Effects of low concentrations of organochlorine compounds in women on calcium transfer in human placental syncytiotrophoblast.

For most Canadians, food represents one of the major sources of environmental contaminants. Among them, organochlorine compounds (OCs) are known to affect calcium (Ca2+) homeostasis. They are neurotoxic by perturbation of Ca2+ channels and pumps, and they interfere with protein kinase C (PKC) and Ca2+ binding protein (CaBP). Ca2+ is an essential element to adequate fetal growth and development. The aim of the present study is to determine the relation between low environmental maternal exposure to OCs, such as polychlorinated biphenyls (PCB 153), Aroclor 1260, p,p'-dichlorodiphenyltrichloroethane (DDT) and p,p'-dichlorodiphenyl-dichloroethane (DDE), Ca2+ levels in serum and placenta, placental Ca2+ transfer, and newborn development. Total Ca2+ and OCs were measured in women's serum samples, as well as in umbilical cord's serum and placenta at term. Placentas were taken for trophoblast cells isolation and Ca2+ incorporation kinetic experiments. Our results were obtained from 30 pregnant women from the southwestern area of Quebec. Concentrations of Aroclor 1260, PCB 153, DDE, and DDT were respectively 6.1, 6.0, 3.1, and 2.9 times lower in the umbilical cord serum than in the mother's serum at term. In the placenta, DDE was accumulated at higher levels than other contaminants. A tendency towards an inverse relation was observed for in OCs found in three compartments and Ca2+ levels in maternal serum and in placental tissues. Maternal Ca2+ concentrations do not influence Ca2+ uptake by syncytiotrophoblast. Only DDE (>/=0.70 mug/l) in maternal serum significantly was associated with a small increase in Ca2+ uptake by syncytiotrophoblast. This study will help us determine if low OC contamination significantly modifies Ca2+ transfer in syncytiotrophoblast.     

Exposure to ethanol and nicotine induces stress responses in human placental BeWo cells

Human placental trophoblastic cancer BeWo cells can be used as a model of placental trophoblasts. We found that combined exposure to relevant exposure concentrations of ethanol (2‰) and nicotine (15 μM) induces an increase in the amount of reactive oxygen species (ROS). Neither ethanol or nicotine alone, nor their combination affected cell viability. However, nicotine decreased cell proliferation, both alone and combined with ethanol. Nicotine increased the expression of the endoplasmic reticulum (ER)-stress related protein GRP78/BiP, but not another marker of ER-stress, IRE1α. We also studied the effects of nicotine and/or ethanol on phosphorylation and expression of three mitogen-activated protein kinases (MAPKs), i.e. JNK, p38 and ERK1/2. Nicotine decreased the phosphorylation of JNK and also had similar effect on total amount of this protein. Phosphorylation and expression of p38 were increased 1.7- and 1.6-fold, respectively, by nicotine alone, and 1.9- and 2.1-fold by the combined treatment. Some increase (1.8-fold) was also seen in the phosphorylation of ERK2 at 48 h, in cells exposed to both ethanol and nicotine. This study shows that ethanol and nicotine, which harm the development of fetus may induce both oxidative and ER stress responses in human placental trophoblastic cells, implicating these mechanisms in their fetotoxic effects.     

Secretion of human chorionic gonadotropin in superfused young placental tissue exposed to cadmium

The effect of various concentrations of cadmium (Cd) in levels ranging from 0.75 to 12 μg/ml medium, on the secretion of human chorionic gonadotropin (hCG) in first-trimester placental expiants, after 6 or 24 h incubation, employing both static and dynamic systems was examined. Later the unbound Cd was washed for 45 min with fresh medium devoid of Cd, followed by superfusion with the latter medium for 75 min, during which time samples were collected for hCG assay. For the superfusion experiments the parameters used for evaluating the hCG secretion pattern were: mean peak amplitude (MPA), pulse frequency (PF) and the area under the hCG secretion curve (AUC). The results indicate that in the dynamic system the hCG secretion increased significantly, and this increase was dose dependent. There was also a dose-related increase in mean total hCG secreted by the explants exposed to Cd. Maximal hCG secretion was observed after 24 h exposure of explants to 6 μg of the metal/ml. Both the MPA and AUC parameters showed a statistically significant increase for this dose level. At 12 μg/ml, the pulsatile secretion of hCG decreased, the value for the mean hCG secretion being comparable to that observed for 0.75 μg/ml. After 6 h incubation, however, there were no significant changes from the control, as judged by all of the above parameters. The levels of hCG secreted by the explants into the media in the static system were not significantly different from their respective controls, for both incubation periods and Cd levels. These results indicate that Cd may affect the normal placental function, as reflected in its hCG secretion pattern.     

