Platelet Serotonin Research Articles

Concordance Between Platelet Expression Assay (PEA) and Serotonin Release Assay (SRA) in Heparin-Induced Thrombocytopenia: Implications for Diagnostic Accuracy and Laboratory Test Utilization

Abstract Introduction The Serotonin Release Assay (SRA) serves as the gold standard functional assay for heparin-induced thrombocytopenia (HIT) diagnosis at our institution. The present turnaround time (TAT) for SRA results ranges from 4-5 days, occasionally extending beyond 8 days, given outsourcing to a reference laboratory. Recently, an alternative functional assay, the Platelet Expression Assay (PEA), has been introduced. The PEA detects platelet activation through p-selectin expression by flow cytometry, with a reported sensitivity of 100% and specificity of 95% for HIT. The PEA is also a send-out test, and thus has similar TAT and cost profiles as the SRA, but with potential to transition into an in-house assay in the future. Herein, we sought to determine the concordance of the PEA and SRA for the detection and diagnosis of HIT within our patient population. Methods A retrospective review was conducted on all cases in which a HIT ELISA (screening immunoassay) was performed by the Special Coagulation Laboratory during a one-year period. A 4Ts score was calculated if not already documented by chart review. In a subset analysis, specimens with a positive screening ELISA were concurrently tested by both SRA and PEA to compare performance. Results Of the 1341 cases, a 4Ts score was calculated and found to be less than 4 for 30-50% of cases. A total of 490 cases were sent out for SRA, of which 49 (10%) returned positive results. In a subset analysis of 20 samples from 14 patients, all with positive ELISAs, results revealed concordance between the SRA and PEA for all but one sample (19/20, 95%). Specifically, three successive samples from one patient had [negative, negative, positive] results for SRA, and [negative, positive, positive] results for PEA, respectively. This discordant result suggests a potential difference in sensitivity between the two assays. Further subset analysis focused on an additional 13 samples from 10 patients, all with SRA-positive results. Only 8 samples were concordant (8/13, 62%). One case showed a negative PEA and presumed false positive SRA, given the clinical history, while 4 samples showed likely true positive SRA results, given strength of ELISA results and 4Ts score, but were negative by PEA. Conclusions The lack of adherence to the 4Ts score algorithm to drive laboratory test utilization resulted in unnecessary ELISA and functional assay testing, potentially resulting in increased costs and false positive results. This result underscores the need for vigilance in assessing and refining diagnostic strategies. Additionally, our discordant findings in the subset analysis underscore the importance of evaluating the concordance and discordance between SRA and PEA results, providing insights into the diagnostic accuracy and potential limitations of each assay in identifying HIT.

Role of serotonin and serotonergic-related metabolites in the pathogenesis of vasovagal syncope

BackgroundSerotonin is an important neurohormone that regulates vascular tone and autonomic reflexes, though its pathophysiological role in vasovagal syncope (VVS) remains uncertain. ObjectiveThis study sought to explore the involvement of serotonin and serotonergic-related metabolites in the pathogenesis of VVS. MethodsSixty-six patients (mean age 45.6±17.0 years; 33 women) with recurrent VVS underwent a head-up tilt test (HUTT). Blood samples were collected from all patients in a resting supine position, with an additional sample obtained from HUTT-positive patients during syncope. Plasma and platelet serotonin levels and plasma concentrations of serotonergic-related metabolites—including serotonin’s precursor 5-hydroxytryptophan (5-HTP), major metabolite 5-hydroxyindoleacetic acid, and synthesis source tryptophan—were measured using the liquid chromatography tandem mass spectrometry method. ResultsHUTT was positive in 45 patients and negative in 21 patients. Significant differences were observed in plasma 5-HTP and 5-hydroxyindoleacetic acid levels between HUTT-positive and HUTT-negative patients (P<.001 and P=.040, respectively) as well as before and after syncope (P<.001 for all), whereas no significant changes were found in serotonin and tryptophan levels. Notably, plasma serotonin levels significantly increased during syncope in patients with drug-free VVS (P=.037), and a greater change in serotonin correlated with a shorter time to syncope (R2=0.38; P=.015). Furthermore, certain serotonergic-related metabolites exhibited significant correlations with hemodynamic changes during VVS episodes, with 5-HTP demonstrating the highest sensitivity. ConclusionDespite the unchanged plasma and platelet serotonin levels, certain serotonergic-related metabolites significantly changed and correlated with hemodynamic parameters during VVS episodes, suggesting the potential involvement of an altered serotonergic metabolic pathway in VVS.

