Clinical and diagnostic significance of endothelial dysfunction and serotonin levels in children with hemolytic-uremic syndrome

Hemolytic-uremic syndrome is a serious problem in pediatrics and pediatric nephrology. Hemolytic-uremic syndrome is one of the leading causes of acute kidney injury with potential transformation into terminal chronic kidney disease. Currently, the endothelial dysfunction is strongly associated with changes in the serotonergic system in the pathogenesis of hemolytic-uremic syndrome. There are few studies that have revealed an increase in the blood plasma serotonin concentration in children with hemolytic-uremic syndrome, but its role in the pathogenesis of chronic kidney disease has been insufficiently studied. The progressive course of hemolytic-uremic syndrome, up to the terminal stage of renal failure, requires the search for markers of renal tissue damage as prognostically significant factors for the development of nephrosclerosis, which is of particular importance for optimizing the management of such children.

Effects of dietary leucine and tryptophan on serotonin metabolism and growth performance of growing pigs

An experiment was conducted to test the hypothesis that increased dietary Trp is needed in high-Leu diets for growing pigs to prevent a drop in plasma serotonin and hypothalamic serotonin concentrations and to maintain growth performance of animals. A total of 144 growing pigs (initial weight: 28.2 ± 1.9 kg) were assigned to 9 treatments in a randomized complete block design with 2 blocks, 2 pigs per pen, and 8 replicate pens per treatment. The 9 diets were formulated in a 3 × 3 factorial with 3 levels of dietary Leu (101, 200, or 299% standardized ileal digestible [SID] Leu:Lys), and 3 levels of dietary Trp (18, 23, or 28% SID Trp:Lys). A basal diet that met requirements for SID Leu and SID Trp was formulated and 8 additional diets were formulated by adding crystalline L-Leu and (or) L-Trp to the basal diet. Individual pig weights were recorded at the beginning of the experiment and at the conclusion of the 21-d experiment. On the last day of the experiment, one pig per pen was sacrificed, and blood and hypothalamus samples were collected to measure plasma urea N, plasma serotonin, and hypothalamic serotonin concentrations. Results indicated that increasing dietary Trp increased (P < 0.05) hypothalamic serotonin, whereas increases (P < 0.05) in average daily gain (ADG) and average daily feed intake (ADFI) were observed only in pigs fed diets containing excess Leu. Increasing dietary Leu reduced (P < 0.05) ADG, ADFI, and hypothalamic serotonin. However, the increase in ADG and ADFI caused by dietary Trp was greater if 299% SID Leu:Lys was provided than if 101% SID Leu:Lys was provided (interaction, P < 0.05). Plasma Leu concentration was positively affected by dietary Leu and negatively affected by dietary Trp, but the negative effect of Trp was greater if 299% SID Leu:Lys was provided than if 101% SID Leu:Lys was provided (interaction, P < 0.05). Plasma concentration of Trp was positively affected by increased dietary Trp and increased dietary Leu, but the increase in plasma concentration of Trp was greater if Leu level was at 101 % SID Leu:Lys ratio than at 299% SID Leu:Lys ratio (interaction, P < 0.05). In conclusion, increased dietary Leu reduced ADG, ADFI, and hypothalamic serotonin concentration, and influenced metabolism of several indispensable amino acids, but Trp supplementation partly overcame the negative effect of excess Leu. This demonstrates the importance of Trp in regulation of hypothalamic serotonin, and therefore, feed intake of pigs.

Low plasma serotonin linked to higher nigral iron in Parkinson’s disease

A growing body of evidence suggests nigral iron accumulation plays an important role in the pathophysiology of Parkinson’s disease (PD), contributing to dopaminergic neuron loss in the substantia nigra pars compacta (SNc). Converging evidence suggests this accumulation might be related to, or increased by, serotonergic dysfunction, a common, often early feature of the disease. We investigated whether lower plasma serotonin in PD is associated with higher nigral iron. We obtained plasma samples from 97 PD patients and 89 controls and MRI scans from a sub-cohort (62 PD, 70 controls). We measured serotonin concentrations using ultra-high performance liquid chromatography and regional iron content using MRI-based quantitative susceptibility mapping. PD patients had lower plasma serotonin (p < 0.0001) and higher nigral iron content (SNc: p < 0.001) overall. Exclusively in PD, lower plasma serotonin was correlated with higher nigral iron (SNc: r(58) = − 0.501, p < 0.001). This correlation was significant even in patients newly diagnosed (< 1 year) and stronger in the SNc than any other region examined. This study reveals an early, linear association between low serotonin and higher nigral iron in PD patients, which is absent in controls. This is consistent with a serotonin-iron relationship in the disease process, warranting further studies to determine its cause and directionality.