In vitro evaluation of the effects of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) on IL‐2 production in human T‐cells

Perfluorinated compounds, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), have been shown to alter various immune functions suggesting they are immunotoxic. This study assessed the effects of PFOS and PFOA on interleukin (IL)‐2 production in the human Jurkat T‐cell line and PFOS in healthy human primary T cells. Jurkat cells were stimulated with phytohemagglutinin (PHA)/phorbol myristate acetate (PMA), anti CD‐3/anti CD‐28, or anti CD‐3, and dosed with 0, 0.05, 0.1, 0.5, 1, 5, 10, 50, 75, or 100 µg ml^?1 PFOS or 0, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 5, or 10 µg ml^?1 PFOA. Jurkat cells stimulated with PHA/PMA or anti CD‐3 exhibited decreased IL‐2 production beginning at 50 µg PFOS ml^?1 and 5 µg PFOS ml^?1 respectively, but stimulation with anti‐CD3/anti‐CD28 resulted in no changes compared with the control. Addition of the PPAR‐alpha antagonist GW6471 to PFOS‐dosed cells stimulated with PHA/PMA resulted in decreases in IL‐2 production starting at 50 µg PFOS ml^?1, which suggests PFOS affected T‐cell IL‐2 production via PPAR‐alpha‐independent mechanisms. Exposure to PFOA, PFOA + GW6471, or PFOS + PFOA in Jurkat cells resulted in no significant differences in IL‐2 production. In vitro dosing studies using healthy primary human CD4+ T cells were consistent with the Jurkat results. These data demonstrated that PFOA did not impact IL‐2 production, but PFOS suppressed IL‐2 production in both a human cell line and human primary cells at dose levels within the high end of the human exposure range. A decrease in IL‐2 production is characteristic of autoimmune diseases such as systemic lupus erythematosus and should be further investigated. Copyright © 2014 John Wiley & Sons, Ltd.     

Endocrine and cardiovascular responses to a series of graded physical and psychological stress stimuli in healthy volunteers

To investigate the endocrine and cardiovascular responses to a series of psychological and physical stress stimuli and to investigate the possibility of a stimulus intensity-response relation of endocrine and cardiovascular reactivity, 18 healthy volunteers were exposed to psychological and physical stimuli of increasing intensity. Each volunteer participated in three experimental sessions on separate days. The sequence of the sessions was such that all volunteers first participated in a session in which they were not exposed to a stress stimulus, i.e. the control session. Then they were randomly assigned to enter two trial sessions in which they were consecutively exposed to a series of psychological stressors and a series of physical stressors. During each session blood pressure (BP) and heart rate (HR) were assessed and blood samples were taken, to determine cortisol and noradrenaline levels.

During the physical stress session increments in systolic and diastolic blood pressure and noradrenaline were observed, proportional to the intensity of the stimuli. In contrast, during the psychological stress session pronounced increments in heart rate were observed, with maximum responses at the second and third stimuli. Diastolic blood pressure responses showed a similar pattern, whereas no changes in noradrenaline were observed. Plasma cortisol was not increased by the psychological stressor, whereas it was stimulated by the physical stressor but at the highest stimulus intensity only. Although the size of the study population precludes any firm conclusions, the results suggest that a stimulus intensity approach in human stress research is possible. Furthermore, the results also appear to indicate that the cardiovascular and pituitary-adrenal systems may display stress-specific responses.     

