Sample records for stria terminalis bnst

  1. PAC1 receptor antagonism in the bed nucleus of the stria terminalis (BNST) attenuates the endocrine and behavioral consequences of chronic stress. (United States)

    Roman, Carolyn W; Lezak, Kim R; Hartsock, Matthew J; Falls, William A; Braas, Karen M; Howard, Alan B; Hammack, Sayamwong E; May, Victor


    Chronic or repeated stressor exposure can induce a number of maladaptive behavioral and physiological consequences and among limbic structures, the bed nucleus of the stria terminalis (BNST) has been implicated in the integration and interpretation of stress responses. Previous work has demonstrated that chronic variate stress (CVS) exposure in rodents increases BNST pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) and PAC1 receptor (Adcyap1r1) transcript expression, and that acute BNST PACAP injections can stimulate anxiety-like behavior. Here we show that chronic stress increases PACAP expression selectively in the oval nucleus of the dorsolateral BNST in patterns distinct from those for corticotropin releasing hormone (CRH). Among receptor subtypes, BNST PACAP signaling through PAC1 receptors not only heightened anxiety responses as measured by different behavioral parameters but also induced anorexic-like behavior to mimic the consequences of stress. Conversely, chronic inhibition of BNST PACAP signaling by continuous infusion with the PAC1 receptor antagonist PACAP(6-38) during the week of CVS attenuated these stress-induced behavioral responses and changes in weight gain. BNST PACAP signaling stimulated the hypothalamic-pituitary-adrenal (HPA) axis and heightened corticosterone release; further, BNST PACAP(6-38) administration blocked corticosterone release in a sensitized stress model. In aggregate with recent associations of PACAP/PAC1 receptor dysregulation with altered stress responses including post-traumatic stress disorder, these data suggest that BNST PACAP/PAC1 receptor signaling mechanisms may coordinate the behavioral and endocrine consequences of stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Neuronal Correlates of Fear Conditioning in the Bed Nucleus of the Stria Terminalis (United States)

    Haufler, Darrell; Nagy, Frank Z.; Pare, Denis


    Lesion and inactivation studies indicate that the central amygdala (CeA) participates in the expression of cued and contextual fear, whereas the bed nucleus of the stria terminalis (BNST) is only involved in the latter. The basis for this functional dissociation is unclear because CeA and BNST form similar connections with the amygdala and…

  3. Ventromedial prefrontal cortex damage alters resting blood flow to the bed nucleus of stria terminalis. (United States)

    Motzkin, Julian C; Philippi, Carissa L; Oler, Jonathan A; Kalin, Ned H; Baskaya, Mustafa K; Koenigs, Michael


    The ventromedial prefrontal cortex (vmPFC) plays a key role in modulating emotional responses, yet the precise neural mechanisms underlying this function remain unclear. vmPFC interacts with a number of subcortical structures involved in affective processing, including the amygdala, hypothalamus, periaqueductal gray, ventral striatum, and bed nucleus of stria terminalis (BNST). While a previous study of non-human primates shows that vmPFC lesions reduce BNST activity and anxious behavior, no such causal evidence exists in humans. In this study, we used a novel application of magnetic resonance imaging (MRI) in neurosurgical patients with focal, bilateral vmPFC damage to determine whether vmPFC is indeed critical for modulating BNST function in humans. Relative to neurologically healthy subjects, who exhibited robust rest-state functional connectivity between vmPFC and BNST, the vmPFC lesion patients had significantly lower resting-state perfusion of the right BNST. No such perfusion differences were observed for the amygdala, striatum, hypothalamus, or periaqueductal gray. This study thus provides unique data on the relationship between vmPFC and BNST, suggesting that vmPFC serves to promote BNST activity in humans. This finding is relevant for neural circuitry models of mood and anxiety disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Neuregulin 1-ErbB4 signaling in the bed nucleus of the stria terminalis regulates anxiety-like behavior. (United States)

    Geng, Fei; Zhang, Jie; Wu, Jian-Lin; Zou, Wen-Jun; Liang, Zhi-Ping; Bi, Lin-Lin; Liu, Ji-Hong; Kong, Ying; Huang, Chu-Qiang; Li, Xiao-Wen; Yang, Jian-Ming; Gao, Tian-Ming


    The bed nucleus of the stria terminalis (BNST), a nucleus defined as part of the extended amygdala, is involved in the expression of anxiety disorders. However, the regulatory mechanisms of BNST inhibitory activity that is involved in anxiety are unknown. Here, we showed that blocking neuregulin 1 (NRG1)-ErbB4 signaling in the BNST of mice, by either neutralizing endogenous NRG1 with ecto-Erbb4 or antagonizing the ErbB4 receptor with its specific inhibitor, produced anxiogenic responses. Interestingly, application of exogenous NRG1 into the BNST induced no anxiolytic effects, suggesting saturating activity of endogenous NRG1. While infusion of the GABAA receptor antagonist bicuculline into the BNST also led to anxiety-related behaviors, it did not worsen the anxiogenic effects produced by blocking NRG1-ErbB4 signaling, suggesting possible involvement of GABAergic neurotransmission. Further, in vitro electrophysiological recordings showed that BNST NRG1-ErbB4 signaling regulated the presynaptic GABA release. Together, these results suggest that NRG1-ErbB4 signaling in the BNST may play an important role in regulating anxiety-like behaviors. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Allopregnanolone in the bed nucleus of the stria terminalis modulates contextual fear in rats

    Directory of Open Access Journals (Sweden)

    Naomi eNagaya


    Full Text Available Trauma- and stress-related disorders are among the most common types of mental illness affecting the U.S. population. For many of these disorders, there is a striking sex difference in lifetime prevalence; for instance, women are twice as likely as men to be affected by posttraumatic stress disorder (PTSD. Gonadal steroids and their metabolites have been implicated in sex differences in fear and anxiety. One example, allopregnanolone (ALLO, is a neuroactive metabolite of progesterone that allosterically enhances GABAA receptor activity and has anxiolytic effects. Like other ovarian hormones, it not only occurs at different levels in males and females but also fluctuates over the female reproductive cycle. One brain structure that may be involved in neuroactive steroid regulation of fear and anxiety is the bed nucleus of the stria terminalis (BNST. To explore this question, we examined the consequences of augmenting or reducing ALLO activity in the BNST on the expression of Pavlovian fear conditioning in rats. In Experiment 1, intra-BNST infusions of ALLO in male rats suppressed freezing behavior (a fear response to the conditioned context, but did not influence freezing to a discrete tone conditioned stimulus (CS. In Experiment 2, intra-BNST infusion of either finasteride, an inhibitor of ALLO synthesis, or 17-phenyl-(3α,5α-androst-16-en-3-ol, an ALLO antagonist, in female rats enhanced contextual freezing; neither treatment affected freezing to the tone CS. These findings support a role for ALLO in modulating contextual fear via the BNST and suggest that sex differences in fear and anxiety could arise from differential steroid regulation of BNST function. The susceptibility of women to disorders such as PTSD may be linked to cyclic declines in neuroactive steroid activity within fear circuitry.

