Blood Serotonin Concentrations Research Articles

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.

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<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.

Blood serotonin concentration in children with COVID-19

COVID-19 has a risk of thrombotic complications. Serotonin plays an important role in pathogenesis of thrombosis.Purpose. To evaluate level of serotonin and its metabolite in the blood of children with COVID-19.Methods. This study included 72 children aged 3 to 17 years. Of these, 43 patients (mean age 11.2 ± 4.8 years) diagnosed with COVID-19 without comorbidities made up the study group, 29 healthy children (mean age 11.8 ± 3.8 years) — the control group. Concentration of serotonin and its metabolite (5-HIAA) in the blood was determined using high performance liquid chromatography with electrochemical detection. Computed tomography data were used to determine severity of lung damage.Results. In our study children with COVID-19 aged 3 to 17 years had significantly higher serotonin and its metabolite levels compared to the control group. Concentration of serotonin in plasma in main group was 20–30 times higher than in the same-age control. The 5-HIAA/serotonin ratio in children with COVID-19 is significantly lower than in the control group. Levels of serotonin and 5-HIAA in children with COVID-19 depending on the severity of CT-scan lung damage showed no significant differences.Conclusion. Serotonin and its metabolite levels in plasma of children with COVID-19 is significantly increased. It may be related to platelet hyperactivation in SARS-CoV-2 infection and increased risk of thrombosis, which requires further research.

The FVB mouse strain as a spontaneous model of degenerative mitral valve disease

Mitral valve disease is a complex entity with diverse origins, degeneration occurring following an extrinsic aggression (infection, autoimmune attack, drug), genetic malformation or being due to a hemodynamic abnormality (dilatation of the left ventricle, myocardial infarction). The aim is to present the main cardiovascular characteristics of the FVB mouse strain with a particular focus on spontaneous mitral valve degeneration and the serotonergic system in comparison with the C57BL/6 J, the usual background strain of many cardiovascular studies. 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 in FVB/NJ and FVB/NRj mice strains (males and females) obtained from Janvier and Charles River Labs in comparison to the usual C57BL/6 background at different ages (12, 16, 20 and 24-week-old). To know if the mitral valve was remodeled, cardiac anatomy and function were assessed by echocardiography and mitral valves were finally characterized by histology. The expression of 5-HT2A and 5-HT2B receptors was measured by RTqPCR in the anterior leaflet of the valve. No significant difference in C57BL/6 J compared to FVB mice strains regarding body weight increase, arterial blood pressure and heart rate was observed. A progressive augmentation of plasma pro-ANP was observed in FVB mice. However, no cardiac hypertrophy or left-ventricular fibrosis were observed. 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 (100% of 24-week-old FVB/NRj males). 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. No difference regarding serotonergic receptors expression was observed. 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 meaning the absence of mitral valve prolapse. Spontaneous mitral myxomatous degeneration is highly prevalent in FVB mice. A contribution of the serotonergic system is suggested

The positive impact of 12weeks of dance and balance training on the circulating amyloid precursor protein and serotonin concentration as well as physical and cognitive abilities in elderly women.

The study aimed to compare the effectiveness of 12-weeks dance training with balance training on fall risk, physical and cognitive functions. The study's second aim was to evaluate the association between physical and cognitive functions with circulating markers of neurodegeneration and cognitive impairments in elders. 30 older women (aged 73.3±4.5) were randomly assigned into three groups: balance training (BG), dance training (DG) and control group (CG). To assess the study aims Time up and go test (TUG), 6minute walk test (6MWT), determination test (DT), blood amyloid precursor protein (APP) and serotonin concentration were performed. The results showed an improvement in 6MWT (p=0.0001 for DG and BD), walking speed (p=0.0001 for DG and BG) and TUG, only for DG (p=0.0013). The number of correct responses in DT increased in both groups (p=0.014 and p=0.005, for DG and BG, respectively). In DG the increase in the total number of reactions was observed (p=0.013). The improvement in cognitive and physical functions was associated with an increase in APP (p=0.036 and p=0.014) and a decrease in serotonin concentrations (p=0.042 and p=0.049), respectively in DG and BG. Dance training intervention could have more benefits on elders' physical and cognitive functions. However, both trainings may be important factors modifying the concentration of circulating proteins associated with neurodegenerative and cognitive disorders.

