Plasma Serotonin Levels Research Articles

Plasma Serotonin and Cardiovascular Outcomes in Chronic Kidney Disease.

Background Platelet-poor plasma serotonin levels are associated with adverse cardiovascular outcomes. Although plasma serotonin levels increase in chronic kidney disease, the cardiovascular implications remain unknown. Methods and Results In 1114 participants from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we evaluated the association between plasma serotonin, categorized as undetectable, intermediate, and high (≥20 ng/mL) levels, and cross-sectional findings on echocardiography, including left ventricular hypertrophy, left ventricular ejection fraction, and pulmonary hypertension. We also analyzed whether serotonin was associated with time-to-event cardiovascular outcomes, including heart failure hospitalization and atherosclerotic cardiovascular disease (ASCVD) events, in addition to mortality. Because selective serotonin reuptake inhibitors decrease plasma serotonin levels, we specifically evaluated the influence of selective serotonin reuptake inhibitor use in the relationship between serotonin and outcomes. Plasma serotonin level inversely correlated with estimated glomerular filtration rate and directly correlated with blood pressure. High plasma serotonin was associated with left ventricular hypertrophy (adjusted odds ratio, 2.74 [95% CI, 1.11-7.41]). In contrast, undetectable plasma serotonin level was associated with the highest risk of heart failure (adjusted hazard ratio [HR], 2.26 [95% CI, 1.40-3.66]) and ASCVD events (adjusted HR, 1.96 [95% CI, 1.15-3.32]). Conclusions In a large chronic kidney disease cohort, plasma serotonin levels correlated with blood pressure, and elevated serotonin levels were associated with left ventricular hypertrophy. In contrast, undetectable plasma serotonin was associated with the highest risk of heart failure and ASCVD events.

Pulmonary ILC2-derived serotonin mediates RSV-evoked airway hyperreactivity in mice

Abstract Respiratory syncytial virus (RSV) infection is epidemiologically linked to asthma. During RSV infection, lung epithelial cell-released IL-33 is elevated and promotes group 2 innate lymphoid cells (ILC2s) activation, leading to type 2 cytokines production and asthma development. Serotonin is a neurotransmitter involved in numerous biological functions in the central nervous system as well as peripheral tissues. Previous studies have found elevated serotonin levels in plasma and bronchoalveolar lavage fluid (BALF) from asthma patients, implying that serotonin may involve in the pathogenesis of asthma. Therefore, we aimed to elucidate the role of ILC2-released serotonin in the regulation of RSV-induced airway hyperreactivity (AHR). To investigate whether ILC2 would secrete serotonin upon activation, pulmonary ILC2s were sorted from C57BL/6 mice and then treated with IL-33 in vitro, and we found an increase in the production of serotonin from IL-33-activated ILC2s. Furthermore, elevated BALF serotonin levels were also found in RSV-infected mice. Moreover, we clarified that ILC2 as a major source of serotonin during RSV infection. Next, to determine the role of serotonin in RSV-evoked AHR, we found that the treatment of Clozapine (serotonin receptor inhibitor) significantly attenuated AHR and decreased IL-13 expression. Meanwhile, we demonstrated that the administration of exogenous serotonin exacerbated RSV-caused AHR. Furthermore, serotonin enhanced IL-5 and IL-13 production from IL-33-activated ILC2 in vitro. Taken together, our results indicated that pulmonary ILC2-derived serotonin contributes to RSV-evoked AHR and exacerbates type 2 cytokines through a positive regulation of ILC2 function.

The modulation of Plasma Levels of Dopamine, Serotonin, and Brain-derived neurotrophic factor in response to variation in iron availability.

