Food preservatives sodium sulfite and sorbic acid suppress mitogen-stimulated peripheral blood mononuclear cells

Antioxidant preservatives prolong the quality of food and ensure the nutritional adequacy, palatability and safety of many processed foods and beverages. Effects of sodium sulfite (E221) and sorbic acid (E200) were investigated in human peripheral blood mononuclear cells (PBMC) which were purified from blood of healthy donors. Cells were stimulated with the mitogen phytohaemagglutinin in vitro, which induces proliferation of T-cells and the production of Th1-type cytokines like interferon-γ. The latter triggers enzyme indoleamine (2,3)-dioxygenase, which degrades tryptophan, and GTP cyclohydrolase I, which leads to increased neopterin production, in monocyte-derived macrophages. Sodium sulfite and sorbic acid suppressed both these biochemical changes in a dose-dependent way (P < 0.01 at 1 mM sodium sulfite and 50 mM sorbic acid). Data demonstrate a suppressive influence of sodium sulfite and sorbic acid on the activated Th1-type immune response.     

L-tryptophan injection fails to alter nutrient selection by rats

Nutritional studies on rats given a choice between two diets differing in protein content have led to the proposal that brain 5-HT content regulates protein intake [2]. Pharmacologic studies under similar conditions of dietary self-selection suggest that brain 5-HT controls carbohydrate intake [41]. We tested the effect of elevating brain 5-HT via tryptophan injection (100 mg/kg) on short-term food intake and selection by rats choosing between two diets differing in protein and carbohydrate content. Under these conditions neither total food intake nor protein and carbohydrate selection were affected despite increases of 50% in brain concentrations of 5-HT and 5-HIAA. The effect of Trp administration was selective to serotonin metabolism as brain concentrations of NE, DA and DOPAC were not affected. These results suggest that alterations in brain 5-HT content which may occur following meal ingestion may not be of physiological importance in regulating nutrient intake and selection.     

Weight loss in patients with hematological neoplasias is associated with immune system stimulation

Summary Weight loss is the main symptom of so-called tumor cachexia. The pathogenetic mechanisms underlying cachexia are poorly understood; however, it appears that enhanced formation of cytokines such as interferon- and tumor necrosis factor- are involved. In 94 patients suffering from hematological neoplasias we compared body weight changes with serum neopterin, tryptophan, and kynurenine. Biochemical changes, the formation of neopterin, the degradation of tryptophan are closely related to interferon- activity. The majority of our patients had increased neopterin and decreased tryptophan concentrations. Weight loss was seen particularly in patients with higher neopterin and lower tryptophan values. An association between higher neopterin levels and greater weight loss was apparent at study entry and during the follow-up of patients. Our data support the concept that weight loss is closely linked to endogenous interferon- activity.Abbreviations NHL non-Hodgkin's lymphoma - HD Hodgkin's disease - MM multiple myeloma - MGUS monoclonal gammopathy of unknown significance - IFN- interferon- - TNF- tumor necrosis factor-     

中枢性疲劳症候群临床与血清色氨酸的研究

目的：对珠海市中学生中枢性疲劳症候群的临床,患病率及与血清色氨酸的关系进行研究。方法：采用单纯随机抽样和整群一级抽样方法,对4年中学1594人进行问卷调查作为初筛,筛出有症状的部分人在医院进行以排除其它疾病为 的精查,并做血清色氨酸含量的测量,结果：临床表现自主神经症状,睡眠障碍,精神症状,推测珠海市中学生中患病率为11％,血清色氨酸含量较正常对照组低,两组有显著差异（P＜0．01）,结论：中枢性疲劳症候群是珠海地区中学生中的常见病,应积极于以防治;血中色氨酸含量的测定对诊断该疾病有一定的价值。     

Serotonergic mechanisms of cocaine effects in humans

The objective of this study was to investigate the role of serotonin (5-HT) in mediating the effects of cocaine in humans. To accomplish this, 12 subjects each participated in two randomized, double-blind test sessions separated by 1 week. In one session, subjects underwent acute depletion of the 5-HT amino acid precursor tryptophan (TRP), followed by a test dose of intranasal cocaine. In the other session, the cocaine test dose was preceded by sham depletion. Subject ratings of cocaine high were significantly lower following active TRP depletion than after the sham procedure. Subjects also showed an earlier but less sustained rise in self-rated nervousness during active TRP depletion. These findings are consistent with the hypothesis that 5-HT may be involved in mediating the euphorigenic and modulating the anxiogenic effects of cocaine in humans, either directly or through actions on other (e.g., dopaminergic) systems.     

