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The Journal of Cardiovascular Nursing 2019Clinical response to left ventricular assist devices (LVADs), as measured by health-related quality of life, varies among patients after implantation; however, it is... (Comparative Study)
Comparative Study
BACKGROUND
Clinical response to left ventricular assist devices (LVADs), as measured by health-related quality of life, varies among patients after implantation; however, it is unknown which pathophysiological mechanisms underlie differences in clinical response by health-related quality of life.
OBJECTIVE
The purpose of this study was to compare changes in sympathetic markers (β-adrenergic receptor kinase-1 [βARK1], norepinephrine [NE], and 3,4-dihydroxyphenylglycol [DHPG]) between health-related quality of life clinical responders and nonresponders from pre- to post-LVAD implantation.
METHODS
We performed a secondary analysis on a subset of data from a cohort study of patients from pre- to 1, 3, and 6 months after LVAD implantation. Clinical response was defined as an increase of 5 points or higher on the Kansas City Cardiomyopathy Questionnaire Clinical Summary score from pre- to 6 months post-LVAD implantation. We measured plasma βARK1 level with an enzyme-linked immunosorbent assay and plasma NE and DHPG levels with high-performance liquid chromatography with electrochemical detection. Latent growth curve modeling was used to compare the trajectories of markers between groups.
RESULTS
The mean (SD) age of the sample (n = 39) was 52.9 (13.2) years, and most were male (74.4%) and received LVADs as bridge to transplantation (69.2%). Preimplantation plasma βARK1 levels were significantly higher in clinical responders (n = 19) than in nonresponders (n = 20) (P = .001), but change was similar after LVAD (P = .235). Preimplantation plasma DHPG levels were significantly lower in clinical responders than in nonresponders (P = .002), but the change was similar after LVAD (P = .881). There were no significant differences in plasma NE levels.
CONCLUSIONS
Preimplantation βARK1 and DHPG levels are differentiating factors between health-related quality of life clinical responders and nonresponders to LVAD, potentially signaling differing levels of sympathetic stimulation underlying clinical response.
Topics: Adult; Aged; Biomarkers; Cohort Studies; Female; G-Protein-Coupled Receptor Kinase 2; Heart-Assist Devices; Humans; Male; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Quality of Life; Sympathetic Nervous System; Treatment Outcome
PubMed: 31094762
DOI: 10.1097/JCN.0000000000000580 -
Brain Research Oct 2015Metabotropic and ionotropic glutamate receptors are closely clustered in postsynaptic membranes and are believed to interact actively with each other to control...
Metabotropic and ionotropic glutamate receptors are closely clustered in postsynaptic membranes and are believed to interact actively with each other to control excitatory synaptic transmission. Metabotropic glutamate receptor 5 (mGluR5), for example, has been well documented to potentiate ionotropic NMDA receptor activity, although underlying mechanisms are poorly understood. In this study, we investigated the role of mGluR5 in regulating trafficking and subcellular distribution of NMDA receptors in adult rat striatal neurons. We found that the mGluR1/5 agonist DHPG concentration-dependently increased NMDA receptor GluN1 and GluN2B subunit expression in the surface membrane. Meanwhile, DHPG reduced GluN1 and GluN2B levels in the intracellular compartment. The effect of DHPG was blocked by an mGluR5 selective antagonist MTEP but not by an mGluR1 selective antagonist 3-MATIDA. Pretreatment with an inhibitor or a specific inhibitory peptide for synapse-enriched Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) also blocked the DHPG-stimulated redistribution of GluN1 and GluN2B. In addition, DHPG enhanced CaMKIIα activity and elevated GluN2B phosphorylation at a CaMKII-sensitive site (serine 1303). These results demonstrate that mGluR5 regulates trafficking of NMDA receptors in striatal neurons. Activation of mGluR5 appears to induce rapid trafficking of GluN1 and GluN2B to surface membranes through a signaling pathway involving CaMKII.
