Fluoxetine exposure during pregnancy and lactation: effects on acute stress response and behavior in the novelty-suppressed feeding are age and gender-dependent in rats

Fluoxetine (FLX) is commonly used to treat anxiety and depressive disorders in pregnant women. Since FLX crosses the placenta and is excreted in milk, maternal treatment with this antidepressant may expose the fetus and neonate to increased levels of serotonin (5-HT). Long-term behavioral abnormalities have been reported in rodents exposed to higher levels of 5-HT during neurodevelopment. In this study we evaluated if maternal exposure to FLX during pregnancy and lactation would result in behavioral and/or stress response disruption in adolescent and adult rats. Our results indicate that exposure to FLX influenced restraint stress-induced Fos expression in the amygdala in a gender and age-specific manner. In male animals, a decreased expression was observed in the basolateral amygdala at adolescence and adulthood; whereas at adulthood, a decrease was also observed in the medial amygdala. A lack of FLX exposure effect was observed in females and also in the paraventricular nucleus of both genders. Regarding the behavioral evaluation, FLX exposure did not induce anhedonia in the sucrose preference test but decreased the latency to feed of both male and female adolescent rats evaluated in the novelty-suppressed feeding test. In conclusion, FLX exposure during pregnancy and lactation decreases acute amygdalar stress response to a psychological stressor in males (adolescents and adults) as well as influences the behavior of adolescents (males and females) in a model that evaluates anxiety and/or depressive-like behavior. Even though FLX seems to be a developmental neurotoxicant, the translation of these findings to human safe assessment remains to be determined since it is recognized that not treating a pregnant or lactating woman may also impact negatively the development of the descendants.

The putative role of ovary removal and progesterone when considering the effect of formaldehyde exposure on lung inflammation induced by ovalbumin

OBJECTIVE: Formaldehyde exposure during the menstrual cycle is known to affect the course of allergic lung inflammation. Because our previous data demonstrated that formaldehyde combined with an ovariectomy reduced allergic lung inflammation, we investigated the putative role of ovary removal and progesterone treatment when considering the effect of formaldehyde on allergic lung inflammation. METHOD: Ovariectomized rats and their matched controls were exposed to formaldehyde (1%, 3 days, 90 min/day) or vehicle, and immediately after exposure, the rats were sensitized to ovalbumin by a subcutaneous route. After 1 week, the rats received a booster by the same route, and after an additional week, the rats were challenged with ovalbumin (1%) by an aerosol route. The leukocyte numbers, interleukin-10 (IL-10) release, myeloperoxidase activity, vascular permeability, ex vivo tracheal reactivity to methacholine and mast cell degranulation were determined 24 h later. RESULTS: Our results showed that previous exposure to formaldehyde in allergic rats decreased lung cell recruitment, tracheal reactivity, myeloperoxidase activity, vascular permeability and mast cell degranulation while increasing IL-10 levels. Ovariectomy only caused an additional reduction in tracheal reactivity without changing the other parameters studied. Progesterone treatment reversed the effects of formaldehyde exposure on ex vivo tracheal reactivity, cell influx into the lungs and mast cell degranulation. CONCLUSION: In conclusion, our study revealed that formaldehyde and ovariectomy downregulated allergic lung inflammation by IL-10 release and mast cell degranulation. Progesterone treatment increased eosinophil recruitment and mast cell degranulation, which in turn may be responsible for tracheal hyperreactivity and allergic lung inflammation

Biomarkers of exposure to metal contamination and lipid peroxidation in the benthic fish Cathorops spixii from two estuaries in South America, Brazil

Biomarkers as lipid peroxidation, metallothionein and delta-aminolevulinic acid dehydratase were determined in Cathorops spixii to compare the biological responses of this fish from estuaries with distinct anthropogenic influence. Three areas were selected in two estuaries in accordance with the levels of contamination for the polluted (Santos/So Vicente) and with the hydrodynamic characteristics for the non-polluted (Canan,ia) estuary. Water characteristics and mercury levels in C. spixii confirmed a high human influence in the polluted system. In general, the biomarkers showed differences between the estuaries, suggesting disturbances in the specific cell mechanisms due to the presence of multiple xenobiotics in the contaminated system. Therefore, these biomarkers are recommended to promote more accurate information about the exposure to pollutants. Additionally, the study of the effect of the multiple xenobiotics on resident species such as the benthic fish C. spixii can favor a better assessment of the environmental quality of these systems.