Fetal behavior and gestational serotonin reuptake inhibitor exposure: relationships between behavior, drug dosage, plasma drug level, and a measure of drug bioeffect

Determination of the relationships between drug dosage, maternal and infant (cord blood) plasma drug concentrations, and serotonin reuptake inhibitor (SRI) bioeffect on offspring neurobehavior is crucial to assessing the effects of gestational SRI exposure. Measurement of maternal and cord blood platelet serotonin (5-HT) provides an index of inhibitory bioeffect at the 5-HT transporter and complements other measures of drug exposure. Three groups of mother-infant pairs were evaluated: (1) mothers with depression untreated with SRIs (DEP, n = 17), (2) mothers treated for depression with SRIs (DEP + SRI, n = 17), and (3) mothers who were not depressed and untreated (ND, n = 29). Fetal movement was assessed using a standardized ultrasound imaging and rating protocol. Maternal and cord blood platelet 5-HT levels were obtained from all participants. For the SRI + DEP group, maternal and infant plasma drug concentrations and an estimate of third-trimester maternal SRI drug exposure were obtained. As expected, substantially lower median platelet 5-HT levels were observed in the DEP + SRI group than in the non-exposed, combined ND and DEP groups. In non-exposed mothers and infants, platelet 5-HT levels were not affected by the presence of maternal depression. Lower maternal and infant platelet 5-HT levels were associated with more immature fetal movement quality. Although these data are limited by small sample size, the bioeffect index of in vivo platelet 5-HT transporter inhibition appears to provide a valuable approach for elucidating and possibly predicting the effects of gestational SRI exposure on fetal and perinatal neurobehavior.

Platelet-serotonin dynamics: elucidating their role in pulmonary arterial hypertension

Background and Objectives:&lt;br /&gt; Pulmonary arterial hypertension (PAH) is a significant complication in pediatric patients with congenital heart disease (CHD). The role of platelets and serotonin in the pathogenesis of PAH has been increasingly recognized. This study aims to investigate the correlation between platelet count, serotonin levels, and PAH in children with CHD, and to understand the impact of surgical intervention on these parameters.&lt;br /&gt; &lt;br /&gt; Material and Methods:&lt;br /&gt; This study included 26 children with CHD and PAH (Group I) and an 11-child control group without PAH. Pre- and post-operative platelet counts, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), and serotonin levels in plasma and platelets were measured. Group I underwent surgical correction for CHD, and the control group received no such intervention. Data were analyzed to determine the relationships between these hematological and biochemical markers and PAH.&lt;br /&gt; &lt;br /&gt; Results:&lt;br /&gt; Group I showed higher pre-operative platelet counts and serotonin levels compared to the control group. Post-surgical data indicated a significant decrease in platelet serotonin levels, aligning more closely with the control group. The study also observed lower plasma serotonin levels in the control group, suggesting altered serotonin metabolism in PAH patients.&lt;br /&gt; &lt;br /&gt; Conclusion:&lt;br /&gt; The study suggests a strong association between elevated platelet counts, increased serotonin levels, and the presence of PAH in children with CHD. Surgical correction of CHD appears to normalize these parameters, indicating a potential pathophysiological link. These findings emphasize the need for further research to understand the underlying mechanisms and to explore targeted therapeutic strategies for PAH in pediatric CHD patients.