In the context of iron deficiency anemia, central dopamine, serotonin, and brain-derived neurotrophic factor (BDNF) are intensively investigated. However, peripheral isoforms are poorly investigated. This study aimed to investigate the modulation of plasma levels of dopamine, serotonin, and BDNF among children with iron deficiency anemia. A total of seventy-three iron-deficient (n=38) and iron-sufficient (n=35) children were included in the study. Twenty-nine subjects were showing clinical presentations and were diagnosed with iron deficiency anemia and forty-four were asymptomatic normal children. Plasma levels of dopamine, serotonin, and brain-derived neurotrophic factor were determined by enzyme-linked immunosorbent assay. As compared to corresponding levels among control subjects, Anemic subjects were having significantly higher plasma dopamine and lower plasma brain-derived neurotrophic factor levels. A significant linear and monotonic association of plasma dopamine and brain-derived neurotrophic factor with hemoglobin concentration (r=-0.520, P < 0.001 and ρ = 0.411, P = 0.001), respectively. Furthermore, there were significantly higher plasma serotonin levels among iron-deficient subjects with a significant inverse linear association with serum ferritin levels (r = -0.337, P = 0.005). Iron deficiency anemia is associated with the modulation of peripheral dopamine, serotonin, and brain-derived neurotrophic factor. Upregulation of dopamine and downregulation of brain-derived neurotrophic factor are correlated to the anemic status. The upregulation of plasma serotonin levels is iron-dependent and, probably, is attributed to the impairment of its metabolic fate. Further investigation is required to explore the pathophysiological and clinical association of these peripheral biomolecules in the context of iron deficiency anemia. (www.actabiomedica.it).

Effects of Preoperative Acupuncture on Prevention of Nausea and Vomiting and Plasma Serotonin Values in the Hysterectomy Postoperative Period: a Randomized Clinical Trial.

Nausea and vomiting are frequent complications of anesthesia in the postoperative period. Acupuncture at the pericardium point 6 (PC6) is known to be effective in preventing postoperative nausea and vomiting (PONV). The objective of the present study is to investigate the effects of acupuncture performed at the PC6 point in the prevention of PONV in women undergoing elective open hysterectomy under general inhalational anesthesia and to assess its association with plasma serotonin levels. 97 patients undergoing elective open hysterectomy were randomly divided into two groups: acupuncture group (bilateral acupuncture at PC6, n = 49), and a control group (no acupuncture, n = 48). All patients prophylactically received ondansetron and dexamethasone and, as rescue medication, metoclopramide in case of occurrence of PONV. The primary outcome evaluated was occurrence of nausea and vomiting within 24 hours after surgery. Serotonin plasma levels were measured before and after acupuncture prior to anesthesia induction. For the control group, the repeat measurement was performed 30 minutes after admission to the preoperative unit. Acupuncture at PC6 significantly reduced the incidence of nausea (29.2% vs. 6.1%; p > 0.003), and the need of rescue medication (metoclopramide) (33.3% vs. 10.2%; p > 0.006), but not vomiting (4.2 vs. 4.1; p > 0.98). The plasma serotonin levels between control and acupuncture groups did not differ. This study shows that acupuncture at PC6 resulted in a lower incidence of postoperative nausea in patients undergoing hysterectomy.

Aggression Assessment and Plasma Serotonin Level amongst Pakistani Youngsters

Background: Aggressive behavior is a multifaceted construct involving various physiological modulators and genetic factors with a variable frequency in different populations. Of multiple genetic factors, serotonin is known to have profound role with disagreement exists in relation to its expressional alignment with the intensity of aggression. The existing study is designed to develop alignment of the psychological scale of aggression with the plasma serotonin levels. Methodology: Buss Perry Aggression Questionnaires (BP-AQs) were distributed among male and female students of different universities of Karachi. Among those, 2000 properly filled questionnaires were selected to be scrutinized and scored which led to selection of 80 students each of score lower than 60 (least aggressive individuals) or higher than 100 (most aggressive individuals). Plasma serotonin levels of the 160 individuals were then measured by ELISA. Results: Cumulatively, males tend to have higher BP-AQ score than females (79.14+16.22 vs. 75.28+16.97) and also in physical aggression (23.81+6.44 vs. 21.05+6.17) statistically significant difference of p=0.0011 and p&lt;0.0001, respectively. All scores of different forms of aggression were found positively correlated with each other and with strong statistical significance. Level of serotonin was found significantly higher (p=0.0004) in females (244ng/ml) compared to males (70.39ng/ml). Plasma serotonin levels were negatively correlated with BP-AQ scores especially in females (p=0.0222) and in whole of the assessed subjects (p=0.0069). Practical implication: In order to facilitate a better understanding of aggressive behaviour, this study helps to align a physiological biomarker with psychological tools. Additionally, serotonin can be used as a biomarker to comprehend the physiological underpinnings of aggression, and future studies can be planned that use serotonin or its receptors in relation to aggressive behaviour. And it will positively impact the mental health of any society. Conclusion: The findings in total suggest male holds more aggressive behavior especially physical aggression compared to females. Additionally, the aggression in female is more profoundly associated with the low plasma serotonin level. Keywords: Aggression, Behavior, Hostility, Adolescents, Neurotransmitters, Serotonin,

