Blood Serotonin Research Articles

The Coordinated Changes in Platelet Glycan Patterns with Blood Serotonin and Exosomes

The structures of glycans, specifically their terminal positions, play an important role as ligands for receptors in regulating the adhesion ability of platelets. Recent advances in our understanding of free/unbound serotonin (5-HT) in blood plasma at supraphysiological levels implicate it as one of the most profound influencers in remodeling the platelet’s surface N-glycans. Proteomic analysis of the membrane vesicles identified enzymes, specifically glycosyltransferases, only on the surface of the platelets isolated from the supraphysiological level of 5-HT-containing blood plasma. However, these enzymes can only be effective on the cell surface under certain biological conditions, such as the level of their substrates, temperature, and pH of the environment. We hypothesize that exosomes released from various cells coordinate the required criteria for the enzymatic reaction on the platelet surface. The elevated plasma 5-HT level also accelerates the release of exosomes from various cells, as reported. This review summarizes the findings from a wide range of literature and proposes mechanisms to coordinate the exosomes and plasma 5-HT in remodeling the structures of N-glycans to make platelets more prone to aggregation.

Humoral serotonin and neuropsychological status of patients with dizziness

Dizziness is often accompanied by affective disorders such as anxiety and depression, in the occurrence of which the role of the serotonergic system is discussed.Objective: to investigate the serotonin content in blood serum and neuropsychological status in patients with vestibular and non-vestibular dizziness.Material and methods. The study included 97 patients. Two observation groups were formed according to the type of dizziness complaints. The first group (n=47) comprised patients with vestibular (systemic) dizziness against a background of peripheral vestibulopathy, the second group (n=35) comprised patients with non-vestibular (non-systemic) dizziness with a diagnosis of probable persistent postural-perceptual dizziness (PPPD). The control group (n=15) consisted of patients without complaints of dizziness. Neurological and otoneurological status, psychoemotional parameters (level of anxiety and depression) and cognitive functions were analyzed, and the quantitative level of serotonin in blood serum was determined by enzyme immunoassay.Results. The study revealed a significant decrease in the serum serotonin levels in vestibular and non-vestibular dizziness; a lower serotonin level was found in non-vestibular dizziness (p<0.05). The presence of affective disorders did not correlate with a decrease in serotonin levels in vestibular dizziness against a background of peripheral vestibulopathy. It is assumed that a decrease in serotonin content plays a role in pathogenesis of vestibular dizziness on the background of peripheral part of vestibular system involvement.Conclusion. We demonstrated possibility of using the level of serotonin in peripheral blood as an objective laboratory marker of vestibular and non-vestibular dizziness in general clinical medical practice.

The effects of magnitude of calcium decline at the onset of lactation on serotonin dynamics and the serotonin-calcium axis

The onset of lactation is characterized by marked increases in calcium (Ca) metabolism. Recently emphasis was placed on understanding the profile and dynamics of blood Ca and serotonin in the peripartal cow in response to this change using a randomized 2x2 factorial design. The aims of our study were to determine i) how a prepartum dietary cation anion difference (DCAD) diet and the magnitude of Ca decline at the onset of lactation alter circulating blood serotonin and iCa concentrations dynamics in the periparturient cow, and ii) the relationship Ca versus serotonin during the peripartal period. Thirty-two multiparous Holstein cows were blocked by parity (2 vs > 2) to ensure equal parity number across the experiment, previous 305 d milk yield and expected parturition date and randomly allocated to either positive (+120 mEq/kg; +DCAD) or negative (-120 mEq/kg; -DCAD) DCAD diets from 251 d of gestation until parturition (n = 16/diet). Immediately after calving cows were continuously infused for 24 h with i) an intravenous solution of 10% dextrose or ii) calcium gluconate (CaGlc) to maintain blood ionized Ca concentrations at 1.2 mM (normocalcemia); forming the following 4 treatment groups: negative DCAD and CaGlc (NCa), negative DCAD and dextrose (NDex), positive DCAD and CaGlc (PCa), and positive DCAD and dextrose (PDex) (n = 8/treatment). Blood was sampled every 6 h from 102 h before parturition until 96 h post parturition. During the continuous infusion period (the 24 h immediately following parturition) cows were sampled every 30 min. Cows fed a -DCAD diet prepartum had greater circulating serotonin concentrations pre and postpartum. Time series analyses demonstrated that the pooled mean effect size (ES) of the relationship between ionized Ca and serotonin 36 h before parturition was significantly positive (ES = 0.164) prepartum. We also observed that the overall pooled mean ES of the relationship between prepartum blood pH 24 h prior and serotonin was significantly positive (ES = 0.111); however, for individual treatment groups, relationships were identified between blood pH and serotonin 18 and 6 h before only for the NDex group. Our data suggest that serotonin is an important factor in the regulation of Ca homeostasis during the prepartal period and that the mechanism may be integrated with blood pH.

The Impact of DAZZEON αSleep® Far-Infrared Blanket on Sleep, Blood Pressure, Vascular Health, Muscle Function, Inflammation, and Fatigue.