Combined effects of perfluorooctane sulfonate (PFOS) and maternal restraint stress on hypothalamus adrenal axis (HPA) function in the offspring of mice

Although it is known that prenatal exposure to perfluorooctane sulfonate (PFOS) can cause developmental adverse effects in mammals, the disruptive effects of this compound on hormonal systems are still controversial. Information concerning the effects of PFOS on hypothalamus adrenal (HPA) axis response to stress and corticosterone levels is not currently available. On the other hand, it is well established that stress can enhance the developmental toxicity of some chemicals. In the present study, we assessed the combined effects of maternal restraint stress and PFOS on HPA axis function in the offspring of mice. Twenty plug-positive female mice were divided in two groups. Animals were given by gavage 0 and 6 mg PFOS/kg/day on gestation days 12-18. One half of the animals in each group were also subjected to restraint stress (30 min/session, 3 sessions/day) during the same period. Five plug-positive females were also included as non-manipulated controls. At 3 months of age, activity in an open-field and the stress response were evaluated in male and female mice by exposing them to 30 min of restraint stress. Male and female offspring were subsequently sacrificed and blood samples were collected to measure changes in corticosterone levels at four different moments related to stress exposure conditions: before stress exposure, immediately after 30 min of stress exposure, and recuperation levels at 60 and 90 min after stress exposure. Results indicate corticosterone levels were lower in mice prenatally exposed to restraint. In general terms, PFOS exposure decreased corticosterone levels, although this effect was only significant in females. The recuperation pattern of corticosterone was mainly affected by prenatal stress. Interactive effects between PFOS and maternal stress were sex dependent. The current results suggest that prenatal PFOS exposure induced long-lasting effects in mice.     

Anti-adjuvant arthritis of recombinant human endostatin in rats via inhibition of angiogenesis and proinflarnmatory factors

AIM: To investigate the profile of endostatin on adjuvant arthritis (AA) and angiogenesis blockade in synovitis. METHODS: The model of rat AA was induced by injection of intradermal complete Freund's adjuvant (CFA). Hind paw volume of rat was measured by volume meter and the activities of interleukin-1 (IL-1) and IL-2 were measured by the assay of thymocytes proliferation. IL-1β and tumor necrosis factor-a (TNF-α) produced     

丙泊酚对高糖诱导的人肾小球系膜细胞氧化应激和炎症反应的影响

目的探讨丙泊酚对高糖诱导的人肾小球系膜细胞损伤的影响。方法该研究于 2021年 3月至 2022年 3月进行。体外培养人肾小球系膜细胞,采用 30 mol/L葡萄糖诱导建立人肾小球系膜细胞细胞损伤模型,用丙泊酚浓度 10、20、40 μmol/L处理细胞,细胞分为对照组、高糖组、高糖 +低、中、高剂量丙泊酚组。酶联免疫吸附测定( ELISA)检测超氧化物歧化酶( SOD)、谷胱甘肽过氧化物酶( GSH-PX)、丙二醛、活性氧、白细胞介素( IL)-10、肿瘤坏死因子 α(TNF-α)IL-1β表达;蛋白质印迹法检测诱导型一氧化氮合酶( iNOS)、细胞间黏附分子 -1(ICAM-1)、单核细胞趋化蛋白 -1(MCP-1)、 IL-10、TNF-α、IL-1β蛋白表达。结果高糖组的丙二醛［( 16.7±1.7)mmol/L比( 3.8±0.4)mmol/L］、活性氧［( 9.6±0.9)μg/L比( 3.5±0.3)μg/L］、 IL-10［( 65.3±6.9)ng/L比(26.9±3.2)ng/L］、 TNF-α［( 105.6±10.9)ng/L比( 42.8±4.8)ng/L］和 IL-1β［( 79.7±8.2)ng/L比( 31.2±3.6)ng/L］明显高于对照组; iNOS、ICAM-1、MCP-1、IL-10、TNF-α、IL-1β蛋白表达明显高于对照组; SOD、GSH-Px明显低于对照组,均 P<0.05。高糖 +低剂量丙泊酚组、高糖 +中剂量丙泊酚组、高糖 +高剂量丙泊酚组的丙二醛、活性氧、 IL-10、TNF-α和 IL-1β明显低于高糖组; iNOS、 ICAM-1、MCP-1、IL-10、TNF-α、IL-1β蛋白表达明显低于高糖组,均 P<0.05;SOD、GSH-Px明显高于高糖组,均 P<0.05。结论丙泊酚能减轻高糖诱导的人肾小球系膜细胞氧化应激和炎症反应,发挥保护肾脏的作用。     

Neuroendocrine responses to nicotine and stress: enhancement of peripheral stress responses by the administration of nicotine