Topics: Analysis of Variance; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Corpus Striatum; Dose-Response Relationship, Drug; Enzyme Inhibitors; Excitatory Amino Acid Agents; Gene Expression; In Vitro Techniques; Male; Methoxyhydroxyphenylglycol; Neurons; Phosphorylation; Pyridines; Rats; Rats, Wistar; Receptor, Metabotropic Glutamate 5; Receptors, N-Methyl-D-Aspartate; Thiazoles
PubMed: 26256252
DOI: 10.1016/j.brainres.2015.07.053 -
Journal of Nutritional Science and... 2018The effect of soy and casein peptide intake on the metabolism of amino acids and monoamine neurotransmitters in the serum and brain were examined in C57BL/6 mice. Acute... (Comparative Study)
Comparative Study
The effect of soy and casein peptide intake on the metabolism of amino acids and monoamine neurotransmitters in the serum and brain were examined in C57BL/6 mice. Acute oral administration of soy peptide (0.026 g/30 g body weight) caused a notable increase in tyrosine, a catecholamine precursor, in the serum and cerebral cortex, whereas casein peptide administration at the same dose led to an increase in tyrosine in the serum, but not in the cerebral cortex. In addition to tyrosine, soy peptide administration also led to an effective augmentation of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), a principal metabolite of noradrenaline, and significant facilitation of noradrenergic turnover in the cerebral cortex, brainstem, and hippocampus compared to the vehicle control. Casein peptide administration also led to an increase in MHPG only in the cerebral cortex, and caused facilitation of noradrenergic turnover in the cerebral cortex and brainstem. These in vivo observations suggest that both soy and casein peptide intake at this concentration can lead to an increased availability of tyrosine and stimulation of noradrenergic turnover in the brain.
Topics: Animals; Brain; Brain Stem; Caseins; Catecholamines; Cerebral Cortex; Hippocampus; Male; Methoxyhydroxyphenylglycol; Mice, Inbred C57BL; Neurotransmitter Agents; Norepinephrine; Peptides; Soybean Proteins; Tyrosine
PubMed: 30381622
DOI: 10.3177/jnsv.64.329 -
International Journal of Molecular... Jan 2022Norepinephrine is a neurotransmitter that also has an immunomodulatory effect and is involved in multiple sclerosis (MS) pathogenesis. This study aimed to clarify the...
Norepinephrine is a neurotransmitter that also has an immunomodulatory effect and is involved in multiple sclerosis (MS) pathogenesis. This study aimed to clarify the role of the β-adrenoreceptor in the norepinephrine-mediated modulation of interleukin-17 (IL-17) and interferon-γ (IFN-γ) production, which play a critical pathogenetic role in MS. CD4 T cells obtained from twenty-five relapsing-remitting MS patients and sixteen healthy subjects were cultured ex vivo with norepinephrine and/or β-adrenoreceptor antagonist or agonist, followed by a cytokine production analysis using ELISA. Norepinephrine suppressed IL-17 and IFN-γ production by the anti-CD3/anti-CD28-microbead-stimulated CD4 T cells in both groups. Blockade of the β-adrenoreceptor with the specific antagonist ICI 118.551 enhanced norepinephrine-mediated IL-17 suppression but decreased its inhibitory effect on IFN-γ production in MS patients. In contrast, the β-adrenoreceptor agonist formoterol did not influence norepinephrine's inhibitory effect on cytokine production in both groups. The blockade of the β-adrenoreceptor, even in the absence of exogenous norepinephrine, suppressed IL-17 production but did not influence IFN-γ production in both groups. Conversely, β-adrenoreceptor activation by formoterol decreased IFN-γ production and did not affect IL-17 production in both groups. These data illustrate the inhibitory effect of norepinephrine on IL-17 and IFN-γ production by CD4 T cells in MS. The inhibitory effect of norepinephrine on IFN-γ production by CD4 T cells in MS could be mediated via β-adrenoreceptor activation.