Learned helplessness in the rat: Effect of response topography in a within-subject design

Three experiments investigated learned helplessness in rats manipulating response topography within-subject and different intervals between treatment and tests among groups. In Experiment 1, rats previously exposed to inescapable shocks were tested under an escape contingency where either jumping or nose poking was required to terminate shocks: tests were run either 1, 14 or 28 days after treatment. Most rats failed to jump, as expected, but learned to nose poke, regardless of the interval between treatment and tests and order of testing. The same results were observed in male and female rats from a different laboratory (Experiment 2) and despite increased exposure to the escape contingencies using a within-subject design (Experiment 3). Furthermore, no evidence of helplessness reversal was observed, since animals failed to jump even after having learned to nose-poke in a previous test session. These results are not consistent with a learned helplessness hypothesis, which claims that shock (un)controllability is the key variable responsible for the effect. They are nonetheless consistent with the view that inescapable shocks enhance control by irrelevant features of the relationship between the environment and behavior. (C) 2010 Elsevier B.V. All rights reserved.

Dose-dependent effect of Resveratrol on bladder cancer cells: Chemoprevention and oxidative stress

Background: Over 6 million people die annually in the world because of cancer. Several groups are focused on studying cancer chemoprevention approaches. Resveratrol, a polyphenol, at high dosages, has been reported as antitumor and chemopreventive. However, it has a dose-dependent effect on cell death, even on some cancer cells. Objectives: Our aim was to investigate this dose-dependent effect on human bladder carcinoma ECV304 cells during oxidative stress condition. Methods: For this purpose. ECV304 cells incubated with different Resveratrol concentrations were analyzed as for their metabolic rate, membrane permeability, DNA fragmentation, anti/proapoptotic protein levels and phosphatidylserine exposure after oxidative stress. Results: Resveratrol induced cell death at high concentrations (>20 mu M), but not at low ones (0.1-20 mu M). Pretreatment with 2.5 mu M protected the cells from oxidative damage, whereas 50 mu M intensified the cell death and significantly increased Bad/Bcl-2 ratio (proapoptotic/antiapoptotic proteins). Resveratrol was able to modulate NO and PGE(2) secretion and performed an anti-adhesion activity of neutrophils on PMA-activated ECV304 cells. Conclusions: Resveratrol at high doses induces cell death of ECV304 cells whereas low doses induce protection. Modulation of Bcl-2 protein induced by Resveratrol could be mediating this effect. This information about the role of Resveratrol on cancer alerts us about its dose-dependent effects and could lead the design of future chemoprevention strategies. Published by Elsevier Ireland Ltd.

Effect of humidity and solvent vapor phase on cellulose esters films

In the present study the effect of relative humidity (RH) during spin-coating process on the structural characteristics of cellulose acetate (CA), cellulose acetate phthalate (C-A-P), cellulose acetate butyrate (CAB) and carboxymethyl cellulose acetate butyrate (CMCAB) films was investigated by means of atomic force microscopy (AFM), ellipsometry and contact angle measurements. All polymer solutions were prepared in tetrahydrofuran (THF), which is a good solvent for all cellulose esters, and used for spin-coating at RH of (35 +/- A 5)%, (55 +/- A 5)% or (75 +/- A 5)%. The structural features were correlated with the molecular characteristics of each cellulose ester and with the balance between surface energies of water and THF and interface energy between water and THF. CA, CAB, CMCAB and C-A-P films spin-coated at RH of (55 +/- A 5)% were exposed to THF vapor during 3, 6, 9, 60 and 720 min. The structural changes on the cellulose esters films due to THF vapor exposition were monitored by means of AFM and ellipsometry. THF vapor enabled the mobility of cellulose esters chains, causing considerable changes in the film morphology. In the case of CA films, which are thermodynamically unstable, dewetting was observed after 6 min exposure to THF vapor. On the other hand, porous structures observed for C-A-P, CAB and CMCAB turned smooth and homogeneous after only 3 min exposure to THF vapor.