Dysregulation of platelet serotonin, 14–3–3, and GPIX in sudden infant death syndrome

Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality, but the underlying cause(s) are unclear. A subset of SIDS infants has abnormalities in the neurotransmitter, serotonin (5-hydroxytryptamine [5-HT]) and the adaptor molecule, 14–3–3 pathways in regions of the brain involved in gasping, response to hypoxia, and arousal. To evaluate our hypothesis that SIDS is, at least in part, a multi-organ dysregulation of 5-HT, we examined whether blood platelets, which have 5-HT and 14–3–3 signaling pathways similar to brain neurons, are abnormal in SIDS. We also studied platelet surface glycoprotein IX (GPIX), a cell adhesion receptor which is physically linked to 14–3–3. In infants dying of SIDS compared to infants dying of known causes, we found significantly higher intra-platelet 5-HT and 14–3–3 and lower platelet surface GPIX. Serum and plasma 5-HT were also elevated in SIDS compared to controls. The presence in SIDS of both platelet and brainstem 5-HT and 14–3–3 abnormalities suggests a global dysregulation of these pathways and the potential for platelets to be used as a model system to study 5-HT and 14–3–3 interactions in SIDS. Platelet and serum biomarkers may aid in the forensic determination of SIDS and have the potential to be predictive of SIDS risk in living infants.

Feasibility of Using Serum, Plasma, and Platelet 5-hydroxytryptamine as Peripheral Biomarker for the Depression Diagnosis and Response Evaluation to Antidepressants: Animal Experimental Study.

Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue. Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured. In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats' model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice. Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.

Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration.

We believe there are serious problems with a recently published and highly publicized paper entitled "Serotonin reduction in post-acute sequelae of viral infection." The blood centrifugation procedure reportedly used by Wong et al would produce plasma that is substantially (over 95%) depleted of platelets. Given this, their published mean plasma serotonin values of 1.2 uM and 2.4 uM for the control/contrast groups appear to be at least 30 to 60 times too high and should be disregarded. The plasma serotonin values reported for the long COVID and viremia patients also should be disregarded, as should any comparisons to the control/contrast groups. We also note that the plasma serotonin means for the two control/contrast groups are not in good agreement. In the "Discussion" section, Wong et al state that their results tend to support the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of COVID-19, and they encourage further clinical trials of SSRIs. While they state that, "Our animal models demonstrate that serotonin levels can be restored and memory impairment reversed by precursor supplementation or SSRI treatment", it should be noted that no data are presented showing an increase or restoration in circulating serotonin with SSRI administration. In fact, one would expect a marked decline in platelet serotonin due to SSRIs' effective inhibition of the platelet serotonin transporter. Wong et al hypothesize that problems of long COVID arise from too little peripheral serotonin. However, given the frequent presence of a hyperaggregation state in long COVID, and the known augmenting effects of platelet serotonin on platelet aggregation, it is plausible to suggest that reductions in platelet serotonin might be associated with a lessening of the cardiovascular sequelae of COVID-19.

