Plasma 5-hydroxyindoleacetic Acid Research Articles

Membrane Transporter of Serotonin and Hypercholesterolemia in Children.

The serotonin membrane transporter is one of the main mechanisms of plasma serotonin concentration regulation. Serotonin plays an important role in the pathogenesis of various cardiovascular diseases, stimulating the proliferation of smooth muscle cells, key cells in the process of hypertrophic vascular remodeling. Vascular remodeling is one of the leading prognostically unfavorable factors of atherosclerosis, the main manifestation of familial hypercholesterolemia. Familial hypercholesterolemia is one of the most common genetically determined lipid metabolism disorders and occurs in 1 in 313 people. The aim of our study was to investigate the levels of plasma and platelet serotonin, 5-hydroxyindoleacetic acid, and membrane transporter in a cross-sectional study of two pediatric groups, including patients with familial hypercholesterolemia and the control group, which consisted of apparently healthy children without cardiovascular diseases. The study involved 116 children aged 5 to 17 years old. The proportion of boys was 50% (58/116) and the average age of the children was 10.5 years (CI 2.8-18.1). The concentrations of serotonin in blood plasma and platelets and 5-hydroxyindoleacetic acid were higher in children with familial hypercholesterolemia than in the controls. The concentration of the serotonin transporter in platelets in healthy children, compared with the main group, was 1.3 times higher. A positive correlation was revealed between the level of serotonin (5-HT and PWV: ρ = 0.6, p < 0.001), its transporter (SERT and PWV: ρ = 0.5, p < 0.001), and the main indicators of arterial vascular stiffness. Our study revealed the relationship between high serotonin and SERT concentrations and markers of arterial stiffness. The results we obtained suggest the involvement of serotonin and SERT in the process of vascular remodeling in familial hypercholesterolemia in children.

Plasma or serum 5-hydroxyindoleacetic acid can be used interchangeably in patients with neuroendocrine tumours

5-hydroxyindole acetic acid, a metabolite of serotonin, is used in the diagnosis and monitoring of patients with neuroendocrine tumours, in particular patients with small intestinal neuroendocrine tumours associated with the carcinoid syndrome. Analysis of 5-hydroxyindole acetic acid was commonly performed in urine, but blood-based assays are now becoming available. The objective of this study was to assess how 5-hydroxyindole acetic acid compares in plasma and serum as a biochemical marker of neuroendocrine tumours. Twenty-four-hour urine, plasma and serum samples were obtained from 80 patients with neuroendocrine tumours and 30 healthy volunteers. We developed a liquid chromatography tandem mass spectrometry assay for plasma and serum 5-hydroxyindole acetic acid. Comparison was made between them, and their cut-off was determined using a receiver-operating characteristic curve. A close correlation was shown between plasma and serum 5-hydroxyindole acetic acid. At a cut-off of 135 nmol/l, a sensitivity of 91.2% with a specificity of 61.9% was obtained for both compared to the urinary assay. A statistically significant agreement was shown when plasma and serum 5-hydroxyindole acetic acid were compared with the currently used urine assay in patients with neuroendocrine tumours; κ = 0.675 (95% CI 0.49 to 0.86), p < 0.001 and healthy volunteers; 0.967 (95% CI 0.828 to 0.999), p = <0.001. In conclusion, 5-hydroxyindole acetic acid in plasma and serum were comparable, hence either sample type can be used interchangeably.

The role of N-terminal pro-brain natriuretic peptide, chromogranin A, and 5-hydroxyindoleacetic acid in screening for carcinoid heart disease.