  6. How Human Amygdala and Bed Nucleus of the Stria Terminalis May Drive Distinct Defensive Responses. (United States)

    Klumpers, Floris; Kroes, Marijn C W; Baas, Johanna M P; Fernández, Guillén


    The ability to adaptively regulate responses to the proximity of potential danger is critical to survival and imbalance in this system may contribute to psychopathology. The bed nucleus of the stria terminalis (BNST) is implicated in defensive responding during uncertain threat anticipation whereas the amygdala may drive responding upon more acute danger. This functional dissociation between the BNST and amygdala is however controversial, and human evidence scarce. Here we used data from two independent functional magnetic resonance imaging studies [ n = 108 males and n = 70 (45 females)] to probe how coordination between the BNST and amygdala may regulate responses during shock anticipation and actual shock confrontation. In a subset of participants from Sample 2 ( n = 48) we demonstrate that anticipation and confrontation evoke bradycardic and tachycardic responses, respectively. Further, we show that in each sample when going from shock anticipation to the moment of shock confrontation neural activity shifted from a region anatomically consistent with the BNST toward the amygdala. Comparisons of functional connectivity during threat processing showed overlapping yet also consistently divergent functional connectivity profiles for the BNST and amygdala. Finally, childhood maltreatment levels predicted amygdala, but not BNST, hyperactivity during shock anticipation. Our results support an evolutionary conserved, defensive distance-dependent dynamic balance between BNST and amygdala activity. Shifts in this balance may enable shifts in defensive reactions via the demonstrated differential functional connectivity. Our results indicate that early life stress may tip the neural balance toward acute threat responding and via that route predispose for affective disorder. SIGNIFICANCE STATEMENT Previously proposed differential contributions of the BNST and amygdala to fear and anxiety have been recently debated. Despite the significance of understanding their

  7. CRF receptor type 2 neurons in the posterior bed nucleus of the stria terminalis critically contribute to stress recovery. (United States)

    Henckens, M J A G; Printz, Y; Shamgar, U; Dine, J; Lebow, M; Drori, Y; Kuehne, C; Kolarz, A; Eder, M; Deussing, J M; Justice, N J; Yizhar, O; Chen, A


    The bed nucleus of the stria terminalis (BNST) is critical in mediating states of anxiety, and its dysfunction has been linked to stress-related mental disease. Although the anxiety-related role of distinct subregions of the anterior BNST was recently reported, little is known about the contribution of the posterior BNST (pBNST) to the behavioral and neuroendocrine responses to stress. Previously, we observed abnormal expression of corticotropin-releasing factor receptor type 2 (CRFR2) to be associated with post-traumatic stress disorder (PTSD)-like symptoms. Here, we found that CRFR2-expressing neurons within the pBNST send dense inhibitory projections to other stress-related brain regions (for example, the locus coeruleus, medial amygdala and paraventricular nucleus), implicating a prominent role of these neurons in orchestrating the neuroendocrine, autonomic and behavioral response to stressful situations. Local CRFR2 activation by urocortin 3 depolarized the cells, increased the neuronal input resistance and increased firing of action potentials, indicating an enhanced excitability. Furthermore, we showed that CRFR2-expressing neurons within the pBNST are critically involved in the modulation of the behavioral and neuroendocrine response to stress. Optogenetic activation of CRFR2 neurons in the pBNST decreased anxiety, attenuated the neuroendocrine stress response, ameliorated stress-induced anxiety and impaired the fear memory for the stressful event. Moreover, activation following trauma exposure reduced the susceptibility for PTSD-like symptoms. Optogenetic inhibition of pBNST CRFR2 neurons yielded opposite effects. These data indicate the relevance of pBNST activity for adaptive stress recovery.

  8. Involvement of the oxytocin system in the bed nucleus of the stria terminalis in the sex-specific regulation of social recognition (United States)

    Dumais, Kelly M.; Alonso, Andrea G.; Immormino, Marisa A.; Bredewold, Remco; Veenema, Alexa H.


    Sex differences in the oxytocin (OT) system in the brain may explain why OT often regulates social behaviors in sex-specific ways. However, a link between sex differences in the OT system and sex-specific regulation of social behavior has not been tested. Here, we determined whether sex differences in the OT receptor (OTR) or in OT release in the posterior bed nucleus of the stria terminalis (pBNST) mediates sex-specific regulation of social recognition in rats. We recently showed that, compared to female rats, male rats have a three-fold higher OTR binding density in the pBNST, a sexually dimorphic area implicated in the regulation of social behaviors. We now demonstrate that OTR antagonist (5 ng/0.5 μl/side) administration into the pBNST impairs social recognition in both sexes, while OT (100 pg/0.5 μl/side) administration into the pBNST prolongs the duration of social recognition in males only. These effects seem specific to social recognition, as neither treatment altered total social investigation time in either sex. Moreover, baseline OT release in the pBNST, as measured with in vivo microdialysis, did not differ between the sexes. However, males showed higher OT release in the pBNST during social recognition compared to females. These findings suggest a sex-specific role of the OT system in the pBNST in the regulation of social recognition. PMID:26630388

  9. CRF1 and CRF2 receptors in the bed nucleus of stria terminalis differently modulate the baroreflex function in unanesthetized rats. (United States)

