Hypoglycemia induces vascular endothelial dysfunction in subjects with normal glucose tolerance.

This prospective study determined the effects of hypoglycemic stimulation on vascular endothelial function in non-diabetic patients using reactive hyperemia peripheral arterial tonometry (RH-PAT). The study included non-diabetic patients who were hospitalized for an insulin tolerance test (ITT) for the diagnosis of hypoadrenocorticism or hypopituitarism. Vascular endothelial function was assessed using the reactive hyperemia index (RHI) measured by the RH-PAT. We also measured the levels of anterior pituitary hormone, adrenaline, noradrenaline, and dopamine at the time of hypoglycemia. The primary endpoint was a change in the RHI at 120 min after insulin administration. The study included 27 patients. ITT was associated with significant increases in systolic blood pressure, pulse rate, and the blood levels of adrenocorticotropic hormone, cortisol, growth hormone, adrenaline, noradrenaline, and dopamine. RHI significantly decreased after ITT from 2.24 ± 0.51 to 1.71 ± 0.42. A significant inverse correlation was observed between the change in RHI and change in adrenaline (r = - 0.670, p = 0.012). We concluded that hypoglycemic stimulation altered vascular endothelial function, as measured by RH-PAT, even in patients free of glucose intolerance. The observed deterioration in vascular endothelial function correlated with increases in catecholamine levels during hypoglycemia.Trial registration: UMIN000033244.

Triple-enzyme mimetic activity of Fe3O4@C@MnO2 composites derived from metal-organic frameworks and their application to colorimetric biosensing of dopamine.

Novel Fe3O4@C@MnO2 composites were successfully synthesized for the first time via an interfacial reaction between magnetic porous carbon and KMnO4, in which the magnetic porous carbon was derived from the pyrolysis of Fe-MIL-88A under N2 atmosphere. Interestingly, the obtained Fe3O4@C@MnO2 composites were found to have triple-enzyme mimetic activity including peroxidase-like, catalase-like, and oxidase-like activity. As a peroxidase mimic, Fe3O4@C@MnO2 composites could catalyze the oxidation of TMB into a blue oxidized product by H2O2. As a catalase mimic, Fe3O4@C@MnO2 could catalyze the decomposition of H2O2 to generate O2 and H2O. As an oxidase mimic, Fe3O4@C@MnO2 could catalyze the direct oxidation of TMB to produce a blue oxidized product without H2O2. Reactive oxygen species measurements revealed that the oxidase-like activity originated from 1O2 and O2-∙and little∙OH generated by the dissolved oxygen, which was catalyzed by the Fe3O4@C@MnO2 in the TMB oxidation reaction. The oxidase-like activity of Fe3O4@C@MnO2 was investigated in detail. Under the optimized conditions, a rapid, sensitive, visual colorimetric method for dopamine detection was developed based on the inhibitory effect of dopamine on the oxidase-like activity. The proposed method allows for dopamine detection with a limit of detection of 0.034 µM and a linear range of 0.125-10 µM. This new colorimetric method was successfully used for the determination of dopamine in human blood samples.

Val158Met polymorphisms of COMT gene and serum concentrations of catecholaminergic neurotransmitters of ADHD in Chinese children and adolescents.

ABSTRACT: This study analyzed the Val158Met polymorphisms of the catechol-O-methyltransferase (COMT) gene and serum concentrations of catecholaminergic neurotransmitters in attention deficit hyperactivity disorder (ADHD) children and adolescents.All the subjects (180 paired ADHD and non-ADHD children and adolescents) were genotyped for the Val158Met polymorphisms of the COMT gene, and determined by the difference of dopamine and noradrenalin from a 1:1 paired case-control study.The frequencies of methionine (A)/A, valine (G)/A, and G/G were 51.67%, 41.11%, and 7.22% in the case group, and 62.22%, 31.11%, and 6.67% in the control group. There was a significant difference in the distribution of all genotypes of the COMT gene between the 2 groups (odds ratio = 1.85, 95% confidence interval: 1.62-2.08; χ2 = 7.80, P < .05). The serum concentrations of dopamine and noradrenalin were 1.42 ±â€Š0.34 ng/mL and 177.70 ±â€Š37.92 pg/mL in the case group, and 1.94 ±â€Š0.42 ng/mL and 206.20 ±â€Š42.45 pg/mL in the control group. There were the significant differences in the levels of dopamine and noradrenalin between the 2 groups (dopamine: t = 4.30, P < .01; noradrenalin: t = 2.24, P < .05).Our study suggested that the Val158Met polymorphisms of the COMT gene and serum concentrations of catecholaminergic neurotransmitters were associated with ADHD children and adolescents.