Topics: Adult; CD4-Positive T-Lymphocytes; Case-Control Studies; Cytokines; Epinephrine; Female; Humans; Interferon-gamma; Interleukin-17; Male; Methoxyhydroxyphenylglycol; Multiple Sclerosis; Norepinephrine; Receptors, Adrenergic, beta-2; T-Lymphocytes
PubMed: 35054851
DOI: 10.3390/ijms23020668 -
BMJ Open Feb 2016To compare the acute effects of uninterrupted sitting with sitting interrupted by brief bouts of light-intensity walking on self-reported fatigue, cognition,... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To compare the acute effects of uninterrupted sitting with sitting interrupted by brief bouts of light-intensity walking on self-reported fatigue, cognition, neuroendocrine biomarkers and cardiometabolic risk markers in overweight/obese adults.
DESIGN
Randomised two-condition crossover trial.
SETTING
Laboratory study conducted in Melbourne, Australia.
PARTICIPANTS
19 overweight/obese adults (45-75 years).
INTERVENTIONS
After an initial 2 h period seated, participants consumed a meal-replacement beverage and completed (on 2 days separated by a 6-day washout period) each condition over the next 5 h: uninterrupted sitting (sedentary condition) or sitting with 3 min bouts of light-intensity walking every 30 min (active condition).
PRIMARY OUTCOME MEASURES
Self-reported fatigue, executive function and episodic memory at 0 h, 4 h and 7 h.
SECONDARY OUTCOME MEASURES
Neuroendocrine biomarkers and cardiometabolic risk markers (blood collections at 0 h, 4 h and 7 h, blood pressure and heart rate measured hourly and interstitial glucose measured using a continuous glucose monitoring system).
RESULTS
During the active condition, fatigue levels were lower at 4 h (-13.32 (95% CI -23.48 to -3.16)) and at 7 h (-10.73 (95% CI -20.89 to -0.58)) compared to the sedentary condition. Heart rate was higher at 4 h (4.47 (95% CI 8.37 to 0.58)) and at 7 h (4.32 (95% CI 8.21 to 0.42)) during the active condition compared to the sedentary condition. There were no significant differences between conditions by time for other variables. In the sedentary condition, changes in fatigue scores over time correlated with a decrease in heart rate and plasma dihydroxyphenylalanine (DOPA) and an increase in plasma dihydroxyphenylglycol (DHPG).
CONCLUSIONS
Interrupting prolonged sitting with light-intensity walking breaks may be an effective fatigue countermeasure acutely. Fatigue levels corresponded with the heart rate and neuroendocrine biomarker changes in uninterrupted sitting in this pilot study. Further research is needed to identify potential implications, particularly for the occupational health context.
TRIAL REGISTRATION NUMBER
ACTRN12613000137796; Results.
Topics: Aged; Blood Glucose; Blood Pressure; Cognition; Cross-Over Studies; Dihydroxyphenylalanine; Fatigue; Female; Heart Rate; Humans; Male; Methoxyhydroxyphenylglycol; Middle Aged; Obesity; Overweight; Pilot Projects; Sedentary Behavior; Walking
PubMed: 26920441
DOI: 10.1136/bmjopen-2015-009630 -
Hippocampal protein kinase D1 is necessary for DHPG-induced learning and memory impairments in rats.PloS One 2018Understanding molecular mechanisms underlying the induction of learning and memory impairments remains a challenge. Recent investigations have shown that the activation...
BACKGROUND
Understanding molecular mechanisms underlying the induction of learning and memory impairments remains a challenge. Recent investigations have shown that the activation of group I mGluRs (mGluR1 and mGluR5) in cultured hippocampal neurons by application of (S)-3,5-Dihydroxyphenylglycine (DHPG) causes the regulated internalization of N-methyl-D-aspartate receptors (NMDARs), which subsequently activates protein kinase D1 (PKD1). Through phosphorylating the C-terminals of the NMDAR GluN2 subunits, PKD1 down-regulates the activity of remaining (non-internalized) surface NMDARs. The knockdown of PKD1 does not affect the DHPG-induced inhibition of AMPA receptor-mediated miniature excitatory post-synaptic currents (mEPSCs) but prevents the DHPG-induced inhibition of NMDAR-mediated mEPSCs in vitro. Thus, we investigated the in vivo effects of bilateral infusions of DHPG into the hippocampal CA1 area of rats in the Morris water maze (MWM) and the novel object discrimination (NOD) tests.