Carcinoid heart disease (CHD) is a serious complication for patients with neuroendocrine tumors (NETs), and early detection is crucial. We aimed to investigate N-terminal pro-brain natriuretic peptide (NT-proBNP), chromogranin A (CgA), and plasma 5-hydroxyindoleacetic acid (P-5-HIAA) as a screening tool for detection of CHD. We prospectively included patients with disseminated small intestinal NETs (SI-NETs) and performed transthoracic echocardiography (TTE), questionnaires, and biochemical assessment of NT-proBNP, CgA, and P-5-HIAA. The presence and severity of CHD was assessed using a scoring system based on echocardiographic characteristics. A total of 93 patients were included in the final analysis. Fifteen (16%) were diagnosed with CHD. The median NT-proBNP (219 ng/L vs. 124 ng/L, p = .05), CgA (3930 pmol/L vs. 256 pmoL/L, p < .0001), and P-5-HIAA (1160 nmol/L vs. 210 nmoL/L, p < .0001) were significantly higher in patients with CHD compared to non-CHD patients. For NT-proBNP, the area under the receiver operating characteristic (AUROC) curve for detection of CHD was 0.67 (95% CI: 0.50-0.84), and at a 260 ng/L cutoff level, the sensitivity and specificity were 46% and 79%. For CgA, the AUROC was 0.91 (95% CI: 0.84-0.97), and at a cutoff level of 598 pmol/L, the sensitivity and specificity were 100% and 69%. For P-5-HIAA, the AUROC was 0.89 (95% CI: 0.80-0.98), and at a cutoff level of 752 nmol/L, the sensitivity and specificity were 92% and 85%. In conclusion, CgA and P-5-HIAA proved excellent markers of CHD while NT-proBNP lacked the required diagnostic accuracy to be used as a screening tool.

Impact of Plasma 5 Hydroxyindoleacetic Acid, a Serotonin Metabolite, on Clinical Severity in Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is characterized by dysregulated vascular permeability. The clinical outcomes remain poor, and the disease burden is widespread. We demonstrated that plasma 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, is a pivotal severity indicator of ARDS. Serotonin is an effector of cellular contraction and a modulator of vascular permeability. Plasma 5-HIAA levels were significantly elevated in severe ARDS cases with shock status (p = 0.047) and positively correlated with SOFA (p < 0.0001) and APACHE-II score (p < 0.0001). In the longitudinal analysis, plasma 5-HIAA levels were also a strong independent predictor of mortality rate (p = 0.005). This study indicates that plasma 5-HIAA is a biomarker of ARDS severity and highlights the importance of evaluating vascular leakage levels for ARDS treatment.

Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability

Septic shock is characterized by dysregulated vascular permeability. We hypothesized that the vascular permeability of endothelial cells (ECs) would be regulated by serotonin via serotonin-Rho-associated kinase (ROCK) signaling. We aimed to determine the impact of 5-hydroxyindoleacetic acid (5-HIAA) on septic shock as a novel biomarker. Plasma 5-HIAA levels and disease severity indices were obtained from 47 patients with sepsis. The association between 5-HIAA levels and severity indices was analyzed. Permeability upon serotonin stimulation was determined using human pulmonary microvascular ECs. 5-HIAA were significantly higher in septic shock patients than in patients without shock or healthy controls (p = 0.004). These elevated levels were correlated with severity indexes (SOFA score [p < 0.001], APACHE II [p < 0.001], and PaO2:FiO2 [p = 0.02]), and longitudinally associated with worse clinical outcomes (mechanical ventilation duration [p = 0.009] and ICU duration [p = 0.01]). In the experiment, serotonin increased the permeability of ECs, which was inhibited by the ROCK inhibitor (p < 0.001). Serotonin increases vascular permeability of ECs via ROCK signaling. This suggests a novel mechanism by which serotonin disrupts endothelial barriers via ROCK signaling and causes the pathogenesis of septic shock with a vascular leak. Serotonin serves as a novel biomarker of vascular permeability.

SUN-914 Peptide Receptor Radionuclide Therapy for an Inoperable Small Cell Neuroendocrine Tumor in the Philippines

