Elevated Plasma Serotonin Research Articles

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.

Plasma Serotonin is Elevated in Adult Patients with Sudden Sensorineural Hearing Loss.

The roles of thrombophilia and cardiovascular risk factors in sudden sensorineural hearing loss (SSNHL) remain controversial. Cochlear microthrombosis and vasospasm have been hypothesized as possible pathogenic mechanisms of SSNHL. This article investigates the circulating serotonin and homocysteine levels besides thrombophilia screening in patients with idiopathic SSNHL. A total of 133 SSNHL patients and age- and sex-matched controls were investigated (discovery cohort). Measurement included common inherited natural coagulation inhibitors, factor VIII, von Willebrand factor (VWF), antiphospholipid antibodies, homocysteine, and serotonin (whole blood, platelet, and plasma) levels, along with frequent relevant genetic variants. A validation cohort (128 SSNHL patients) was studied for homocysteine and serotonin levels. In the discovery cohort, 58.6% of patients exhibited thrombophilia, of which most had a low to moderate titers of antiphospholipid antibodies and high levels of factor VIII/VWF. Twenty-seven patients (20%) had mild-to-moderate hyperhomocysteinemia or were homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Regarding serotonin, SSNHL patients had elevated whole blood levels that remained within the normal range and normal platelet content. However, approximately 90% patients of both cohorts had elevated plasma serotonin. Elevated plasma serotoninemia was accompanied by serotonylation of platelet rhoA protein. This study shows that increased plasma serotonin appears as a biomarker of SSNHL (specificity: ∼96%, sensitivity: ∼90%) and could participate in the pathophysiology of SSNHL.

Plasma levels of serotonin, gastrointestinal symptoms,and sleep problems in children with autism

Autism is a neurodevelopmental disorder identified with higher frequency of serotonin abnormalities and gastrointestinal (GI) and sleep problems. This study aimed to evaluate the plasma levels of serotonin, GI symptoms, and sleep problems, and their relationship with autism severity in children with autism. Thirty-five children with autism and 31 healthy subjects were studied. GI problems, sleep disorders, and severity of disorder were assessed. Plasma serotonin was determined using ELISA. There was no significant association between GI problems and autism severity, but a significant positive correlation was seen between different indicators of sleep disorder and severity of autism. Plasma levels of serotonin were significantly higher in autistic children and a significant negative correlation was observed between plasma levels of serotonin and autism severity (r = -0.39, P = 0.02). Elevated plasma serotonin in autistic children and its negative correlation with disease severity may indicate involvement of the neurotransmitter in the neurophysiologic mechanism of autism.

Abstract 9819: Elevated Plasma Serotonin and Endothelin-1 in Coronary Artery Disease Patients: A Potential for Novel Pharmacotherapeutic Targets?

Background: High on-treatment platelet reactivity (HTPR) was reported in patients with coronary artery disease (CAD) on dual antiplatelet therapy with aspirin and clopidogrel, particularly in diabetic patients. We sought to investigate the potential for targeting platelet and endothelium-derived vasoactive substances (such as thromboxane A 2 [TXA 2 ], serotonin [5-HT], and endothelin-1 [ET-1]) released upon platelet activation to complement current antiplatelet therapy without increasing the risk of bleeding. Methods: Three groups of subjects were recruited: a) 20 diabetic patients with known CAD (DM), b) 24 non-diabetic patients with known CAD (ND) and c) 27 healthy subjects without diabetes or CAD (CTL). Subject groups were compared to each other with respect to plasma and platelet concentrations of various vasoactive substances measured by ELISA and to platelet reactivity measured by light transmission aggregometry (LTA) and VerifyNow ® . Results: Significantly higher ET-1 (CTL: 0.372 0.1 pg/mL; ND: 0.564 ± 0.2 pg/mL, P<0.005 vs. CTL; DM: 0.961 ± 0.2 pg/mL, P<0.02 vs. CTL) and 5-HT (CTL: 600.5 ± 52.5 ng/mL; ND: 679.6 ± 68.7 ng/mL, P<0.05 vs. CTL; DM: 729.7 ± 81.8 pg/mL, P<0.02 vs. CTL) plasma concentrations were found in CAD patients, with a more pronounced increase in the DM group. Platelet 5-HT was lower in the DM group (335.8 ± 71 ng/10 9 platelets) compared to both CTL subjects (447.1 ± 88.5 ng/10 9 platelets) and ND patients (374.6 ± 58.8 ng/10 9 platelets), which may be due to increased platelet activation and release. Plasma TXB 2 concentrations were higher in the DM group (557.4 ± 172.4 pg/mL) compared to the ND group (350.7 ± 42.4 pg/mL), which indicates higher platelet reactivity in DM patients despite the regular use of ASA. Platelet function tests such as VerifyNow ® (ASA) and LTA (AA 1.6 mM) showed higher HTPR in DM patients (VerifyNow ® : 445 ± 29.1 ARU; LTA: 16.78 ± 3.9% aggregation) compared to ND patients (VerifyNow®: 419.1 ± 13.4 ARU; LTA: 3.76 ± 0.8% aggregation). Conclusion: This study identifies ET-1 and 5-HT as new potential pharmacological targets in the platelet activation pathway for management of HTPR in CAD patients to reduce the risk of incidence and recurrence of ischemic events.