The application of far-infrared blankets has shown certain benefits in health promotion and therapy, such as improving blood circulation and alleviating muscle pain. However, the effects of such blankets on increasing deep sleep, reducing blood pressure, enhancing memory, dilating microvessels for blood flow, reducing chronic inflammation, and decreasing fatigue remain to be studied. We aim to investigate the effects of the DAZZEON αSleep® far-infrared blanket on these indicators. This study adopted a double-blind design, recruiting 24 male participants aged over 45 years, divided into two groups of 12 each: (A) a placebo group and (B) a DAZZEON αSleep® group. The participants used the blanket every night for two weeks, with sleep records taken using a wearable device and blood pressure, blood oxygen levels, arterial stiffness, and surface temperature measured before and after the intervention. Blood samples were collected for an analysis of inflammation and sleep-related blood indicators (serotonin and melatonin), and exercise tests were conducted to assess fatigue improvement. Compared with before the intervention, the blanket significantly increased changes in grip strength and reaction time. Additionally, it significantly increased blood serotonin, melatonin, and nitric oxide concentrations (p < 0.05), thus significantly increasing deep sleep and REM sleep durations (p < 0.05) and improving subjective sleep quality (p < 0.05). This study confirmed that using the DAZZEON αSleep® far-infrared blanket for 14 consecutive days helps to improve blood circulation, reduce vascular age and arterial stiffness, increase serotonin and melatonin levels, and improve sleep quality, as well as enhances muscle strength and reaction time.

Effects of weaning and inactivated Lactobacillus helveticus supplementation on dairy calf behavioral and physiological indicators of affective state

The objectives of this study were to determine if weaning would induce behavioral and physiological indicators of a negative affective state, and if supplementation of inactivated Lactobacillus helveticus (ILH) to dairy calves would reduce those indicators of negative affect during weaning. Male Holstein calves (n = 23) were enrolled in the study on d 1 of life. The calves were housed in individual pens in 1 of 4 rooms for the 42 d study. Calves began a stepdown weaning from 9 L/d of milk replacer (MR), at 150 g of MR powder/L, on d 35 and received 6 L/d on d 35 - 36, 3 L/d on d 37 - 38, and 0.4 L/d on d 39 - 42. The MR was divided between 3 meals/d until the last 0.4 L/d phase which was divided between 2 meals/d. Calves had ad libitum water access throughout the study and calf starter from d 28 onwards. Within room, calves were assigned to 1 of 2 treatments: 1) control (CON; n = 11) and 2) 5 g of ILH/d split over and mixed into the 0800 h and 2000 h milk feedings from d 3-42 (ILH; n = 12). Lying behavior was recorded using HOBO data loggers from d 21-41. On d 33, 37 and 41, infrared eye images were taken to determine maximum eye temperature (MET), saliva samples were collected to determine cortisol concentration, and play assessments were conducted to quantify play behavior. On d 34, 38, and 42, blood samples were collected to determine blood serotonin concentration, whereas on d 38 and 39, calves were tested with a cognitive task. A subset of calves (n = 5/treatment) were euthanized to collect gut and brain tissue samples for serotonin concentration on d 43. Weaning resulted in fewer (d 37-41, tendency: d 36), but longer (d 38-41, tendency: d 37), lying bouts and reduced play (d 41), although no changes in lying time, MET, saliva cortisol, nor blood serotonin were detected with initiation of weaning. Supplementation of ILH was associated with lower lying time throughout the study, and reduced play duration and higher salivary cortisol and MET during weaning. No differences in lying bouts, play count, blood and tissue (colon, ileum, prefrontal cortex and brain stem) serotonin concentration, and time to complete the cognitive task were detected between the treatments. Overall, weaning induced behavioral changes indicative of negative affective state, and some behavioral differences were observed with ILH supplementation both before and during weaning, with some physiological changes observed during weaning.

Hemostatic mechanism of Jianpi Yiqi Shexue decoction in treatment of immune thrombocytopenia.