    Oliveira, Leandro A; Almeida, Jeferson; Gomes-de-Souza, Lucas; Benini, Ricardo; Crestani, Carlos C


    The baroreflex is an important blood pressure regulating mechanism. The bed nucleus of stria terminalis (BNST) modulates the baroreflex function. However, the local BNST neurochemical mechanisms involved in control of baroreflex responses are not completely understood. Therefore, in this study, we investigated the involvement of corticotropin-releasing factor (CRF) receptors within the BNST in baroreflex control of heart rate in unanesthetized rats. For this, we evaluated effects of bilateral microinjection into the BNST of either the selective CRF 1 receptor antagonist CP376395 (5 nmol/100 nL) or the selective CRF 2 receptor antagonist antisauvagine-30 (5 nmol/100 nL) in bradycardiac response evoked by blood pressure increases caused by intravenous infusion of phenylephrine as well as tachycardiac response to blood pressure decrease caused by intravenous infusion of sodium nitroprusside. Bilateral microinjection of CP376395 into the BNST decreased the baroreflex bradycardiac response without affecting the reflex tachycardia. Conversely, BNST treatment with antisauvagine-30 decreased heart rate response during blood pressure drop without affecting the reflex bradycardia. Overall, these findings provide evidence of an involvement of CRF neurotransmission within the BNST in baroreflex activity. Nevertheless, data indicate that local CRF 1 and CRF 2 receptors differently modulate the baroreflex control of heart rate. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. Molecular phenotyping of transient postnatal tyrosine hydroxylase neurons in the rat bed nucleus of the stria terminalis. (United States)

    Carter, David A


    The bed nucleus of the stria terminalis (BNST) is a complex integrative centre in the forebrain, composed of multiple sub-nuclei, each with discrete populations of neurons. Progress in understanding BNST function, both in the adult and during postnatal maturation, is dependent upon a more complete characterization of neuronal phenotypes in the BNST. The aim of the current study was to define the molecular phenotype of one postnatal BNST neuronal population, in order to identify molecular factors that may underlie both (protein marker-related) immaturity, and secondly, the transience of this phenotype. This BNST population was originally identified by high, but transient expression of the EGR1 transcription factor (TF) in postnatal rat lateral intermediate BNST (BNSTLI). The current results confirm a high level of Egr1 activation in postnatal day 10 (PN10) male BNSTLI that is lost at PN40, and now demonstrate a similar pattern of transient activation in female brains. Apparent cellular immaturity in this population, as indicated by low levels of the adult neuronal marker NeuN/RBFOX3, was found to be uncorrelated with both key neuronal regulator protein expression (SOX2 and REST), and also RBFOX2 protein levels. The BNSTLI neurons have a partial catecholaminergic phenotype (tyrosine hydroxylase-positive/dopa decarboxylase-negative; TH+ve/DDC-ve) that is lost at PN40. In contrast, the co-expressed neuropeptide, somatostatin, is maintained, albeit at lower levels, at PN40. The transcriptional basis of the transient and partial catecholaminergic phenotype was investigated by analysing TFs known to maintain adult dopaminergic (TH+ve/DDC+ve) neuronal phenotypes. The BNSTLI neurons were shown to lack forkhead TFs including FOXA1, FOXA2 and FOXO1. In addition, the BNSTLI neurons had low, primarily cytoplasmic, expression of NR4A2/NURR1, an orphan nuclear receptor that is critical for adult maintenance of midbrain dopamine neurons. These results detail the molecular features

  11. Oxytocin receptor neurotransmission in the dorsolateral bed nucleus of the stria terminalis facilitates the acquisition of cued fear in the fear-potentiated startle paradigm in rats. (United States)

    Moaddab, Mahsa; Dabrowska, Joanna


    Oxytocin (OT) is a hypothalamic neuropeptide that modulates fear and anxiety-like behaviors. Dorsolateral bed nucleus of the stria terminalis (BNST dl ) plays a critical role in the regulation of fear and anxiety, and expresses high levels of OT receptor (OTR). However, the role of OTR neurotransmission within the BNST dl in mediating these behaviors is unknown. Here, we used adult male Sprague-Dawley rats to investigate the role of OTR neurotransmission in the BNST dl in the modulation of the acoustic startle response, as well as in the acquisition and consolidation of conditioned fear using fear potentiated startle (FPS) paradigm. Bilateral intra-BNST dl administration of OT (100 ng) did not affect the acquisition of conditioned fear response. However, intra-BNST dl administration of specific OTR antagonist (OTA), (d(CH 2 ) 5 1 , Tyr(Me) 2 , Thr 4 , Orn 8 , des-Gly-NH 2 9 )-vasotocin, (200 ng), prior to the fear conditioning session, impaired the acquisition of cued fear, without affecting a non-cued fear component of FPS. Neither OTA, nor OT affected baseline startle or shock reactivity during fear conditioning. Therefore, the observed impairment of cued fear after OTA infusion resulted from the specific effect on the formation of cued fear. In contrast to the acquisition, neither OTA nor OT affected the consolidation of FPS, when administered after the completion of fear conditioning session. Taken together, these results reveal the important role of OTR neurotransmission in the BNST dl in the formation of conditioned fear to a discrete cue. This study also highlights the role of the BNST dl in learning to discriminate between threatening and safe stimuli. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Involvement of the oxytocin system in the bed nucleus of the stria terminalis in the sex-specific regulation of social recognition. (United States)

    Dumais, Kelly M; Alonso, Andrea G; Immormino, Marisa A; Bredewold, Remco; Veenema, Alexa H


    Sex differences in the oxytocin (OT) system in the brain may explain why OT often regulates social behaviors in sex-specific ways. However, a link between sex differences in the OT system and sex-specific regulation of social behavior has not been tested. Here, we determined whether sex differences in the OT receptor (OTR) or in OT release in the posterior bed nucleus of the stria terminalis (pBNST) mediates sex-specific regulation of social recognition in rats. We recently showed that, compared to female rats, male rats have a three-fold higher OTR binding density in the pBNST, a sexually dimorphic area implicated in the regulation of social behaviors. We now demonstrate that OTR antagonist (5 ng/0.5 μl/side) administration into the pBNST impairs social recognition in both sexes, while OT (100 pg/0.5 μl/side) administration into the pBNST prolongs the duration of social recognition in males only. These effects seem specific to social recognition, as neither treatment altered total social investigation time in either sex. Moreover, baseline OT release in the pBNST, as measured with in vivo microdialysis, did not differ between the sexes. However, males showed higher OT release in the pBNST during social recognition compared to females. These findings suggest a sex-specific role of the OT system in the pBNST in the regulation of social recognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Mechanisms of Neuroplasticity and Ethanol's Effects on Plasticity in the Striatum and Bed Nucleus of the Stria Terminalis. (United States)