Interaction of dietary vitamin D-3 and sunlight exposure on B. indicus cattle: Animal performance, carcass traits, and meat quality

Attempts to improve beef tenderness through supplementation with dietary vitamin D-3 have been challenged by null results and negative impacts on animal performance and carcass traits. Because vitamin D-3 is also synthesised by the animal via ultraviolet radiation from sunlight, the effectiveness of supplementation with dietary vitamin D-3 may be modulated by the degree of exposure of the animal to sunlight. Hence, this work aimed to verify whether dietary vitamin D-3 modifies meat quality without negatively affecting animal performance and carcass traits in B. indicus beef cattle that were either exposed to or protected from natural sunlight. Forty-two (411 +/- 38 kg) Nellore-type castrated males were fed a high-concentrate diet for 45 days after assignment to a treatment group. The treatments comprised combinations of three levels of vitamin D3 [ViTD - none (V0) or 2 x 10(6) IU of vitamin D-3 administered for either 2 (V2) or 8 (V8) consecutive days pre-slaughter] and two shading conditions (SHADE - unshaded or shaded). The post-mortem (pm) measurements were taken in the Longissimus thoracis et lumborum muscle. The animal performance and carcass traits were unaffected by ViTD or SHADE The V2 treatment increased the Myofibrillar Fragmentation Index in shaded animals compared to unshaded ones. Animals under shade had higher muscle calcium concentration. There was no effect of either ViTD or SHADE on the shear force. The L* values were higher at 24 h pm than at 0 and 1 h pm, with no differences among the animals in the ViTD or SHADE groups. Higher a* values were observed among animals in the V8 group than in the V0 group, and higher b* values were observed among animals in the V8 group than in the V2 or V0 groups, which were not different. In conclusion, ViTD and SHADE did not affect animal performance, carcass traits or shear force, whereas animals receiving a lower ViTD dosage and SHADE exhibited altered myofibrillar fragmentation. ViTD affected the colour parameters, and changes in the lightness of the beef related to the time pm were found in meat from animals under SHADE. (c) 2012 Elsevier B.V. All rights reserved.

Maternal exposure to picrotoxin modifies the response of the GABA(A) receptor during sexual behavior of adult male rat offspring

This study investigated whether perinatal exposure to picrotoxin, a GABA(A) antagonist, modifies the effect of muscimol, a GABA(A) agonist, on the sexual behavior of adult male rats. Two hours after birth and then once daily during the next 9 days of lactation, dams received picrotoxin (0.75 mg/kg subcutaneously) or saline (1 ml/kg subcutaneously). The adult male offspring from the picrotoxin and saline groups received saline (1 ml/kg intraperitoneally) or muscimol (1 mg/kg intraperitoneally), and 15 min later, their sexual behavior was assessed. Muscimol treatment in the saline-exposed group increased the mount and intromission latencies. However, these effects were absent in the picrotoxin-exposed groups. The latencies to first ejaculation, postejaculatory mount, and intromission were decreased in both picrotoxin-exposed groups relative to the saline-exposed groups. The picrotoxin + muscimol-treated rats required more intromissions to ejaculate and the picrotoxin-exposed groups made more ejaculations than the saline-exposed groups. Thus, muscimol treatment did not increase the mount and intromission latencies following picrotoxin exposure, but increased the ejaculation frequency, which did not differ between the picrotoxin + muscimol and the picrotoxin + saline groups. These data indicate that perinatal picrotoxin treatment interfered with GABA(A) receptor development Behavioural Pharmacology 23:703-709 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Transthoracic cardiac ultrasonic stimulation induces a negative chronotropic effect