Gastrointestinal tract and neuroendocrine system responses of young turkeys to the early administration of antibiotics or feeding a diet containing a coccidiostat

This study investigated the effects of early and short-term administration of an antibiotic or feeding a diet containing a coccidiostat on gastrointestinal function and the blood levels of selected hormones in young turkeys. A total of 1540 Hybrid Converter turkeys were allocated to 4 groups on the day of hatch. Each group consisted of 7 pens with 55 birds per pen. Group ENR was treated with enrofloxacin for the first 5 d of life, group DOX received doxycycline for 5 d and group MON was administered monensin for 84 d. CON birds served as a control group without any antibiotic treatment or MON administration. An analysis of the activity of bacterial enzymes revealed that the cecal microbiota of turkeys were less sensitive to MON than to the other 2 antibiotics. Turkeys subjected to ENR and DOX treatments were characterized by lower (P < 0.05) extracellular activity of cecal bacterial β-glucosidase, compared with groups CON and MON. The extracellular activity of cecal bacterial α-galactosidase and β-galactosidase decreased significantly in response to the experimental treatment with DOX (P < 0.05 vs. CON). Turkeys treated with ENR had higher total activity of bacterial β-galactosidase than those administered DOX or MON. Despite the differences in the enzymatic activity of microbiota, the use of antibiotics did not affect the concentrations of total short-chain fatty acids or ammonia in the cecal digesta of turkeys. A diet containing MON and the early administration of ENR or DOX induced an increase in blood noradrenaline levels (P = 0.004) in 56-day-old turkeys. Early DOX use increased plasma cortisol concentrations (P < 0.001) and decreased plasma serotonin levels (P = 0.006) in 56-day-old turkeys. Over the entire experiment (up to 12 wk of age), the use of MON improved the BW gain of turkeys (P = 0.055) and feed conversion (P = 0.016), compared with the DOX treatment.

Antidepressive-like Behavior-Related Metabolomic Signatures of Sigma-1 Receptor Knockout Mice

Sigma-1 receptor (Sig1R) has been proposed as a therapeutic target for neurological, neurodegenerative, and psychiatric disorders, including depression and anxiety. Identifying metabolites that are affected by Sig1R absence and cross-referencing them with specific mood-related behaviors would be helpful for the development of new therapies for Sig1R-associated disorders. Here, we examined metabolic profiles in the blood and brains of male CD-1 background Sig1R knockout (KO) mice in adulthood and old age and correlated them with the assessment of depression- and anxiety-related behaviors. The most pronounced changes in the metabolic profile were observed in the plasma of adult Sig1R KO mice. In adult mice, the absence of Sig1R significantly influenced the amino acid, sphingolipid (sphingomyelin and ceramide (18:1)), and serotonin metabolic pathways. There were higher serotonin levels in plasma and brain tissue and higher histamine levels in the plasma of Sig1R KO mice than in their age-matched wild-type counterparts. This increase correlated with the reduced behavioral despair in the tail suspension test and lack of anhedonia in the sucrose preference test. Overall, these results suggest that Sig1R regulates behavior by altering serotonergic and histaminergic systems and the sphingolipid metabolic pathway.

Advantages of the combined use of dexmedetomidine and magnesium sulphate in alcohol withdrawal delirium