To explore the early hemostatic mechanism of Jianpi Yiqi Shexue decoction (, JYSD) in treating immune thrombocytopathy (ITP), based on the functional homeostasis of brain-intestine axis and blood neurotransmitter METHODS: Non-drug treatment cases: Healthy volunteers were selected as normal control group and compared with patients with dysfunctional uterine bleeding, gastrointestinal tumors with bleeding and ITP, to detect the changes of blood 5-hydroxytryptamine (5-HT), β-endorphin (β-EP), vasoactive intestinal peptide (VIP) and compare the changes of blood neuro-transmitters in patients with different disease symptoms. Drug treatment cases: According to the randomized controlled multicenter clinical trial, 272 ITP patients were randomly divided into three groups: treatment group (JYSD) combined group (JYSD + Prednisone) control group (Prednisone). The changes of blood neuro-transmitter (5-HT, β-EP, VIP) before and after treatment were detected on the basis of peripheral blood platelet (PLT) and grade score. Non-drug treatment cases: compared with the normal control group, the 5-HT level was higher, and the VIP and β-EP levels were both lower in the ITP group (P < 0.001), and the 5-HT, VIP and β-EP levels in the Gastrointestinal tumors with bleeding group were also lower compared with the normal control group (P < 0.05, 0.001). Drug treatment cases: The PLT grading scores of the combination group and the control group after treatment were lower than that before treatment (P < 0.05, 0.001). The PLT grading score of the 3 groups were compared in pairs after treatment: the combination group was the lowest among the 3 groups, which was better than the treatment group, but no better than the control group (vs the treatment group, P = 0.005, vs the control group, P = 0.709). The statistical results of full analysis set (FAS) and per protocol set (PPS) were consistent. The bleeding symptom scores of the treatment and combination groups began to drop 7 d after treatment, and kept dropping 14 d after treatment until the end of the study (P < 0.05). On the other hand, the control group started to show favorable results 14 d after treatment (P < 0.05). The FAS and PPS analysis results were consistent. In the control group, the 5-HT level was higher and VIP level was lower after treatment, compared with those before treatment (P < 0.05, 0.001). The β-EP levels were both increased in the treatment and combination group after treatment, compared with those before treatment (P < 0.05). After treatment, the β-EP levels in the treatment and control groups were significantly lower compared with the combination groups (P < 0.05). After treatment, compared with the control group, the VIP levels in the treatment and combination groups were up-regulated, and the differences were statistically significant by rank sum test (P < 0.01), and by t-test (P = 0.0002, 0.0001). The prednisone tablet is better than the JYSD in increasing the level of PLT, while prednisone tablet combined with JYSD has more advantages in improving patients' peripheral blood PLT levels. However, in improving the bleeding time of ITP patients, the combination of the two drugs was significantly delayed compared with the single usage, showing the characteristics and advantages of traditional Chinese medicine. JYSD can regulate the neurotransmitter level of ITP patients through the function of the brain-gut axis, mobilize 5-HT in the blood of ITP patients to promote the contraction of blood vessels and smooth muscles, and activate the coagulation mechanism are the early hemostatic mechanisms of JYSD. Up-regulate the levels of β-EP and balancing VIP levels may be an important part of the immune mechanism of JYSD for regulating ITP patients.

Screening for carcinoid heart disease: Trends and future Perspectives

BackgroundScreening for carcinoid heart disease (CHD), has historically lacked consensus expert guidelines. In 2017, the North American Neuroendocrine Tumor Society (NANETS) released expert recommendations for CHD screening among NET patients to improve CHD detection. The objective of this study is to evaluate CHD screening trends and utility of screening guidelines over more than two decades at a single tertiary care center. Materials and methodsPatients with NETs referred for abdominal surgical evaluation at a single tertiary care center were included, 300 patients from 1999 to 2018 and 34 patients from 2021 to 2022. Lab values for the following NANETS-proposed criteria at any point during their treatments were recorded: NETs with liver metastasis, blood serotonin >5 times upper limit of normal (>1000 ng/mL), NT-ProBNP >260 pg/mL and clinical features suggestive of CHD. Results85 % (285/334) of patients included in this study met one or more expert-recommended CHD screening criteria. However, 40 % (132/285) of patients meeting one or more criteria received CHD screening via echocardiogram at some point following NET diagnosis. While rates of screening for patients increased from the first decade to the second decade (32 % vs 40.6 %), the rates were much higher after guideline publication (70 %, 24/34). Furthermore, patients meeting multiple screening criteria were more likely to have evidence of structural valve disease. ConclusionsResults of this study suggest that utilization of these four expert-recommended screening criteria have greatly increased rates of CHD screening via echocardiogram and could assist in improving early CHD detection, especially for patients meeting multiple criteria.

A Systematic Review on Autism and Hyperserotonemia: State-of-the-Art, Limitations, and Future Directions.

Hyperserotonemia is one of the most studied endophenotypes in autism spectrum disorder (ASD), but there are still no unequivocal results about its causes or biological and behavioral outcomes. This systematic review summarizes the studies investigating the relationship between blood serotonin (5-HT) levels and ASD, comparing diagnostic tools, analytical methods, and clinical outcomes. A literature search on peripheral 5-HT levels and ASD was conducted. In total, 1104 publications were screened, of which 113 entered the present systematic review. Of these, 59 articles reported hyperserotonemia in subjects with ASD, and 26 presented correlations between 5-HT levels and ASD-core clinical outcomes. The 5-HT levels are increased in about half, and correlations between hyperserotonemia and clinical outcomes are detected in a quarter of the studies. The present research highlights a large amount of heterogeneity in this field, ranging from the characterization of ASD and control groups to diagnostic and clinical assessments, from blood sampling procedures to analytical methods, allowing us to delineate critical topics for future studies.