Correlation of Antibodies to Neurotransmitters in the Sera of Women with Alcohol Dependence and Depressive Disorders.

Comparative analysis of blood sera from women with alcohol dependence and depressive disorders or from conditionally healthy women revealed reduced level of antibodies to dopamine, norepinephrine, serotonin, glutamate, and GABA in blood serum in women with dysthymic disorder and a depressive episode and their increased content in women with alcohol dependence in combination with depressive disorders.

Study of stability and interference for catecholamines and metanephrines, 3-methoxytyramine: key point of an accurate diagnosis for pheochromocytoma and paraganglioma.

BACKGROUND: Accurate diagnosis of pheochromocytoma and paraganglioma (PPGLs) is highly dependent on the detection of metanephrines and catecholamines. However, the systematic investigation on influencing factors including specimen (plasma or whole blood), anticoagulant, storage conditions, and interference factors need further confirmation. METHODS: Blood with heparin-lithium or EDTA-K2 were collected, stability of epinephrine (EPI), norepinephrine (NE), dopamine (DA), metanephrine (MN), normetanephrine (NMN), 3-methoxytyramine (3-MT) in whole blood and plasma at room temperature and 4 °C for different storage times, stability of plasma MN, NMN and 3-MT at -20 °C and -80 °C were investigated. Plasma with hemoglobin (1 g/L, 2 g/L, 3 g/L, 4 g/L, 6 g/L), TG (<5 mmol/L, 5-8 mmol/L, >8 mmol/L) were prepared. RESULTS: EPI, NE, DA were prone to degrade at room temperature, samples should be centrifuged at 4 °C. EPI and NE were stable in whole blood at 4 °C for 4 h and in plasma for 2 h. For MN, NMN, 3-MT, plasma can be stable at room temperature and 4 °C for at least 6 h, which is better than whole blood; there was no significant difference when stored at -20 °C and -80 °C for 7 days. Heparin-lithium had a slight advantage over EDTA-K2. EPI, NE, DA should not be performed when Hb > 1 g/L or TG > 5 mmol/L. MN, NMN, 3-MT should not be performed when Hb > 2 g/L, whereas TG had no interference. CONCLUSIONS: According to the actual clinical application scenario, this study provided a reliable basis for the accurate diagnosis of PPGLs.

Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients.

INTRODUCTION: In dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the pathophysiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations. METHODS: Concentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and correlated with concentrations of metabolites. RESULTS: A significantly higher concentration of 3-methoxytyramine (0.03 vs. 0.02 nmol/L, p < 0.01), a metabolite of dopamine, and a reduced concentration of tryptophan (50 vs. 53 µmol/L, p = 0.03), the precursor of serotonin was found in dystonia patients compared to controls. The dopamine/levodopa ratio was higher in CD patients compared to other dystonia groups (p < 0.01). Surprisingly, relatively high concentrations of levodopa were found in the untreated DRD patients. Low concentrations of levodopa were associated with severity of dystonia (rs = -0.3, p < 0.01), depression (rs = -0.3, p < 0.01) and fatigue (rs = -0.2, p = 0.04). CONCLUSION: This study shows alterations in the dopaminergic and serotonergic metabolism of patients with dystonia, with dystonia subtype specific changes. Low concentrations of levodopa, but not of serotonergic metabolites, were associated with both motor and non-motor symptoms. Further insight into the dopaminergic and serotonergic systems in dystonia with a special attention to the kinetics of enzymes involved in these pathways, might lead to better treatment options.

Rationally designed f-MWCNT-coated bismuth molybdate (f-MWCNT@BMO) nanocomposites for the voltammetric detection of biomolecule dopamine in biological samples.

