Norepinephrine Transporter Blockade as a Pathophysiological Biomarker in Neurogenic Orthostatic Hypotension - ARD 6103
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PROVIDER: PRJNA471112 | ENA |
REPOSITORIES: ENA
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Project description:Norepinephrine Transporter Blockade as a Pathophysiological Biomarker in Neurogenic Orthostatic Hypotension - ARD 6103
| PRJNA471111 | ENA
Project description:<p>The clinical picture of autonomic failure is dominated by disabling orthostatic hypotension. Recent developments in the understanding of the underlying pathophysiology of the discrete clinical forms of autonomic failure have revealed that participants with multiple system atrophy (MSA) are characterized by impairment of central autonomic pathways crucial for autonomic cardiovascular control, but have intact peripheral postganglionic noradrenergic fibers. Participants with MSA have peripheral residual sympathetic tone that is no longer modulated by central autonomic centers and is not under baroreflex control and, therefore, cannot be harnessed to improve their orthostatic hypotension. On the other hand, participants with pure autonomic failure (PAF) and with Parkinson' s disease (PD) are characterized by neurodegeneration and loss of peripheral noradrenergic fibers, as evidenced by low levels of plasma norepinephrine and absent cardiac uptake of labeled catechols. Pharmacological inhibition of the norepinephrine transporter (NET) is an example of an approach that can take advantage of the participants' own residual sympathetic tone. NET inhibition will increase synaptic norepinephrine that is tonically released in MSA participants by preventing its reuptake. This should result in an increase in blood pressure. </p> <p>This is a longitudinal study of 50 participants, age 18-80 years with neurogenic orthostatic hypotension associated with impaired reflexes. The purpose of this study is to determine if the magnitude of the pressor response to atomoxetine at study entry, will be useful as a biomarker to differentiate those participants that will ultimately be shown to have pre-ganglionic (central) lesions (MSA) with those shown to have post ganglionic (peripheral) lesions (PAF and PD). </p>
| phs001595 | dbGaP
Project description:Safety and Efficacy of Intravenous Norepinephrine for Orthostatic Hypotension - ARD 6104
| PRJNA514385 | ENA
Project description:Safety and Efficacy of Intravenous Norepinephrine for Orthostatic Hypotension - ARD 6104
| PRJNA514386 | ENA
Project description:Background: The goal of this study was to determine the transcriptional consequences of norepinephrine transporter (NET) gene deletion in noradrenergic neuron differentiation. The norepinephrine transporter (NET) is the target of powerful mind-altering substances, such as tricyclic antidepressants and the drug of abuse, cocaine. NET function in adult noradrenergic neurons of the peripheral and central nervous systems is that of a scavenger that internalizes norepinephrine from the synaptic cleft. By contrast, norepinephrine (NE) transport has a different role in embryogenesis. It promotes differentiation of neural crest cells and locus ceruleus progenitors into noradrenergic neurons, whereas NET inhibitors, such as the tricyclic antidepressant desipramine and the drug of abuse, cocaine, inhibit noradrenergic differentiation. While NET structure und regulation of NET function is well described, little is known about downstream targets of NE transport. Results: We have determined by long serial analysis of gene expression (LongSAGE) the gene expression profiles of in vitro differentiating wild type and norepinephrine transporter-deficient (NETKO) neural crest derivatives. Comparison analyses with the wild type library (GSM 105765) have identified a number of important differentially expressed genes, including genes relevant to noradrenergic neuron differentiation and to the phenotype of NETKO mice. Furthermore we have identified novel differentially expressed genes. Conclusions: Loss of NET function during embryonic development deregulates signaling pathways that are critically involved in neural crest formation and noradrenergic neuron differentiation. The library was constructed from total RNA of 60 neural crest culture at culture day 7. The neural tubes were dissected from E9.5 embryos that lack the norepinephrine transporter gene.