The objective of this study is to investigate cardiac bioeffects resulting from ultrasonic stimulation using a specific set of acoustical parameters. Ten Sprague-Dawley rats were anesthetized and exposed to 1-MHz ultrasound pulses of 3-MPa peak rarefactional pressure and approximately 1% duty factor. The pulse repetition frequency started slightly above the heart rate and was decreased by 1 Hz every 10 s, for a total exposure duration of 30 s. The control group was composed of five rats. Two-way analysis of variance for repeated measures and Bonferroni post hoc tests were used to compare heart rate and ejection fraction, which was used as an index of myocardial contractility. It was demonstrated for the first time that transthoracic ultrasound has the potential to decrease the heart rate by similar to 20%. The negative chronotropic effect lasted for at least 15 min after ultrasound exposure and there was no apparent gross damage to the cardiac tissue.

Effect of Temperature on the Degree of Conversion and Working Time of Dual-Cured Resin Cements Exposed to Different Curing Conditions

Objectives: This study evaluated the degree of conversion (DC) and working time (WT) of two commercial, dual-cured resin cements polymerized at varying temperatures and under different curing-light accessible conditions, using Fourier transformed infrared analysis (FTIR). Materials and Methods: Calibra (Cal; Dentsply Caulk) and Variolink II (Ivoclar Vivadent) were tested at 25 degrees C or preheated to 37 degrees C or 50 degrees C and applied to a similar-temperature surface of a horizontal attenuated-total-reflectance unit (ATR) attached to an infrared spectrometer. The products were polymerized using one of four conditions: direct light exposure only (600 mW/cm(2)) through a glass slide or through a 1.5- or 3.0-mm-thick ceramic disc (A2 shade, IPS e.max, Ivoclar Vivadent) or allowed to self-cure in the absence of light curing. FTIR spectra were recorded for 20 min (1 spectrum/s, 16 scans/spectrum, resolution 4 cm(-1)) immediately after application to the ATR. DC was calculated using standard techniques of observing changes in aliphatic-to-aromatic peak ratios precuring and 20-min postcuring as well as during each 1-second interval. Time-based monomer conversion analysis was used to determine WT at each temperature. DC and WT data (n=6) were analyzed by two-way analysis of variance and Tukey post hoc test (p=0.05). Results: Higher temperatures increased DC regardless of curing mode and product. For Calibra, only the 3-mm-thick ceramic group showed lower DC than the other groups at 25 degrees C (p=0.01830), while no significant difference was observed among groups at 37 degrees C and 50 degrees C. For Variolink, the 3-mm-thick ceramic group showed lower DC than the 1-mm-thick group only at 25 degrees C, while the self-cure group showed lower DC than the others at all temperatures (p=0.00001). WT decreased with increasing temperature: at 37 degrees C near 70% reduction and at 50 degrees C near 90% for both products, with WT reduction reaching clinically inappropriate times in some cases (p=0.00001). Conclusion: Elevated temperature during polymerization of dual-cured cements increased DC. WT was reduced with elevated temperature, but the extent of reduction might not be clinically acceptable.

In vivo hydroquinone exposure causes tracheal hyperresponsiveness due to TNF secretion by epithelial cells