Annotation. The search for effective sedation schedule in management of alcohol withdrawal delirium, which would ensure both an adequate sedation level and sufficient safety profile, is an urgent problem of modern anesthesiology and intensive care medicine. In this respect, the aim of our study is to research the use of dexmedetomidine combined with magnesium preparations, which seems to be promising. The study was conducted on 80 patients with alcoholic delirium randomized into 4 groups, in which the following parameters were evaluated: delirium duration, plasma magnesium, hemodynamics parameters, presence of respiratory disorders, as well as the levels of urea, creatinine, transaminase, cortisol and serotonin in plasma. The control group patients underwent standard sedation therapy. In experimental group 1, standard sedation with benzodiazepines was supplemented magnesium sulfate. In group 2, we maintained infusion of dexmedetomidine. In group 3, we combined intravenous magnesium sulfas with dexmedetomidine infusion. Statistical processing was performed using: Mann-Whitney U-test, Wilcoxon T-test, and Kruskal-Wallace H-test. Duration of delirium proved to be significantly shorter in all study groups as compared to the controls, p &lt;0.05. The best sedation therapy results were recorded in group 3, p &lt;0.05. On the first day of treatment, all patients were found to have elevated MAP and heart rate, while significant improvement in hemodynamic parameters was observed on the third day, p &lt;0.05. Cases of hypotension were detected in groups 1 and 2. On the third day of treatment, the patients of groups 2 and 3 showed significant improvement in plasma levels of cortisol and serotonin as compared to the controls, p&lt;0.05, while serotonin level was higher in experimental group 3 as compared to the control patients, p&lt;0.05. The use of combination of magnesium with dexmedetomidine infusion proved to be beneficial and effective in treatment of patients with alcohol withdrawal delirium improving the quality of patients’ care and shortening delirium duration.

Integrated fecal microbiome–metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome

ABSTRACT To gain insight into the complex microbiome-gut-brain axis in irritable bowel syndrome (IBS), several modalities of biological and clinical data must be combined. We aimed to identify profiles of fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. Fecal metabolites were measured using proton nuclear magnetic resonance (1H-NMR) spectroscopy and gut microbiome using shotgun metagenomic sequencing (MGS) in a combined dataset of 142 IBS patients and 120 healthy controls (HCs) with extensive clinical, biological and phenotype information. Data were analyzed using support vector classification and regression and kernel t-SNE. Microbiome and metabolome profiles could distinguish IBS and HC with an area-under-the-receiver-operator-curve of 77.3% and 79.5%, respectively, but this could be improved by combining microbiota and metabolites to 83.6%. No significant differences in predictive ability of the microbiome–metabolome data were observed between the three classical, stool pattern-based, IBS subtypes. However, unsupervised clustering showed distinct subsets of IBS patients based on fecal microbiome–metabolome data. These clusters could be related plasma levels of serotonin and its metabolite 5-hydroxyindoleacetate, effects of psychological stress on gastrointestinal (GI) symptoms, onset of IBS after stressful events, medical history of previous abdominal surgery, dietary caloric intake and IBS symptom duration. Furthermore, pathways in metabolic reaction networks were integrated with microbiota data, that reflect the host-microbiome interactions in IBS. The identified microbiome–metabolome signatures for IBS, associated with altered serotonin metabolism and unfavorable stress response related to GI symptoms, support the microbiota-gut-brain link in the pathogenesis of IBS.

Antidepressant-like effects of aqueous extracts of miswak (Salvadora persica) and date palm (Phoenix dactylifera) on depression-like behaviors using CUMS model in male rats.

This study aimed to evaluate the antidepressant-like effects of aqueous extracts of miswak (Salvadora persica) and date palm (Phoenix dactylifera) and their combination on depression-like behaviors using a chronic unpredictable mild stress (CUMS) rat model of depression and to investigate the underlying possible mechanisms. Results showed that CUMS induced depression-like behaviors and anxiety in male rats, as determined by behavioral tests (FST, EPM, and OFT). CUMS significantly increased the levels of plasma malondialdehyde (MDA), cortisol, and pro-inflammatory cytokines (TNF-α and IL-6), in addition to enhancing acetylcholinesterase (ACHE) activity while plasma total antioxidant capacity and serotonin level were reduced. In the prefrontal cortex, CUMS decreased the expression of CREB and BDNF mRNA. However, aqueous extracts of miswak and date palm and their combination effectively ameliorated depressive-like behaviors, body weight loss, and oxidative stress induced by CUMS and restored serotonin and cortisol secretion to normal levels. Furthermore, the studied extracts improved the levels of plasma pro-inflammatory cytokines and CREB and BDNF mRNA expression in the prefrontal cortex. In conclusion, aqueous extracts of miswak and date palm have significant antidepressant-like effects on depression-like behaviors in CUMS model in rats. Moreover, their combination has higher antidepressant-like effects than either extract alone, suggesting that it may be an effective treatment for stress-induced depression-like behaviors acting through modulating pro-inflammatory cytokines and CREB/BDNF signaling pathway in the prefrontal cortex. PRACTICAL APPLICATIONS: Chronic stress is a major contributor to the development of depression. In recent years, there has been a significant increase in the use of herbal remedies for the treatment of a variety of diseases, particularly mood disorders. Because of the side effects encountered by antidepressant drugs such as anxiety, sexual dysfunction, loss of appetite, and inadequate response or developing tolerance to these medications, there is a need for more efficient and convenient antidepressant treatments. According to this study, aqueous extracts of miswak and date palm are effective treatments for stress-induced depression-like behaviors.