Keel bone damage affects behavioral and physiological responses related to stress and fear in two strains of laying hens.

Keel bone damage (KBD) is more prevalent in alternative laying hen housing systems than in conventional cages, and its incidence differs from strain to strain. However, the information of KBD in Lindian chickens, a native Chinese strain, is limited. To investigate the effect of KBD on fearfulness and physiological indicators of stress in Lindian chickens and commercial laying hens, a total of two hundred 25-wk-old chickens (100 Hy-line Brown and 100 Lindian chickens) were studied for 7wk. The birds were housed in furnished cages with 10 birds per cage for each strain. At 32-wk of age, the birds in each strain were divided into normal (NK), deviated (DK), and fractured (FK) hens according to the keel bone status. Ten birds in each keel bone status per strain were subsequently selected to collect blood for the determination of stress and fear-related indicators, including corticosterone, serotonin, interleukin-1β, and interleukin-6, and measure fear responses, including novel object test (NOT), human approach test (HAT), and tonic immobility (TI) test. The results showed that egg production was lower and the incidence of keel bone fractures was higher in Lindian chickens than in Hy-line Brown hens (P < 0.05). Lindian chickens showed a significantly increased whole blood serotonin content, NOT-latency, HAT-score, and TI induction times (P < 0.05) and decreased serum interleukin-6 content and TI-duration (P < 0.05) compared with Hy-line Brown hens. Additionally, FK hens had significantly elevated whole blood corticosterone, serum interleukin-1β and interleukin-6 levels, TI-duration, and NOT-latency (P < 0.05), and a reduced whole blood serotonin content (P < 0.05) compared with NK and DK hens. Our results indicated that KBD affected stress and fear responses, and this impact was mainly reflected by FK hens compared with NK and DK hens. We suggest that keel bone fractures are the main factor impairing hen welfare. Besides, the incidence of keel bone fractures and stress and fear responses of Lindian chickens are more severe than Hy-line Brown laying hens, indicating that the strain type can affect the health and welfare of laying hens.

Characterization of the spontaneous degenerative mitral valve disease in FVB mice.

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. 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. 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. 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. The FVB mouse strain is highly prone to spontaneous mitral myxomatous degeneration. A contribution of the peripheral serotonergic system is suggested.

Central Serous Chorioretinopathy and Blood Serotonin Concentrations.

Background: To investigate blood serotonin (5-hydroxytryptamine (5-HT)) concentrations and their relationships with selected characteristics in patients with central serous chorioretinopathy (CSC). Methods: This was a prospective study including 93 patients with active CSC. Blood concentrations of 5-HT, adrenocorticotropic hormone, and cortisol were measured in patients with CSC. Selected patient characteristics, including disease history (acute or chronic), medication use, smoking history, mood status, best-corrected visual acuity (BCVA), subfoveal choroidal thickness (SCT), findings on fluorescein and indocyanine green angiography, and anatomical changes were evaluated during follow-up. Results: Eleven of the 93 patients had low 5-HT concentrations (<57 ng/mL) (12%, eight men and three women; mean age 55 years); we identified no significant relationship with acute/chronic disease status. The patients with low 5-HT were significantly more likely to have five or more fluorescein leakage sites (p = 0.0275), recurrence of subretinal fluids (p < 0.0001), and failure to achieve significant improvement in BCVA during follow-up (p = 0.862) than patients with 5-HT within the normal range. Conclusions: Blood serotonin concentrations may influence the pathophysiology and prognosis of CSC.