The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial

Background and AimsSleep quality is a pivotal part of health and there is growing evidence on the association between gut microbiota composition and sleep quality. 5-Hydroxytryptophan (5-HTP) is known as a precursor of the sleep regulating neurotransmitter and hormone however, efficacy of 5-HTP supplementation for improving sleep quality in older adults is unclear. Hence, the aim of this study is to assess the impact of 5-HTP supplementation on sleep quality and gut microbiota composition in older adults. MethodsThis is a single-blinded, 12-week parallel randomized controlled. Thirty older adults (66 ± 3 years) in Singapore were randomly assigned to either consume or not consume 100 mg 5-HTP daily. Every 4 weeks, sleep quality was assessed via both subjective (Pittsburg Sleep Quality Index) and objective (actigraphy watch) measures. A global sleep score (GSS) was obtained from the PSQI, where a GSS>5 defines as poor sleeper while a GSS≤5 defines as good sleeper. Blood serotonin level, urine melatonin concentration, gut microbiota composition and stool short chain fatty acids (SCFA) content was assessed at week 0 and 12. This study was registered in clinicaltrials.gov as NCT04078724 (https://clinicaltrials.gov/ct2/show/NCT04078724) Results5-HTP supplementation showed an overall favorable effect on certain sleep quality components and an increase in serum serotonin concentration. In particular, at week 12, not good sleepers but poor sleepers with 5-HTP supplementation were able to significantly improve subjective GSS (ΔSL5-HTP: -2.80 ± 1.10 mins, p-value=0.005). In addition, they showed an increase in microbiota diversity (Simpson5-HTP vs. SimpsonControl: 0.037 ± 0.032 a.u. vs. -0.007 ± 0.022 a.u.; pinteraction: 0.013) and relative abundance of SCFA producing bacteria in the gut. Conclusions5-HTP supplementation can improve certain sleep quality components in older adults and this benefit was more prominently observed in poor sleepers. 5-HTP was also able to improve the gut microbiota composition in poor sleepers.

Effect of lairage time prior to slaughter on stress in pigs: a path analysis

BackgroundPre-slaughter process during transportation, handling, and lairage causes stress in pigs, affecting animal welfare and meat quality. Therefore, lairage factors are important for relieving stress. A total of 24 LYD (Landrace × Yorkshire × Duroc) barrows were used to investigate the effect of 6 and 20 h lairage time (LT) on cortisol, serotonin, and catecholamine in blood and physiological factors in muscle, and to verify the causal relationship between these factors.ResultsThe results revealed that cortisol was increased (0.064 ± 0.007 µg/ml), and epinephrine (0.020 ± 0.002 µg/ml) and norepinephrine (1.518 ± 0.071 µg/ml) were lower at a LT of 20 h than those at 6 h, and there was no significant effect on the muscle and carcass characteristic factors. In addition, cortisol and norepinephrine showed a negative correlation (r = -50,346, p = 0.0121), epinephrine and glycogen had a positive correlation (r = 0.4417, p = 0.0307), and serotonin and heat shock protein 70 (HSP70) were positively correlated (r = 0.4715, p = 0.0200). Path analysis indicated that the increase in LT had a direct effect on cortisol, epinephrine, and norepinephrine, and an indirect effect on muscle glycogen.ConclusionThis study confirmed the effect of the increase in LT from 6 to 20 h in the lairage room on the stress response of pigs. These findings support the legal requirements that advocate for shorter lairage times, in alignment with enhanced animal welfare standards.

Biomarkers of stress in children with asthenic syndrome associated with aluminum contamination in biological media and A/G polymorphism of the HTR2A (rs7997012) serotonin receptor gene

Introduction. Ambient air pollution with heavy metals, included aluminum, creates their elevated levels in children and leads to rather early decompensation of weak genetically heritable systems of the body including the nervous system.&#x0D; Materials and methods. We examined eighty six 4–7 years children with asthenic syndrome. Fifty two of them (the test group) lived and attended preschool facilities in a zone influenced by emissions from aluminum production (a dose created by a non-ferrous metallurgic plant is 5.65•10–5 mg/(kg•day)). The reference group was made of 34 children who lived on a conditionally clean territory and were exposed to airborne aluminum in a dose of 3.0•10–6 mg/(kg•day). Within this study, there were examined several children’s biological media including urine (aluminum), blood (serotonin and cortisol), and buccal epithelium (HTR2A rs7997012 gene). Differences were considered to be significant at a p&lt;0.05.&#x0D; Results. We established statistically significantly higher aluminum levels in urine (1.3 times higher) in the test group against the reference one (0.012±0.0001 and 0.0092±0.0012 respectively); authentically higher prevalence of the minor allele G of the HTR2A (rs7997012) serotonin receptor gene (authentically 1.6 times higher in the test group against the reference one). Both these factors create an elevated risk of asthenic syndrome, 1.86 times higher in the test group (OR=1.86; 95%CI (1.02–3.67)) together with lower serotonin levels (130.28±32.42 ng/ml and 183.35±34.57 ng/ml respectively) and higher cortisol levels (278.08±25.90 nmol/cm3 and 191.28±21.62 nmol/cm3 respectively).&#x0D; Limitations. The limitation is application of the identified stress biomarkers for diagnostics of nervous system disorders that manifest themselves in children through asthenic syndrome associated with exposure to aluminum.&#x0D; Conclusion. A/G replacement of the HTR2A (rs7997012) gene creates a 1.86 times higher risk of asthenic syndrome (OR=1.86; 95%CI (1.02–3.67)) for children with elevated aluminum levels in urine under inhalation exposure to it in a dose equal to 5.65•10–5 mg/kg•day). The disease would have such a peculiarity as longer recurrence and its biomarkers include an imbalance between indicators of a developing stress, cortisol, and serotonin.