METHODS
A total of 300 adult male Sprague Dawley rats (250-280 g) were used for behavioral tests. One hundred ninety four were used in MWM test and the other 106 rats in the NOD test. Following one week of habituation to the vivarium, rats were bilaterally implanted under deep anesthesia with cannulas aimed at the CA1 area of the hippocampus (CA1 coordinates in mm from Bregma: AP -3.14; lateral +/-2; DV -3.0). Through implanted cannulas artificial cerebrospinal fluid (ACSF), the group1 mGluR antagonist 6-Methyl-2-(phenylethynyl)pyridine (MPEP), the dynamin-dependent internalization inhibitor Dynasore, or the PKD1 inhibitor CID755673 were infused into the bilateral hippocampal CA1 areas (2 μL per side, over 5 min). The effects of these infusions and the effects of PKD1 knockdown were examined in MWM or NOD test.
RESULTS
DHPG infusion increased the latency to reach the platform in the MWM test and reduced the preference for the novel object in the NOD task. We found that the DHPG effects were dose-dependent and could be maintained for up to 2 days. Notably, these effects could be prevented by pre-infusion of the group1 mGluR antagonist MPEP, the dynamin-dependent internalization inhibitor Dynasore, the PKD1 inhibitor CID755673, or by PKD1 knockdown in the hippocampal CA1 area.
CONCLUSION
Altogether, these findings provide direct evidence that PKD1-mediated signaling may play a critical role in the induction of learning and memory impairments by DHPG infusion into the hippocampal CA1 area.
Topics: Animals; CA1 Region, Hippocampal; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Knockout Techniques; Hippocampus; Learning; Learning Disabilities; Locomotion; Male; Maze Learning; Memory; Memory Disorders; Methoxyhydroxyphenylglycol; Protein Kinase C; Rats; Spatial Memory
PubMed: 29614089
DOI: 10.1371/journal.pone.0195095 -
Psychiatry Research Sep 2015Glutamate-related genes have been associated with schizophrenia, but the results have been ambiguous and difficult to replicate. Homovanillic acid (HVA),...
Glutamate-related genes have been associated with schizophrenia, but the results have been ambiguous and difficult to replicate. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major degradation products of the monoamines dopamine, serotonin and noradrenaline, respectively, and their concentrations in the cerebrospinal fluid (CSF), mainly HVA, have been associated with schizophrenia. In the present study, we hypothesized that CSF HVA, 5-HIAA and MHPG concentrations represent intermediate phenotypes in the association between glutamate-related genes and psychosis. To test this hypothesis, we searched for association between 238 single nucleotide polymorphisms (SNPs) in ten genes shown to be directly or indirectly implicated in glutamate transmission and CSF HVA, 5-HIAA and MHPG concentrations in 74 patients with psychotic disease. Thirty-eight nominally significant associations were found. Further analyses in 111 healthy controls showed that 87% of the nominal associations were restricted to the patients with psychosis. Some of the psychosis-only-associated SNPs found in the d-amino acid oxidase activator (DAOA) and the kynurenine 3-monooxygenase (KMO) genes have previously been reported to be associated with schizophrenia. The present results suggest that CSF monoamine metabolite concentrations may represent intermediate phenotypes in the association between glutamate-related genes and psychosis.
Topics: Adult; Biogenic Monoamines; Biomarkers; Dopamine; Female; Glutamic Acid; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Kynurenine 3-Monooxygenase; Male; Methoxyhydroxyphenylglycol; Norepinephrine; Phenotype; Polymorphism, Single Nucleotide; Psychotic Disorders; Serotonin
PubMed: 26142836
DOI: 10.1016/j.psychres.2015.06.023 -
Cell Reports Dec 2018A major mechanism contributing to synaptic plasticity involves alterations in the number of AMPA receptors (AMPARs) expressed at synapses. Hippocampal CA1 synapses,...