Effects of 16 Weeks of Taekwondo Training on the Cerebral Blood Flow Velocity, Circulating Neurotransmitters, and Subjective Well-Being of Obese Postmenopausal Women

We investigated the effects of Taekwondo training on the body composition, serum lipid profiles, plasma neurotransmitter levels, cerebral blood flow velocities, and subjective well-being of 24 obese postmenopausal women. The women were randomly assigned into the experimental (n = 12) and control (n = 12) groups. The experimental group underwent Taekwondo training five times per week for 16 weeks, while the control group did not. All participants underwent evaluation for the following parameters before and after the intervention: body composition; serum lipid profiles; plasma serotonin and dopamine levels; cerebral blood flow velocities; positive and negative affect schedule (PANAS) scores; satisfaction with life scale (SWLS) scores. After the intervention, it was observed that the weight, body mass index, body fat percentage, total cholesterol, low-density lipoprotein cholesterol, and PANAS-NA (negative affect in the PANAS questionnaire) scores were significantly decreased (p < 0.05)—while the plasma serotonin levels were significantly increased (p < 0.05)—in the experimental group. Conversely, there were no significant changes in the cerebral blood flow velocities (p > 0.05). Taekwondo training can be effective in not only reducing obesity, but also in increasing the circulating neurotransmitters and enhancing the subjective well-being of obese postmenopausal women.

Characterization of the spontaneous degenerative mitral valve disease in FVB mice

Background The development of new non-surgical treatments dedicated to mitral valve degeneration is limited by the absence of relevant spontaneous and rapidly progressing animal experimental models. Animals We characterized the spontaneous mitral valve degeneration in two inbred FVB mouse strains compared to C57BL/6J and investigated a contribution of the serotonergic system. Methods Males and females FVB/NJ and FVB/NRj were compared to the putative C57BL/6J control at 12, 16, 20 and 24 weeks of age. Body weight, systolic blood pressure, heart rate, urinary 5-hydroxyindoleacetic acid (5-HIAA), whole blood and plasma serotonin, tail bleeding time, blood cell count, plasma TGF-β1 and plasma natriuretic peptide concentrations were measured. Myocardium and mitral valves were characterized by histology. mRNA mitral expression of 5-HT2A and 5-HT2B receptors was measured in the anterior leaflet. Cardiac anatomy and function were assessed by echocardiography. Results Compared to C57BL/6J, FVB mice strains did not significantly differ regarding body weight increase, arterial blood pressure and heart rate. A progressive augmentation of plasma pro-ANP was observed in FVB mice. Nevertheless, no cardiac hypertrophy or left-ventricular fibrosis were observed. Accordingly, plasma TGF-β1 was not different among the three strains. Conversely, FVB mice demonstrated a high prevalence of fibromyxoid highly cellularized and enriched in glycosaminoglycans lesions, inducing major mitral leaflets thickening without increase in length. The increased thickness was correlated with urinary 5-HIAA and blood platelet count. Whole blood serotonin concentration was similar in the two strains but, in FVB, a reduction of plasma serotonin was observed together with an increase of the bleeding time. Finally, echocardiography identified left atrial and left ventricular remodeling associated with thickening of both mitral leaflets and mitral insufficient in 30% of FVB mice but no systolic protrusion of mitral leaflets towards the atrium. Conclusion The FVB mouse strain is highly prone to spontaneous mitral myxomatous degeneration. A contribution of the peripheral serotonergic system is suggested.

Assessment of Platelet and Plasma Serotonin in Canine Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease

Background: Pulmonary hypertension (PH) is a common complication of degenerative mitral valve disease (DMVD), the most common cardiovascular disease in dogs. Serotonin has been suspected to play a role in the pathogenesis of PH, so this study aimed to investigate the differences in platelet and plasma serotonin between normal, DMVD and DMVD with PH (DMVD+PH) dogs.Materials and Methods: Sixty-two small-breed dogs were enrolled to the study and divided into the normal (n = 22), DMVD (n = 20), and DMVD+PH (n = 20) groups. The platelet and plasma serotonin concentrations were measured by the competitive ELISA.Results: The Kruskal–Wallis revealed the difference among the four groups of normal (179.73 [102.37–352.24] ng/109 platelets), DMVD (325.99 [96.84–407.66] ng/109 platelets), DMVD with intermediate probability of PH (291.11 [106.69–400.84] ng/109 platelets) and DMVD with high probability of PH (35.82 [2.69–126.35] ng/109 platelets) (p = 0.014). The Dunn's post-hoc test showed a decrease in the platelet serotonin concentration of the DMVD dogs with high probability of PH compared to the DMVD group (p = 0.008). The plasma serotonin concentration was not different between normal, DMVD, and DMVD+PH dogs.Conclusion: In conclusion, a decrease in platelet serotonin concentration, which is associated with a degree of PH probability was found in DMVD dogs with PH. Further studies investigating roles of platelet serotonin in PH secondary to DMVD should be performed.