Evaluation of serotonin levels in full-term newborns of diabetic mothers

BACKGROUND: The growth of neurological and mental diseases in the offspring of patients with pre- and gestational diabetes mellitus determines the need to study the regulatory function of the serotoninergic system of the brain in newborns. This plays a key role in its morphofunctional development in early ontogenesis, which is necessary for timely diagnosis of disorders and prevention of long-term consequences.&#x0D; AIM: The aim of this study was to evaluate serotonin levels in full-term newborns with diabetic fetopathy from mothers with pre- and gestational diabetes mellitus.&#x0D; MATERIALS AND METHODS: The main group consisted of 45 newborns with diabetic fetopathy, of whom 30 individuals were from mothers with type 1 diabetes mellitus and 15 ones from mothers with gestational diabetes mellitus. The control group comprised 20 healthy full-term newborns from healthy mothers without pregnancy complications. Serotonin concentrations were determined in platelet-rich plasma of blood from the umbilical cord vein, and in a platelet suspension prepared from venous blood taken on the first day of life, using high-performance liquid chromatography with electrochemical detection.&#x0D; RESULTS: Platelet-rich plasma serotonin level in umbilical cord blood taken from newborns of the main group was more than two times lower compared to children of healthy mothers. This parameter in venous blood taken from mothers with type 1 diabetes (0.744 ± 0.117 µmol/l) corresponded to that in healthy patients, while in mothers with gestational diabetes mellitus, it was significantly lower and amounted to 0.331 ± 0.071 µmol/l (p 0.05). Moreover, platelet-rich plasma serotonin level in all newborns correlated with that in their mothers (R = 0.505; p 0.05). Serotonin levels in venous blood platelets of newborns of the main group was almost 2.5 times lower than in healthy ones.&#x0D; CONCLUSIONS: The data obtained indicate the need to use platelet serotonin values as a biochemical marker of disorders of functional brain development in children with diabetic fetopathy.

Duloxetine improves chronic orofacial pain and comorbid depressive symptoms in association with reduction of serotonin transporter protein through upregulation of ubiquitinated serotonin transporter protein.

Chronic orofacial pain (COP) is relieved by duloxetine (DLX) and frequently causes depressive symptoms. The aim of this study was to confirm effects of DLX on pain and depressive symptoms, and to associate with their effectiveness in platelet serotonin transporter (SERT) expression, which is a target molecule of DLX and plasma serotonin concentration in COP patients with depressive symptoms. We assessed for the severity of pain and depressive symptoms using the Visual Analog Scale (VAS) and 17-item Hamilton Depression Rating Scale (HDRS), respectively. Chronic orofacial pain patients were classified into 2 groups based on their HDRS before DLX-treatment: COP patients with (COP-D) and without (COP-ND) depressive symptoms. We found that the VAS and HDRS scores of both groups were significantly decreased after DLX treatment compared with those before DLX treatment. Upregulation of total SERT and downregulation of ubiquitinated SERT were observed before DLX treatment in both groups compared with healthy controls. After DLX treatment, there were no differences in total SERT of both groups and in ubiquitinated SERT of COP-D patients compared with healthy controls; whereas, ubiquitinated SERT of COP-ND patients remained downregulated. There were positive correlations between changes of serotonin concentrations and of VAS or HDRS scores in only COP-D patients. Our findings indicate that DLX improves not only pain but also comorbid depressive symptoms of COP-D patients. Duloxetine also reduces platelet SERT through upregulation of ubiquitinated SERT. As the result, decrease of plasma serotonin concentrations may be related to the efficacy of DLX in relieving pain and depression in COP patients.

Membrane Transporter of Serotonin and Hypercholesterolemia in Children.

The serotonin membrane transporter is one of the main mechanisms of plasma serotonin concentration regulation. Serotonin plays an important role in the pathogenesis of various cardiovascular diseases, stimulating the proliferation of smooth muscle cells, key cells in the process of hypertrophic vascular remodeling. Vascular remodeling is one of the leading prognostically unfavorable factors of atherosclerosis, the main manifestation of familial hypercholesterolemia. Familial hypercholesterolemia is one of the most common genetically determined lipid metabolism disorders and occurs in 1 in 313 people. The aim of our study was to investigate the levels of plasma and platelet serotonin, 5-hydroxyindoleacetic acid, and membrane transporter in a cross-sectional study of two pediatric groups, including patients with familial hypercholesterolemia and the control group, which consisted of apparently healthy children without cardiovascular diseases. The study involved 116 children aged 5 to 17 years old. The proportion of boys was 50% (58/116) and the average age of the children was 10.5 years (CI 2.8-18.1). The concentrations of serotonin in blood plasma and platelets and 5-hydroxyindoleacetic acid were higher in children with familial hypercholesterolemia than in the controls. The concentration of the serotonin transporter in platelets in healthy children, compared with the main group, was 1.3 times higher. A positive correlation was revealed between the level of serotonin (5-HT and PWV: ρ = 0.6, p < 0.001), its transporter (SERT and PWV: ρ = 0.5, p < 0.001), and the main indicators of arterial vascular stiffness. Our study revealed the relationship between high serotonin and SERT concentrations and markers of arterial stiffness. The results we obtained suggest the involvement of serotonin and SERT in the process of vascular remodeling in familial hypercholesterolemia in children.