    Lovinger, David M; Kash, Thomas L


    Long-lasting changes in synaptic function (i.e., synaptic plasticity) have long been thought to contribute to information storage in the nervous system. Although synaptic plasticity mainly has adaptive functions that allow the organism to function in complex environments, it is now clear that certain events or exposure to various substances can produce plasticity that has negative consequences for organisms. Exposure to drugs of abuse, in particular ethanol, is a life experience that can activate or alter synaptic plasticity, often resulting in increased drug seeking and taking and in many cases addiction.Two brain regions subject to alcohol's effects on synaptic plasticity are the striatum and bed nucleus of the stria terminalis (BNST), both of which have key roles in alcohol's actions and control of intake. The specific effects depend on both the brain region analyzed (e.g., specific subregions of the striatum and BNST) and the duration of ethanol exposure (i.e., acute vs. chronic). Plastic changes in synaptic transmission in these two brain regions following prolonged ethanol exposure are thought to contribute to excessive alcohol drinking and relapse to drinking. Understanding the mechanisms underlying this plasticity may lead to new therapies for treatment of these and other aspects of alcohol use disorder.

  14. Endogenous oxytocin is necessary for preferential Fos expression to male odors in the bed nucleus of the stria terminalis in female Syrian hamsters. (United States)

    Martinez, Luis A; Levy, Marisa J; Petrulis, Aras


    Successful reproduction in mammals depends on proceptive or solicitational behaviors that enhance the probability of encountering potential mates. In female Syrian hamsters, one such behavior is vaginal scent marking. Recent evidence suggests that the neuropeptide oxytocin (OT) may be critical for regulating this behavior. Blockade of OT receptors in the bed nucleus of the stria terminalis (BNST) or the medial preoptic area (MPOA) decreases vaginal marking responses to male odors; lesion data suggest that BNST, rather than MPOA, mediates this effect. However, how OT interacts with sexual odor processing to drive preferential solicitation is not known. To address this issue, intact female Syrian hamsters were exposed to male or female odors and their brains processed for immunohistochemistry for Fos, a marker of recent neuronal activation, and OT. Additional females were injected intracerebroventricularly (ICV) with an oxytocin receptor antagonist (OTA) or vehicle, and then tested for vaginal marking and Fos responses to sexual odors. Colocalization of OT and Fos in the paraventricular nucleus of the hypothalamus was unchanged following exposure to male odors, but decreased following exposure to female odors. Following injections of OTA, Fos expression to male odors was decreased in BNST, but not in MPOA or the medial amygdala (MA). Fos expression in BNST may be functionally relevant for vaginal marking, given that there was a positive correlation between Fos expression and vaginal marking for BNST, but not MPOA or MA. Together, these data suggest that OT facilitation of neuronal activity in BNST underlies the facilitative effects of OT on solicitational responses to male odors. © 2013.

  15. The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors. (United States)

    Gomes, Felipe V; Resstel, Leonardo B M; Guimarães, Francisco S


    Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic-like effects in rodents and humans after systemic administration. Previous results from our group showed that CBD injection into the bed nucleus of the stria terminalis (BNST) attenuates conditioned aversive responses. The aim of this study was to further investigate the role of this region on the anxiolytic effects of the CBD. Moreover, considering that CBD can activate 5-HT1A receptors, we also verified a possible involvement of these receptors in those effects. Male Wistar rats received injections of CBD (15, 30, or 60 nmol) into the BNST and were exposed to the elevated plus-maze (EPM) or to the Vogel conflict test (VCT), two widely used animal models of anxiety. CBD increased open arms exploration in the EPM as well as the number of punished licks in the VCT, suggesting an anxiolytic-like effect. The drug did not change the number of entries into the enclosed arms of the EPM nor interfered with water consumption or nociceptive threshold, discarding potential confounding factors in the two tests. Moreover, pretreatment with the 5-HT1A receptor antagonist WAY100635 (0.37 nmol) blocked the effects of CBD in both models. These results give further support to the proposal that BNST is involved in the anxiolytic-like effects of CBD observed after systemic administration, probably by facilitating local 5-HT1A receptor-mediated neurotransmission.

  16. Recovery of stress-impaired social behavior by an antagonist of the CRF binding protein, CRF6-33,in the bed nucleus of the stria terminalis of male rats. (United States)

    Vasconcelos, Mailton; Stein, Dirson J; Albrechet-Souza, Lucas; Miczek, Klaus A; de Almeida, Rosa Maria M


    Social stress is recognized to promote the development of neuropsychiatric and mood disorders. Corticotropin releasing factor (CRF) is an important neuropeptide activated by social stress, and it contributes to neural and behavioral adaptations, as indicated by impaired social interactions and anhedonic effects. Few studies have focused on the role of the CRF binding protein (CRFBP), a component of the CRF system, and its activity in the bed nucleus of stria terminalis (BNST), a limbic structure connecting amygdala and hypothalamus. In this study, animals' preference for sweet solutions was examined as an index of stress-induced anhedonic responses in Wistar rats subjected to four brief intermittent episodes of social defeat. Next, social approach was assessed after local infusions of the CRFBP antagonist, CRF fragment 6-33 (CRF 6-33 ) into the BNST. The experience of brief episodes of social defeat impaired social approach behaviors in male rats. However, intra-BNST CRF 6-33 infusions restored social approach in stressed animals to the levels of non-stressed rats. CRF 6-33 acted selectively on social interaction and did not alter general exploration in nether stressed nor non-stressed rats. These findings suggest that BNST CRFBP is involved in the modulation of anxiety-like responses induced by social stress. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Activation of Hypocretin-1/Orexin-A Neurons Projecting to the Bed Nucleus of the Stria Terminalis and Paraventricular Nucleus Is Critical for Reinstatement of Alcohol Seeking by Neuropeptide S. (United States)