An exploratory study on the association between serotonin and sleep breathing disorders

This exploratory observational study aimed to evaluate whether the blood levels of serotonin and enzymes involved in serotonin synthesis are associated with sleep breathing parameters. A total of 105 patients were included in this study, who were subjected to single-night polysomnography with simultaneous audio–video recordings. Peripheral blood samples were collected to estimate the serum levels of serotonin, tryptophan hydroxylase 1 (TPH1), and aromatic l-amino acid decarboxylase (AADC). Results showed a negative correlation between blood serotonin levels, and oxygen desaturation index (ODI) (p = 0.027), central apnea (p = 0.044) and obstructive apnea (OA) (p = 0.032) scores. Blood TPH1 levels were negatively correlated with average (p = 0.003) and minimal saturation (p = 0.035) and positively correlated with apnea–hypopnea index (p = 0.010), OA (p = 0.049), and hypopnea index (p = 0.007) scores. A tendency to sleep-disordered breathing seemed to co-occur with lower blood serotonin and higher TPH1 levels.Clinical Trial Registration :www.ClinicalTrials.gov, identifier NCT04214561

The effect of inflammation, SARS-CoV-2 infection, age and mental health on serotonin, and kynurenine and catecholamine pathway metabolites

BackgroundA high prevalence of mental disorders following COVID-19 has been described. It is therefore essential to elucidate underlying biological mechanisms linking SARS-CoV-2 infection and mental health. The kynurenine and catecholamine metabolic pathways are modulated by inflammation and can affect systemic levels of serotonin and dopamine. Their activity may hence link physical disorders with mental health. We investigated factors that affect kynurenine and catecholamine pathway activity in SARS-CoV-2 infection and recovery. MethodsThe cross-sectional SIMMUN (n = 165) and longitudinal INCOV cohort (n = 167, Su et al. 2022) were analyzed. Demographic and clinical characteristic, inflammatory markers, SARS-CoV-2 infection, symptoms of depression and anxiety (HADS), and mental stress (PSS-4) served as explanatory variables. Blood serotonin and markers of kynurenine (kynurenine/tryptophan ratio), and catecholamine pathway activity (dopamine 3-O-sulfate, phenylalanine/tyrosine ratio) were modeled by multi-parameter linear regression. ResultsIn the SIMMUN cohort, the inflammatory marker neopterin (β = 0.47 [95% CI: 0.34–0.61]), SARS-CoV-2-positivity (0.42 [0.16–0.68]), mental stress (0.18 [0.055–0.31]), and age (0.26 [0.12-0.39]) were positively associated with the kynurenine/tryptophan ratio. The phenylalanine/tyrosine ratio was lower in SARS-CoV-2-positive than uninfected participants (−0.38 [−0.68 to −0.08]). In the INCOV cohort, markers of inflammation were associated with lower serotonin (IL6: −0.22 [−0.38 to −0.053]) and dopamine 3-O-sulfate levels (interferon-gamma: −0.15 [−0.26 to −0.036]). Serotonin (0.76 [0.34–1.2]) and dopamine 3-O-sulfate levels (0.63 [0.28–0.99]) were higher during recovery than in acute SARS-CoV-2 infection. ConclusionSARS-CoV-2 infection, inflammation, age and mental stress are key independent predictors of kynurenine pathway activity, which may influence serotonin availability. The catecholamine pathway was also affected in SARS-CoV-2 infection. Altered activity of these pathways may contribute to impaired mental health following COVID-19.

Neuroprotective Effect of White Nelumbo nucifera Gaertn. Petal Tea in Rats Poisoned with Mancozeb.

Nelumbo nucifera Gaertn. (N. nucifera) tea is used as food and folk medicine to reduce toxicity in Southeast Asia. Mancozeb (Mz) is used for controlling fungi in agriculture and contains heavy metals. This study aimed to examine the effect of white N. nucifera petal tea on cognitive behavior, hippocampus histology, oxidative stress, and amino acid metabolism in rats poisoned with mancozeb. Seventy-two male Wistar rats were divided into nine groups (n = 8 in each). Y-maze spontaneous alternation test was used to assess cognitive behavior, and amino acid metabolism was investigated by nuclear magnetic resonance spectroscopy (1H-NMR) from blood. There was a significant increase in relative brain weight in the Mz co-administered with the highest dose (2.20 mg/kg bw) of white N. nucifera group. The levels of tryptophan, kynurenine, picolinic acid, and serotonin in blood showed a significant decrease in the Mz group and a significant increase in the Mz co-administered with low dose (0.55 mg/kg bw) of white N. nucifera group. However, there was no significant difference in cognitive behavior, hippocampus histology, oxidative stress, and corticosterone. This study demonstrated that a low dose of white N. nucifera petal tea has a neuroprotective effect against mancozeb.