Performance evaluation of heparin-induced platelet aggregation vs serotonin release assay.

Heparin-induced thrombocytopenia (HIT) is a rare but life-threatening condition that requires rapid diagnosis for proper management. Laboratory testing should only be performed on patients with intermediate- or high-risk pretest probability. The platelet factor 4 (PF4) enzyme-linked immunosorbent assay (ELISA) is the screening test that should be confirmed by higher specificity testing such as the heparin-induced platelet aggregation (HIPA) or the serotonin release assay (SRA). This study aims to evaluate the performance of the HIPA in comparison to the SRA, establish cutoffs of the PF4 ELISA to predict positivity for HIPA/SRA, and study the mortality rate between patients with suspected HIT confirmed as HIT positive vs negative. All positive PF4 ELISA cases with confirmatory HIPA and SRA testing were included. As the SRA was considered the gold standard, the HIPA performance was evaluated in comparison to SRA before and after the implementation of a new standardized interpretation guide in 2022. The mortality of these cases was also documented by chart reviews. In total, 232 cases with positive or indeterminate anti-PF4 IgG ELISA had confirmatory testing with HIPA and SRA. The sensitivity of the HIPA improved from 55.4% in 2018 to 2021 to 73.8% in 2022. The specificity remained similarly high in 2018 to 2021 vs 2022 (94.9% vs 87.5%). The negative predictive value (NPV) improved in 2022. The PF4 optical density cutoff to predict the positivity of SRA was 0.85 vs 1.47 to predict the positivity of HIPA but decreased to 0.83 when combining HIPA and/or SRA. There was no significant difference in mortality between patients with suspected HIT confirmed positive vs negative. Although the HIPA has a lower sensitivity than the SRA, the new standardized interpretation guide improved its sensitivity and NPV in 2022. Future improvements are needed to use the HIPA as a stand-alone confirmatory test with the goal to shorten hospital length of stay and expedite proper anticoagulation management.

Polysaccharide-rich extract of Genipa americana leaves exerts anti-inflammatory effects modulated by platelet mediators

Ethnopharmacological relevanceGenipa americana L. (Rubiaceae) leaves are traditionally used to treat fever, pharyngitis, healing, luxation and bruises. Aim of the studyThis study aimed to investigate the anti-inflammatory effect of the polysaccharide-rich extract of G. americana leaves (PE-Ga) in acute inflammation models and underlying mechanisms associated with platelet activity. Materials and methodsRats received PE-Ga (0.3–3.0 mg/kg; IV) 30 min before injection (IP or SC) of zymosan, serotonin, PGE2, PLA2, PAF or L-arginine, and evaluated in the models of paw edema and acute peritonits. The blockage of plasma serotonin reuptake into platelets was performed with fluoxetine (40 mg/kg; IP). ResultsIn vitro, PE-Ga inhibited ADP-induced platelet aggregation up to 49%. In the edema model, PE-Ga reduced (41%) the time-course of the edema induced by zymosan, mainly the last phase (62%), as well as that induced by PLA2 (32%), PAF (35%), L-arginine (36%), PGE2 (49%) or serotonin (54% AUC); and reversed paw hypernociception induced by PGE2 or serotonin. In the peritonitis model, PE-Ga reversed abdominal hypernociception and reduced leukocyte migration induced by zymosan to blood (38%) and peritoneal cavity (55%), mainly neutrophils (70%). PE-GA also decreased leukocyte rolling (32%) and adhesion (47%), and increased the rolling velocity 2.2-fold. In the peritoneal fluid, PE-Ga reversed P-selectin and reduced total proteins (17%), MDA (40%), NO2−/NO3− (27%), and MPO activity (43%) but increased catalase activity 3.3-fold compared to zymosan. In addition, fluoxetine reversed PE-Ga anti-inflammatory effect on leukocyte migration and adhesion. ConclusionsPE-Ga exerts antiplatelet and anti-inflammatory effects in acute inflammation induced by zymosan, being modulated by P-selectin and platelet serotonin, among other inflammatory mediators.