Background: Peptide Receptor Radionuclide Therapy treatment for neuroendocrine tumors is a well-tolerated treatment option for patients not amenable to receiving chemotherapy and radiotherapy. Clinical Case: A 42-year-old female was evaluated by a cardiologist for complaints of new onset recurrent throat discomfort, chest pain and palpitations. Two-Dimensional echo showed a large extra-cardiac mass compressing the main pulmonary artery. Chest CT with contrast reveal a 5.8 x 6.0 x 7.2 cm enhancing lobulated anterior mediastinal mass. Attempts to excise the mass failed due to the proximity to major blood vessels. Biopsy revealed a Carcinoid Tumor that was Chromogranin A positive but was asymptomatic for carcinoid syndrome. Everolimus treatment was given but was halted due to stomatitis. The patient remained fully functional. Re-evaluation of the mass with FDG PET show an increase in tumor size. Biopsy tissue re-testing showed small cell neuroendocrine carcinoma. Urine 5-hydroxyindoleacetic acid, plasma 5-hydroxyindoleacetic acid, and serum Chromogranin A were normal. A 68Ga-DOTATATE PET/CT scan reveal a slight increase in the mass that was intensely DOTATATE-avid. Two sessions of Peptide Receptor Radionuclide Therapy (PRRT) Lutetium-177 DOTATATE given at an 8-month interval were given. SPECT/CT re-evaluation showed good response and no evidence of metastases. A 68Ga-DOTA-octreotate PET-CT scan was done and showed good response to treatment. According to treatment guidelines, small cell neuroendocrine carcinoma that are non-resectable are treated with radiotherapy plus chemotherapy. But since the patient is fully functional and has minimal symptoms, other means of treatment such as PRRT may be well suited due to good tolerability and good treatment outcomes. Conclusion: PRRT is a promising treatment for NETs that is well tolerated giving better functionality and quality of life for patients opting not to undergo chemotherapy and radiotherapy. Reference: Cadiot, G. (2019). French and European Neuroendocrine Tumor Society consensus guidelines. Annales d’Endocrinologie, 80(3), p.174.

Electro-Acupuncture Alleviates Cisplatin-Induced Anorexia in Rats by Modulating Ghrelin and Monoamine Neurotransmitters.

Anorexia is common in patients with cancer, mostly as a side effect of chemotherapy. The effect of electro-acupuncture (EA) on ameliorating cancer-related symptoms have been studied in animal models and in clinical trials. The aim of this study was to determine optimal conditions for the application of EA to alleviate anorexia, followed by the study of molecular mechanisms affecting its therapeutics. Anorexia was induced in male Wistar rats by injecting cisplatin, which was then followed by EA treatment at CV12, the acupuncture point located in the center of the abdominal midline. Body weight and food intake were measured daily throughout the duration of the study. The levels of monoamine neurotransmitters in the plasma were quantitatively analyzed by HPLC-ECD. Gastrointestinal hormone concentrations were elucidated with ELISA kits. RT-qPCR was performed to evaluate the mRNA expression of ghrelin (GHRL), neuropeptide Y (NPY), and pro-opiomelanocortin. The expression of c-Fos in the nucleus tractus solitarii was detected using western blotting analysis. The optimal conditions of EA to alleviate anorexia in rats was determined to be 1 unit for intensity and 10 Hz for frequency. EA treatment at CV12 reduced the levels of plasma monoamine neurotransmitters 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, dopamine, and norepinephrine; as well as stimulated the expression of GHRL and NPY to alleviate cisplatin-induced anorexia in rats. EA stimulation at CV12 could be used to treat cisplatin-induced anorexia in rats.

Sargassum swartzii extracts ameliorate memory functions by neurochemical modulation in a rat model.

Recently, considerable attention has been paid to drug exploration from natural sources for treating memory loss, a major manifestation of various neurodegenerative diseases. Increasing evidences implicate brain serotonin metabolism in learning and memory, supporting the notion that targeting 5-HT (5-hydroxytryptamine) and its receptors would be beneficial in the treatment of cognitive disorders. In the present study, behavioral and neurochemical effects were examined following administration of Sargassum swartzii extracts in albino Wistar rats. Increase in spatial working memory and recognition memory was exhibited by the seaweed-treated rats as compared to controls. Plasma tryptophan, brain 5-HT, and 5-hydroxyindoleacetic acid levels were measured using HPLC-ECD, and a significant increase in brain 5-HT metabolism was observed in the seaweed-treated rats. The increase in memory functions following repeated administration of S. swartzii extracts is suggested to be due to the increased serotonergic neurotransmission in the brain of seaweed-treated rats.

Tumor interstitial fluid promotes malignant phenotypes of lung cancer independently of angiogenesis.