A RANDOMIZED CASE–CONTROL PILOT STUDY ON THE NEUROCHEMICAL BASIS OF PAIN MODULATION IN PATIENTS WITH MIGRAINE, WHO PRACTICED INTEGRATED AMRITA MEDITATION TECHNIQUE

Objective: The objective of the study was to determine the changes in duration and intensity of headache and associated changes in the plasma levels of neurochemicals, serotonin, glutamate, vasoactive intestinal peptide (VIP), and nitric oxide (NO) in patients with migraine after 6 months of regular practice of integrated Amrita meditation (IAM). Methods: Sixteen patients aged 18–50 with migraine were randomly assigned to 2 groups, one with standard medical care and IAM, and the other only standard medical care. Data were collected before IAM, after 3 and 6 months of IAM practice. Results: After 6 months, a significant decrease in the duration of headache from 2.4±0.54 to 1.4±0.54 (p=0.034) hours and intensity of pain from 3.6±0.54 to 2.6±0.89, (p=0.035) was seen in patients who practiced IAM. Plasma levels of serotonin dropped from 47.29±26.85 to 31.88±8.07 ng/ml, (p=0.050), glutamate reduced from 31.47±8.23 to 21.77±13.62 μg/ml, (p=0.010) and NO levels increased from 423.17±97.90 to 540±88.30 μmol/L, and (p=0.023) in the IAM group in comparison with control after 6 months. A correlating trend was seen within the IAM group in serotonin (47.29±26.85 to 53.85±29.73 ng/ml), glutamate (38.47±8.2 to 29.68±12.57 μg/ml), VIP (28.01±13.64 to 22.23±7.79 pg/ml), and NO (642.26±167.42 to 423.18±97.96 μmol/L). Discussion: The results of our study have been discussed with other migraine and meditation-related studies. Conclusion: Regular practice of IAM reduces the intensity and duration of headache in migraine patients and is associated with alterations in the neurotransmitter levels.

Effects of Lactiplantibacillus plantarum PS128 on alleviating canine aggression and separation anxiety

Certain strains of Lactiplantibacillus were found to have a positive impact on host neuromodulation through the gut-brain axis and thus ameliorate emotional and behavioral problems. A number of researches have been performed on humans, mice and rats; however, studies on dogs are limited. Forty-five dogs with behavioral problems were enrolled in this study, including aggression (n = 22), separation anxiety (n = 15), compulsive disorder (n = 7) and unclassifiable inappropriate behavior (n = 1, excessive barking). The behavioral diagnosis was made based on the primary behavioral consultation questionnaires and the careful interrogations at interviews. Lactiplantibacillus plantarum PS128 (PS128) probiotic was administered to these physically healthy dogs with behavioral problems over a course of two weeks to determine the probiotic effectiveness on canine behaviors. Dogs were evaluated and scored using the Evaluation of Dog’s Emotional and cognitive Disorders (EDED) scale and the Canine Behavioral Checklist (CBC) questionnaire at the visits before and after the probiotic treatment. Plasma serotonin levels were measured using high-performance liquid chromatography- electrochemical detection (HPLC-ECD) and the serotonin turnover ratios (5-HIAA/5-HT) were compared pre- and post-treatment. The results showed that the general behavioral stability was improved, and the problems of aggression and separation anxiety were ameliorated after treatment. A significant decrease in 5-HIAA/5-HT ratio was observed in dogs with separation anxiety, suggesting a serotonin-related mechanism. These results proved that PS128 was beneficial for emotional stabilization, which might be useful as a therapeutic supplement for canine aggression and separation anxiety.

Age-Associated Gut Dysbiosis, Marked by Loss of Butyrogenic Potential, Correlates With Altered Plasma Tryptophan Metabolites in Older People Living With HIV.