Selective and sensitive dopamine (DPA) sensor was developed using hydrothermally prepared functionalized multi-walled carbon nanotube-coated bismuth molybdate (f-MWCNT@BMO). The f-MWCNT@BMO-reinforced electrode exhibited an outstanding electrocatalytic activity towards DPA oxidation. The nanocomposite-reinforced electrode displayed a rapid response towards DPA sensing and possessed the minimized potential of (Epa + 0.285 V vs Ag/AgCl) in 0.1 M phosphate buffer (PB). The electrochemical results of prepared sensors were analyzed using the differential pulse voltammetry method (DPV). As a result, the f-MWCNT@BMO-reinforced electrode exhibited a widelinear range of 10 nM - 814 µM with a very low detection limit of 3.4 nM towards DPA oxidation. The developed sensor shows excellent selectivity in presence of similar functional group biomolecules. The detection of DPA in real samples was evaluated in human serum, as the results of the proposed sensor possessed good recoveries.

Synthesis of POMOFs with 8-fold helix and its composite with carboxyl functionalized SWCNTs for the voltammetric determination of dopamine.

Although many satisfactory studies have been developed for biomolecule detection, the complexity of biofluids still poses a major challenge to improve the performance of nanomaterials as electrochemical sensors. Herein, unprecedented polyoxometalate-based metal-organic frameworks (POMOFs) with 8-fold meso-helical feature, [Ag5(trz)4]2[PMo12O40] (PAZ), were synthesized and explored as electrochemical sensors to detect dopamine (DA). To improve the conductivity of PAZ and the binding ability with single-walled carbon nanotubes (SWCNTs), the nanocomposite of carboxyl functionalized SWCNTs (SWCNTs-COOH) with nano-PAZ (NPAZ), NPAZ@SWCNTs-COOH, was fabricated, and transmission electron microscopy (TEM) shows that NPAZ can interact stably and uniformly with SWCNTs-COOH, owing to more defect sites on the surface of SWCNTs-COOH. The electrochemical result of NPAZ@SWCNTs-COOH/GCE towards detecting DA shows that the linear range was from 0.05 to 100 µM with a detection limit (LOD) of 8.6 nM (S/N = 3). A new electrochemical biosensing platform by combining 8-fold helical POMOFs with SWCNTs-COOH was developed for enhancing detection of dopamine for the first time, exhibiting the lowest detection limit to date.

Optimized procedures for testing plasma metanephrines in patients on hemodialysis.

Diagnosis of pheochromocytomas and paragangliomas in patients receiving hemodialysis is troublesome. The aim of the study was to establish optimal conditions for blood sampling for mass spectrometric measurements of normetanephrine, metanephrine and 3-methoxytyramine in patients on hemodialysis and specific reference intervals for plasma metanephrines under the most optimal sampling conditions. Blood was sampled before and near the end of dialysis, including different sampling sites in 170 patients on hemodialysis. Plasma normetanephrine concentrations were lower (P < 0.0001) and metanephrine concentrations higher (P < 0.0001) in shunt than in venous blood, with no differences for 3-methoxytyramine. Normetanephrine, metanephrine and 3-methoxytyramine concentrations in shunt and venous blood were lower (P < 0.0001) near the end than before hemodialysis. Upper cut-offs for normetanephrine were 34% lower when the blood was drawn from the shunt and near the end of hemodialysis compared to blood drawn before hemodialysis. This study establishes optimal sampling conditions using blood from the dialysis shunt near the end of hemodialysis with optimal reference intervals for plasma metanephrines for the diagnosis of pheochromocytomas/paragangliomas among patients on hemodialysis.

Peroxidase-Like Platinum Clusters Synthesized by Ganoderma lucidum Polysaccharide for Sensitively Colorimetric Detection of Dopamine.

The sensitive and selective detection of dopamine (DA) is very important for the early diagnosis of DA-related diseases. In this study, we reported the colorimetric detection of DA using Ganoderma lucidum polysaccharide (GLP) stabilized platinum nanoclusters (Ptn-GLP NCs). When Pt600-GLP NCs was added, 3,3',5,5'-tetramethylbenzidine (TMB) was rapidly catalyzed and oxidized to blue oxTMB, indicating the peroxidase-like activity of Pt600-GLP NCs. The catalytic reaction on the substrate TMB followed the Michaelis-Menton kinetics with the ping-pong mechanism. The mechanism of the colorimetric reaction was mainly due to the formation of hydroxyl radical (•OH). Furthermore, the catalytic reaction of Pt600-GLP NCs was used in the colorimetric detection of DA. The linear range for DA was 1-100 µM and the detection limit was 0.66 µM. The sensitive detection of DA using Pt-GLP NCs with peroxidase-like activity offers a simple and practical method that may have great potential applications in the biotechnology field.