Angiogenesis is necessary for cancer progression, but antiangiogenic therapy actually promotes tumor recurrence, progression, and metastasis. This study focused on the contribution of the tumor interstitial fluid (TIF) to lung cancer progression. TIF was isolated and quantified for 10 μg protein/mL. Malignant driver characteristics of TIF were examined by tumor-initiating cells (TIC), self-renewal, epithelial-mesenchymal transition (EMT), autophagy, and apoptosis in vitro. In vivo tumor model was used to investigate the mechanistic roles of TIF in lung cancer progression. In vitro, TIF exhibited distinct malignant driver characteristics, which led to increased numbers of TICs, increased self-renewal and EMT, as well as to decreased autophagy and apoptosis under cell starvation conditions. In vivo, the contribution of TIF was similar, as judged by increased TICs indicated by the cancer stem cell marker Nanog, the proliferation marker proliferating cell nuclear antigen, and the EMT marker N-cadherin; TIF also increased the formation of pulmonary tumors. Interestingly, the blockers of inflammation, Na-K-ATPase, and aldosterone receptor decreased TIF-induced tumor progression but increased angiogenesis. Further, we found that the water content of the tissue was positively correlated with the levels of plasma 5-hydroxyindoleacetic acid or tissue aquaporin-1 but not with CD31. However, vadimezan reduced angiogenesis but promoted TIF-induced tumor progression. Our results suggested that TIF could provide better nutrition to the tumor than angiogenesis and that it could promote the development of malignant phenotypes of lung cancer independently of angiogenesis.

Reduced plasma serotonin and 5-hydroxyindoleacetic acid levels in Parkinson's disease are associated with nonmotor symptoms.

Accumulating evidence suggests that serotonergic system may be implicated in the pathophysiology of Parkinson's disease (PD), and particularly in nonmotor symptoms such as depression, fatigue, sleep disorders, sensory and autonomic dysfunction. This study aimed to evaluate plasma levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in PD patients, and investigate their associations with nonmotor symptoms. Eighty-two PD patients and sixty-four controls underwent a series of clinical assessments, including Hamilton Depression Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Visual Analog Scale for Pain, and Scale for Outcomes in PD for Autonomic Symptoms. Plasma 5-HT and 5-HIAA levels were measured by HPLC-ECD. PD patients exhibited worse performance on nonmotor symptom scales (all P-values <0.001) and presented lower plasma levels of 5-HT (P < 0.001) and 5-HIAA (P < 0.001) than control individuals. Within the PD group, decreased concentrations of plasma 5-HT and 5-HIAA were correlated with more severe depression (r = -0.447, P < 0.001; r = -0.407, P < 0.001, respectively) and pain (r = -0.485, P < 0.001; r = -0.416, P < 0.001, respectively). After performing multiple linear regression, plasma 5-HT (P = 0.01) and 5-HIAA (P = 0.006) remained significantly associated with depression. Our results suggest that serotonergic dysfunction might exist in PD, and specifically correlated with depression and pain in PD. Plasma levels of 5-HT and 5-HIAA may be considered as peripheral markers for depression in PD.

Catha edulis chewing effects on treatment of paranoid schizophrenic patients.

BackgroundThe current study’s aim is to evaluate the possible interaction effects of khat chewing on treatment of paranoid schizophrenic patients.Patients and methodsIn the study group, 42 male subjects suffered from paranoid schizophrenia and were classified according to their khat chewing habits into two subgroups: either khat-chewer subgroup (SKc; n=21; r=11, h=10) or non-khat-chewer subgroup (SNKc; n=21, r=11, h=10). Each subgroup was further subdivided according to type of treatment into r (risperidone) and h (haloperidol). Healthy male subjects (37) were subdivided into healthy khat-chewer as positive controls (HKc, n=17) and healthy non-khat-chewer as negative controls (HNKc, n=20). Plasma dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid, 5-hydroxytryptamine (serotonin), 5-hydroxyindoleacetic acid, epinephrine, and norepinephrine were estimated.ResultsANOVA and post hoc analysis showed that dopamine was illustrating significant elevation in all khat chewing groups. DOPAC was illustrating significant decrease in all khat chewing groups with an interesting outcome showing significant increase in DOPAC in SNKcr group due to risperidone effect. Homovanillic acid, serotonin, hydroxyindoleacetic acid, and norepinephrine were illustrating significant elevations in all khat chewing groups. Epinephrine was illustrating significant elevation in all chewers than non-chewers groups. Unexpected significant decrease in epinephrine in the SNKcr group indicated that risperidone drug is decreasing epinephrine through indirect mechanism involving calcium.ConclusionKhat chewing in schizophrenic patients is contraindicated because it aggravates the disease symptoms, attenuates all used treatment medications, and deteriorates all biochemical markers of the patients.