Platelet Serotonin Level: An Essential Role in Human Behavior, Stress Reaction and the Selection of Psychotropic Drugs

Platelet Serotonin Level: An Essential Role in Human Behavior, Stress Reaction and the Selection of Psychotropic Drugs

Serotonin secretion by blood platelets: accuracy of high-performance liquid chromatography-electrochemical technique compared with the isotopic test and use in a clinical laboratory

BackgroundMild secretion defects are the most frequent and challenging blood platelet disorders to diagnose. Most δ-granule secretion tests lack validation, are not quantitative, or have unreliable response to weak platelet agonists. ObjectivesTo compare platelet serotonin secretion by HPLC-electrochemical detection technique (HPLC-ECD) with the reference isotopic test (3H-5-HT), evaluating its performance in clinical laboratories. MethodsThe assay validation followed STARD-2015 recommendations. HPLC-ECD measured the nonsecreted serotonin remaining in platelet pellets after aggregation, comparing it with the reference 3H-5-HT assay. We studied subjects with inherited and aspirin-induced blood platelet disorders and assessed the HPLC-ECD operation for routine clinical diagnosis. ResultsCalibration curves were linear (R2 = 0.997), with SD for residuals of 3.91% and analytical sensitivity of 5ng/mL. Intra- and interassay imprecision bias ranged between −8.5% and 2.1% and −9% and 3.1%, respectively. Serotonin recovery and stability were >95%, and the variability range of measurements was −5.5% to 4.6%. Statistical differences detected between tests were biologically irrelevant, with bias of 1.48% (SD, 8.43) and CI agreement of −18% to 15%. Both assays distinctly detected platelet secretion induced by 10 μM epinephrine and 4 μmM adenosine diphosphate. However, HPLC-ECD is quantitative and more sensitive to low serotonin content in blood platelets. Reference cutoffs for each agonist were determined in 87 subjects. Initially, the HPLC-ECD requires relatively expensive equipment and trained operators but has remarkably cheap running costs and a turn-around time of 24-36 hours. We have used this diagnostic tool routinely for >8 years. ConclusionHPLC-ECD assay for platelet serotonin secretion is highly accurate, has advantages over the reference 3H-5-HT test, and is suitable as a clinical laboratory technique.

Platelet Serotonin (5-HT) Concentration, Platelet Monoamine Oxidase B (MAO-B) Activity and HTR2A, HTR2C, and MAOB Gene Polymorphisms in Asthma.

The complex role of the serotonin system in respiratory function and inflammatory diseases such as asthma is unclear. Our study investigated platelet serotonin (5-HT) levels and platelet monoamine oxidase B (MAO-B) activity, as well as associations with HTR2A (rs6314; rs6313), HTR2C (rs3813929; rs518147), and MAOB (rs1799836; rs6651806) gene polymorphisms in 120 healthy individuals and 120 asthma patients of different severity and phenotypes. Platelet 5-HT concentration was significantly lower, while platelet MAO-B activity was considerably higher in asthma patients; however, they did not differ between patients with different asthma severity or phenotypes. Only the healthy subjects, but not the asthma patients, carrying the MAOB rs1799836 TT genotype had significantly lower platelet MAO-B activity than the C allele carriers. No significant differences in the frequency of the genotypes, alleles, or haplotypes for any of the investigated HTR2A, HTR2C and MAOB gene polymorphisms have been observed between asthma patients and healthy subjects or between patients with various asthma phenotypes. However, the carriers of the HTR2C rs518147 CC genotype or C allele were significantly less frequent in severe asthma patients than in the G allele carriers. Further studies are necessary to elucidate the involvement of the serotonergic system in asthma pathophysiology.