Functional dynamics of dopamine synthesis during monetary reward and punishment processing.

The assessment of dopamine release with the PET competition model is thoroughly validated but entails disadvantages for the investigation of cognitive processes. We introduce a novel approach incorporating 6-[18F]FDOPA uptake as index of the dynamic regulation of dopamine synthesis enzymes by neuronal firing. The feasibility of this approach is demonstrated by assessing widely described sex differences in dopamine neurotransmission. Reward processing was behaviorally investigated in 36 healthy participants, of whom 16 completed fPET and fMRI during the monetary incentive delay task. A single 50 min fPET acquisition with 6-[18F]FDOPA served to quantify task-specific changes in dopamine synthesis. In men monetary gain induced stronger increases in ventral striatum dopamine synthesis than loss. Interestingly, the opposite effect was discovered in women. These changes were further associated with reward (men) and punishment sensitivity (women). As expected, fMRI showed robust task-specific neuronal activation but no sex difference. Our findings provide a neurobiological basis for known behavioral sex differences in reward and punishment processing, with important implications in psychiatric disorders showing sex-specific prevalence, altered reward processing and dopamine signaling. The high temporal resolution and magnitude of task-specific changes make fPET a promising tool to investigate functional neurotransmitter dynamics during cognitive processing and in brain disorders.

Anderson polyoxometalates with intrinsic oxidase-mimic activity for "turn on" fluorescence sensing of dopamine.

Anderson-type polyoxometalate containing Fe3+ and Mo6+, (NH4)3[H6Fe(III)Mo6O24] (FeMo6), was found to work as an oxidase-mimicking nanoenzyme for the first time, exhibiting the ability of catalytic oxidation of o-phenylenediamine (OPD), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTs), and 3,3',5,5'-tetramethylbenzidine (TMB), which features easy synthesis, low cost, simple operation, and low consumption. Attributed to the nature of FeMo6 and Fenton-like effect, a novel sensor based on two consecutive "turn on" fluorescence was developed for detecting dopamine (DA) by employing the FeMo6-OPD system, and the linear range was from 1 to 100 µM with the detection limit 0.0227 µM (3σ/s). Moreover, to increase oxidase-mimic activity of FeMo6, reduced graphene oxide (rGO) loading FeMo6 composites (FeMo6@rGO (n), n = 5%, 10%, 15%) was fabricated, and results show that oxidase-like activities of FeMo6@rGO (n) are dependent on the mass ratio of FeMo6/rGO, and FeMo6@rGO (10%) exhibits the highest oxidase-mimic activity and the fastest respond time (4 min) among all reported oxidase mimic of DA to date. Graphical abstract Anderson-type Mo-POMs FeMo6 was found to work as an oxidase-mimicking nanoenzyme for the first time and was used to detect DA for two consecutive "turn on" fluorescence sensor modes.

Lithium cobalt phosphate electrode for the simultaneous determination of ascorbic acid, dopamine, and serum uric acid by differential pulse voltammetry.

Lithium cobalt phosphate (LCP) was prepared and modified on the surface of glassy carbon electrode (GCE) to fabricate the electrochemical sensor (LCP/GCE) for the simultaneous determination of ascorbic acid (AA), dopamine (DA), and serum uric acid (UA). The homogenous incorporation of carbon improved the conductivity of LCP. Benefiting from the small particle size distribution, LCP/GCE has a large active surface and responds to AA, DA, and UA sensitively and rapidly. For the simultaneous detection with differential pulse voltammetry the anodic peaks of AA, DA, and UA were well-separated and appeared at ~0 V, ~0.19 V, and ~ 0.33 V (vs. Ag/AgCl), respectively. The linear responses toward AA, DA, and UA were in the range 10 µM-8.0 mM, 10 nM-10 µM, and 0.020 µM-25 µM; the detection limits were estimated to be 8.10 µM, 7.50 nM, and 22.7 nM (S/N = 3), respectively. The excellent selectivity and reproducibility of LCP/GCE enable serum UA to be detected without the interference of AA and DA. The recoveries of DA and AA in the serum sample were in the range 95 to 111%. The results indicate that LCP has the potential to be developed as the sensing devices to be applied to in vitro diagnosis. The lithium-ion battery cathodic material, LCP with the excellent adsorption and catalytic behavior, was utilized to fabricate the electrochemical sensor for the sensitive and simultaneous detection of AA, DA, and UA, which achieved the low detection limits and the wide concentration ranges. LCP/GCE can be used for the quantitative detection of serum UA without the interference of DA and AA. In addition, the recoveries of DA and AA in human serum were satisfactory, which illustrate the reliability of LCP/GCE to be applied to in vitro diagnosis.