Short communication: The effect of ruminal administration of 5-hydroxy-l-tryptophan on circulating serotonin concentrations

The monoamine serotonin has been shown to regulate peripartal calcium homeostasis in multiparous cows and be a possible mitigation tool for hypocalcemia. Increasing circulating serotonin concentrations via prepartum intravenous (IV) administration of the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP) increases postpartum calcium concentrations. However, the ability of 5-HTP to be used orally or ruminally to alter circulating serotonin concentrations has not been established. Hence, our objective was to determine if ruminal administration of 5-HTP altered circulating serotonin concentrations. Four ruminally cannulated, nonlactating, nonpregnant multiparous Holstein dairy cows were randomly assigned to 1 of 4 treatments in a 4 × 4 replicated Latin square with 4-d periods separated by a 7-d washout. On d 1 and 2 of each period, cows were dosed with 1 of 4 experimental treatments as follows: (1) 0 mg/kg of body weight (BW) of 5-HTP, (2) 1 mg/kg of BW of intraruminal 5-HTP, (3) 2 mg/kg of BW of intraruminal 5-HTP, or (4) 1 mg/kg of BW of IV 5-HTP. Infusions were administered over a 1-h period, and all groups not receiving 5-HTP IV were infused with an equal volume of IV saline to that of IV 1 mg/kg of BW of 5-HTP treatment. Continuous serial blood samples were collected beginning after d 2 of treatment administration. Whole blood serotonin concentrations were higher in cows dosed with 2 mg/kg of BW of intraruminal 5-HTP immediately after dosing when compared with cows dosed with 0 mg/kg of BW of 5-HTP on d 2, but were similar on d 3 and 4 of the experimental period. Cows receiving IV 5-HTP had the highest circulating serotonin concentrations relative to all other treatments. These findings demonstrated that 2 intraruminal dosings of 5-HTP at 2 mg/kg of BW resulted in elevated circulating serotonin concentrations relative to the control immediately after dosing. This supports the potential for 5-HTP to be used orally to manipulate circulating serotonin concentrations.

Free movement: A key for welfare improvement in sport horses?

Horses, and in particular sport horses, remain housed predominantly in single stalls. One of the main reported reasons is the fear that they will become agitated and injure themselves and thereby impair their performance if released in paddocks. The hour spent daily at work is also assumed to be sufficient to satisfy the horses’ needs for locomotion. Growing scientific evidence shows that single stall housing has negative consequences on horses’ welfare and that time for free movement is necessary. Our aim was to assess the feasibility of allowing sport horses used to staying permanently in their stall (except for 1 h riding/day) daily free time in a paddock and to evaluate its potential impact on their welfare using two behavioural reliable indicators (stereotypic behaviours and ear position), as well as selected blood parameters (blood cell count, oxytocin and serotonin concentrations). Two experiments were conducted on the same site. The first experiment evaluated sport horses’ habituation to the novel situation of daily sessions in a paddock, and recorded welfare indicators in their stall before and during the experiment, comparing horses that were taken outdoors (experimental) and those that stayed in their stall (control). The second experiment evaluated the impact of this daily free time in a paddock on horses’ welfare and its durability, focusing on positive indicators. Behavioural observations in paddocks showed that even horses that had never experienced free movement outside their stall habituated rapidly to this situation. The presence of hay in the paddock, may have speeded up habituation. Their restricted living conditions were associated with abnormalities in blood cell count that were not overcome during the time of daily paddock sessions but behavioural indicators showed that their welfare improved. In the second study, the experimental horses’ welfare improved during the paddock release period, in particular their stereotypic behaviours decreased and oxytocin levels increased. No effects on serotonin concentrations could be evidenced. These effects were directly associated with being in paddock, as the indicators returned rapidly to their previous levels indicating compromised welfare when the paddock release sessions stopped. In conclusion, it can be recommended to release sport horses for free movement in paddocks as welfare is improved and subjective assessment by caretakers indicated minimal risks.

