Publications by authors named "Elisa Schmidt"

4 Publications

  • Page 1 of 1

Changes of central noradrenaline transporter availability in immunotherapy-naïve multiple sclerosis patients.

Sci Rep 2020 09 4;10(1):14651. Epub 2020 Sep 4.

Department of Neurology, University of Leipzig, Leipzig, Germany.

The neurotransmitter noradrenaline (NA) mediates arousal, attention and mood, and exerts anti-inflammatory and neuroprotective effects. Alterations of monoamine signalling were reported in multiple sclerosis (MS) and psychiatric illness and may account for the high prevalence of comorbid depression and fatigue in MS patients. We assessed central noradrenaline transporter (NAT) availability using positron emission tomography (PET) and the NAT selective radiotracer S,S-[C]O-methylreboxetine in immunotherapy-naïve patients with relapsing-remitting MS (RRMS; n = 11) compared to healthy controls (HC; n = 12), and its association to lesion load, time since manifestation, the expanded disability status scale (EDSS), the fatigue scale Würzburger Erschöpfungsinventar bei MS (WEIMuS) and Beck Depression Inventory (BDI). We found NAT availability to be increased in the thalamus, amygdala, putamen and pons/midbrain of MS patients. No relation to clinical or psychometric variables was found. These first data indicate higher NAT availability in subcortical brain regions of immunotherapy-naïve RRMS patients. If these changes of noradrenergic neurotransmission predispose to psychiatric symptoms or associate with disease activity needs to be investigated in longitudinal studies or a larger sample which allows subgroup analyses.
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September 2020

Effects of Different Doses of Remote Ischemic Preconditioning on Kidney Damage Among Patients Undergoing Cardiac Surgery: A Single-Center Mechanistic Randomized Controlled Trial.

Crit Care Med 2020 08;48(8):e690-e697

Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Münster, Münster, Germany.

Objectives: We have previously shown that remote ischemic preconditioning reduces acute kidney injury (acute kidney injury) in high-risk patients undergoing cardiopulmonary bypass and that the protective effect is confined to patients who exhibit an increased urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 in response to remote ischemic preconditioning. The purpose of this study was to determine the optimal intensity of remote ischemic preconditioning to induce required [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] changes and further explore mechanisms of remote ischemic preconditioning.

Design: Observational and randomized controlled, double-blind clinical trial.

Setting: University Hospital of Muenster, Germany.

Patients: High-risk patients undergoing cardiac surgery as defined by the Cleveland Clinic Foundation Score.

Interventions: In the interventional part, patients were randomized to receive either one of four different remote ischemic preconditioning doses (3 × 5 min, 3 × 7 min, 3 × 10 min remote ischemic preconditioning, or 3 × 5 min remote ischemic preconditioning + 2 × 10 min remote ischemic preconditioning in nonresponders) or sham-remote ischemic preconditioning (control).

Measurements And Main Results: The primary endpoint of the interventional part was change in urinary [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] between pre- and postintervention. To examine secondary objectives including acute kidney injury incidence, we included an observational cohort. A total of 180 patients were included in the trial (n = 80 observational and n = 100 randomized controlled part [20 patients/group]). The mean age was 69.3 years (10.5 yr), 119 were men (66.1%). Absolute changes in [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] were significantly higher in all remote ischemic preconditioning groups when compared with controls (p < 0.01). Although we did not observe a dose-response relationship on absolute changes in [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] across the four different remote ischemic preconditioning groups, in the 15 patients failing to respond to the lowest dose, nine (60%) responded to a subsequent treatment at a higher intensity. Compared with controls, fewer patients receiving remote ischemic preconditioning developed acute kidney injury within 72 hours after surgery as defined by both Kidney Disease: Improving Global Outcomes criteria (30/80 [37.5%] vs 61/100 [61.0%]; p = 0.003).

Conclusions: All doses of remote ischemic preconditioning significantly increased [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] and significantly decreased acute kidney injury compared with controls. High-dose remote ischemic preconditioning could stimulate [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] increases in patients refractory to low-dose remote ischemic preconditioning.
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August 2020

Central noradrenaline transporter availability is linked with HPA axis responsiveness and copeptin in human obesity and non-obese controls.

Stress 2019 01 29;22(1):93-102. Epub 2018 Oct 29.

a Integrated Research and Treatment Center (IFB) Adiposity Diseases , Leipzig University Medical Center , Leipzig , Germany.