Habitual smokers frequently report that when they are stressed smoking helps them to relax. One potential explanation for the reported stress ameliorating effect of smoking is that cigarette consumption (nicotine self-administration) may decrease the sympathetic autonomic nervous system activity which is associated with the stress response. In the present study, rabbits prepared with chronic vascular cannulae were used to study the effects of nicotine administation on plasma corticosterone, catecholamine (epinephrine, norepinephrine and dopamine) and glucose responses to physical restraint stress. Nicotine (0.025, 0.05 or 0.10 mg nicotine base/kg body weight) was administered for 10 days prior to the stress test to allow for the development of habituation/tolerance to its acute toxic effects. Independent administration of nicotine, or the application of the physical restraint stressor, resulted in increases in the plasma concentrations of corticosterone, epinephrine, norepinephrine, and glucose. Nicotine administration during restraint stress enhanced the increase in plasma corticosterone and epinephrine, as compared to the responses induced by either factor alone. The results suggest that the stress ameliorating effect of continued cigarette smoking, as reported by habitual smokers, is not due to a reduction in the activity of the peripheral sympathetic autonomic nervous system.     

Concurrent exposure to perfluorooctane sulfonate and restraint stress during pregnancy in mice: effects on postnatal development and behavior of the offspring.

The combined effects of maternal restraint stress and perfluorooctane sulfonate (PFOS) on postnatal development and behavior of the offspring were assessed in mice. Thirty-four plug positive females were randomly divided into two groups. Animals were given by gavage 0 and 6 mg PFOS/kg/day on gestation days 12-18. One-half of the animals in each group was subjected to restraint stress (30 min per session, three sessions per day) during the same period. Neither restraint nor PFOS exposure significantly modified maternal food or water consumption. Pups of dams exposed to 6 mg/kg of PFOS showed a reduced body weight on postnatal days 4 and 8. Moreover, PFOS exposure induced some delay in developmental landmarks and neuromotor maturation. Maternal restraint stress reduced activity in an open-field when combined with 6 mg PFOS/kg/day. In addition, in males prenatal restraint stress impaired motor coordination in a rotarod. The current results indicate that concurrent exposure to PFOS and restraint stress during pregnancy induces opposite effects on developmental parameters in the pups. These effects consist in a general delayed maturation trend induced by PFOS exposure, and a general accelerated maturation pattern induced by prenatal stress. Interactive effects between PFOS and maternal stress were observed in young adult mice. These effects consisted mainly in a diminished activity in an open-field test.     

Endothelial cationic amino acid transporter‐1 overexpression blunts the effects of oxidative stress on pressor responses to behavioural stress in mice

Observational studies indicate that psychological stress may contribute to the pathogenesis of hypertension and this may be further accentuated by factors such as endothelial dysfunction. On this basis, we aimed to determine whether oxidative stress enhances pressor responses to stressful stimuli and whether augmenting endothelial function by increasing the transport of l ‐arginine can counter the effects of oxidative stress. Telemetry probes were used to measure mean arterial pressure (MAP) in wild‐type (WT; n = 6) and endothelial cationic amino acid transporter‐1 (CAT‐1)‐overexpressing (CAT+) mice (n = 6) before and during an aversive (restraint) and non‐aversive (almond feeding) stressor. The superoxide dismutase inhibitor diethyldithiocarbamic acid (DETCA; 30 mg/kg per day; 14 days) was then administered via a minipump to induce oxidative stress. Stress responses to feeding and restraint were repeated during Days 11–12 of DETCA infusion. In WT mice, pressor responses to restraint and feeding were augmented during infusion of DETCA (35 ± 1 and 28 ± 1 mmHg, respectively) compared with respective pretreatment responses (28 ± 2 and 24 ± 1 mmHg, respectively; P ≤ 0.01). In CAT+ mice, pressor responses to feeding were blunted during DETCA (20 ± 1 mmHg) compared with the control response (23 ± 1 mmHg; P = 0.03). In these mice, pressor responses to restraint were similar before (28 ± 1 mmHg) and during (26 ± 1 mmHg) DETCA infusion (P = 0.26). We conclude that endothelial CAT‐1 overexpression can counter the ability of oxidative stress to augment pressor responses to behavioural stress.     