Increasing serotonin bioavailability in preweaned dairy calves impacts hematology, growth, and behavior

Peripheral serotonin has been shown to regulate important physiological functions such as energy homeostasis and immunity, particularly in rodent and humans, but its role is poorly understood in livestock species. Herein, we tested the safety and effectiveness of increasing serotonin bioavailability in preweaned dairy calves by oral supplementation of a serotonin precursor (5-hydroxytryptophan, 5-HTP) or a serotonin reuptake inhibitor (fluoxetine, FLX). Bull Holstein calves (21 ± 2 d old; N = 24) were fed milk replacer (8 L/d) supplemented with either saline as control (CON, 8 mL/d, n = 8), FLX (40 mg/d, approx. 0.8 mg/kg; n = 8), or 5-HTP (90 mg/d, approx. 1.8 mg/kg; n = 8) for 10 consecutive days in a complete randomized block design. Heart rate (HR), respiration rate, rectal temperature, and health scores were recorded daily. Hip height and body weight were measured at d 1, 5, and 10 relative to initiation of supplementation. Blood samples were collected once before the supplementation period (d 1), during the 10-d supplementation period (daily), and during a 14-d withdrawal period (d 2, 3, 4, 7, and 14 relative to initiation of withdrawal). Cerebrospinal fluid and muscle tissue were collected from a subset of calves (n = 12) that were euthanized after the 10-d supplementation or 14-d withdrawal period. Whole blood serotonin concentrations increased in 5-HTP calves and decreased in FLX calves compared with CON (P < 0.001), indicating that serotonin bioavailability was increased in both groups. Whole blood serotonin concentrations of 5-HTP and FLX calves returned to CON levels after 7 d of withdrawal. All calves grew and were considered healthy throughout the study. In fact, calves fed 5-HTP had higher average daily gain compared with CON (0.87 vs 0.66 ± 0.12 kg/d, P = 0.05). Calves fed FLX had lower HR (P = 0.02) and greater red blood cells and hemoglobin counts on d 10 of supplementation compared with CON (P < 0.01). After the 14-d withdrawal period, FLX was not detected in circulation of FLX calves, but was still present in the muscle tissue. Our results demonstrate that manipulation of the serotonin pathway by supplementing FLX or 5-HTP is a feasible and safe approach in preweaned dairy calves; however, it takes more than 14 d for FLX to be completely withdrawn from the body.

Serotonin signals through a gut-liver axis to regulate hepatic steatosis

Nonalcoholic fatty liver disease (NAFLD) is increasing in worldwide prevalence, closely tracking the obesity epidemic, but specific pharmaceutical treatments for NAFLD are lacking. Defining the key molecular pathways underlying the pathogenesis of NAFLD is essential for developing new drugs. Here we demonstrate that inhibition of gut-derived serotonin synthesis ameliorates hepatic steatosis through a reduction in liver serotonin receptor 2A (HTR2A) signaling. Local serotonin concentrations in the portal blood, which can directly travel to and affect the liver, are selectively increased by high-fat diet (HFD) feeding in mice. Both gut-specific Tph1 knockout mice and liver-specific Htr2a knockout mice are resistant to HFD-induced hepatic steatosis, without affecting systemic energy homeostasis. Moreover, selective HTR2A antagonist treatment prevents HFD-induced hepatic steatosis. Thus, the gut TPH1-liver HTR2A axis shows promise as a drug target to ameliorate NAFLD with minimal systemic metabolic effects.

Serotonin hormonally regulates lacrimal gland secretory function via the serotonin type 3a receptor

Tears are extracellular fluid secreted from the lacrimal gland (LG). Tears consist of a dynamic tri-layered film composed of secretions from the LG, Meibomian gland, and conjunctival goblet cells. The LG secretes the aqueous component of the tear, the Meibomian gland secretes the lipid component, and conjunctival goblet cells secrete mucin. The regulation of LG activity via the autonomic nervous system has been recognized as fundamental to maintaining aqueous tear flow. Here, we describe the role of a hormone, peripheral serotonin, in tear secretion. We found that blood serotonin concentration, changed by feeding a diet deprived of the serotonin precursor tryptophan, correlated with tear secretion, and that a sustained decrease in serotonin resulted in LG atrophy and autophagy. The combination of a decrease in serotonin with the interruption of autonomic neural stimuli to the LG preceded these alterations. Furthermore, we found that the serotonin type 3a receptor expressed in LG acinar cells is involved in tear secretion via intracellular calcium mobilization. Our findings demonstrate that hormonal regulation by serotonin, in cooperation with the autonomic nervous system, regulates tear secretion.