Hydroquinone (HQ) is the main oxidative substance in cigarette smoke and a toxic product of benzene biotransformation. Although the respiratory tract is an inlet pathway of HQ exposure, its effect on airway muscle responsiveness has not been assessed. We thus investigated the effects of low dose in vivo HQ-exposure on tracheal responsiveness to a muscarinic receptor agonist. Male Swiss mice were exposed to aerosolised 5% ethanol/saline solution (HQ vehicle; control) or 0.04 ppm HQ (1 h/day for 5 days) and tracheal rings were collected 1 h after the last exposure. HQ exposure caused tracheal hyper-responsiveness to methacholine (MCh), which was abolished by mechanical removal of the epithelium. This hyperresponsiveness was not dependent on neutrophil infiltration, but on tumour necrosis factor (TNF) secretion by epithelial cells. This conclusion was based on the following data: (1) trachea from HQ-exposed mice presented a higher amount of TNF, which was abrogated following removal of the epithelium; (2) the trachea hyperresponsiveness and TNF levels were attenuated by in vivo chlorpromazine (CPZ) treatment, an inhibitor of TNF synthesis. The involvement of HQ-induced TNF secretion in trachea mast cell degranulation was also demonstrated by the partial reversion of tracheal hyperresponsiveness in sodium cromoglicate-treated animals, and the in vivo HQ-exposure-induced degranulation of trachea connective tissue and mucosal mast cells, which was reversed by CPZ treatment. Our data show that in vivo HQ exposure indirectly exacerbates the parasympathetic-induced contraction of airway smooth muscle cells, mediated by TNF secreted by tracheal epithelial cells, clearly showing the link between environmental HQ exposure and the reactivity of airways. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization

Ferrao FM, Lara LS, Axelband F, Dias J, Carmona AK, Reis RI, Costa-Neto CM, Vieyra A, Lowe J. Exposure of luminal membranes of LLC-PK1 cells to ANG II induces dimerization of AT(1)/AT(2) receptors to activate SERCA and to promote Ca2+ mobilization. Am J Physiol Renal Physiol 302: F875-F883, 2012. First published January 4, 2012; doi:10.1152/ajprenal.00381.2011.-ANG II is secreted into the lumens of proximal tubules where it is also synthesized, thus increasing the local concentration of the peptide to levels of potential physiological relevance. In the present work, we studied the effect of ANG II via the luminal membranes of LLC-PK1 cells on Ca2+-ATPase of the sarco(endo) plasmic reticulum (SERCA) and plasma membrane (PMCA). ANG II (at concentrations found in the lumen) stimulated rapid (30 s) and persistent (30 min) SERCA activity by more than 100% and increased Ca2+ mobilization. Pretreatment with ANG II for 30 min enhanced the ANG II-induced Ca2+ spark, demonstrating a positively self-sustained stimulus of Ca2+ mobilization by ANG II. ANG II in the medium facing the luminal side of the cells decreased with time with no formation of metabolites, indicating peptide internalization. ANG II increased heterodimerization of AT(1) and AT(2) receptors by 140%, and either losartan or PD123319 completely blocked the stimulation of SERCA by ANG II. Using the PLC inhibitor U73122, PMA, and calphostin C, it was possible to demonstrate the involvement of a PLC -> DAG(PMA)-> PKC pathway in the stimulation of SERCA by ANG II with no effect on PMCA. We conclude that ANG II triggers SERCA activation via the luminal membrane, increasing the Ca2+ stock in the reticulum to ensure a more efficient subsequent mobilization of Ca2+. This first report on the regulation of SERCA activity by ANG II shows a new mechanism for Ca2+ homeostasis in renal cells and also for regulation of Ca2+-modulated fluid reabsorption in proximal tubules.

Effects of tributyltin exposure in hermit crabs: Clibanarius vittatus as a model

Tributyltin (TBT) contamination affects the reproductive system of many species of invertebrates worldwide. The present study was designed to evaluate the effects of exposure to TBT pollution on the reproduction of the hermit crab Clibanarius vittatus. An orthogonal experiment was designed with two treatments: contamination (with or without TBT in the food) and crab sex (males and females). The animals were reared in the laboratory for nine months, and macroscopic and histological analyses of reproductive organs were carried out after the end of the experiment. Tributyltin was recorded in exposed crabs, but no morphological alterations were detected in the gonads of males, regardless of whether they were exposed to TBT. In contrast, females exposed to TBT displayed disorganization and atrophy of their ovaries, thus directly affecting reproduction in this hermit crab species. This effect observed in female hermit crabs may harm populations located in harbor regions, where TBT concentration is high, even after the worldwide TBT ban.