Serial surveillance of carcinoid heart disease: factors associated with echocardiographic progression and mortality.

Background:Carcinoid heart disease is a complication of metastatic neuroendocrine tumours (NETs). We sought to identify factors associated with echocardiographic progression of carcinoid heart disease and death in patients with metastatic NETs.Methods:Patients with advanced non-pancreatic NETs and documented liver metastases and/or carcinoid syndrome underwent prospective serial clinical, biochemical, echocardiographic and radiological assessment. Patients were categorised as carcinoid heart disease progressors, non-progressors or deceased. Multinomial regression was used to assess the univariate association between variables and carcinoid heart disease progression.Results:One hundred and thirty-seven patients were included. Thirteen patients (9%) were progressors, 95 (69%) non-progressors and 29 (21%) patients deceased. Baseline median levels of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and plasma 5-hydroxyindoleacetic acid (5-HIAA) were significantly higher in the progressors. Every 100 nmol l−1 increase in 5-HIAA yielded a 5% greater odds of disease progression (OR 1.05, 95% CI: 1.01, 1.09; P=0.012) and a 7% greater odds of death (OR 1.07, 95% CI: 1.03, 1.10; P=0.001). A 100 ng l−1 increase in NT-proBNP did not increase the risk of progression, but did increase the risk of death by 11%.Conclusions:The biochemical burden of disease, in particular baseline plasma 5-HIAA concentration, is independently associated with carcinoid heart disease progression and death. Clinical and radiological factors are less useful prognostic indicators of carcinoid heart disease progression and/or death.

Determination of the Optimal Echocardiographic Scoring System to Quantify Carcinoid Heart Disease

Background: Carcinoid heart disease (CHD) is an important complication of metastatic neuroendocrine disease, requiring regular monitoring to enable intervention prior to right heart failure. We aimed to identify the most appropriate echocardiographic scoring systems for the quantitative assessment of CHD. Methods: In this prospective study conducted between April and October 2012 in two European Neuroendocrine Tumor Society (ENETS) Centres of Excellence, patients with neuroendocrine tumours with liver metastases and/or carcinoid syndrome underwent transthoracic echocardiography and blood sampling for serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and plasma 5-hydroxyindoleacetic acid (5-HIAA). Each patient was assessed according to six echocardiographic scoring systems. The individual scoring systems' feasibility, observer variability, sensitivity, specificity and correlation with the concentration biomarkers were determined. Results: 100 patients were included; 21% had echocardiographic evidence of CHD. All scores discriminated highly between those with/without CHD, with no single score performing significantly better than another. The severity, determined using all of the scoring systems, correlated with the concentration of both biomarkers, but the strongest correlations were seen between the Bhattacharyya score and serum NT-proBNP. Conclusion: All scoring systems are comparable in terms of sensitivity and specificity for the detection of CHD. There is a variation in the feasibility of the scoring systems due to varying complexity of the score components. All scores correlate with NT-proBNP and plasma 5-HIAA. The Westberg score appears to be the most optimal scoring system for use in screening of CHD whereas the more complex scoring systems are more suited to the patient with established disease who may require surgical intervention.

Increased Concentrations of Serotonin and 5-Hydroxyindoleacetic Acid in Blood Plasma from Patients with Pulmonary Hypertension due to Mitral Valve Disease

Serotonin content in the plasma and platelets and 5-hydroxyindoleacetic acid concentration in the plasma were shown to increase in patients with pulmonary arterial hypertension due to mitral valve disease. A positive correlation was found between the severity of pulmonary arterial hypertension and concentrations of serotonin (r=0.48) and 5-hydroxyindoleacetic acid in the plasma (r=0.9).