Background:Imbalance in tryptophan (TRP) metabolism and its neuroactive metabolites, serotonin and kynurenine (KYN), is a known pathogenic mechanism underlying neurocognitive impairment. Gut microbiota plays an important role in TRP metabolism, and the production of these neuroactive molecules affects neurocognitive function. Although both HIV infection and normal aging independently induce gut dysbiosis and influence TRP metabolism, their interactive effects on compositional/functional changes in gut microbiota and consequent alterations in TRP metabolites remain largely undetermined.Methods:Older people living with HIV infection (PLWH, aged 50–70 years, n = 22) were enrolled in this cross-sectional pilot study. Metagenomic analysis of fecal microbiome using 16S Ribosomal ribonucleic acid gene sequencing and metabolomics analysis of plasma using mass spectrometry with a reverse-phase iquid chromatography tandem mass spectrometry were performed. Statistical analyses included the univariate linear regression and Spearman correlation analyses.Results:Age-associated changes in plasma levels of key neuroactive TRP metabolites, serotonin and KYN, were seen in PLWH. Specifically, we observed age-dependent decreases in serotonin and increases in KYN and KYN-to-TRP ratio, indicative of dysfunctional TRP metabolism. Furthermore, the gut dysbiosis seen in older PLWH is characterized by a reduction of Firmicutes/Bacteroidetes ratio and butyrate-producing microbial families Lachnospiraceae and Lactobacillaceae. Of importance, correspondent with gut dysbiosis, increasing age was significantly associated with decreased plasma butyrate levels, which in turn correlated positively with serotonin and negatively with KYN/TRP ratio.Conclusions:Age-dependent gut microbial dysbiosis distinguished by a decrease in butyrogenic potential is a key pathogenic feature associated with the shift in TRP metabolism from serotonin to KYN in older PLWH.

How mind-body therapies might reduce pathological features of Alzheimer's disease.

How mind-body therapies might reduce pathological features of Alzheimer's disease.

Maternal plasma serotonin level not suitable as postpartum depression diagnostic biomarker: Results from a prospective cohort study

BackgroundWhether plasma serotonin (5-HT) levels could be a biomarker for postpartum depression (PPD) diagnosis is under dispute. MethodsA total of 979 of pregnant women without antenatal depression at the time of delivery (TD) were enrolled and followed up at six weeks postpartum (SWP) in Changsha, China. The odds ratio (OR) and 95% confidence interval (CI) for plasma 5-HT level at TD, at SWP, changes in 5-HT, and risk of PPD and deterioration in EPDS scores at SWP were estimated by Logistic regressions. Restricted cubic spline (RCS) functions were also used to assess the dose-response relationships. ResultsThe 6-week cumulative incidence of PPD was 12.05% (95%CI:10.08%, 14.26%). The average level of plasma 5-HT changed from 223.65 ± 131.47 ng/ml at TD to 216.43 ± 122.73 ng/ml at SWP, with an average change of −7.22 ± 96.54 ng/ml. Plasma 5-HT at TD was negatively correlated with EPDS score at TD and SWP (p < 0.05), as was the correlation between 5-HT at SWP and EPDS scores at SWP (p = 0.038). However, the changes in 5-HT were not associated with the EPDS score at SWP (p = 0.346). Neither plasma 5-HT level at TD nor changes in 5-HT was associated with PPD at SWP or deterioration in EPDS scores (p < 0.05). Plasma 5-HT at delivery had insignificant discriminatory power for diagnosing PPD and prediction of deterioration in EPDS scores (p ≥ 0.05). ConclusionPlasma 5-HT level at delivery was associated with EPDS score at delivery and SWP, but not with PPD at SWP suggesting that plasma 5-HT is not suitable as PPD diagnostic biomarker.

Оптимізація діагностики вторинних метаболічних порушень та лікувальної тактики у пацієнтів із анемією злоякісного новоутворення при колоректальному раку