Transcriptomic analysis of adipose, hepatic, and mammary gland tissues in lactating cows with elevated peripheral serotonin

Lactation is a highly energy intensive state, particularly for dairy cattle, which have been genetically selected for copious milk secretion. Blood serotonin content is greatly increased during lactation, at least in part because of increased production by the lactating mammary glands. We hypothesized that increasing peripheral serotonin in lactating cows, by infusion of the serotonin precursor 5-hydroxytryptophan (5-HTP), would alter gene expression in metabolically active tissues to support energy partitioning towards lactation.To test this hypothesis, multiparous midlactation Holstein cows (n=8/treatment) were intravenously infused with 5-HTP (1mg/kg bodyweight) or saline over two 10-day treatment periods. Treatments were infused via jugular catheters for 1h/day starting at 0700, on days 1–3 and 8–10, with no infusions on days 4–7. On day 10, 6h after the last infusion, biopsies of subcutaneous white adipose (WAT), hepatic, and mammary tissues were performed. Total RNAs were extracted from these tissues, and followed by whole transcriptome sequencing. Adapter-trimmed sequences were mapped to the cattle reference genome (ARS-UCD 1.2) using STAR. Differential gene expression analysis was done using DEseq2. A combinatory cutoff of mean read count≥5, fold-change≥2, and p-value&lt;0.01 was used to determine differentially expressed genes (DEG). Relative to saline-infused cows, 5-HTP cows had 152 genes downregulated and 38 upregulated in WAT, 117 genes downregulated and 141 upregulated in hepatic tissue, and 79 genes downregulated and 86 upregulated in mammary tissue.DEG from each tissue were then analyzed by QIAGEN Ingenuity Pathway Analysis (IPA) to identify enriched pathways and functions impacted by 5-HTP. In WAT, downregulated genes were enriched in triacylglycerol biosynthesis and upregulated genes were enriched in PPAR signaling, with upregulated gene enrichment in several apoptosis-related pathways as well. Decreased biological function categories in WAT included carbohydrate metabolism and lipid metabolism. In hepatic tissue, downregulated genes were enriched in superpathway of cholesterol biosynthesis while upregulated genes were enriched in cAMP-mediated signaling and citrulline biosynthesis. In mammary tissue, 5-HTP infusion exclusively upregulated genes involved in lipid metabolism, including functions in transport, export, flux and efflux of lipids and cholesterol. In conclusion, lactating cows with elevated peripheral serotonin developed a systemic response, altering the expression of genes in energy metabolic pathways, including reduced lipid synthesis and cell survival in WAT, reduced cholesterol synthesis in the liver, and increased lipid trafficking in the mammary tissue. Together, these changes may function to shift energy partitioning towards milk synthesis. This work was supported by USDA-NIFA Predoctoral Fellowship grant #2021-67034-35172 and research funding provided by Adisseo Bluestar Co. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Interleukin-33 facilitates liver regeneration through serotonin-involved gut-liver axis.

Insufficient liver regeneration causes post-hepatectomy liver failure and small-for-size syndrome. Identifying therapeutic targets to enhance hepatic regenerative capacity remains urgent. Recently, increased IL-33 was observed in patients undergoing liver resection and in mice after partial hepatectomy (PHx). The present study aims to investigate the role of IL-33 in liver regeneration after PHx and to elucidate its underlying mechanisms. We performed PHx in IL-33 -/- , suppression of tumorigenicity 2 (ST2) -/- , and wild-type control mice, and found deficiency of IL-33 or its receptor ST2 delayed liver regeneration. The insufficient liver regeneration could be normalized in IL-33 -/- but not ST2 -/- mice by recombinant murine IL-33 administration. Furthermore, we observed an increased level of serotonin in portal blood from wild-type mice, but not IL-33 -/- or ST2 -/- mice, after PHx. ST2 deficiency specifically in enterochromaffin cells recapitulated the phenotype of delayed liver regeneration observed in ST2 -/- mice. Moreover, the impeded liver regeneration in IL-33 -/- and ST2 -/- mice was restored to normal levels by the treatment with (±)-2,5-dimethoxy-4-iodoamphetamine, which is an agonist of the 5-hydroxytrytamine receptor (HTR)2A. Notably, in vitro experiments demonstrated that serotonin/HTR2A-induced hepatocyte proliferation is dependent on p70S6K activation. Our study identified that IL-33 is pro-regenerative in a noninjurious model of liver resection. The underlying mechanism involved IL-33/ST2-induced increase of serotonin release from enterochromaffin cells to portal blood and subsequent HTR2A/p70S6K activation in hepatocytes by serotonin. The findings implicate the potential of targeting the IL-33/ST2/serotonin pathway to reduce the risk of post-hepatectomy liver failure and small-for-size syndrome.