The immune responses in juvenile rockfish,Sebastes schlegelii for the stress by the exposure to the dietary lead (II)

The aim of this study was to evaluate the lead toxic effects on the stress parameters and immune responses of Sebastes schlegelii. Juvenile rockfish, S. schlegelii (mean length 14.2 ± 1.9 cm, and mean weight 57.3 ± 5.2 g) were exposed for 4 weeks with the different levels of dietary lead (Pb²⁺) at 0, 30, 60, 120 and 240 mg/L. The plasma cortisol and heat shock protein 70 was evaluated as stress indicators. The plasma cortisol of S. schlegelii was significantly increased in response to the dietary lead exposure over 60 mg/kg at 2 weeks. After 4 weeks, the significant increase in the plasma cortisol was observed at 30 and 60 mg/kg, but the level was decreased over 120 mg/kg. The heat shock protein 70 of S. schlegelii was also notably elevated over 60 mg/kg for 4 weeks. In the immune response, the immunoglobulin M of S. schlegelii was considerably increased over 120 mg/kg for 4 weeks. A significant increase was observed in lysozyme activity. The plasma lysozyme activity of S. schlegelii was elevated over 120 mg/kg after 2 weeks and 60 mg/kg after 4 weeks, and kidney lysozyme activity was also increased at 240 mg/kg after 2 weeks and over 120 mg/kg after 4 weeks. The results indicate that dietary Pb exposure can cause a significant stress and immune stimulation of S. schlegelii.     

Translational responses of Mytilus galloprovincialis to environmental pollution: integrating the responses to oxidative stress and other biomarker responses into a general stress index

Heavy metals are commonly associated with the generation of reactive oxygen species (ROS), which may cause oxidative damage to several cellular macromolecules and organelles. In an attempt to correlate biomarker responses to oxidative stress, caged mussels (Mytilus galloprovincialis) were exposed for 30 days in a relatively clean site and two areas (Stations 1 and 2) unevenly polluted by heavy metals in Gulf of Patras (Greece). Three periods of caging were: one in winter, the second in spring, and the third in autumn. Heavy metal content was determined in digestive glands of the exposed mussels as a measure of metal pollution, metallothionein content as an adaptive and detoxifying index, lysosomal membrane stability as a biomarker of general stress, superoxide radical production and lipid peroxidation as indicators of oxidative stress, and micronucleus frequency in gill cells as an index of chromosomal damage. Considering that protein-synthesizing machinery is one of the candidate targets for ROS, the in vivo activity of ribosomes in digestive glands was also tested. Compared with the reference samples, mussels transplanted to Station 1 showed increased levels of heavy metals and metallothionein in digestive glands, lower lysosomal membrane stability, higher values in oxidative stress indices, reduced activity of ribosomes, and increased chromosomal damage in gill cells. In addition, run-off ribosomes isolated from mussels transplanted to Station 1 were less efficient at initiating protein synthesis in a cell-free system than those from mussels in the reference site. Mussels transplanted to Station 2 exhibited similar but less pronounced responses. Statistical analysis revealed a strong positive correlation of ribosomal activity with lysosomal membrane stability, as well as a significant negative correlation with the oxidative stress indices, metallothionein content, micronucleus frequency, and the digestive gland content in Cr, Cu and Mn. Integration of all the measured biomarker responses into one general "stress index" demonstrated a clear distinction between the sampling sites, allowing classification along a pollution gradient (reference site相似文献   

Bidirectional placental transfer of Bisphenol A and its main metabolite,Bisphenol A-Glucuronide,in the isolated perfused human placenta

The widespread human exposure to Bisphenol A (BPA), an endocrine disruptor interfering with developmental processes, raises the question of the risk for human health of BPA fetal exposure. In humans, highly variable BPA concentrations have been reported in the feto-placental compartment. However the human fetal exposure to BPA still remains unclear. The aim of the study was to characterize placental exchanges of BPA and its main metabolite, Bisphenol A-Glucuronide (BPA-G) using the non-recirculating dual human placental perfusion. This high placental bidirectional permeability to the lipid soluble BPA strongly suggests a transport by passive diffusion in both materno-to-fetal and feto-to-maternal direction, leading to a calculated ratio between fetal and maternal free BPA concentrations of about 1. In contrast, BPA-G has limited placental permeability, particularly in the materno-to-fetal direction. Thus the fetal exposure to BPA conjugates could be explained mainly by its limited capacity to extrude BPA-G.     