    Ubaldi, Massimo; Giordano, Antonio; Severi, Ilenia; Li, Hongwu; Kallupi, Marsida; de Guglielmo, Giordano; Ruggeri, Barbara; Stopponi, Serena; Ciccocioppo, Roberto; Cannella, Nazzareno


    Environmental conditioning is a major trigger for relapse in abstinent addicts. We showed that activation of the neuropeptide S (NPS) system exacerbates reinstatement vulnerability to cocaine and alcohol via stimulation of the hypocretin-1/orexin-A (Hcrt-1/Ox-A) system. Combining pharmacologic manipulations with immunohistochemistry techniques, we sought to determine how NPS and Hcrt-1/Ox-A systems interact to modulate reinstatement of alcohol seeking in rats. Intrahypothalamic injection of NPS facilitated discriminative cue-induced reinstatement of alcohol seeking. This effect was blocked by the selective Hcrt-1/Ox-A antagonist SB334867 microinjected into the hypothalamic paraventricular nucleus (PVN) or into the bed nucleus of the stria terminalis (BNST) but not into the ventral tegmental area or the locus coeruleus. Combining double labeling and confocal microscopy analyses, we found that NPS-containing axons are in close apposition to hypothalamic Hcrt-1/Ox-A positive neurons, a significant proportion of which express NPS receptors, suggesting a direct interaction between the two systems. Retrograde tracing experiments showed that intra-PVN or intra-BNST red fluorobead unilateral injection labeled bilaterally Hcrt-1/Ox-A somata, suggesting that NPS could recruit two distinct neuronal pathways. Confirming this assumption, intra-BNST or PVN Hcrt-1/Ox-A injection enhanced alcohol seeking similarly to hypothalamic NPS injection but to a lesser degree. Results suggest that the Hcrt-1/Ox-A neurocircuitry mediating the facilitation of cue-induced reinstatement by NPS involves structures critically involved in stress regulation such as the PVN and the BNST. These findings open to the tempting hypothesis of a role of the NPS system in modulating the interactions between stress and environmental conditioning factors in drug relapse. Copyright © 2016. Published by Elsevier Inc.

  18. Role of bed nucleus of the stria terminalis corticotrophin-releasing factor receptors in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction. (United States)

    Micioni Di Bonaventura, Maria Vittoria; Ciccocioppo, Roberto; Romano, Adele; Bossert, Jennifer M; Rice, Kenner C; Ubaldi, Massimo; St Laurent, Robyn; Gaetani, Silvana; Massi, Maurizio; Shaham, Yavin; Cifani, Carlo


    We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This "frustration stress" manipulation also activates the hypothalamic-pituitary-adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model. We also assessed the role of CRF receptors in the bed nucleus of the stria terminalis (BNST), a brain region implicated in stress responses and stress-induced drug seeking, in stress-induced binge eating. We used four groups that were first exposed or not exposed to repeated intermittent cycles of regular chow food restriction during which they were also given intermittent access to high-caloric palatable food. On the test day, we either exposed or did not expose the rats to the sight of the palatable food for 15 min (frustration stress) before assessing food consumption for 2 h. We found that systemic injections of the CRF1 receptor antagonist R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7 dipropylamino pyrazolo[1,5-a]pyrimidine) (10-20 mg/kg) and BNST (25-50 ng/side) or ventricular (1000 ng) injections of the nonselective CRF receptor antagonist D-Phe-CRF(12-41) decreased frustration stress-induced binge eating in rats with a history of food restriction. Frustration stress also increased Fos (a neuronal activity marker) expression in ventral and dorsal BNST. Results demonstrate a critical role of CRF receptors in BNST in stress-induced binge eating in our rat model. CRF1 receptor antagonists may represent a novel pharmacological treatment for bingeing-related eating disorders. Copyright © 2014 the authors 0270-6474/14/3411316-09$15.00/0.


    Dumont, É. C.; Rycroft, B. K.; Maiz, J.; Williams, J. T.


    The bed nucleus of the stria terminalis (BST) is a brain structure located at the interface of the cortex and the cerebrospinal trunk. The BST is a cluster of nuclei organized in a complex intrinsic network that receives inputs from cortical and subcortical sources, and that sends a widespread top-down projection. There is growing evidence that the BST is a key component in the neurobiological basis of substance abuse. In the present study, the regulation of excitatory inputs onto identified neurons in the BST was examined in rats treated chronically with morphine. Neurons projecting to the ventral tegmental area (VTA) were identified by retrograde transport of fluorescent microspheres and recorded in the whole-cell voltage clamp configuration in brain slices. Selective excitatory inputs to these neurons were electrically evoked with electrodes placed in the medial and lateral aspects of the dorsal BST. The chronic morphine treatment selectively increased AMPA-dependent excitatory postsynaptic currents in a subset of inputs activated by dorso-lateral stimulation in the BST. Inputs activated by medial stimulation were not affected by morphine. Likewise, the inputs to neurons that did not project to the VTA were not changed by morphine. Altogether, these results extend the understanding of neuronal circuits intrinsically sensitive to drugs of abuse within the BST. PMID:18343592

  20. PACAP in the BNST produces anorexia and weight loss in male and female rats. (United States)

    Kocho-Schellenberg, Margaret; Lezak, Kimberly R; Harris, Olivia M; Roelke, Erin; Gick, Niklas; Choi, Inyop; Edwards, Shaquille; Wasserman, Emily; Toufexis, Donna J; Braas, Karen M; May, Victor; Hammack, Sayamwong E


    Recent gene association studies have implicated pituitary adenylate cyclase-activating peptide (PACAP) systems in several psychiatric disorders associated with stressor exposure, and we have argued that many of the behavioral consequences of repeated stressor exposure may depend on the expression of PACAP in the bed nucleus of the stria terminalis (BNST). One behavioral consequence of the activation of stress systems can be anorexia and subsequent weight loss, and both the activation of central PACAP systems as well as neuronal activity in the BNST have also been associated with anorexic states in rodents. Hence, we investigated the regulation of food and water intake and weight loss following BNST PACAP infusion. BNST PACAP38 dose-dependently decreased body weight, as well as food and water intake in the first 24 h following infusion. Because different BNST subregions differentially regulate stress responding, we further examined the effects of PACAP38 in either the anterior or posterior BNST. Anterior BNST PACAP38 infusion did not alter weight gain, whereas posterior PACAP38 infusion resulted in weight loss. PACAP38 infused into the lateral ventricles did not alter weight, suggesting that the effects of BNST-infused PACAP were not mediated by leakage into the ventricular system. These data suggest that PACAP receptor activation in posterior BNST subregions can produce anorexia and weight loss, and corroborate growing data implicating central PACAP activation in mediating the consequences of stressor exposure.