The central noradrenaline (NA) stress-response network co-mediates hypothalamic-pituitary-adrenal (HPA) axis activation and arginine-vasopressin (AVP) release. Dysregulation of these systems contributes to stress-related diseases such as human obesity, but their interrelation remains unclear. The study was aimed to test for the first time in vivo whether central noradrenergic activity quantitatively indexed by the availability of the presynaptic NA transporter (NAT) is associated with HPA axis responsiveness as measured with the combined dexamethasone suppression/corticotropin releasing hormone stimulation (dex/CRH) test and copeptin as a surrogate marker of the serum AVP tone in highly obese, otherwise, healthy individuals compared to age- and sex-matched non-obese, healthy controls. In order to assess central NAT availability, positron emission tomography (PET) was applied using the NAT-selective radiotracer S,S-[C]O-methylreboxetine (MRB) and correlated with curve indicators derived from the dex/CRH test (maximum, MAX, and area under the curve, AUC, for cortisol and adrenocorticotropic hormone, ACTH) as well as with copeptin. In non-obese controls, positive correlations were found between the NAT distribution volume ratios (DVR) of the orbitofrontal cortex (OFC) and the amygdala with the HPA response (OFC: ACTH r = 0.87, p = .001; cortisol r = 0.86, p = .002; amygdala: ACTH r = 0.86, p = .002; cortisol r = 0.79, p = .006), while in obesity, the hypothalamic DVR correlated inversely with the HPA axis response (cortisol, r = -0.66, p = .04) and with copeptin (r = -0.71, p = .02). This association of central NAT availability with HPA axis responsiveness and copeptin suggests a mechanistic interaction between noradrenergic transmission with HPA axis activity and the serum AVP system that differs between non-obese individuals with prefrontal-limbic involvement and obesity with a hypothalamic-centered relationship. Whether the latter finding contributes to obesogenic behavior needs to be further explored.
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January 2019

Post-dexamethasone serum copeptin corresponds to HPA axis responsiveness in human obesity.

Psychoneuroendocrinology 2017 04 16;78:39-47. Epub 2017 Jan 16.

Department of Neurology, University of Leipzig, Leipzig, Germany; Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany. Electronic address:

Context: Increased activities of the arginine-vasopressin (AVP) system and the hypothalamic-pituitary-adrenal (HPA) axis were shown to be associated with human obesity, but relationships between these systems in obesity remain unclear.

Objectives: To assess HPA axis responsiveness and its relation to serum concentrations of the AVP-surrogate copeptin in subjects with obesity (OB) in comparison to non-obesity controls (NOC).

Methods: In a cross-sectional monocentric study, thirty-nine OB (f/m 25/14; age 36.5±10.0years; body mass index, BMI, 41.5±4.7kg/m) were compared to twenty-two NOC (f/m 12/10; age 35.3±8.5years; BMI 23.1±2.4kg/m), matched for age and sex. All individuals underwent the combined dexamethasone/CRH test.

Main Outcome Measures: Plasma ACTH and cortisol curve indicators derived from the dex/CRH test (post-CRH concentrations 30min after 100μg CRH; maximum concentration, MAX; area-under-the-curve, AUC; ACTH/cortisol ratios). Copeptin was assessed in 1500h samples of the dex/CRH test (after 1.5mg of oral dexamethasone, prior to CRH administration).

Results: Copeptin serum concentrations were higher in OB (median [IQR]: OB 4.62 [2.60-5.88] vs. NOC 3.04 [2.52-4.29] pmol/l, P=0.04). Correspondingly, OB showed higher post-CRH cortisol concentrations (OB: 51.5 [25.9-159.3] vs. NOC: 28.6 [20.0-41.6] nmol/l, P=0.01) and a lower post-CRH ACTH/cortisol ratio (OB: 0.028 [0.016-0.053] vs. NOC: 0.048 [0.034-0.070] pmol/nmol, P<0.01). Serum copeptin was significantly associated with HPA responsiveness in OB (post-CRH ACTH: R=0.42, P<0.01), driven by OB men (post-CRH ACTH: R=0.76, P<0.01, post-CRH cortisol: R=0.64, P=0.02). All associations withstand adjustments for BMI and age.

Conclusions: The association between increased copeptin with ACTH and cortisol release suggests a potential mechanistic interaction of the AVP system with HPA activation in human obesity. The relation of copeptin and HPA responsiveness should be further validated in situations with pronounced HPA activation, such as depression or multiple sclerosis.
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April 2017