Efficiacy of Pharmacotherapy in Patients with Hypothimic Mental Disorders Suffered from Covid-19 Infection

IntroductionIn organic mental disorders in people who have undergone COVID-19, it has been established that the complex use of periciazine in combination with paroxetine, diazepam, 3-hydroxypyridine succinate and hyperbaric oxygenation is superior in effectiveness to traditional therapy with an antipsychotic drug, antidepressant and anxiolytic. The inclusion of 3-hydroxypyridine succinate, hyperbaric oxygenation in the complex therapy of this pathology corrects the concentrations of adrenaline, norepinephrine, dopamine, serotonin in the peripheral blood of patients, eliminates hormonal status disorders and humoral immune responses.ObjectivesThe aim of the work was to optimize approaches to the treatment of hypothymic disorders in organic mental illness, to substantiate the complex use of periciazine in combination with paroxetine, diazepam, 3-hydroxypyridine succinate and hyperbaric oxygenation in patients who underwent COVID-19.MethodsThe object of the clinical study were patients with organic mental disorders who underwent COVID-19. To assess the condition, laboratory research methods were selected taking into account the etio- and pathogenesis of diseases: determining the level of catecholamines, some indicators of humoral immune responses, and the hormonal profile.ResultsTable 2.3 - Nosological structure of patients included in the studyNosological formAssociated hypothymic disorder Number of patientsGender Average age (years)MalesFemalesOrganic mental disorderOrganic anxiety disorder F06.42115628,7±6,3Depressive Episode F3322129Organic mental disorder associated with COVID-19Organic anxiety disorder F06.418153Depressive Episode F331610643,7±7,4ConclusionsIn patients with organic mental disorders, occurring with hypothymic symptoms, compared with healthy donors, there is a complex of disorders in plasma concentrations of catecholamines. Traditional and, to a greater extent, combination therapy increase the levels of serotonin, dopamine, norepinephrine, both in the group of patients who did not have COVID-19, and in those who underwent a new coronovirus infection.In patients with organic mental disorders, occurring with hypothymic symptoms, compared with healthy donors, there is a complex of disorders in plasma concentrations of catecholamines. Traditional and, to a greater extent, combination therapy increase the levels of serotonin, dopamine, norepinephrine, both in the group of patients who did not have COVID-19, and in those who underwent a new coronovirus infection.Complex therapy with periciazine, paroxetine, diazepam in combination with 3-hydroxypyridine succinate and HBO for organic mental disorders causes a more complete reduction of hypothymic disorders both in the group of patients who did not have COVID-19, and in those who underwent a new coronovirus infection.Disclosure of InterestNone Declared

Effectiveness of Motivational Counseling for Lifestyle Modification in Obese Patients Using a Patient-centered Approach

Obesity is a predictor of a significant number of non-communicable diseases. Reduction of body weight by 5–10 % in 6 months, has a positive effect on the prognosis of life and is one of the goals of treatment. To achieve such goals, there is a need for a patient-oriented approach, where the degree of individualization corresponds to the personal risks and needs of the patient with his involvement in the process of choosing a treatment strategy and forming new flexible life habits through the use of motivational counseling. The objective: is to determine the effectiveness of motivational counseling for lifestyle modification in obese patients of prime working age using a patient-oriented approach. Materials and methods. 37 patients with obesity I (27 people) and II (10 people) degree, aged 38.03±1.27 years (20 women and 17 men) were examined. Patients were given motivational counseling according to the «5 As» system, the patient-oriented approach included recommendations regarding the regime and caloric content of food, physical activity (monitoring with a pedometer), compliance with sleep hygiene, correction of psycho-emotional disorders. Clinical laboratory examination in dynamics after 1 month, 3 months and 6 months included measurements of BMI, waist and hip circumference, body surface area, waist/hip ratio, conicity index, body shape index, abdominal volume index, blood pressure, levels of blood glucose, insulin, HOMA index, cholesterol, lipidogram indicators, serotonin and leptin. In addition, surveys were conducted using the HADS hospital anxiety and depression scale, Beck’s scale, Hamilton scale, Dutch Eating Behavior Questionnaire, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Questionnaire, SF-36, The International Physical Activity Questionnaire, The Finnish Diabetes Risk Score. Statistical analysis was performed using IBM SPSS Statistics, Statistica 12, descriptive statistics Excel 2010. Results. During 6 months of observation, patients lost more than 5 % of their body weight (p&lt;0.05), which was accompanied by a significant decrease in BMI (p&lt;0.01) and an increase in the level of physical activity (p&lt;0.001). The levels of lipid and carbohydrate metabolism exceeded the recommended values and had a positive tendency to decrease during treatment (p&gt;0.05). Assessments of the manifestations of anxiety and depression according to the HADS depression and Hamilton scales, eating disorders, serotonin and leptin levels, quality of sleep, quality of life of patients improved. The prediction of the risk of developing diabetes had significant positive dynamics (p&lt;0.05). Conclusions. The obtained results make prove that the application of of motivational counseling according to the step-bystep system «5 As» with a patient-oriented approach in patients of working age with obesity is an effective method, which is confirmed by reliable positive results and allows to reduce body weight by more than 5 % in 6 months, reduce levels of metabolic disorders, blood pressure, increase physical activity, reduce the manifestations of depression and anxiety, eating disorders, improve the quality of sleep and life of patients, improve the prognosis and reduce the risk of non-infectious diseases. If it is necessary to achieve stricter targets of indicators in obese patients and/or in a shorter time, it is necessary to carry out a further search for effective measures and consider the additional use of pharmaceutical products in prevention.