The purpose of the study was to study the content of free fraction of heparin, histamine and serotonin in plasma of peripheral venous blood of patients with malignant neoplasm anemia in colorectal cancer, depending on the severity of anemia. Materials and methods. The material for the study was the blood plasma of 445 patients (228 men and 217 women). Among them, 53 patients (31 women and 22 men) with iron deficiency anemia were examined and included in the first observation group (І) and 392 patients (206 men (52.55 %) and 186 women (47.45 %)) with colorectal cancer whose course of the underlying disease was burdened with malignant neoplasm anemia (ICD-10 code: D63.0) were included in the second observation group (II). Among the patients in the second (II) observation group, there were 222 individuals (119 men and 103 women) with malignant neoplasms of the colon (ICD-10 code: С.18), 29 individuals (16 men and 13 women) with malignant neoplasms of the rectosigmoid junction (ICD-10 code: C.19), 138 individuals (82 men and 56 women) with malignant neoplasms of the rectum (code ICD-10 C.20) and 3 patients (2 men and 1 woman) with malignant neoplasms of the anus (ICD-10 code: C.21). The mean age of the patients was 63.3 ± 1.2 years old. The plasma level of free fraction of heparin of the examined patients was determined using the photocolorimetric method on photoelectric colorimeter 56-M after its preliminary isolation by electrophoretic method according to the appropriate procedure (B. V. Mykhailychenko, S. V. Vydyborets (2000)). The plasma level of free histamine and serotonin of the examined patients was studied using the method of fluorometric analysis on the analyzer “BIAN-130”-“BIAN-100” according to the procedure of B. V. Mykhailychenko, S. V. Vydyborets (1999). Results and discussion. It was found that prior to the initiation of treatment in patients with malignant neoplasm anemia, regardless of the course of colorectal cancer, there was a significant increase in the plasma level of free fraction of heparin, histamine, serotonin (p &lt; 0.001); the ratio of free histamine to free serotonin was also changed in comparison with the values in the control group (p &lt; 0.05), which indicated both an increased release of heparin, histamine and serotonin from the depot, and an impaired inactivation processes of these biologically active substances. Considering all of the above and the quite obvious reasons, namely, the secondary metabolic disorders of serotonin, histamine, heparin which manifested by a significant increase in their plasma level of patients with malignant neoplasm anemia in colorectal cancer, we suggested the need to use a medicinal product in a complex of therapeutic measures which can cause antihypoxic, membrane stabilizing and anti-edema action. Conclusion. Malignant neoplasm anemia in colorectal cancer is accompanied by significant changes in the metabolism of biologically active substances – free fraction of heparin, histamine, serotonin, and the ratio of free histamine to serotonin. It was correctly concluded that in addition to the baseline therapy the administration of arginine glutamate which causes both antihypoxic and membrane-stabilizing action, reliably contributes to the normalization of secondary metabolic disorders of histamine, serotonin and heparin metabolism in malignant neoplasm anemia in patients with colorectal cancer

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.

The Relationship Between Sleep Quality, Sleep-Related Biomarkers, and Motor Skill Acquisition in People With Multiple Sclerosis: A Pilot Study.

Neurorehabilitation that involves learning new motor skills is one of the promising clinical methods for motor recovery in people with multiple sclerosis (PwMS); therefore, factors that influence the acquisition of motor skills in PwMS need to be investigated. Sleep disturbances are common in PwMS; however, no study has investigated the effect of sleep and sleep-related biomarkers on skill acquisition in PwMS. This study aimed to examine the effect of sleep and sleep-related biomarkers on motor acquisition in PwMS. Forty participants with MS and 40 controls were recruited in this study. To assess motor acquisition, each participant was asked to perform a novel game through a virtual reality (VR) system 5 times (blocks). The main outcome measures for each block were the required time to complete the VR game and the recorded errors. The difference in scores between Block 5 and Block 1 for both outcomes were considered to represent motor skill acquisition. Sleep was assessed by self-report using the Pittsburgh Sleep Quality Index (PSQI) and objectively using sleep monitor technology. Serotonin level was assessed using means of enzyme-linked immunosorbent assay using plasma samples. There were significant positive correlations in both groups between motor skill acquisition and PSQI score. In PwMS, significant negative correlation between motor skill acquisition and sleep efficiency and significant positive correlation between motor skill acquisition and sleep latency were also observed. Interestingly, a significant negative correlation was observed between motor skill acquisition and the plasma serotonin level in both groups. Most of these correlations remained significant after controlling for disease severity, fatigue, baseline performance, and cognitive status. Sleep quality may influence motor skill acquisition in PwMS. Circulatory serotonin level might explain this relationship. Physical therapists are encouraged to be aware of sleep quality and sleep assessment. Sleep management strategies should be considered when treating PwMS.

Pathophysiological mechanisms underlying gastrointestinal symptoms in patients with COVID-19.

