Pregnancy following kidney transplantation - impact on mother and graft function and focus on childrens’ longitudinal development

BACKGROUND: Pregnancy after kidney transplantation has been considered as high risk for maternal and fetal complications. After careful patient selection successful pregnancies are described. Little is known about fetal outcomes and data is particularly scarce on childrens´ early development up to two years when born to kidney/-pancreas transplant recipients. Here, we analyzed maternal and fetal risk and evaluated graft function during pregnancy in transplanted women. We aimed to identify factors affecting the outcomes of mothers and their grafts during pregnancy and of children up to 2 years after delivery/ birth. METHODS: All consecutive pregnancies in kidney/ kidney-pancreas recipients with live-born children from 2002 to 2016 were evaluated in two transplant centers (Charité Berlin/ University Tuebingen). All data was gathered from medical records. Impact of pregnancy on obstetrical risks, graft function and fetal development was evaluated. Additionally, for the first time development of children, including physical examination and assessment of neurological function were evaluated at 12 and 24 months. RESULTS: Thirty-two pregnancies in 28 patients with a median duration of 34 gestational weeks (range, 24-38) were analyzed. 13 patients (46.4%) developed deterioration of kidney graft function > 10 ml/min during pregnancy. In majority, caesarean section was performed (75%). Twenty-five (78.1%) children were born prematurely, thereof (16%) < 28 weeks. Almost 70% had low birth weights (LBW) (< 2.500 g); median birth weight was 2.030 g. General health and physical constitution of children were unremarkable with normal development in 94% at 12 and 24 months of corrected age, respectively. CONCLUSION: Despite the high rate of preterm birth and LBW, development up to two years was age-appropriate in this cohort. Due to low absolute numbers, increasing efforts in centralized counseling, diagnostics and committed specialist support are required. Decisive treatment of these high-risk patients in specialized units leading to better performance of these patients (mother/ fetus) is deemed superior. In order to confirm this, prospective studies on neonatal and pediatric outcomes with a standard-of-care comparator arm will be conducted

In vitro and in vivo properties of GLP-1 producing neurons: The brain actions of a gut hormone

Glucagon-like peptide-1 (GLP-1) is an incretin and neuropeptide primarily known for its role in glucose homeostasis. GLP-1 also has potent anti-obesogenic potential, and is known to inhibit food intake, food reward, and diet-induced obesity. In addition, brain GLP-1 increases heart rate and mediates effects of acute stress. Within the brain, GLP-1 is produced by preproglucagon (PPG) neurons in the caudal brainstem. Although the potential role of GLP-1 has been studied through pharmacological activation of brain GLP-1 receptors, little is known about the cellular properties and physiological role(s) of PPG neurons. In this thesis, a complementary array of in vitro and in vivo techniques was used to study the physiological roles of PPG neurons. In vitro Ca2+ imaging revealed that PPG neuron activity is modulated by a range of compounds relaying signals of energy balance, satiety, and visceral illness. In vivo, I selectively manipulated PPG neurons in mice using chemogenetic tools. Activation of PPG neurons dramatically reduced feeding, supporting a role for brain-derived GLP-1 in appetite control. Although selective inactivation of PPG neurons had no effect on ad libitum feeding, large meal- or stress-induced reductions in food intake were abolished when PPG neurons were silenced. In freely-behaving mice, systemic GLP-1 receptor activation had no effect on arterial blood pressure, but increased heart rate via stimulation of the sympathetic nervous system. Although permanent ablation of PPG neurons had no effect on heart rate and blood pressure, selective activation of PPG neurons using chemogenetic tools increased heart rate. These results provide the first evidence of the physiological role played by the GLP-1 producing neurons in the caudal brainstem. Activity of these neurons is modulated by diverse neural and humoral signals. They are critically important in the prevention of overeating as well as stress-induced hypophagia and may contribute to central nervous mechanisms of cardiovascular control

Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1

BACKGROUND: Creatine (Cr) is synthesized by a two-step mechanism involving arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and is taken up by cells through a specific Cr transporter, CT1. Recently, genetic defects of this pathway have been described, that lead to Cr deficiency, neurological symptoms in early infancy and severe neurodevelopmental delay. To investigate the involvement of Cr synthesis and uptake pathways during embryonic development, we determined the spatiotemporal expression of AGAT, GAMT and CT1 during the rat embryogenesis, at the mRNA and protein level. RESULTS: We show that AGAT and GAMT are expressed in hepatic primordium as soon as 12.5 days, then progressively acquire their adult pattern of expression, with high levels of AGAT in kidney and pancreas, and high levels of GAMT in liver and pancreas. AGAT and CT1 are prominent in CNS, skeletal muscles and intestine, where they appear earlier than GAMT. High levels of CT1 are found in epithelia. CONCLUSION: Our results suggest that de novo synthesis of Cr by AGAT and GAMT, as well as cellular Cr uptake by CT1, are essential during embryonic development. This work provides new clues on how creatine can be provided to developing tissues, and suggests that Cr deficiencies might induce irreversible damages already in utero, particularly on the nervous system

