designer molecules blocked nerve fiber repulsion in vitro, therapeutic administration in vivo did not change CIA. Possible strategies to overcome negative effects demonstrated in vivo are discussed. (C) 2016 Elsevier Inc. All rights reserved

Peripheral elimination of the sympathetic nervous system stimulates immunocyte retention in lymph nodes and ameliorates collagen type II arthritis

Objectives: In collagen type H-induced arthritis (CIA), early activation of the sympathetic nervous system (SNS) is proinflammatory. Here, we wanted to find new target organs contributing to proinflammatory SNS effects. In addition, we wanted to clarify the importance of SNS-modulated immunocyte migration. Methods: A new technique termed spatial energy expenditure configuration (SEEC) was developed to demonstrate bodily areas of high energy demand (to find new targets). We studied homing of labeled cells in vivo, lymphocyte expression of CCR7, supernatant concentration of CCL21, and serum levels of sphingosine-1-phosphate (S1P) in sympathectomized control/arthritic animals. Results: During the course of arthritis, SEEC identified an early marked increase of energy expenditure in draining lymph nodes and spleen (nowhere else!). Although early sympathectomy ameliorated later disease, early sympathectomy increased energy consumption, organ weight, and cell numbers in arthritic secondary lymphoid organs, possibly a sign of lymphocyte retention (also in controls). Elimination of the SNS retained lymph node cells, elevated expression of CCR7 on lymph node cells, and increased CCL21. Serum levels of SIP, an important factor for lymphocyte egress, were higher in arthritic than control animals. Sympathectomy decreased SIP levels in arthritic animals to control levels. Transfer of retained immune cells from draining lymph nodes of sympathectomized donors to sympathectomized recipients markedly increased arthritis severity over weeks. Conclusions: By using the SEEC technique, we identified draining lymph nodes and spleen as major target organs of the SNS. The data show that the SNS increases egress of lymphocytes from draining lymph nodes to stimulate arthritic inflammation. (C) 2016 Elsevier Inc. All rights reserved

Associations between Prenatal Physical Activity and Neonatal and Obstetric Outcomes—A Secondary Analysis of the Cluster-Randomized GeliS Trial

Prenatal physical activity (PA) was discussed to decrease the incidence of obstetric and neonatal complications. In this secondary cohort analysis of the cluster-randomized GeliS (“healthy living in pregnancy”) trial, associations between prenatal PA and such outcomes were investigated. PA behavior was assessed twice, before or during the 12th week (baseline, T0) and after the 29th week of gestation (T1), using the self-reported Pregnancy Physical Activity Questionnaire. Obstetric and neonatal data were collected in the routine care setting. Data were available for 87.2% (n = 1994/2286) of participants. Significant differences between the offspring of women who adhered to PA recommendations at T1 and offspring of inactive women were found in birth weight (p = 0.030) but not in other anthropometric parameters. Sedentary behavior was inversely associated with birth weight at T1 (p = 0.026) and, at both time points, with an increase in the odds of low birth weight (T0: p = 0.004, T1: p = 0.005). Light-intensity PA at T0 marginally increased the odds of caesarean section (p = 0.032), but neither moderate-intensity nor vigorous-intensity activity modified the risk for caesarean delivery at any time point. The present analyses demonstrated associations between prenatal PA and some neonatal and obstetric outcomes