  1. Neurogenetic and morphogenetic heterogeneity in the bed nucleus of the stria terminalis

    International Nuclear Information System (INIS)

    Bayer, S.A.


    Neurogenesis and morphogenesis in the rat bed nucleus of the stria terminalis (strial bed nucleus) were examined with [ 3 H]thymidine autoradiography. For neurogenesis, the experimental animals were the offspring of pregnant females given an injection of [ 3 H]thymidine on 2 consecutive gestational days. Nine groups of embryos were exposed to [ 3 H]thymidine on E13-E14, E14-E15,... E21-E22, respectively. On P60, the percentage of labeled cells and the proportion of cells originating during 24-hour periods were quantified at six anteroposterior levels in the strial bed nucleus. On the basis of neurogenetic gradients, the strial bed nucleus was divided into anterior and posterior parts. The anterior strial bed nucleus shows a caudal (older) to rostral (younger) neurogenetic gradient. Cells in the vicinity of the anterior commissural decussation are generated mainly between E13 and E16, cells just posterior to the nucleus accumbens mainly between E15 and E17. Within each rostrocaudal level, neurons originate in combined dorsal to ventral and medial to lateral neurogenetic gradients so that the oldest cells are located ventromedially and the youngest cells dorsolaterally. The most caudal level has some small neurons adjacent to the internal capsule that originate between E17 and E20. In the posterior strial bed nucleus, neurons extend ventromedially into the posterior preoptic area. Cells are generated simultaneously along the rostrocaudal plane in a modified lateral (older) to medial (younger) neurogenetic gradient. Ventrolateral neurons originate mainly between E13 and E16, dorsolateral neurons mainly between E15 and E16, and medial neurons mainly between E15 and E17. The youngest neurons are clumped into a medial core area just ventral to the fornix

  2. Neurogenetic and morphogenetic heterogeneity in the bed nucleus of the stria terminalis

    Energy Technology Data Exchange (ETDEWEB)

    Bayer, S.A.


    Neurogenesis and morphogenesis in the rat bed nucleus of the stria terminalis (strial bed nucleus) were examined with (/sup 3/H)thymidine autoradiography. For neurogenesis, the experimental animals were the offspring of pregnant females given an injection of (/sup 3/H)thymidine on 2 consecutive gestational days. Nine groups of embryos were exposed to (/sup 3/H)thymidine on E13-E14, E14-E15,... E21-E22, respectively. On P60, the percentage of labeled cells and the proportion of cells originating during 24-hour periods were quantified at six anteroposterior levels in the strial bed nucleus. On the basis of neurogenetic gradients, the strial bed nucleus was divided into anterior and posterior parts. The anterior strial bed nucleus shows a caudal (older) to rostral (younger) neurogenetic gradient. Cells in the vicinity of the anterior commissural decussation are generated mainly between E13 and E16, cells just posterior to the nucleus accumbens mainly between E15 and E17. Within each rostrocaudal level, neurons originate in combined dorsal to ventral and medial to lateral neurogenetic gradients so that the oldest cells are located ventromedially and the youngest cells dorsolaterally. The most caudal level has some small neurons adjacent to the internal capsule that originate between E17 and E20. In the posterior strial bed nucleus, neurons extend ventromedially into the posterior preoptic area. Cells are generated simultaneously along the rostrocaudal plane in a modified lateral (older) to medial (younger) neurogenetic gradient. Ventrolateral neurons originate mainly between E13 and E16, dorsolateral neurons mainly between E15 and E16, and medial neurons mainly between E15 and E17. The youngest neurons are clumped into a medial core area just ventral to the fornix.

  3. Resting-state functional connectivity of the bed nucleus of the stria terminalis in post-traumatic stress disorder and its dissociative subtype. (United States)

    Rabellino, Daniela; Densmore, Maria; Harricharan, Sherain; Jean, Théberge; McKinnon, Margaret C; Lanius, Ruth A


    The bed nucleus of the stria terminals (BNST) is a subcortical structure involved in anticipatory and sustained reactivity to threat and is thus essential to the understanding of anxiety and stress responses. Although chronic stress and anxiety represent a hallmark of post-traumatic stress disorder (PTSD), to date, few studies have examined the functional connectivity of the BNST in PTSD. Here, we used resting state functional Magnetic Resonance Imaging (fMRI) to investigate the functional connectivity of the BNST in PTSD (n = 70), its dissociative subtype (PTSD + DS) (n = 41), and healthy controls (n = 50). In comparison to controls, PTSD showed increased functional connectivity of the BNST with regions of the reward system (ventral and dorsal striatum), possibly underlying stress-induced reward-seeking behaviors in PTSD. By contrast, comparing PTSD + DS to controls, we observed increased functional connectivity of the BNST with the claustrum, a brain region implicated in consciousness and a primary site of kappa-opioid receptors, which are critical to the dynorphin-mediated dysphoric stress response. Moreover, PTSD + DS showed increased functional connectivity of the BNST with brain regions involved in attention and salience detection (anterior insula and caudate nucleus) as compared to PTSD and controls. Finally, BNST functional connectivity positively correlated with default-mode network regions as a function of state identity dissociation, suggesting a role of BNST networks in the disruption of self-relevant processing characterizing the dissociative subtype. These findings represent an important first step in elucidating the role of the BNST in aberrant functional networks underlying PTSD and its dissociative subtype. © 2017 Wiley Periodicals, Inc.