Thermoregulatory responses to environmental toxicants: the interaction of thermal stress and toxicant exposure

Thermal stress can have a profound impact on the physiological responses that are elicited following environmental toxicant exposure. The efficacy by which toxicants enter the body is directly influenced by thermoregulatory effector responses that are evoked in response to high ambient temperatures. In mammals, the thermoregulatory response to heat stress consists of an increase in skin blood flow and moistening of the skin surface to dissipate core heat to the environment. These physiological responses may exacerbate chemical toxicity due to increased permeability of the skin, which facilitates the cutaneous absorption of many environmental toxicants. The core temperature responses that are elicited in response to high ambient temperatures, toxicant exposure or both can also have a profound impact on the ability of an organism to survive the insult. In small rodents, the thermoregulatory response to thermal stress and many environmental toxicants (such as organophosphate compounds) is often biphasic in nature, consisting initially of a regulated reduction in core temperature (i.e., hypothermia) followed by fever. Hypothermia is an important thermoregulatory survival strategy that is used by small rodents to diminish the effect of severe environmental insults on tissue homeostasis. The protective effect of hypothermia is realized by its effects on chemical toxicity as molecular and cellular processes, such as lipid peroxidation and the formation of reactive oxygen species, are minimized at reduced core temperatures. The beneficial effects of fever are unknown under these conditions. Perspective is provided on the applicability of data obtained in rodent models to the human condition.     

平武县抗震官兵应激反应测试及干预方法

目的分析抗震救灾官兵创伤后应激反应的相关因素,探讨有效降低军事应激条件下官兵应激水平干预方法。方法采用创伤后应激障碍自评量表(PTSD-SS)、简易应对方式问卷(SCSQ)、个人自评量表(PEI)及一般情况调查表对5.12地震救灾过程中的某部869名救灾官兵进行调查。在此基础上采用不同方案进行干预,并观察和对比疗效。结果抗震救灾官兵创伤后应激障碍的检出率为24.4%。PTSD-SS总分与职务、心理卫生知识了解情况、社会支持、生活条件、PEI总分及部分因子呈显著负相关(P<0.01～0.05),与负性应对方式呈显著正相关(P<0.01)。Ridit分析显示:不同干预方法效果不同(R=9.158,P<0.05),其中以综合心理干预方法效果最好。结论救灾官兵存在明显的心理创伤后应激反应,应激反应与心理和社会因素有关,应激状态下心理干预应首选综合心理干预方法。     

Exposure to Polystyrene nanoparticles induces liver damage in rat via induction of oxidative stress and hepatocyte apoptosis

Plastic products are widely used in different applications. Thus, exposure of human and other organisms to these products may affect their biological system. The current study was conducted to investigate the potential deleterious effect of Polysterene nanoparticles (PS-NPs) on the liver and to state the cellular and molecular mechanisms associated with exposure to PS-NPs.30 male rats were divided randomly and equally into 3 groups; control (distilled water), low dose (3 mg/kg/day) and high dose (10 mg/kg/day) exposed group via oral gavage for 5 successive weeks. PS-NPs caused elevation in ALT, AST and MDA, upregulation of apoptosis-related genes and significant decrease in GSH and mRNA expression for antioxidant-related genes (Nrf-2 and GPx). Moreover, alterations in hepatic tissue architecture and positive caspase-3 expression was noticed in a dose- dependent manner. Collectively, PS-NPs can induce hepatoxicity in rats in a dose dependent manner, so the health risk of PS-NPs should not be ignored.     

The functional importance of increased brain tryptophan in the serotonergic response to restraint stress

The increase in brain tryptophan induced by restraint stress in rats has been shown to be prevented by prior administration of valine, 200 mg/kg (i.p.). Brain 5-hydroxytryptamine (5-HT) was not depleted, but the stress-induced increase in 5-hydroxyindoleaeetic acid (5-HIAA) was prevented. A 5-HT-mediated functional response to stress, elevated plasma corticosterone, was however significantly attenuated by valine pretreatment, but was not affected by valine treatment alone. This suggests that the increase in 5-HIAA in brain is not merely secondary to increased brain tryptophan but indicates an increase in functional 5-HT activity, which is in turn at least partly dependent on the increase in brain tryptophan.Measurement of kynurenine levels in the same animals indicated an increase in synthesis in stress, but did not support the hypothesis that competition occurs between the kynurenine and 5-hydroxyindole pathways of tryptophan metabolism in brain.