A Perspective on the Safety of Supplemental Tryptophan Based on Its Metabolic Fates

Over the past 50 y, tryptophan has been ingested in amounts well in excess of its dietary requirement. This use is based on extensive findings that ingesting tryptophan increases brain tryptophan concentrations, which stimulates the synthesis and release of the neurotransmitter serotonin, from which it is derived. Such increases in serotonin function may improve mood and sleep. However, tryptophan ingestion has other effects, such as increasing serotonin production in the gut, increasing serotonin concentrations in blood, stimulating the production of the hormone melatonin (a tryptophan metabolite), stimulating tryptophan metabolism via the kynurenine pathway, and possibly stimulating the production of tryptophan metabolites in the gut microbiome. Several of the kynurenine metabolites have actions on excitatory glutamate receptors in the gut and brain and on cells of the immune system. In addition, metabolites of tryptophan produced by colonic bacteria are reported to cause adverse effects in some species. This review examines each of these tryptophan pathways to determine if any of the metabolites increase after tryptophan ingestion, and if so, whether effects are seen on target body functions. In this regard, recent research suggests that it may be useful to examine kynurenine pathway metabolites and some microbial tryptophan metabolites to determine whether supplemental tryptophan consumption increases their concentrations in the body and amplifies their actions.

Changes in EEG indices and serotonin concentrations in depression and anxiety disorders

Electroencephalogram (EEG) is an important tool to study brain function. EEG can evaluate the current functional state of the brain with high temporal resolution and identify metabolic and ion disorders that cannot be detected by magnetic resonance imaging. Objective: to analyze the relationship between some neurophysiological and biochemical parameters with a Neuro-KM hardware-software complex for the topographic mapping of brain electrical activity. Patients and methods. 75 patients with depression, 101 with anxiety disorders (AD), and 86 control individuals were examined. EEG spectrum and coherence changes were estimated in the depression and AD groups versus the control group. Correlation analysis of EEG indices and blood serotonin concentrations was carried out. Results and discussion. The patients with depression and those with AD as compared to the controls were observed to have similar EEG spectral changes in the beta band. Coherence analysis in the beta-band showed that both disease groups versus the control group had oppositely directed changes: a reduction in intra- and interhemispheric coherence for depression and its increase for AD (p < 0.001). That in the theta and alpha bands revealed that both disease groups had unidirectional interhemispheric coherence changes: a decrease in integration in the alpha band and its increase in the theta and delta bands in the depression and AD groups (p < 0.05) and multidirectional changes in intrahemispheric coherence: its reduction in the depression group and an increase in the AD group (p < 0.05). Correlation analysis of EEG parameters and platelet serotonin concentrations showed opposite correlations of serotonin concentrations and EEG percentage power in the theta and beta bands. When there were higher serotonin concentrations in the patients with depression, EEG demonstrated a preponderance of a synchronization pattern; when these were in the patients with AD, there was a predominance of a desynchronization pattern. Conclusion. The specific features of EEG in the depression and AD groups may indicate serotonin metabolic disorders and the efficiency of therapy with selective serotonin reuptake inhibitors.

Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial

To determine safety and efficacy of the 5HT1A serotonin partial agonist buspirone on core autism and associated features in children with autism spectrum disorder (ASD). Children 2-6 years of age with ASD (N = 166) were randomized to receive placebo or 2.5 or 5.0 mg of buspirone twice daily. The primary objective was to evaluate the effects of 24 weeks of buspirone on the Autism Diagnostic Observation Schedule (ADOS) Composite Total Score. Secondary objectives included evaluating the effects of buspirone on social competence, repetitive behaviors, language, sensory dysfunction, and anxiety and to assess side effects. Positron emission tomography measures of tryptophan metabolism and blood serotonin concentrations were assessed as predictors of buspirone efficacy. There was no difference in the ADOS Composite Total Score between baseline and 24 weeks among the 3 treatment groups (P = .400); however, the ADOS Restricted and Repetitive Behavior score showed a time-by-treatment effect (P = .006); the 2.5-mg buspirone group showed significant improvement (P = .003), whereas placebo and 5.0-mg buspirone groups showed no change. Children in the 2.5-mg buspirone group were more likely to improve if they had fewer foci of increased brain tryptophan metabolism on positron emission tomography (P = .018) or if they showed normal levels of blood serotonin (P = .044). Adverse events did not differ significantly among treatment groups. Treatment with 2.5 mg of buspirone in young children with ASD might be a useful adjunct therapy to target restrictive and repetitive behaviors in conjunction with behavioral interventions. ClinicalTrials.gov: NCT00873509.

Microscopic Carcinoid: An Unusual Presentation of Gastric Carcnioid

51 year old Caucasian male with history of hyperlipidemia presented with complain of melena. Patient had noticed one episode of bright red blood per rectum. On questioning patient also complained of feeling tired lately with generalized body aches. He also had some numbness and tingling in both lower extremities which had been gradually worsening. Neurological exam showed decreased sensation, vibration and position sensation in both lower extremities. Digital rectal exam was positive for frank blood in rectal vault. Initial laboratory work up showed hemoglobin of 8.5 with MCV of 110. Patient underwent upper endoscopy which showed non-bleeding gastric ulcer. Also there were few scattered small focal areas of erythematous lesions in gastric cardia and proximal body with significant loss of the gastric folds. Biopsy of the lesions showed increase in fibrous tissue with moderate active inflammation of lamina propria and Chronic atrophic gastritis while rapid urease test was negative. Interestingly, carcinoid changes with chronic intestinal metaplasia were found on biopsy suspicious for carcinoid tumor. Given the finding on biopsy, fasting serum Gastrin Chromogranin A levels, Parietal cell antibodies, Intrinsic Factor antibodies, 24 hour urine for 5-HIAA, Computerized tomography (CT) scan of the abdomen and pelvis, and Octreotide scan were ordered to look for primary location of carcinoid tumor. Fasting serum Gastrin Chromogranin A levels, Parietal cell antibodies, Intrinsic Factor antibodies were found to be elevated the diagnosis of Carcinoid Tumor but there were no mass lesions but only scattered cells in the stomach. Patient subsequently underwent frequent endoscopies with biopsies which reconfirmed well differentiated carcinoid tumor cells scattered in the stomach but no mass lesion. Meanwhile patient underwent extensive work up for peripheral neuropathy and was found to have vitamin B12 deficiencies in setting of atrophic gastritis leading towards diagnosis of pernicious anemia which was likely cause of the underlying carcinoid changes. Patient is currently treated with vitamin B12 with marked improvement in his symptoms and is undergoing Surveillance endoscopies of carcinoid changes. Discussion: Carcinoid tumors Originate from Enterochromaffin-like (ECL) cells, found in gastric wall. There are three types of gastric carcinoid tumors. Type 1 are smaller and less than 1 cm, multiple, polypoid lesions with central ulceration associated with chronic atrophic gastritis and pernicious anemia. Type 2 occurs in association with gastrinomas (Zollinger-Ellison syndrome), often in setting of MEN type 1 and are mostly indolent in nature. While type 3 are Sporadic as they occur in the absence of atrophic gastritis or the Zollinger-Ellison /MEN1 syndromes and are very aggressive in nature. They are characterized by normal gastrin level. Diagnosis for carcinoid tumors include biochemical testing including urinary excretion of 5-HIAA, Chromogranin level, Blood serotonin concentration, Gastrin level and Anti parietal cell antibodies. Tumor localization is done by CT, Magnetic resonance Imaging, Octreotide scan. Type 1 and 2 are treated with endoscopic resections and survelliant endoscopies. Treatment for type 3 gastric carcinoid tumors is partial or total gatstrectomy considering the aggressive nature. Conclusions: Carcinoid tumors usually appear as discrete masses but microscopic carcinoid tumor in stomach is a very rare.