Serotonin and cyclic sleep organization in full-term newborn infants with intrauterine growth retardation

BACKGROUND: The high frequency of neurological and mental diseases in children who had intrauterine retardatiojn development indicates the need to study specific markers of disorders of fetal brain functional development, in particular, the state of the serotonergic system, which plays a key role in the morpho-functional development of the brain in early ontogenesis.&#x0D; AIM: To study the content of serotonin in full-term newborns with intrauterine development delay in comparison with quantitative and qualitative characteristics of sleep.&#x0D; MATERIALS AND MЕTHODS: The main group consisted of 26 newborns, whose intrauterine development took place in conditions of chronic placental insufficiency, which led to the formation of an asymmetric form of intrauterine retardatiojn development. The control group consisted of 72 healthy newborns from healthy mothers without pregnancy complications. Children of each group are divided into three subgroups depending on gestational age: I 37, II 38, III 3940 weeks. In all children, 712 hours after birth, an electropoligram of sleep was recorded (an electroencephalograph of the company Mizar, Russia) and its quantitative and qualitative analyses were carried out, highlighting the orthodox, paradoxical phase and undifferentiated state. The serotonin content was determined in platelet-rich plasma of blood from the umbilical cord vein after birth, as well as in a platelet suspension prepared from venous blood taken on the first day of life. The content of serotonin in platelets was judged by the indicator obtained by dividing the amount of serotonin in the platelet suspension by the platelet level. The amount of serotonin was determined by high-performance liquid chromatography with electrochemical detection. Statistical analysis was performed using the Statistica 6 program (Statsoft Inc, USA).&#x0D; RESULTS: We report here a low content of serotonin in platelet-rich plasma and platelets of newborns with intrauterine growth retardation and the absence of its normal increase in weeks 3739 of intrauterine development, as well as a violation of the genetic programming for the sleep-wake cycle organization.&#x0D; CONCLUSIONS: Assessment of the serotonin-producing system of the brain in comparison with the newborn sleep pattern can serve as a diagnostic marker of brain damage and substantiate the need for timely application of neuroprotection.

Baseline platelet serotonin in a multi-site treatment study of depression in veterans administration patients: Distribution and effects of demographic variables and serotonin reuptake inhibitors

BackgroundThe objectives of the study were: (1) to examine the overall distribution of baseline platelet serotonin (5-hydroxytryptamine, 5-HT) values in patients seeking treatment for depression and to define subgroups based on the apparent presence or absence of drug exposure; (2) to assess the bioeffect of 5-HT reuptake inhibitors (SRIs) at the platelet 5-HT transporter; and (3) to examine the relationships of demographic variables including population (ancestry), sex, age, and season of sampling to platelet 5-HT concentration. MethodsPlatelet 5-HT levels were measured in a cross-sectional study of 1433 Veterans Administration (VA) patients participating in a pragmatic multi-site pharmacogenomic treatment study of depression. Patients were characterized medically and demographically using VA health records and self-report. ResultsA clearly bimodal distribution was observed for platelet 5-HT levels with the lower mode associated with patients exposed to SRIs at baseline. Median transporter blockade bioeffects were similar across the various selective 5-HT reuptake inhibitors (SSRIs) and 5-HT/norepinephrine reuptake inhibitors (SNRIs). In a subset of patients apparently not exposed to an SRI, significant effects of population and sex were observed with group mean platelet 5-HT levels being 25 % greater (p < 0.001) in African-American (AA) individuals compared to European-Americans (EAs). The female group mean was 14 % (p < 0.001) greater than male group mean. An effect of age was observed (r = −0.11, p < 0.001) and no effect of season or month of sampling was seen. ConclusionsFurther research is warranted to understand the bases and clinical implications of the population and sex differences. The apparent similarity in bioeffect at the 5-HT transporter across SSRIs and when comparing SSRIs and SNRIs informs discussions about initiating, dose adjustment and switching of 5-HT reuptake inhibitors.