Calibration curve-free electrochemical quantitation by micro-nano multi-scale gap devices.

Quantitation without relying on the calibration curve has long been an issue of overcoming analytical problems accompanied with the inherent limitations of the calibration curve fitting errors. Here, we report on a calibration curve-free method for electrochemical quantitation based on a multi-scale gap device (MGD). The MGD is an integrated device having a series of interdigitated electrodes (IDE) with micro-to-nano gap distances. The device shows a gap-dependent redox current of the analyte when subjected to the electrochemical cycling between the two facing electrodes of its componential IDEs. Based on the fact that the current increases as the gap distance decreases, the analyte concentration could be directly estimated: the rate of increase in the current was directly proportional to the analyte concentration. The calibration curve was not necessary for the quantitation. The accuracy of this MGD approach was better than that of an IDE collection of the same gap distance, which was deteriorated at the larger gap distances particularly. The MGD-based quantitation of dopamine, potassium ferricyanide, and aminophenol was demonstrated in a relatively broad range of concentrations (100 nM-5 mM).

Neurobehavioral effects of acute low-dose whole-body irradiation.

Radiation exposure has multiple effects on the brain, behavior and cognitive functions. It has been reported that high-dose (>20 Gy) radiation-induced behavior and cognitive aberration partly associated with severe tissue destruction. Low-dose (<3 Gy) exposure can occur in radiological disasters and cerebral endovascular treatment. However, only a few reports analyzed behavior and cognitive functions after low-dose irradiation. This study was undertaken to assess the relationship between brain neurochemistry and behavioral disruption in irradiated mice. The irradiated mice (0.5 Gy, 1 Gy and 3 Gy) were tested for alteration in their normal behavior over 10 days. A serotonin (5-HT), Dopamine, gamma-Aminobutyric acid (GABA) and cortisol analysis was carried out in blood, hippocampus, amygdala and whole brain tissue. There was a significant decline in the exploratory activity of mice exposed to 3 Gy and 1 Gy radiation in an open field test. We observed a significant short-term memory loss in 3 Gy and 1 Gy irradiated mice in Y-Maze. Mice exposed to 1 Gy and 3 Gy radiation exhibited increased anxiety in an elevated plus maze (EPM). The increased anxiety and memory loss patterns were also seen in 0.5 Gy irradiated mice, but the results were not statistically significant. In this study we observed that neurotransmitters are significantly altered after irradiation, but the neuronal cells in the hippocampus were not significantly affected. This study suggests that the low-dose radiation-induced cognitive impairment may be associated with the neurochemical in low-dose irradiation and unlike the high-dose scenario might not be directly related to the morphological changes in the brain.

The association between multiple risk factors, clinical correlations and molecular insights in Parkinson's disease patients from Tamil Nadu population, India.

Parkinson's disease (PD) is a neurodegenerative disease with multifactorial aetiology that influences the quality of life. However, the association of possible factors with PD is need to be investigated in Indian population, hence we aimed to determine the association of lifestyle, environmental factors, biochemical parameters and genetic insights of MT-ND1 gene in PD patients. Using a standardised questionnaire, PD patients and control group of about 146 subjects were interviewed on demographic, lifestyle and environmental factors. The subjects includes n = 73 Parkinson's patients [juvenile (n = 4); early-onset (n = 8); late-onset (n = 61)] with equal number of age and sex matched controls, further we had obtained institutional ethical clearance and informed consent from study participants. Biomarker investigations and MT-ND1 alterations were investigated by appropriate molecular techniques. During the average follow-up years of 5.1, significant association was observed among smoking, alcohol, caffeinated drinks, surgery, pesticide exposure at p < 0.05 in varied PD age groups. Occupational exposure to agriculture and industry showed an increased risk among the late-onset group. The biomarkers uric acid (UA) and dopamine (DA) were significant at p < 0.05 in all the three PD age groups. The MT-ND1 alteration with A3843 G variant was significant at p < 0.05 for AG allele in all the three PD groups but the highest prevalence was observed in late-onset group. From our study, smoking, alcohol, caffeinated drinks, occupational influence of agriculture and industry and pesticide exposure had more association with PD occurrence. Hence, to the best of our knowledge, this is the first kind of study in Tamil Nadu population, India to validate the various factors with PD. Therefore we suggest that further research is mandatory to detect other possible associations among PD, using comprehensive larger sample size.