Симптомы тревоги и депрессии у больных с доброкачественным пароксизмальным позиционным головокружением

The article presents the results of assessing the psychoemotional status and the content of serotonin in peripheral blood in patients with the most common cause of systemic peripheral vertigo–benign paroxysmal positional vertigo (BPPV). 35 patients with otolithiasis accompanied by BPPV were examined. The control group of the study consisted of 15 healthy individuals. The assessment of the psychoemotional status and the level of quality of life of patients was carried out using specialized scales and questionnaires: the Hospital Anxiety and Depression Scale (HADS), the CES-D Questionnaire Scale (depression), the Spielberger–Hanin test (situational and personal anxiety), a questionnaire to identify signs of autonomic changes (Vane A. M., 1998), Vestibular Rehabilitation Benefit Questionnaire (VRBQ). Quantitative determination of serotonin (ng/mL) in peripheral blood serum was carried out by enzyme immunoassay. Statistical data processing was carried out using the program Statistica 10.0 (USA). In the conducted study, clinically significant signs of anxiety and depression according to the HADS and CES-D scales were not detected in patients with BPPV, a moderate level of reactive and personal anxiety was observed according to the Spielberger–Hanin test. There was a significant decrease in the quality of life (48.6%). A significant decrease in the level of peripheral blood serotonin was revealed in BPPV, a statistically significant correlation with the indicator of personal anxiety of this group of patients was obtained. Features of personal and reactive anxiety (as a background state) in patients with BPPV should be considered as a risk of developing functional dizziness. It is likely that a decrease in serotonin in the blood serum may contribute to the pathogenetic mechanisms of vertigo, considering the diverse connections of the serotonergic and vestibular functional systems. The results obtained require further research.

Генетические факторы и течение синдрома раздраженного кишечника: ассоциации и взаимосвязи

Aim: to evaluate the effect of the interaction of genetic and epigenetic factors on the formation and persistence of signs concerning irritable bowel syndrome (IBS). Patients and Methods: the study included 263 patients with IBS (189 female, 74 male, mean age — 29 [25; 35] years), including: IBS with diarrhea (n=84), IBS with constipation (n=92), mixed IBS (n=87); mild (n=110), moderate (n=99), severe (n=54) course. The control group consisted of 40 subjects comparable by gender and age. In each group, the polymorphism prevalence of candidate genes associated with IBS (COMT, DRD2, SLC6A4, LCT, FTO, TLR9), nutritional characteristics, the level of anxiety and depression, including specific gastrointestinal anxiety, life quality, cortisol content in saliva, blood serotonin, dopamine blood level, fecal zonulin. Results: Val/Val genotype of the COMT gene, characterized by high enzyme activity, was more common among patients with IBS with diarrhea and mixed IBS (χ2=55.75, p&lt;0.001), in severe course (χ2=32.66, p&lt;0.001) and was associated with diarrhea (χ2=53.39, p&lt;0.001), anxiety (χ2=20.01, p&lt;0.001); Met/Met genotype was associated with constipation (χ2=16.09, p&lt;0.001), abdominal pain (χ2=11.04, p=0.004) and depression (χ2=13.12, p=0.001). T/T genotype of the DRD2 gene, leading to a decrease in the density of dopamine D2 receptors, was more commonly found in patients with IBS with constipation (χ2=13.05, p=0.042) and severe course (χ2=30.37, p&lt;0.001), and was associated with abdominal pain (χ2=42.84, p&lt;0.001), episodes of overeating (χ2=29.05, p&lt;0.001), sugar cravings (χ2=16.82, p=0.002) and depression (χ2=39.63, p&lt;0.001). S/S genotype of the SLC6A4 gene, leading to a decrease in serotonin reuptake, was more common in patients with IBS with diarrhea (χ2=28.77, p&lt;0.001), and was associated with abdominal pain (χ2=9.15, p&lt;0.001), diarrhea (χ2=39.98, p&lt;0.001) and anxiety (χ2=7.87, p=0.02), genotype L/L — with constipation (χ2=12.4, p=0.002). A/A genotype of the FTO gene was associated with overweight (χ2=41.33, p&lt;0.001), episodes of overeating (χ2=31.49, p&lt;0.001), increased consumption of added sugar (χ2=9.25, p=0.010), and cravings for sweet (χ2=26.19, p=0.001), farinaceous and confectionery products (χ2=7.85, p=0.019). CC genotype of the TLR9 gene, leading to excessive activation of TLR9, was more commonly detected in individuals with a history of acute intestinal infection (χ2=8.45, p=0.038). Conclusion: the identified associations suggest the impact of genetic and environmental factors on the severity and nature of the IBS course. KEYWORDS: irritable bowel syndrome, genetic factors, epigenetic factors, catechol-O-methyltransferase, dopamine D2 receptors, serotonin reuptake transporter, fat mass and obesity-associated gene, LCT gene, toll-like receptors. FOR CITATION: Gaus O.V., Livzan M.A. Genetic factors and the course of irritable bowel syndrome: associations and interactions. Russian Medical Inquiry. 2023;7(5):237–248 (in Russ.). DOI: 10.32364/2587-6821-2023-7-5-1.