Burnt sugarcane harvesting: Particulate matter exposure and the effects on lung function, oxidative stress, and urinary 1-hydroxypyrene

Non-mechanised sugarcane harvesting preceded by burning exposes workers and the people of neighbouring towns to high concentrations of pollutants. This study was aimed to evaluate the respiratory symptoms, lung function and oxidative stress markers in sugarcane workers and the residents of Mendonca, an agricultural town in Brazil, during the non-harvesting and harvesting periods and to assess the population and individual exposures to fine particulate matter (PM2.5). Sugarcane workers and healthy volunteers were evaluated with two respiratory symptom questionnaires, spirometry, urinary 1-hydroxypyrene levels, and the measurement of antioxidant enzymes and plasma malonaldehyde during the non-harvesting and harvesting periods. The environmental assessment was determined from PM2.5 concentration. PM2.5 level increased from 8 mu g/m(3) during the non-harvesting period to 23.5 mu g/m(3) in the town and 61 mu g/m(3) on the plantations during the harvesting period. Wheezing, coughing, sneezing, and breathlessness increased significantly in both groups during the harvesting period, but more markedly in workers. A decrease in lung function and antioxidant enzyme activity was observed in both populations during harvesting; this decrease was greater among the sugarcane workers. The urinary 1-hydroxypyrene levels only increased in the sugarcane workers during the harvesting period. The malonaldehyde levels were elevated in both groups, with a higher increase observed in the workers. This research demonstrates the exposure of sugarcane workers and the inhabitants of a neighbouring town to high PM2.5 concentrations during the sugarcane harvest period. This exposure was higher among the sugarcane workers, as illustrated by both higher PM2.5 concentrations in the sugarcane fields and higher urinary 1-hydroxypyrene levels in the volunteers in this group. The higher incidence of respiratory symptoms, greater decrease in lung function and more marked elevation of oxidative stress markers among the sugarcane workers during the harvest confirms the greater effect magnitude in this population and a dose-dependent relationship between pollution and the observed effects. (C) 2012 Elsevier B.V. All rights reserved.

Diminished Mycophenolic Acid Exposure Caused by Omeprazole May Be Clinically Relevant in the First Week Posttransplantation

Background: Some studies have reported a decreased absorption of mycophenolic acid (MPA) from mycophenolate mofetil (MMF) in renal transplanted (RTx) patients under proton-pump inhibitors (PPIs). There is still a lack of information regarding (1) whether this effect occurs when MMF is administered with either tacrolimus or cyclosporine A [calcineurin inhibitors (CNIs)], (2) whether the effect has the same amplitude during the first year after RTx, and finally (3) whether this decrease in exposure is clinically relevant. Methods: We retrospectively analyzed the omeprazole effect in 348 12-hour pharmacokinetic samplings [area under the curve (AUC) 0-12h] performed on days 7, 14, 30, 60, 180, and 360 after RTx in 77 patients who participated in previous trials. Results: For all periods, the groups with and without PPI did not differ in all variables. By mixed-model analysis of variance, PPI reduced the MPA AUC(0-12h) (P < 0.0008) in the patients under both CNIs mainly due to decreased absorption (P = 0.049). In the tacrolimus group, a lower exposure seemed also due to a decreased MPA reabsorption at 10-12 hours. The PPI effect remains throughout the first year but was clinically more important on day 7. By Cox analysis, the use of PPI was associated with a 25% less chance of being adequately exposed to MPA (95% confidence interval 0.58-0.99, P = 0.04). Similarly, the number of patients underexposed to MPA (AUC < 30 ng.h/mL) was higher at most periods in the PPI group but again not statistically significant. Conclusions: These data indicate that PPI decreases the MPA exposure when associated with both CNIs but particularly in the first week after RTx. In this period, the MMF dose should be increased. This effect lasts throughout the first year but does not seem to be clinically relevant after the first week.