  4. Antidepressants share the ability to increase catecholamine output in the bed nucleus of stria terminalis: a possible role in antidepressant therapy? (United States)

    Cadeddu, Roberto; Ibba, Marcello; Sadile, Adolfo; Carboni, Ezio


    Antidepressants include a relatively wide spectrum of drugs that increase the synaptic concentration of monoamines, mostly through neurotransmitter reuptake blockade. The bed nucleus of stria teminalis (BNST) is considered a relay station in mediating the activation of stress response but also in the acquisition and expression of emotions. BNST is richly innervated by monoamines and sends back projections to the nucleus of origin. We previously showed that the administration of selective blockers of norepinephrine transporter (NET) increases the extracellular concentration (output) of dopamine, suggesting that dopamine could be captured by NET in the BNST. The aim of this study, carried out by means of in vivo microdialysis, was to ascertain the acute effects that antidepressants with varying mechanisms of action have on dopamine and norepinephrine output in the BNST. We observed that all the antidepressants tested (5-20 mg/kg i.p.) increased the output of catecholamines, dose dependently. In particular, the maximum increases (as a percent of basal) for norepinephrine and dopamine respectively, were as follows: desipramine, 239 and 137; reboxetine, 185 and 128; imipramine, 512 and 359; citalopram, 95 and 122; fluoxetine, 122 and 68; bupropion, 255 and 164. These results suggest that catecholamine transmission in the BNST may be part of a common downstream pathway that is involved in the action mechanism of antidepressants. Consequently, it is hypothesized that a dysfunction of neuronal transmission in this brain area may have a role in the etiology of affective disorders.

  5. Projections from Bed Nuclei of the Stria Terminalis, Magnocellular Nucleus: Implications for Cerebral Hemisphere Regulation of Micturition, Defecation, and Penile Erection




    The basic structural organization of axonal projections from the small but distinct magnocellular and ventral nuclei (of the bed nuclei of the stria terminalis) were analyzed with the PHAL anterograde tract tracing method in adult male rats. The former's overall projection pattern is complex, with over 80 distinct terminal fields ipsilateral to injection sites. Innervated regions in the cerebral hemisphere and brainstem fall into 9 general functional categories: cerebral nuclei, behavior cont...

  6. Vasotocin neurons in the bed nucleus of the stria terminalis preferentially process social information and exhibit properties that dichotomize courting and non-courting phenotypes. (United States)

    Goodson, James L; Rinaldi, Jacob; Kelly, Aubrey M


    Neurons within the medial bed nucleus of the stria terminalis (BSTm) that produce arginine vasotocin (VT; in non-mammals) or arginine vasopressin (VP; in mammals) have been intensively studied with respect to their anatomy and neuroendocrine regulation. However, almost no studies have examined how these neurons process stimuli in the animals' immediate environment. We recently showed that in five estrildid finch species, VT-immunoreactive (-ir) neurons in the BSTm increase their Fos expression selectively in response to positively-valenced social stimuli (i.e., stimuli that should elicit affiliation). Using male zebra finches, a highly gregarious estrildid, we now extend those findings to show that VT-Fos coexpression is induced by a positive social stimulus (a female), but not by a positive non-social stimulus (a water bath in bath-deprived birds), although the female and bath stimuli induced Fos equally within a nearby control region, the medial preoptic nucleus. In concurrent experiments, we also show that the properties of BSTm VT-ir neurons strongly differentiate males that diverge in social phenotype. Males who reliably fail to court females ("non-courters") have dramatically fewer VT-ir neurons in the BSTm than do reliable courters, and the VT-ir neurons of non-courters fail to exhibit Fos induction in response to a female stimulus.

  7. Projections from bed nuclei of the stria terminalis, magnocellular nucleus: implications for cerebral hemisphere regulation of micturition, defecation, and penile erection. (United States)

    Dong, Hong-Wei; Swanson, Larry W


    The basic structural organization of axonal projections from the small but distinct magnocellular and ventral nuclei (of the bed nuclei of the stria terminalis) was analyzed with the Phaseolus vulgaris leucoagglutinin anterograde tract tracing method in adult male rats. The former's overall projection pattern is complex, with over 80 distinct terminal fields ipsilateral to injection sites. Innervated regions in the cerebral hemisphere and brainstem fall into nine general functional categories: cerebral nuclei, behavior control column, orofacial motor-related, humorosensory/thirst-related, brainstem autonomic control network, neuroendocrine, hypothalamic visceromotor pattern-generator network, thalamocortical feedback loops, and behavioral state control. The most novel findings indicate that the magnocellular nucleus projects to virtually all known major parts of the brain network that controls pelvic functions, including micturition, defecation, and penile erection, as well as to brain networks controlling nutrient and body water homeostasis. This and other evidence suggests that the magnocellular nucleus is part of a corticostriatopallidal differentiation modulating and coordinating pelvic functions with the maintenance of nutrient and body water homeostasis. Projections of the ventral nucleus are a subset of those generated by the magnocellular nucleus, with the obvious difference that the ventral nucleus does not project detectably to Barrington's nucleus, the subfornical organ, the median preoptic and parastrial nuclei, the neuroendocrine system, and midbrain orofacial motor-related regions.

  8. Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST (United States)

    Pleil, Kristen E.; Helms, Christa M.; Sobus, Jon R.; Daunais, James B.; Grant, Kathleen A.; Kash, Thomas L.