Gastrointestinal (GI) symptoms, such as diarrhea, abdominal pain, vomiting, and anorexia, are frequently observed in patients with coronavirus disease 2019 (COVID-19). However, the pathophysiological mechanisms connecting these GI symptoms to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remain elusive. Previous studies indicate that the entry of SARS-CoV-2 into intestinal cells leads to downregulation of angiotensin converting enzyme 2 (ACE2) receptors resulting in impaired barrier function. While intestinal ACE2 functions as a chaperone for the amino acid transporter B0AT1, the B0AT1/ACE2 complex within the intestinal epithelium acts as a regulator of gut microbiota composition and function. Alternations to the B0AT1/ACE2 complex lead to microbial dysbiosis through increased local and systemic immune responses. Previous studies have also suggested that altered serotonin metabolism may be the underlying cause of GI disorders involving diarrhea. The findings of elevated plasma serotonin levels and high fecal calprotectin in COVID-19 patients with diarrhea indicate that the viral infection evokes a systemic inflammatory response that specifically involves the GI. Interestingly, the elevated proinflammatory cytokines correlate with elevated serotonin and fecal calprotectin levels further supporting the evidence of GI inflammation, a hallmark of functional GI disorders. Moreover, the finding that rectal swabs of COVID-19 patients remain positive for SARS-CoV-2 even after the nasopharynx clears the virus, suggests that viral replication and shedding from the GI tract may be more robust than that of the respiratory tract, further indicating fecal-oral transmission as another important route of viral spread. This review summarized the evidence for pathophysiological mechanisms (impaired barrier function, gut inflammation, altered serotonin metabolism and gut microbiota dysbiosis) underlying the GI symptoms in patients with COVID-19.

How do Spinal Stabilization Exercises Relieve Back Pain? An Analysis of Potential Mechanisms of Analgesia Effected at Muscular, Spinal Cord and Supraspinal Levels

STUDY OBJECTIVE Spinal stabilization exercises have emerged as an effective treatment for low back pain (LBP), but the mechanism of analgesia obtained through these exercises is unknown. The objective of the present research was to derive viable hypotheses for this pain relief based on previously validated analgesic mechanisms. METHODS A literature review was conducted by first considering commonly known methods of both exogenous and endogenous pain control, and then selecting for deeper analysis those mechanisms which could conceivably be operative during the self-generated, low amplitude movements involved in spinal stabilization exercises. The three chosen analgesic processes were related to perfusion, gate control, and endogenous analgesia. RESULTS Mechanism 1: Increased Perfusion Muscle contraction is known to increase perfusion of muscle tissue, leading to increased nutrient delivery and removal of waste products, and ischemia caused by atherosclerosis causes pain in multiple tissues including muscle. The lumbar blood supply derives from the abdominal aorta/lumbar artery system and blockages in this system have been linked to LBP. Gentle stabilization exercises targeting the core which activate these muscles may thus increase perfusion and thereby lessen pain related to ischemia. Mechanism 2: Gate Control-Mediated Analgesia Since Melzack and Wall first proposed the Gate Control Theory, the existence of multiple specific pain-inhibiting circuits linking dorsal horn laminae has been confirmed. Recent studies support a role for muscle spindles and golgi tendon organs in “closing the gate” to pain sensations, via muscle contraction. Pain relief during contract-relax and resistance exercises has been achieved in at least 3 studies, possibly through activation of these receptors. This process may explain in part the achievement of pain relief obtained after a short course of spinal stabilization exercises. Mechanism 3: Exercise-Induced Analgesia Exercise Induced analgesia (EIA) works through multiple endogenous systems that decrease pain perception, including the opioidergic, serotonergic, noradrenergic, endocannabinoid, and nitrergic systems. Numerous studies have shown EIA occurs with aerobic exercise in both humans and animals. The role of EIA in analgesia during isometric and core stabilization exercises is starting to be explored, including findings that both plasma β-endorphin and serotonin levels increase after core exercises. CONCLUSIONS The manner in which spinal stabilization exercises achieve analgesia is unknown. The vascular, gate-control, and exercise-mediated mechanisms outlined above are known to elicit an analgesic effect, and could conceivably be evoked by the gentle, low amplitude movements of these exercises. Rigorous, prospective research on perfusion of the muscles involved in core stabilization, the activation of muscle proprioceptive pathways in dorsal horn pain synapses, and plasma levels of key hormones during and after core stabilization exercises, would help support or refute the existence of this link.