Correlation Between Hormonal and Neurochemical Changes and Depression With Menopausal STATUS: A Systematic Review

Context: Menopause is characterized by amenorrhea and increase in the level of Follicular Stimulating Hormone (FSH) due to the permanent cessation of ovarian function. This process causes changes in hormonal and other serum markers. Depression is the leading cause of disease-related disabilities in women. Objectives: The aim of this review was to investigate the correlation between hormonal and petrochemical changes and depression with menopausal status. Data Sources: We searched in Cochrane Library, MEDLINE, PubMed, Google Scholar, Web of Science and Scopus, Embase, the reference lists of all related studies and major relevant review articles from 1960 to October 2014, and also abstracts from associated congresses and meetings, using terms related to hormonal and serum markers, depression and its symptoms. Study Selection: The survey included prospective, retrospective and case-control studies. The selected studies explored menopause in study population and investigated variables and different markers in depression or anxiety, as well as those measuring depression or anxiety intensity. Data Extraction: Items for which data were extracted included the date and place of publication, study design, sources, human species, age, control groups, selection and appraisal methods, outcome measurement tools, and author’s conclusions. One investigator (Mostafa Chashmposh) collected the relevant reports, whereas two other authors independently reviewed the published data and reported different hormonal markers related to depression as evaluated by different studies. Disagreements were resolved by the fourth reviewer’s decision. Results: The period of menopause is mostly associated with a gradual decline of estrogen activity and increased secretion of nocturnal melatonin. During menopausal transition, overnight cortisol levels were associated with changes in estrone glucuronide, testosterone, and FSH levels. In addition, whole blood serotonin concentration is reduced during menopause. Furthermore, lipid markers including total and LDL cholesterol levels increase during perimenopause. Moreover, plasma Brain Derived Neurotropic Factor (BDNF) concentration decreases significantly in postmenopausal period. Based on different studies, the reduction of hormones including estrogen, serotonin and BDNF during menopause are associated with depression in women. Further studies documented the relationship between depressed mood symptoms and cortisol levels. Conclusions: The available evidence suggests that transition to menopause and its changing hormonal and other serum markers are strongly associated with depressed mood among women.

Effects of feeding fatty acid calcium and the interaction of forage quality on production performance and biochemical indexes in early lactation cow.

Multiparous early lactation Holstein cows (n = 16) were used in a randomized complete block design to determine the effects of feeding fatty acid calcium and the interaction of forage quality on production performance and biochemical indexes in early lactation cow. Treatments were as follows: (i) feeding low-quality forage without supplying fatty acid calcium (Diet A), (ii) feeding low-quality forage with supplying 400 g fatty acid calcium (Diet B), (iii) feeding high-quality forage without supplying fatty acid calcium (Diet C) and (iv) feeding high-quality forage with supplying 400 g fatty acid calcium. This experiment consisted 30 days. The milk and blood samples were collected in the last day of the trail. Intakes were recorded in the last 2 days of the trail. Supplementation of fatty acid calcium decreased significantly dry matter intake (DMI) (p < 0.01). Addition fatty acid calcium decreased milk protein percentage (p < 0.01) and milk SNF percentage (p < 0.01), but increased MUN (p < 0.05). Supplemented fatty acid decreased concentration of blood BHBA (p < 0.05), but increased TG, NEFA, glucagon, GLP-1, CCK, leptin, ApoA-IV, serotonin and MSH concentration in blood, the CCK concentration and feed intake showed a significant negative correlation (p < 0.05).

СЕЛЕЗЕНКА, КАК ОРГАН ОСУЩЕСТВЛЯЮЩИЙ ВЗАИМОСВЯЗЬ СИСТЕМ КРОВООБРАЩЕНИЯ И КРОВЕТВОРЕНИЯ

СЕЛЕЗЕНКА, КАК ОРГАН ОСУЩЕСТВЛЯЮЩИЙ ВЗАИМОСВЯЗЬ СИСТЕМ КРОВООБРАЩЕНИЯ И КРОВЕТВОРЕНИЯ