Effects of tryptophan depletion and tryptophan loading on the affective response to high-dose CO2 challenge in healthy volunteers

It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges. Using a high-dose carbon dioxide (CO2) challenge, we aimed to investigate the effects of acute tryptophan depletion (ATD) and acute tryptophan loading (ATL) on CO2-induced panic response in healthy volunteers. Eighteen healthy volunteers participated in a randomized, double-blind placebo-controlled study. Each subject received ATD, ATL, and a balanced condition (BAL) in separate days, and a double-breath 35% CO2 inhalation 4.5 h after treatment. Tryptophan (Trp) manipulations were obtained adding 0 g (ATD), 1.21 g (BAL), and 5.15 g (ATL) of l-tryptophan to a protein mixture lacking Trp. Assessments consisted of a visual analogue scale for affect (VAAS) and panic symptom list. A separate analysis on a sample of 55 subjects with a separate-group design has also been performed to study the relationship between plasma amino acid levels and subjective response to CO2. CO2-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p <0.05). In the separate-group analysis, Delta VAAS scores were positively correlated to the ratio Trp:I LNAA pound after treatment (r = 0.39; p <0.05). The present results are in line with preclinical data indicating a role for the serotonergic system in promoting the aversive respiratory sensations to hypercapnic stimuli (Richerson, Nat Rev Neurosci 5(6):449-461, 2004). The differences observed in our study, compared to previous findings in PD patients, might depend on an altered serotonergic modulatory function in patients compared to healthy subjects

Association of serum uric acid levels to inflammation biomarkers and endothelial dysfunction in obese prepubertal children

BACKGROUND: High serum uric acid (SUA) levels are present in patients with metabolic syndrome (MetS), when the latter is associated with endothelial dysfunction, inflammation, and hypertension. This increase in SUA levels may have a key role in cardiovascular diseases. OBJECTIVE: We aim to quantify the differences in inflammation biomarkers, endothelial dysfunction, and parameters associated with MetS in obese prepubertal children compared to non-obese children, and determine if there is a relationship between uric acid levels and these variables. METHODS: A cross-sectional study was carried out on obese children (6-9 yr old). The study included 43 obese children and the same number of non-obese children (control group), matched by age and sex. SUA, C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), glucose, insulin, lipid profile, and blood pressure were all measured. RESULTS: SUA levels, CRP, and sICAM-1 were significantly higher in obese children. In the obese group, SUA levels showed a positive correlation with body mass index (BMI), insulin, homeostasis model assessment for insulin resistance (HOMA-IR), CRP, IL-6, sICAM-1, and triglycerides (TGs), and correlated negatively with high-density lipoprotein cholesterol (HDL-C) and Apo-AI, but not with Apo-B. When adjusted for age, sex, and creatinine, it was noted that SUA levels are independent predictive factors for sICAM-1, CRP, and IL-6. CONCLUSIONS: Inflammation biomarkers, endothelial dysfunction, and parameters associated with MetS are elevated in obese prepubertal children and correlate to uric acid levels

Gestational stress and fluoxetine treatment differentially affect plasticity, methylation and serotonin levels in the PFC and hippocampus of rat dams

Women are more likely to develop depression during childbearing years with up to 20% of women suffering from depression during pregnancy and in the postpartum period. Increased prevalence of depression during the perinatal period has resulted in frequent selective serotonin reuptake inhibitor (SSRI) antidepressant treatment; however the effects of such medications on the maternal brain remain limited. Therefore, the aim of the present study is to investigate the effects of the SSRI medication, fluoxetine, on neurobiological differences in the maternal brain. To model aspects of maternal depression, gestational stress was used. Sprague-Dawley rat dams were exposed to either gestational stress and/or fluoxetine (5mg/kg/day) to form the following four groups: 1. Control+Vehicle, 2. Stress+Vehicle, 3. Control+Fluoxetine, and 4. Stress+Fluoxetine. At weaning maternal brains were collected. Main findings show that gestational stress alone increased synaptophysin and serotonin metabolism in the cingulate cortex2 region of the cortex while fluoxetine treatment after stress normalized these effects. In the hippocampus, fluoxetine treatment, regardless of gestational stress exposure, decreased both global measures of methylation in the dentate gyrus, as measured by Dnmt3a immunoreactivity, as well as serotonin metabolism. No further changes in synaptophysin, PSD-95, or Dnmt3a immunoreactivity were seen in the cortical or hippocampal areas investigated. These findings show that gestational stress and SSRI medication affect the neurobiology of the maternal brain in a region-specific manner. This work adds to a much needed area of research aimed at understanding neurobiological changes associated with maternal depression and the role of SSRI treatment in altering these changes in the female brain

Fluoxetine dose and administration method differentially affect hippocampal plasticity in adult female rats.

International audienceSelective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat

Long-term corticosterone exposure decreases insulin sensitivity and induces depressive-like behaviour in the C57BL/6NCrl mouse.