2008-06-23 | E-GEOD-11788 | biostudies-arrayexpress
Project description:Background: The goal of this study was to determine the transcriptional consequences of norepinephrine transporter (NET) gene deletion in noradrenergic neuron differentiation. The norepinephrine transporter (NET) is the target of powerful mind-altering substances, such as tricyclic antidepressants and the drug of abuse, cocaine. NET function in adult noradrenergic neurons of the peripheral and central nervous systems is that of a scavenger that internalizes norepinephrine from the synaptic cleft. By contrast, norepinephrine (NE) transport has a different role in embryogenesis. It promotes differentiation of neural crest cells and locus ceruleus progenitors into noradrenergic neurons, whereas NET inhibitors, such as the tricyclic antidepressant desipramine and the drug of abuse, cocaine, inhibit noradrenergic differentiation. While NET structure und regulation of NET function is well described, little is known about downstream targets of NE transport. Results: We have determined by long serial analysis of gene expression (LongSAGE) the gene expression profiles of in vitro differentiating wild type and norepinephrine transporter-deficient (NETKO) neural crest derivatives. Comparison analyses with the wild type library (GSM 105765) have identified a number of important differentially expressed genes, including genes relevant to noradrenergic neuron differentiation and to the phenotype of NETKO mice. Furthermore we have identified novel differentially expressed genes. Conclusions: Loss of NET function during embryonic development deregulates signaling pathways that are critically involved in neural crest formation and noradrenergic neuron differentiation.
2008-06-23 | GSE11788 | GEO
Project description:<p>Patients with chronic autonomic failure (CAF) often have disabling orthostatic hypotension (OH). OH in CAF patients is often associated with supine hypertension (hypertension while lying down), which can be severe. Drugs to treat OH worsen supine hypertension. Therefore, the combination of OH with supine hypertension poses a difficult therapeutic challenge. This protocol is a first step toward development of a way to maintain blood pressure during standing without worsening hypertension while lying down. The research question is will a drug (norepinephrine) given intravenously (IV) prevent blood pressure from falling in patients with orthostatic hypotension. </p> <p>This is a placebo controlled, blinded study of 15 patients with neurogenic orthostatic hypotension. The study consists of two experimental days per participant. On a day before the day of norepinephrine (NE) infusion, the patient undergoes head-up tilting while blood pressure is monitored. Tilt angles are increased until the patient has orthostatic symptoms, systolic pressure decreases to less than 90 mm Hg, or systolic pressure decreases by more than 80 mm Hg. On the day of NE infusion patients, receive NE and placebo with the sequence of treatments randomized. If the patient has severe supine hypertension (more than 200 mm Hg systolic), then NE is infused beginning with the patient at whatever tilt angle is required for baseline pressure to be less than 200 mm Hg. NE is infused at doses titrated to keep directly recorded systolic blood pressure at or above the baseline value during exposure to higher tilt angles. When placebo is given, angles of tilt are increased until the patient has orthostatic symptoms, systolic pressure decreases to less than 90 mm Hg, or systolic pressure decreases by more than 80 mm Hg. </p>
| phs001769 | dbGaP
Project description:Root and leave samples of 4 different apple genotypes were investigated in order to analyse the gene expression after infection with Apple Replant Disease (ARD). All genotypes were cultivated in ARD-infected soil and gamma-irradiated (disinfected) soil in the greenhouse for 7 days. The ARD soil originated from two different orchards representing two different soil compositions. After 7 days root tissue was collected from each plant and used for the subsequent gene expression analysis. This work was part of the project BonaRes-ORDIAmur funded by the German Federal Ministry of Research and Education within the frame of the program BonaRes (grant no. 031B0025B). It was also funded by the German Research Foundation (DFG) via the research training group GRK1798 "Signaling at the Plant-Soil Interface" and a grant to BL and LB (BE 1174/19-1).
2019-12-09 | GSE135081 | GEO
Project description:Interventions: Phenylephrine (PE):When hypotension occurred,Patients received PE infusion at a starting rate of 5 ml/h of 100µg/ml solution (prepared by diluting 10 mg of PE in 100 ml saline);Norepinephrine (NE):When hypotension occurred,Patients received NE infusion at a starting rate of 5 ml/h of 8 ug/ml solution (prepared by diluting 2 mg NE in 250 ml saline)
Primary outcome(s): First flatus time after surgery;All complications, all-cause mortality, and readmission rates within 28 days after surgery
Study Design: Parallel
| 80763 | ecrin-mdr-crc
Project description:Chronic stress is associated with hormonal alterations that are known to promote cancer progression. The stress hormone norepinephrine promotes migration and metastasis of prostate cancer cells. Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase which is phosphorylated during chronic stress or norepinephrine treatment. Here, we investigated how norepinephrine modulates the gene expression in Myc-CaP prostate cancer cell line. We also focused on the effect of FAK knockdown in norepinephrine-induced changes of the gene expression profile.
2018-08-29 | GSE119157 | GEO