Impact of Elevated Plasma Serotonin on Global Gene Expression of Murine Megakaryocytes

BackgroundSerotonin (5-HT) is a biogenic amine that also acts as a mitogen and a developmental signal early in rodent embryogenesis. Genetic and pharmacological disruption of 5-HT signaling causes various diseases and disorders via mediating central nervous system, cardiovascular system, and serious abnormalities on a growing embryo. Today, neither the effective modulators on 5-HT signaling pathways nor the genes affected by 5-HT signal are well known yet.Methodology/Principal FindingsIn an attempt to identify the genes altered by 5-HT signaling pathways, we analyzed the global gene expression via the Illumina array platform using the mouse WG-6 v2.0 Expression BeadChip containing 45,281 probe sets representing 30,854 genes in megakaryocytes isolated from mice infused with 5-HT or saline. We identified 723 differentially expressed genes of which 706 were induced and 17 were repressed by elevated plasma 5-HT.Conclusions/SignificanceHierarchical gene clustering analysis was utilized to represent relations between groups and clusters. Using gene ontology mining tools and canonical pathway analyses, we identified multiple biological pathways that are regulated by 5-HT: (i) cytoskeletal remodeling, (ii) G-protein signaling, (iii) vesicular transport, and (iv) apoptosis and survival. Our data encompass the first extensive genome-wide based profiling in the progenitors of platelets in response to 5-HT elevation in vivo.

Serotonin: is it a marker for the diagnosis of hepatocellular carcinoma in cirrhotic patients?

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer mortality among men worldwide. Serotonin is biogenic amine, ligand for family of 5-HT receptors reflect the diversity of serotonergic actions.Majority of serotonin in body 90% synthesised by enterochromaffin cells of the gastrointestinal tract and exported to various sites. Serotonin regulate blood flow and vascular tone at portal and sinusoidal levels, serotonin mitogen for hepatocytes and promotes liver regeneration. 5HT emerging as mediator of different pathological conditions (double edged sowrd). It contributes to liver fibrosis, mediates oxidative stress in nonalcoholic steatotic hepatitis and aggravates viral hepatitis, these conditions involved in tumorgenesis of hepatocellular carcinoma (HCC). Impaired metabolic function in liver cirrhosis and slow uptake and storage of serotonin by the platelets is sequelae of kinetic change of serotonin transport mechanisms or abnormal serotonin release from dense granules of activated platelets condition defined “platelet exhaustion”, contributes to elevated plasma serotonin which may facilitate tumor growth of primary liver hepatocellular carcinoma. Aim of this work: was to determine whether serotonin is a marker for the diagnosis of hepatocellular carcinoma in cirrhotic patients. Methods: patients were classified into 2 groups; 45 patients with cirrhosis only and 30 patients with cirrhosis and HCC. 10 healthy subjects was taken as controls. Patients underwent; full history taking,clinical examination,abdominal ultrasonography. Laboratory methods include SGOT, SGPT, GGT, bilirubin, alkaline phosphatase, total proteins, albumin, CBC, prothrombin, INR, APRI score, Child-Pugh score, MELD score, AFP and serum serotonin. Results: plasma serotonin was significantly higher in patients group with cirrhosis with a median level 119.4 ng/ml than in control group showed median value of 51.5 ng/ml p< 0.001.Also a significance difference between cirrhosis &HCC group with median value 478.35 ng/ml than control group and cirrhosis group p<0.001was found. Conclusion: Plasma serotonin level was significantly higher in patients with cirrhosis and HCC than in those with cirrhosis only and it was involved in tumorgenesis of hepatocellular carcinoma.

167 Elevated Plasma Serotonin and Endothelin-1 in Coronary Artery Disease Patients: A Potential for Novel Pharmacotherapeutic Targets?

167 Elevated Plasma Serotonin and Endothelin-1 in Coronary Artery Disease Patients: A Potential for Novel Pharmacotherapeutic Targets?