A major mechanism contributing to synaptic plasticity involves alterations in the number of AMPA receptors (AMPARs) expressed at synapses. Hippocampal CA1 synapses, where this process has been most extensively studied, are highly heterogeneous with respect to their probability of neurotransmitter release, P(r). It is unknown whether there is any relationship between the extent of plasticity-related AMPAR trafficking and the initial P(r) of a synapse. To address this question, we induced metabotropic glutamate receptor (mGluR) dependent long-term depression (mGluR-LTD) and assessed AMPAR trafficking and P(r) at individual synapses, using SEP-GluA2 and FM4-64, respectively. We found that either pharmacological or synaptic activation of mGluR1 reduced synaptic SEP-GluA2 in a manner that depends upon P(r); this process involved an activity-dependent reduction in surface mGluR1 that selectively protects high-P(r) synapses from synaptic weakening. Consequently, the extent of postsynaptic plasticity can be pre-tuned by presynaptic activity.
Topics: Animals; Cell Membrane; Dendritic Spines; Endocytosis; Glutamates; Long-Term Synaptic Depression; Male; Methoxyhydroxyphenylglycol; Neurotransmitter Agents; Probability; Protein Transport; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, Metabotropic Glutamate; Synapses; Theta Rhythm
PubMed: 30590038
DOI: 10.1016/j.celrep.2018.12.010 -
Cellular and Molecular Life Sciences :... Jan 2019Hormones have not been found in concentrations of orders of magnitude higher than nanograms per milliliter. Here, we report urine concentrations of a catecholamine...
Hormones have not been found in concentrations of orders of magnitude higher than nanograms per milliliter. Here, we report urine concentrations of a catecholamine (norepinephrine) ranging from 0.05 to 0.5 g/l, and concentrations of its metabolite DL-3,4-dihydroxyphenyl glycol (DOPEG) ranging from 1.0 to 44.5 g/l, in wild male red deer Cervus elaphus hispanicus after LC-MS analyses. The dark ventral patch of male red deer, a recently described sexually selected signal, contains high amounts of DOPEG (0.9-266.9 mg/l) stuck in the hairs, while DOPEG is not present in non-darkened hair. The formation of this dark patch is explained by the chemical structure of DOPEG, which is a catecholamine-derived o-diphenol susceptible to be oxidized by air and form allomelanins, nitrogen-free pigments similar to cutaneous melanins; by its high concentration in urine; and by the urine spraying behavior of red deer by which urine is spread through the ventral body area. Accordingly, the size of the dark ventral patch was positively correlated with the concentration of DOPEG in urine, which was in turn correlated with DOPEG absorbed in ventral hair. These findings represent catecholamine concentrations about one million higher than those previously reported for any hormone in an organism. This may have favored the evolution of the dark ventral patch of red deer by transferring information on the fighting capacity to rivals and mates. Physiological limits for hormone production in animals are thus considerably higher than previously thought. These results also unveil a novel mechanism of pigmentation based on the self-application of urine over the fur.
Topics: Animals; Catecholamines; Chromatography, High Pressure Liquid; Deer; Hair; Male; Mass Spectrometry; Melanins; Methoxyhydroxyphenylglycol; Pigmentation
PubMed: 30413834
DOI: 10.1007/s00018-018-2962-1 -
Neuropsychopharmacology : Official... Nov 2014Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3...
Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed [(11)C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [(11)C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D3R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [(11)C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [(11)C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen), mixed D2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [(11)C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations.
Topics: Adult; Affect; Brain; Dopamine; Dopamine Agents; Female; Homovanillic Acid; Humans; Male; Methoxyhydroxyphenylglycol; Oxazines; Positron-Emission Tomography; Radiopharmaceuticals; Receptors, Dopamine D2; Receptors, Dopamine D3; alpha-Methyltyrosine
PubMed: 24874713
DOI: 10.1038/npp.2014.125