Modulation of platelet functions by European toad (Bufo Bufo) skin secretions components

Background: A growing number of reports indicate that amphibian skin secretions may have a remarkable medical importance; however, the effects of the components of some dermal secretions on blood platelets and hemostasis are inadequately recognized. Since our previous studies demonstrated that the general Bufo bufo skin secretions induced platelet aggregation in platelet-rich plasma, this work was designed to study the effects of the components of some fractions on platelet functions to comprehend its possible mechanism of action as platelet modulators. Methods: Chromatographic separation of B. bufo general skin secretions was carried out using size exclusion chromatography. Rabbit platelets were purified by column chromatography on Sepharose 4B. Various aspects of platelet function such as activation, aggregation, and adhesion were evaluated. Results: One fraction, out of 7, dose-dependently induced aggregation of isolated platelets and was used in further experiments. The studied fraction was shown to induce platelet adhesion onto fibrinogen-coated surface. Furthermore, the results demonstrated the effects of the fraction on some processes that involved in platelets activation: The fraction components facilitated (Ca2+) i mobilization and attenuated platelets Akt phosphorylation, but had no effect on platelet serotonin secretion. Membrane integrity was determined using lactate dehydrogenase (LDH) assay. No increased LDH release was recorded that means no platelet damage, which could lead to misinterpretation of the data, occurred. Conclusion: The results suggest that components of the B. bufo skin secretions may be a promising source of natural compounds which can modulate platelet functions.

Role of Alkaloid on Platelet Aggregation and Serotonin in Migraine

Role of Alkaloid on Platelet Aggregation and Serotonin in Migraine

Platelet, Plasma, Urinary Tryptophan-Serotonin-Kynurenine Axis Markers in Hyperacute Brain Ischemia Patients: A Prospective Study.

Background and Purpose: Ischemic stroke is one of the most common causes of morbidity and mortality and has numerous clinical mimics. Previous studies have suggested a potential role of the tryptophan-serotonin (5-HT)-kynurenine (TSK) axis in ischemic stroke. Studies assessing this axis in the hyperacute phase of ischemic stroke (<4.5 h) are lacking. This prospective study thus evaluates the TSK axis in transient ischemic attack (TIA) and hyperacute ischemic stroke (AIS) patients.Methods: This study included 28 patients (24 AIS and 4 TIA) and 29 controls. The blood and urine samples of patient were collected within 4.5 h of symptoms onset (day 0, D0), then at 24 h and 3 months. Control blood and urine samples were collected once (D0). The TSK axis markers measured were platelet serotonin transporter (SERT) and 5-HT2A receptor (5-HT2AR) densities and platelet, plasma, and urinary 5-HT, plasma and urinary 5-hydroxyindole acetic acid (5-HIAA), and plasma kynurenine and tryptophan (TRP) levels.Results: At D0, patients exhibited a lower (p = 10−5) platelet SERT density, higher (p < 10−6) platelet 5-HT2AR density, higher (p = 10−5) plasma kynurenine/tryptophan (K/T) ratio, and higher urinary 5-HT (p = 0.011) and 5-HIAA (p = 0.003) levels than controls.Conclusions: We observed, for the first time, a hyperacute dysregulation of the serotonergic axis, and hyperacute and long-lasting activation of the tryptophan-kynurenine pathway in brain ischemia.