Monitoring the treatment of carcinoid disease using blood serotonin and plasma 5-hydroxyindoleacetic acid: three case examples

The results for plasma 5-hydroxyindoleacetic acid (5-HIAA), whole blood serotonin and the chromogranins on three patients following their treatment for carcinoid disease with somatostatin analogues are presented. Two of the patients (a 56-year-old woman and a 55-year-old man) demonstrated a good clinical response following treatment, with initial high blood serotonin and plasma 5-HIAA concentrations showing a significant decline. However, blood serotonin concentrations remained above the reference range during the course of treatment, whereas plasma 5-HIAA remained borderline high or marginally elevated with respect to the clinical cut-off concentration. The third patient, a 79-year-old man, demonstrated saturation of platelets with serotonin and increasing elevation of plasma 5-HIAA, which later fell with the introduction of interferon into this patient's treatment regimen. Results for the plasma chromogranin fragments, pancreastatin (Chromogranin A) and GAWK (Chromogranin B), showed a much greater degree of variability in all three cases. This study shows promise for plasma 5-HIAA as a useful marker for monitoring carcinoid disease. The limitations of blood serotonin expressed to the platelet count are highlighted.

Effect of Centrally Administered Sphingomyelin on Food Intake and HPA Axis in Chicks

Emoto, F., Tomonaga, S., Tachibana, T., Denbow, D.M. and Furuse, M. 2006. Effect of centrally administered sphingomyelin on food intake and HPA axis in chicks. J. Appl. Anim. Res., 29: 91–96. Sphignomyelin (SM) is an abundant lipid in myelin and its metabolites are well recognized as bioactive substances. The aim of the present study was to investigate the functions of SM in the chick brain. Intracerebroventricular (ICV) injection of SM decreased food intake in chicks. No significant changes in plasma corticosterone, glucose, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were detected. Thus anorexia caused by SM injection could be established but its mechanism could not be elucidated.

Rat Tumor Response to the Vascular-Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid as Measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging, Plasma 5-Hydroxyindoleacetic Acid Levels, and Tumor Necrosis

The dose-dependent effects of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) on rat GH3 prolactinomas were investigated in vivo. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to assess tumor blood flow/permeability pretreatment and 24 hours posttreatment with 0, 100, 200, or 350 mg/kg DMXAA. DCE-MRI data were analyzed using Ktrans and the integrated area under the gadolinium time curve (IAUGC) as response biomarkers. Highperformance liquid chromatography (HPLC) was used to determine the plasma concentration of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) following treatment to provide an index of increased vessel permeability and vascular damage. Finally, tumor necrosis was assessed by grading hematoxylin and eosin-stained sections cut from the same tumors investigated by MRI. Both tumor Ktrans and IAUGC were significantly reduced 24 hours posttreatment with 350 mg/kg DMXAA only, with no evidence of dose response. HPLC demonstrated a significant increase in plasma 5-HIAA 24 hours posttreatment with 200 and 350 mg/kg DMXAA. Histologic analysis revealed some evidence of tumor necrosis following treatment with 100 or 200 mg/kg DMXAA, reaching significance with 350 mg/kg DMXAA. The absence of any reduction in Ktrans or IAUGC following treatment with 200 mg/kg, despite a significant increase in 5-HIAA, raises concerns about the utility of established DCE-MRI biomarkers to assess tumor response to DMXAA.

