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Using high-performance liquid chromatography and gas chromatography, we reevaluated the 24-h influence of a serotonin- and dopamine-rich diet on platelet serotonin and serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and major catecholamine metabolites in the urine of 15 healthy adults. Although there were significant responses in urinary free serotonin and catecholamine metabolites, their concentrations did not exceed the upper limits of the reference ranges for any of the participants. For urinary 5-HIAA, pronounced effects were observed within 2-4 h. After 6-8 h, results for 11 participants exceeded the upper limit of the reference range. The median recovery of dietary serotonin as urinary 5-HIAA was 20% and subject to a large range (1-50%). There was no significant change in platelet serotonin. We conclude that, using specific analytical methods, no dietary restrictions need be imposed to diagnose catecholamine (metabolite)-producing tumors. For diagnosis of carcinoids on the basis of urinary 5-HIAA it is appropriate to completely abstain from serotonin-containing foods for greater than or equal to 12 h before testing. Platelet serotonin is a more sensitive marker for carcinoids that produce only small amounts of serotonin, and is unaffected by dietary serotonin.

SUMMARY.A method for the determination of metanephrine (MN; also known as metadrenaline), normetanephrine (NMN; also known as normetadrenaline) and 3-methoxytyramine (3-MT) in human urine using high-performance liquid chromatography followed by electrochemical detection (ECD) was validated primarily by comparing the results with those obtained by a gas chromatography±mass spectrometry (GC±MS) reference method. Correlation coef®cients of 0.93, 0.94 and 0.91 were obtained for MN, NMN and 3-MT, respectively, in a group of healthy controls consisting of 30 women and 30 men. A systematic difference was detected only for 3-MT (2 16%). Further tests of accuracy (linearity and recovery) and precision demonstrated that the described method must be considered to be a reliable approach to assess urinary metanephrines in the diagnosis of phaeochromocytoma. At lower concentrations (MN, 248 nmol/L; NMN, 434 nmol/L; 3-MT, 402 nmol/L), within-assay coef®cients of variation were close to 5% or less (5´3, 4´6 and 2´2%, respectively) and between-assay coef®cients of variation were 8´9, 11´2 and 12´3%, respectively, for the same low levels. This raises the possibility that this method can also be applied to assess urinary free, unconjugated metanephrines. Sex differences were detected for MN and NMN excretion when expressed in nmol per 24 h and nmol/mmol creatinine, respectively, by both ECD and GC±MS methods.

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Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic amine which has a multitude of more or less clearly established effects on peripheral vessels. It influences blood viscosity, platelet aggregation, and vasoconstruction and -dilatation, it enhances capillary permeability, it is the precursor of melatonin (a hormone with diurnal production in the eye). Because of these actions a role for serotonin in the development of glaucoma and diabetic retinopathy might be suspected. In a series of pilot studies on rats the effects of serotonin on the anterior and posterior segments of the eye were studied. Serotonin had marked influence on the retinal and choroidal vasculature. The optic disk seemed to be very sensitive to serotonin. Possibly it had an influence on the blood-retinal barrier. It caused transient cataracts, probably by decreasing the production of aqueous. It blocked tropicamin-induced mydriasis. The techniques and provisional results of measurement of serotonin in human aqueous are also described.

This paper reports the results of a cohort study and randomised clinical trial (RCT) in cross-over design. In the cohort study, the range of urinary oxalate (Uox) and calcium (Uca) excretion was determined within a sample of the Dutch population of dogs and cats, and dietary and animal-related factors associated with these urine parameters were identified. Spot urine samples were collected from privately owned dogs (n=141) and cats (n=50). The RCT determined the effect of a commercial raw meat diet versus a dry diet on Uox and Uca excretion rate in 23 dogs. In the cohort study, Uox excretion ranged from 21.1 to 170.6 mmol oxalate/mol creatinine in dogs and 27.5 to 161.6 in cats. Urinary calcium excretion ranged from 3.4 to 462.8 mmol calcium/mol creatinine in dogs and 10.1 to 128.0 in cats. In dogs, increased Uox and Uca excretion was associated with (1) the intake of a dry diet as the primary source of energy, (2) receiving no snacks and (3) breed. Increased Uox excretion was associated with males as well. In cats, urine collection in anaesthetised subjects was identified as a confounder. In the RCT, feeding the dry diet resulted in higher Uox (P<0.001) and Uca (P=0.021) excretion rates in dogs.

Alzheimer’s disease (AD) is associated with progressive endogenous neurotoxicity and hampered inflammatory regulation. The kynurenine (Kyn) pathway, which is controlled by tryptophan 2,3-dioxygenase (TDO), produces neuroactive and anti-inflammatory metabolites. Age-related Kyn pathway activation might contribute to AD pathology in humans, and inhibition of TDO was found to reduce AD-related cellular toxicity and behavioral deficits in animal models. To further explore the effect of aging on the Kyn pathway in the context of AD, we analyzed Kyn metabolite profiles in serum and brain tissue of the APP23 amyloidosis mouse model. We found that aging had genotype-independent effects on Kyn metabolite profiles in serum, cortex, hippocampus and cerebellum, whereas serum concentrations of many Kyn metabolites were reduced in APP23 mice. Next, to further establish the role of TDO in AD-related behavioral deficits, we investigated the effect of long-term pharmacological TDO inhibition on cognitive performance in APP23 mice. Our results indicated that TDO inhibition reversed recognition memory deficits without producing measurable changes in cerebral Kyn metabolites. TDO inhibition did not affect spatial learning and memory or anxiety-related behavior. These data indicate that age-related Kyn pathway activation is not specific for humans and could represent a cross-species phenotype of aging. These data warrant further investigation on the role of peripheral Kyn pathway disturbances and cerebral TDO activity in AD pathophysiology.

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