Identification of amino-terminal sequences contributing to tryptophan hydroxylase tetramer formation

Tryptophan hydroxylase (TPH) catalyzes the rate-limiting step in the biosynthesis of serotonin. In the rabbit, TPH exists as a tetramer of four identical 51-kDa subunits comprised of 444 amino acids each. The enzyme consists of an amino-terminal regulatory domain and a carboxyl-terminal catalytic domain. Previous studies demonstrated that within the carboxyl-terminus of TPH, there resides an intersubunit binding domain (a leucine zipper) that is essential for tetramer formation. However, it is hypothesized that a 4,3-hydrophobic repeat identified within the regulatory domain of TPH (residues 21–41) may also be involved in macromolecular assembly. To test this hypothesis, a series of amino-terminal deletions (NΔ15, 30, 41, and 90) were created and assessed for macromolecular structure using size-exclusion chromatography. The amino-terminal deletion NΔ15, upstream from the 4,3-hydrophobic repeat, was capable of forming tetramers. However, when a portion of the 4,3-hydrophobic repeat was deleted (NΔ30), a heterogeneous elution pattern of tetramers, dimers, and monomers was observed. Complete removal of the 4,3-hydrophobic repeat (NΔ41) rendered the enzyme incapable of forming tetramers; a monomeric form predominated. In addition, a double-point mutation (V28R-L31R) was created in the hydrophobic region of the enzyme. The introduction of two arginines (R) at positions 28 and 31 respectively, in the helix disrupted the native tetrameric state of TPH. According to size-exclusion chromatography analysis, the double-point mutant (V28R-L31R) formed dimers of 127 kDa. Thus, it is concluded that there is information within the amino-terminus that is necessary for tetramer formation of TPH. This additional intersubunit binding domain in the amino-terminus is similar to that found in the carboxyl-terminus.     

Intensity dependence of auditory evoked potentials (AEPs) as biological marker for cerebral serotonin levels: effects of tryptophan depletion in healthy subjects

Rationale: The intensity dependence of the auditory evoked potentials (AEP) has been suggested to be a specific biological marker of central serotonergic activity. Objective: While previous studies used circumstantial evidence to support this hypothesis, we manipulated (decreased) cerebral levels of serotonin directly by using tryptophan depletion. Methods: Twelve healthy young subjects were investigated using placebo and two different amino acid mixtures in a double blind cross over design on three different occasions. AEPs recorded during tryptophan depletion were analyzed by dipole analysis and regional sources using methods published in the literature. Results: For none of the mixtures a significant effect of tryptophan depletion was found. There was a trend towards reduced intensity dependency after tryptophan depletion, especially in the right hemisphere. This reduction correlated with the amount of reduced tryptophan in plasma. Conclusions: The results indicate, in contrast to earlier indirect studies, that the intensity dependence of AEPs is not a specific marker of central serotonergic activity. Received: 8 March 1999 / Final version: 25 May 1999     

Dependence of 5-HT and catecholamine synthesis on concentrations of precursor amino-acids in rat brain

Summary The short-term influence of varying concentrations of the precursors tryptophan and tyrosine on the formation of 5-hydroxytryptophan and Dopa, respectively, in three different rat-brain regions was investigated. The concentrations of the precursors were either increased by the intraperitoneal administration of the respective precursor or decreased by loading with large neutral amino acids competing with the precursors for the same carrier mechanisms.The formation of 5-hydroxytryptophan was found to depend on the level of tryptophan in the brain in a manner predicted from published kinetic data, except when large doses of non-precursor amino acids had been given (>300 mg/kg). In the latter case the hydroxylation of tryptophan was less rapid than expected. The apparent K _m of tryptophan hydroxylase calculated from these data was about 25 M, which is in reasonably good agreement with earlier published in-vitro and in-vivo data.The formation of Dopa likewise depended on the level of the precursor tyrosine in a predictable manner, in this case without any anomalous results after large doses of non-precursor amino acids. The apparent K _m of tyrosine hydroxylase was calculated from these invivo observations to be about 25 M, which is in fairly close agreement with published in-vitro data.It is concluded that under normal conditions tryptophan hydroxylase in the rat brain is about half-saturated with its amino-acid substrate, whereas tyrosine hydroxylase appears to be about 75% saturated.     

Isoprenaline increases brain concentrations of administered l-dopa and l-tryptophan in the rat

A small dose of isoprenaline or saline was administered intraperitoneally to rats 20 min before the administration of one of the amino acids l-dopa or l-tryptophan. Isoprenaline caused a marked increase in the brain concentration of the administered amino acid. Isoprenaline has previously been shown to cause a decrease in at least some of those plasma amino acids which compete with l-dopa and tryptophan for carrier-mediated transport into the brain. The effect of isoprenaline on the concentrations of dopa and tryptophan in the brain is suggested to be at least partly caused by a change in the relationship between endogeneous and administered amino acids. It is also possible that a direct effect of isoprenaline on the blood-brain barrier transport system contributes to the effect.The reported finding might be of clinical interest in view of the therapeutic importance of aromatic amino acids with a central site of action.