Sex hormones and biogenic amine turnover of sex offenders in relation to their temperament and character dimensions

Relationships between Cloninger's temperament and character dimensions and plasma sex hormone levels and biogenic amine turnover were studied in male prison inmates convicted of rape ( n=61) or child molestation ( n=24) and normal male controls ( n=25). The participants completed the Temperament and Character Inventory (TCI), which includes the temperament dimensions Novelty Seeking, Harm Avoidance, Reward Dependence and Persistence as well as the character dimensions Self-Directedness, Cooperativeness and Self-Transcendence. Plasma levels of testosterone, dihydrotestosterone, sex hormone binding globulin, luteinizing hormone (LH) and follicle-stimulating hormone were estimated in plasma samples and 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine samples. Both sex offender groups had higher Novelty, Seeking and lower Reward Dependence, Self-Directedness and Cooperativeness scores compared with the controls. Plasma levels of testosterone and dihydrotestosterone were significantly higher in rapists than in controls. Novelty Seeking scores were positively correlated with LH levels in rapists, and with testosterone levels in child molesters. Harm Avoidance scores were negatively correlated with 5-HIAA levels in rapists and with HVA levels in child molesters. In rapists, the calculated free androgen index showed a negative correlation with 5-HIAA. For the sex offender sample as a whole, the subgroup with high testosterone levels had higher Harm Avoidance scores, the subgroup with low HVA levels had lower Cooperativeness scores, and the subgroups with high 5HIAA or MHPG levels had lower Persistence scores. The results indicate that Novelty Seeking behavior in the group of rapists is associated with a hyperactive hypothalamic-pituitry-gonadal axis. In addition, low serotonin turnover and low dopamine turnover seem to be associated with a passive-avoidant behavioral style in rapists and child molesters, respectively.

Neuroendocrine tumours of the gastrointestinal tract

Gastrointestinal neuroendocrine tumours are classified as functioning or non-functioning according to the presence or absence of a clinically evident hypersecretion syndrome. In foregut tumours the presence of autonomous hormone secretion and the respective hypersecretion syndrome indicate functionality. Abdominal ultrasound (US), computed tomography (CT), magnetic resonance tomography (MRT) and somatostatin receptor scintigraphy (SRS) are used for localisation of the primary tumour and metastasis. Invasive procedures such as endoscopic US, intraoperative US or intraoperative duodenal transillumination are useful to localise small (< 1 cm) tumours. For localised tumours surgery is the first line treatment. In metastatic disease symptomatic therapy, biotherapy and chemotherapy are available. Cytoreductive therapy such as embolisation, chemoembolisation, thermo- or cryotherapy, or radio-receptor therapy are additional options. The first symptom of most neuroendocrine midgut tumours is abdominal pain. An increased chromogranin-A plasma concentration or 5-hydroxyindoleacetic acid 24-h urinary excretion indicates the neuroendocrine origin of the tumour or the possibility of a carcinoid syndrome, respectively. Surgical therapy prolongs survival but is rarely curative. Biotherapy is effective as symptomatic therapy. However, its cytoreductive potency is low. Chemotherapy is less effective in midgut tumours compared to foregut tumours. Cytoreductive strategies (chemoembolisation, thermo- or cryotherapy, cytoreductive surgery) and radio-receptor therapy may offer new therapeutic options. However, their definitive value has yet to be defined.

Effects of Acute Metabolic Stress on the Peripheral Vasopressinergic System in Schizophrenia

Although both vasopressin and stress have been implicated in the course of schizophrenia, it is unknown whether schizophrenic patients have altered stress-induced function of the vasopressinergic system. We examined the effects of acute metabolic stress induced by pharmacological doses (40 mg/kg) of 2-deoxyglucose (2DG) on plasma concentrations of vasopressin in 13 patients with schizophrenia (with no history of polydipsia and hyponatremia) and 12 healthy control subjects. Baseline vasopressin levels were lower in the schizophrenic patients and progressively increased in both groups throughout the 60 min following 2DG administration to a similar absolute amount, thus remaining lower in the schizophrenic group. Concomitantly, patients with schizophrenia had significantly higher 2DG-induced plasma homovanillic acid (HVA) and 5-hydroxyindoleacetic acid levels. Vasopressin responses correlated positively and significantly with the HVA responses in schizophrenics and with the pituitary-adrenal axis responses in controls. These results suggest two different patterns of neuroendocrine alterations in schizophrenia, namely a relatively normal vasopressin response to 2DG despite significantly decreased baseline levels and exaggerated responses of the peripheral dopaminegic and serotonergic systems in the face of normal baseline concentrations.