Intraindividual comparison of 68Ga-DOTA-TATE and 18F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

To compare the diagnostic impact of (68)Ga-DOTA-TATE and (18)F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). PET/CT using both (68)Ga-DOTA-TATE and (18)F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Patient-based sensitivities were 96% for (68)Ga-DOTA-TATE PET and 56% for (18)F-DOPA PET. (68)Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by (18)F-DOPA PET. Overall, (68)Ga-DOTA-TATE was superior to (18)F-DOPA in 13 patients (two patients showed fewer positive tumour regions with (18)F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of (18)F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive (18)F-DOPA uptake. In patients positive for (18)F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). In this study (68)Ga-DOTA-TATE PET proved clearly superior to (18)F-DOPA PET for detection and staging of NET. (18)F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that (18)F-DOPA PET should be employed in patients with NET with negative (68)Ga-DOTA-TATE PET and elevated plasma serotonin.

Diagnosis and therapy of carcinoid tumors—current state of the art and future directions

Abstract Carcinoid tumors account for less than 1% of all malignancies and the majority arise in the gastrointestinal system. These tumors are slow growing compared with adenocarcinomas and they differ from the other neuroendocrine malignancies by their protean clinical presentation. Carcinoid tumors were previously considered indolent, but they can manifest malignant characteristics with metastatic spread which often results in a poor prognosis. Although there have been advances in diagnostic and treatment modalities, carcinoid tumors are still often diagnosed late, often when the tumor has metastasized and patients develop carcinoid syndrome. Diagnosis, prognosis and treatment options are based on biochemical markers and imaging investigations. High concentration of urinary 5-HIAA, elevated plasma serotonin and chromogranin A levels help to establish the initial diagnosis of carcinoid tumors. In addition to the CT and MRI, molecular imaging modalities such as OctreoScan, MIBG imaging and more recently PET imaging are vital in detection of primary malignancy and metastatic involvement. Surgery is the mainstay of treatment of nonmetastatic carcinoid tumors. Cytotoxic chemotherapy is not beneficial due to the chemoresistant nature of these tumors. Because carcinoid tumors express somatostatin receptors, somatostatin analogues, which inhibit the release of serotonin and other neuroendocrine peptides, are often used, but their use is limited to symptom control. Treatment using high doses of radionuclides such as radiolabeled somatostatin analogues and MIBG is a more recent option which offers a definite advantage in management. In this article, we review typical features of the carcinoid tumors, examine contemporary methods of detecting and assessing carcinoid tumors and discuss the role of various diagnostic and therapeutic options.

Effects of Diacylglycerol on Glucose, Lipid Metabolism, and Plasma Serotonin Levels in Lean Japanese

Diacylglycerol (DAG)-rich oil has been suggested to suppress postprandial hyperlipidemia and promote negative caloric balance by increasing energy expenditure (EE), due to small intestine physiochemical dynamics that differ from triacylglycerol (TAG). We studied the effect of DAG on postprandial glucose/insulin metabolism by loading of carbohydrate with oil. Further, to reveal the mechanism for increased EE by DAG, we measured plasma serotonin, which is mostly present in the small intestine and mediates peripheral sympathetic thermogenesis. Randomized crossover study with 2-week wash-out interval between differing fat ingestion. Seven male, lean, Japanese students ingested DAG or TAG oil with 40 g of carbohydrate. Measurements of metabolic parameters were performed before and at 2, 4, and 6 h after fat ingestion. Plasma serotonin levels and cholesterol concentration in each lipoprotein were measured using high-performance liquid chromatography (HPLC). The substitution of DAG for TAG decreased very-low-density lipoprotein-cholesterol (VLDL-C) by 45.6% at 2 h, and decreased serum insulin by 41.3% at 4 h after ingestion. The incremental area under the curve (IAUC) for VLDL-C was positively correlated with the IAUC for insulin. Concurrently, DAG elevated plasma serotonin levels by 47.3% at 2 h, while TAG did not influence. This study indicates that the substitution of DAG for TAG suppresses the postprandial increase in serum VLDL-C and insulin. This study also demonstrates that DAG ingestion increases plasma serotonin, proposing a possible mechanism for a postprandial increase in EE by DAG.

Allergy and Immunology: An Annotated Bibliography of Recent Literature

Allergy and Immunology: An Annotated Bibliography of Recent Literature

Elevated Serum Acid Phosphatase Levels with Rectal Carcinoid Tumor

A case of rectal carcinoid tumor with liver metastases is reported in which a markedly elevated serum acid phosphatase level was found. Tissue assays of the patient's tumor, liver metastasis, and uninvolved liver were performed which demonstrated very high tumor levels of acid phosphatase. The patient also had elevated plasma serotonin levels and urinary 5-hydroxyindole acetic acid levels and did not exhibit the carcinoid syndrome. Autopsy showed no prostate cancer or metastatic bone lesions. Serum acid phosphatase elevation may occur with carcinoid lesions of the rectum.