Differential Health Effects on Inflammatory, Immunological and Stress Parameters in Professional Soccer Players and Sedentary Individuals after Consuming a Synbiotic. A Triple-Blinded, Randomized, Placebo-Controlled Pilot Study.

The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1ß, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group-administered with placebo, and an experimental group-administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1ß (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1ß, CRH, and dopamine are clearly involved.

Detection of 3-O-methyldopa in dried blood spots for neonatal diagnosis of aromatic L-amino-acid decarboxylase deficiency: The northeastern Italian experience.

OBJECTIVE: Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare inherited autosomal recessive disorder of biogenic amine metabolism. Diagnosis requires analysis of neurotransmitter metabolites in cerebrospinal fluid, AADC enzyme activity analysis, or molecular analysis of the DDC gene. 3-O-methyldopa (3-OMD) is a key screening biomarker for AADC deficiency. METHODS: We describe a rapid method for 3-OMD determination in dried blood spots (DBS) using flow-injection analysis tandem mass spectrometry with NeoBase™ 2 reagents and 13C6-tyrosine as an internal standard, which are routinely used in high-throughput newborn screening. We assessed variability using quality control samples over a range of 3-OMD concentrations. RESULTS: Within-day and between-day precision determined with quality control samples demonstrated coefficients of variation <15%. 3-OMD concentrations in 1000 healthy newborns revealed a mean of 1.33 µmol/L (SD ± 0.56, range 0.61-3.05 µmol/L), 100 non-AADC control subjects (age 7 days - 1 year) showed a mean of 1.19 µmol/L (SD ± 0.35-2.00 µmol/L), and 81 patients receiving oral L-Dopa had a mean 3-OMD concentration of 14.90 µmol/L (SD ± 14.18, range 0.4-80.3 µmol/L). A patient with confirmed AADC was retrospectively analyzed and correctly identified (3-OMD 10.51 µmol/L). In April 2020, we started a pilot project for identifying AADC deficiency in DBSs routinely submitted to the expanded newborn screening program. 3-OMD concentrations were measured in 21,867 samples; no patients with AADC deficiency were identified. One newborn had a high 3-OMD concentration due to maternal L-Dopa treatment. DISCUSSION: We demonstrated a rapid new method to identify AADC deficiency using reagents and equipment already widely used in newborn screening programs. Although our study is limited, introduction of our method in expanded neonatal screening is feasible and could facilitate deployment of screening, allowing for early diagnosis that is important for effective treatment.

Circulating Levels of the Heparan Sulfate Proteoglycan Syndecan-4 Positively Associate with Blood Pressure in Healthy Premenopausal Women.

Syndecans (SDCs) are transmembrane proteins that are present on most cell types where they play a role in multiple physiological processes, including cell-matrix adhesion and inflammation. Growing evidence suggests that elevated levels of both shed SDC1 and SDC4 are associated with hypertension and cardiovascular diseases, but their relationships with cardiovascular risk factors in healthy individuals are unknown. The primary objective of this study was to investigate whether serum levels of SDC4 and SDC1 were associated with body composition, hemodynamic parameters, pro-inflammatory cytokine concentrations, and urinary noradrenaline and dopamine levels in healthy women (17 African American and 20 European American) between the ages of 20 and 40 years old. Univariate analyses revealed only a significant (p < 0.05) inverse correlation between serum SDC1 and body fat percentage. On the other hand, serum SDC4 was positively correlated with systolic blood pressure, diastolic blood pressure, and urinary levels of noradrenaline and dopamine. Serum SDC4 was also a significant predictor of systolic blood pressure in a multivariate regression model that included fat-free mass and urinary dopamine levels as significant independent variables. The result did not change even adjusting for race. Our findings indicate that SDC4 has an important role in the physiological regulation of blood pressure.