The Effects of Androstenone on the Plasma Serotonin, β-Endorphin, and Cortisol Concentrations in Thoroughbred Horses

Androstenone influences the changing behaviors of animals. Previous studies discovered that an androstenone receptor was expressed in horses and treatment with androstenone induced horses to be more compliant. As changes in the level of neuroendocrine factors result in animal behavioral changes, the objective of the study was to monitor the changes in the concentrations of 5-HT, β-endorphin, and cortisol in response to androstenone. Eight thoroughbred horses (five mares and three geldings) were treated with androstenone diluted in jojoba oil (10 µg/mL) and only oil for a control cross-overly. A handler applied the treatments to the horses′ nostril and rubbed for 5 s. Blood samples were collected before, 15, 30, and 60 min after each treatment. The concentrations of each neurotransmitter were analyzed by enzyme-linked immunosorbent assay. The concentrations of each neurotransmitter after the treatment were compared to its baseline concentration. The concentration of 5-HT of the androstenone-treated horses remained consistent throughout the experiment, while the concentration of the control group significantly decreased over time. The plasma concentration of β-endorphin in the androstenone-treated group also remained constant, whereas the concentration increased in the control group. Cortisol levels did not change in either the treated or untreated groups. An androstenone treatment triggers changes in the secretion of 5-HT and β-endorphin in horses.

The influence of whole body cryotherapy on plasma concentration of melatonin and serotonin in patients with osteoarthrosis of the lumbar spine

Background: ‪Osteoarthrosis (OA) is the most common disease affecting mankind. There are many physiotherapeutic methods of treating OA symptoms. One of them is whole body cryotherapy (WBCT). The aim of this study was to present the impact of WBCT combined with kinesiotherapy on functional efficiency and changes in plasma concentrations of serotonin and melatonin in patients with lumbar spine OA.. Material and methods: ‪60 patients underwent a series of WBCT combined with kinesiotherapy (group A). 60 patients underwent a series of kinesiotherapy alone (group B). Before and after the therapy patients were examined by Rolland Morris Disability Questionnaire (RMDQ), and blood samples were collected for laboratory assessment. Results: ‪Following therapy, the functional efficiency (RMDQ) improved by 33% in both study groups (p < 0.0001). After the therapy, both in the group of patients undergoing WBCT combined with exercises (group A, p = 0.032) and the cryotherapy alone (group B, p < 0.0001), the plasma melatonin concentration significantly increased. The rise of plasma serotonin concentrations was higher in group B as compared to group A, but in both study groups the increase in plasma serotonin was statistically significant (p < 0.0001).. Conclusions: ‪WBCT combined with therapeutic exercises as well as kinesiotherapy used alone resulted in an increase in melatonin and serotonin plasma levels and an improvement in functional efficiency in patients with lumbar spine OA.

Blood Plasma Serotonin and von Willebrand Factor as Biomarkers of Unstable Angina Progression Toward Myocardial Infarction

Aim: To investigate the serotonin and von Willebrand factor (vWF) concentrations among unstable angina (UA) patients without and with progression toward myocardial infarction (outcome) and to assess the utility of both as prognostic markers of UA complications. Materials and methods: In observational cohort study, we recruited 103 patients with ischemic heart disease (the median age 65.0 (59.0-69.0) years, 45 females (43.7%)). After full set of investigations including high sensitive Troponin I test and 28-day follow-up period, we defined three groups: Group 1 - stable angina patients (n=22) as control, Group 2 - UA patients without outcome (n=71), Group 3 - UA patients with outcome (n=10). We analyzed the blood plasma serotonin content by the ion-exchange chromatography with measurement of serotonin on fluorescence spectrophotometer. VWF concentration was determined by ELISA. We compared the concentrations of observed parameters among the groups with the Kruskal-Wallis test (with post-hoc Mann-Whitney test with Bonferroni-Holm correction). We assessed binary logistic models, receiver operating characteristic curves, calculated sensitivity (Se), specificity (Sp), and positive likelihood ratio (LR+) for each indicator. Results: We registered elevation in serotonin concentration and decline in vWF concentration in Group 3 in comparison with Group 2 (22.670 (20.687-24.927) μg/ml vs 11.980 (8.120-15.000) μg/ml, p< 0.001, and 0.117 (0.109-0.120) rel.units/ml vs 0.134 (0.127-0.143) rel.units/ml, p < 0.001) and Group 1 (12.340 (10.052-13.619) μg/ml, p < 0.001, and 0.137 (0.127-0.156) rel.units/ml, p < 0.001), respectively. No significant differences in serotonin and vWF concentrations between Group 1 and Group 2 were detected (p=0.81 and p=0.36, respectively). The probability of outcome increased significantly (by 60.7% and 59.7%, LR+ 19.0 [6.0, 60.0] and 18.0 [3.9, 80.0]) if serotonin concentration was above 21.575 μg/ml (Se=80.0%, Sp=95.8%, AUC=0.975) and vWF concentration was below 0.114 rel.units/ml (Se=50.0%, Sp=97.2%, AUC=0.973), respectively. Conclusions: Serotonin and vWF as biomarkers are demonstrated promising results for rule-in the patients with risk of short-term UA progression toward myocardial infarction.