Die Situational Action Theory (SAT)

Manuskriptversion weicht in der Seitenzählung vom Original a

Autonomic cardiac regulation during spontaneous nocturnal hypoglycemia in children with type 1 diabetes

Hypoglycemia is the most common complication in insulin treated diabetes. Though mostly mild, it can be fatal in rare cases: It is hypothesized that hypoglycemia related QTc prolongation contributes to cardiac arrhythmia.; To evaluate influence of nocturnal hypoglycemia on QTc and heart rate variability (HRV) in children with T1D.; Children and adolescents with T1D for at least 6 months participated in an observational study using continuous glucose monitoring (CGM) and Holter electrocardiogram for five consecutive nights. Mean QTc was calculated for episodes of nocturnal hypoglycemia (<3.7 mmol/L) and compared to periods of the same duration preceding hypoglycemia. HRV (RMSSD, low and high frequency power LF and HF) was analyzed for different 15 min intervals: before hypoglycemia, onset of hypoglycemia, before/after nadir, end of hypoglycemia and after hypoglycemia.; Mean QTc during hypoglycemia was significantly longer compared to euglycemia (412 ± 15 vs. 405 ± 18 ms, p = 0.005). HRV changed significantly: RMSSD (from 88 ± 57 to 73 ± 43 ms) and HF (from 54 ± 17 to 47 ± 17nu) decreased from before hypoglycemia to after nadir, while heart rate (from 69 ± 9 to 72 ± 12 bpm) and LF (from 44 ± 17 to 52 ± 21 nu) increased (p = 0.04).; A QTc lengthening effect of nocturnal hypoglycemia in children with T1D was documented. HRV changes occurred even before detection of nocturnal hypoglycemia by CGM, which may be useful for hypoglycemia prediction

Dynamic Contrast-Enhanced Ultrasound of Colorectal Liver Metastases as an Imaging Modality for Early Response Prediction to Chemotherapy

Our aim was to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) can detect early changes in perfusion of colorectal liver metastases after initiation of chemotherapy. Newly diagnosed patients with colorectal cancer with liver metastases were enrolled in this explorative prospective study. Patients were treated with capecitabine or 5-fluorouracil-based chemotherapy with or without bevacizumab. DCE-US was performed before therapy (baseline) and again 10 days after initiation of treatment. Change in contrast-enhancement in one liver metastasis (indicator lesion) was measured. Treatment response was evaluated with a computed tomography (CT) scan after three cycles of treatment and the initially observed DCE-US change of the indicator lesion was related to the observed CT response. Eighteen patients were included. Six did not complete three series of chemotherapy and the evaluation CT scan, leaving twelve patients for analysis. Early changes in perfusion parameters using DCE-US did not correlate well with subsequent CT changes. A subgroup analysis of eight patients receiving bevacizumab, however, demonstrated a statistically significant correlation (p = 0.045) between early changes in perfusion measures of peak enhancement at DCE-US and tumor shrinkage at CT scan. The study indicates that early changes in DCE-US perfusion measures may predict subsequent treatment response of colorectal liver metastases in patients receiving bevacizumab

Surface Studies on the Energy Release of the MOST System 2-Carbethoxy-3-Phenyl-Norbornadiene/Quadricyclane (PENBD/PEQC) on Pt(111) and Ni(111)

Novel energy-storage solutions are necessary for the transition from fossil to renewable energy sources. Auspicious candidates are so-called molecular solar thermal (MOST) systems. In our study, we investigate the surface chemistry of a derivatized norbornadiene/quadricyclane molecule pair. By using suitable push–pull substituents, a bathochromic shift of the absorption onset is achieved, allowing a greater overlap with the solar spectrum. Specifically, the adsorption and thermally induced reactions of 2-carbethoxy-3-phenyl-norbornadiene/quadricyclane are assessed on Pt(111) and Ni(111) as model catalyst surfaces by synchrotron radiation-based X-ray photoelectron spectroscopy (XPS). Comparison of the respective XP spectra enables the distinction of the energy-rich molecule from its energy-lean counterpart and allows qualitative information on the adsorption motifs to be derived. Monitoring the quantitative cycloreversion between 140 and 230 K spectroscopically demonstrates the release of the stored energy to be successfully triggered on Pt(111). Heating to above 300 K leads to fragmentation of the molecular framework. On Ni(111), no conversion of the energy-rich compound takes place. The individual decomposition pathways of the two isomers begin at 160 and 180 K, respectively. Pronounced desorption of almost the entire surface coverage only occurs for the energy-lean molecule on Ni(111) above 280 K; this suggests weakly bound species. The correlation between adsorption motif and desorption behavior is important for applications of MOST systems in heterogeneously catalyzed processes

TanDEM-X DEM 2020: What is new?

In the last years, the TanDEM-X mission systematically acquired data to create another global DEM, the so-called 'TanDEM-X DEM 2020', mainly between September 2017 and mid-2020. This contribution describes the status of the generation of this second global TanDEM-X DEM with special focus on procedural and algorithmic modifications compared to the first global TanDEM-X DEM