Chronic stress or long-term administration of glucocorticoids disrupts the hypothalamus-pituitary-adrenal system leading to continuous high levels of glucocorticoids and insulin resistance (IR). This pre-diabetic state can eventually develop into type 2 diabetes mellitus and has been associated with a higher risk to develop depressive disorders. The mechanisms underlying the link between chronic stress, IR and depression remains unclear. The present study aimed to establish a stress-depression model in mice to further study the effects of stress-induced changes upon insulin sensitivity and behavioural consequences. A pilot study was conducted to establish the optimal administration route and a pragmatic measurement of IR. Subsequently, 6-month-old C57BL/6NCrl mice were exposed to long-term oral corticosterone treatment via the drinking water. To evaluate insulin sensitivity changes, blood glucose and plasma insulin levels were measured at different time-points throughout treatment and mice were behaviourally assessed in the elevated zero maze (EZM), forced swimming test (FST) and open field test to reveal behavioural changes. Long-term corticosterone treatment increased body weight and decreased insulin sensitivity. The latter was revealed by a higher IR index and increased insulin in the plasma, whereas blood glucose levels remained unchanged. Corticosterone treatment induced longer immobility times in the FST, reflecting depressive-like behaviour. No effects were observed upon anxiety as measured in the EZM. The effect of the higher body weight of the CORT treated animals at time of testing did not influence behaviour in the EZM or FST, as no differences were found in general locomotor activity. Long-term corticosterone treatment via the drinking water reduces insulin sensitivity and induces depressive-like behaviour in the C57BL/6 mouse. This mouse model could thus be used to further explore the underlying mechanisms of chronic stress-induced T2DM and its association with increased prevalence of major depressive disorder on the short-term and other behavioural adaptations on the longer term

Dimensões das fibras em bambusáceas Fiber dimensions of bamboos

São apresentados e discutidos os resultados das medições de comprimento e largura das fibras de 27 espécies alienígenas de bambus, compreendendo 12 gêneros, das quais apenas 4 foram anteriormente estudados pelos autores. O material usado nos exames biométricos das fibras de 19 das novas espécies estudadas, foi coletado do "bambusetum" localizado na Estação Experimental de Tatuí, sendo que o dos 4 restantes do base do côlmo de mudos importadas do estrangeiro, mas que não vingaram. Os resultados dos medições mostram que as dimensões das fibras, em comprimento e largura, variaram grandemente segundo as espécies de bambu. O comprimento médio de fibra variou de 1,33 a 2,74 mm, enquanto que a largura variou de 8,39 a 20,90 microns. A relação entre o comprimento e a largura das fibras situou-se entre 63:1 a 264:1. Os resultados encontrados nas medições de comprimento das fibras confirmam, de modo geral, o valor dos bambus como matéria-prima para produção de celulose de fibras longas.<br>This article gives fiber dimensions and derived values obtained for 23 bamboo species, besides similar data for 4 species previously reported by the authors. The average fiber dimensions found for the 27 bamboo species ranged as follows (in milimeters): length, from 1.325 for Bambusa beecheyana to 2.744 for Gigantcchloa apus; width, from 0.00839 for Pleioblastus simoni to 0.02090 for Bambusa beecheyana. The length diameter ratio ranged from 63:1 to 264:1, the shortest ratio being that of Bambusa beecheyana and the highest one of Bambusa vulgaris. The coefficient of variation for fiber length ranged from 26.50% to 42.32% and for fiber width from 17.80% to 60.09%. Considering the ease of bamboo cultivation, the high and rapid production per area, and the quality of the fiber, bamboos areunquestionably the most promising source for cellulose production in the tropical and subtropical regions. As in many other countries where bamboo is being used on a large scale for the pulp and paper industry, it seems likely that in Brazil this plant as a commercial crop will be, in very near future, an important source of long-fibered pulp for blending with short-fibered pulps in papermaking

Mean (± S.E.M.) fasting blood glucose (mmol/l), plasma insulin (ng/ml) values and HOMA-IR index at baseline (t0), after 4 weeks (t1) and after 12 weeks treatment (t2).

<p>CORT: corticosterone; HOMA-IR: homeostasis model assessment of insulin resistance index *<i>P</i><0.01.</p><p>Mean (± S.E.M.) fasting blood glucose (mmol/l), plasma insulin (ng/ml) values and HOMA-IR index at baseline (t0), after 4 weeks (t1) and after 12 weeks treatment (t2).</p

Effect of CORT administration via the drinking water (mean+S.E.M.) upon total distance moved and % time spent in the open arms of the elevated zero maze (EZM).

<p>(*) Trend towards difference between CORT and vehicle treatment (<i>P</i> = 0.09).</p

Effects of corticosterone (CORT) administration via the drinking water upon water intake (mean % change+S.E.M.) during the 12 week treatment period.

<p>Significant increased amounts of water intake in the CORT group are denoted with *(<i>P</i><0.01).</p