    Alterations in hypothalamic-pituitary-adrenal (HPA) axis function contribute to many of the adverse behavioral effects of chronic voluntary alcohol drinking, including alcohol dependence and mood disorders; limbic brain structures such as the bed nucleus of the stria terminalis (BNST) may be key sites for these effects. Here, we measured circulating levels of several steroid hormones and performed whole-cell electrophysiological recordings from acutely-prepared BNST slices of male rhesus monkeys allowed to self-administer alcohol for 12 months or a control solution. Initial comparisons revealed that BNST neurons in alcohol-drinking monkeys had decreased membrane resistance, increased frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) with no change in spontaneous excitatory postsynaptic currents (sEPSCs). We then used a combined variable cluster analysis and linear mixed model statistical approach to determine whether specific factors including stress and sex hormones, age, and measures of alcohol consumption and intoxication are related to these BNST measures. Modeling results showed that specific measures of alcohol consumption and stress-related hormone levels predicted differences in membrane conductance in BNST neurons. Distinct groups of adrenal stress hormones were negatively associated with the frequency of sIPSCs and sEPSCs, and alcohol drinking measures and basal neuronal membrane properties were additional positive predictors of inhibitory, but not excitatory, PSCs. The amplitude of sEPSCs was highly positively correlated with age, independent of other variables. Together, these results suggest that chronic voluntary alcohol consumption strongly influences limbic function in non-human primates, potentially via interactions with or modulation by other physiological variables, including stress steroid hormones and age. PMID:26223349

  9. Vasotocin mRNA expression is sensitive to testosterone and oestradiol in the bed nucleus of the stria terminalis in female Japanese quail. (United States)

    Aste, N; Sakamoto, E; Kagami, M; Saito, N


    Vasotocin-producing parvocellular neurones in the medial part of the bed nucleus of the stria terminalis (BSTM) of many species of birds and mammals show sexual dimorphism and great plasticity in response to hormonal and environmental stimuli. In the BSTM of Japanese quail, vasotocin-immunoreactive neurones are visible and sensitive to testosterone exclusively in males. In males, gonadectomy decreases and testosterone restores vasotocin-immunoreactive cells and fibres by acting on vasotocin mRNA transcription. The insensitivity of female vasotocin-immunoreactive neurones to the activating effects of testosterone is the result of organisational effects of early exposure to oestradiol. Female quail also show vasotocin mRNA-expressing neurones in the BSTM, although it is not known whether the insensitivity of the vasotocinergic neurones to testosterone originates at the level of vasotocin gene transcription in this sex. Therefore, initially, the present study analysed the effects of acute treatment with testosterone on vasotocin mRNA expression in the BSTM of gonadectomised male and female quail using in situ hybridisation. Gonadectomy decreased (and a single injection of testosterone increased) the number of vasotocin mRNA-expressing neurones and intensity of the vasotocin mRNA hybridisation signal similarly in both sexes. Notably, testosterone increased vasotocin mRNA expression in ovariectomised females over that shown by intact quail. However, this treatment had no effect on vasotocin immunoreactivity. A second experiment analysed the effects of testosterone metabolites, oestradiol and 5α-dihydrotestosterone, on vasotocin mRNA expression in female quail. Oestradiol (but not 5α-dihydrotestosterone) fully mimicked the effects of testosterone on the number of vasotocin mRNA-expressing neurones and the intensity of the vasotocin mRNA hybridisation signal. Taken together, these results show, for the first time, that gonadal steroids strongly activate vasotocin m

  10. Overexpression of CRF in the BNST diminishes dysphoria but not anxiety-like behavior in nicotine withdrawing rats. (United States)

    Qi, Xiaoli; Guzhva, Lidia; Yang, Zhihui; Febo, Marcelo; Shan, Zhiying; Wang, Kevin K W; Bruijnzeel, Adriaan W


    Smoking cessation leads to dysphoria and anxiety, which both increase the risk for relapse. This negative affective state is partly mediated by an increase in activity in brain stress systems. Recent studies indicate that prolonged viral vector-mediated overexpression of stress peptides diminishes stress sensitivity. Here we investigated whether the overexpression of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST) diminishes nicotine withdrawal symptoms in rats. The effect of nicotine withdrawal on brain reward function was investigated with an intracranial self-stimulation (ICSS) procedure. Anxiety-like behavior was investigated in the elevated plus maze test and a large open field. An adeno-associated virus (AAV) pseudotype 2/5 vector was used to overexpress CRF in the lateral BNST and nicotine dependence was induced using minipumps. Administration of the nicotinic receptor antagonist mecamylamine and cessation of nicotine administration led to a dysphoria-like state, which was prevented by the overexpression of CRF in the BNST. Nicotine withdrawal also increased anxiety-like behavior in the elevated plus maze test and large open field test and slightly decreased locomotor activity in the open field. The overexpression of CRF in the BNST did not prevent the increase in anxiety-like behavior or decrease in locomotor activity. The overexpression of CRF increased CRF1 and CRF2 receptor gene expression and increased the CRF2/CRF1 receptor ratio. In conclusion, the overexpression of CRF in the BNST prevents the dysphoria-like state associated with nicotine withdrawal and increases the CRF2/CRF1 receptor ratio, which may diminish the negative effects of CRF on mood. Published by Elsevier B.V.

  11. Increased CRF mRNA expression in the sexually dimorphic BNST of male but not female GAD67 mice and TMT predator odor stress effects upon spatial memory retrieval. (United States)

    Janitzky, K; Peine, A; Kröber, A; Yanagawa, Y; Schwegler, H; Roskoden, T


    The bed nucleus of the stria terminalis (BNST) is an important region for 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) predator odor-induced stress responses in mice. It is sexually dimorphic and a region for corticotropin-releasing factor (CRF)-enhanced stress responses. Dense GABAergic and CRF input from the amygdala to the BNST gives point to relevant interactions between CRF and GABA activity in these brain regions. Hence, to investigate sexual dimorphism of stress-induced neuronal changes, we studied effects of acute TMT exposure on CRF mRNA expression in stress-related brain regions in male and female GAD67 mice and their wild-type littermates. In GAD67 mice, heterozygous knock-in of GFP in GABAergic neurons caused a 50% decrease of GAD67 protein level in the brain [91,99]. Results show higher CRF mRNA levels in the BNST of male but not female GAD67 mice after TMT and control odor exposure. While CRF neurons in the BNST are predominantly GABAergic and CRF enhances GABAergic transmission in the BNST [20,51], the deficit in GABAergic transmission in GAD67 mice could induce a compensatory CRF increase. Sexual dimorphism of the BNST with greater density of GABA-ir neurons in females could explain the differences in CRF mRNA levels between male and female GAD67 mice. Effects of odor exposure were studied in a radial arm maze (RAM) task. Results show impaired retrieval of spatial memory after acute TMT exposure in both sexes and genotypes. However, only GAD67 mice show increased working memory errors after control odor exposure. Our work elicits GAD67 mice as a model to further study interactions of GABA and CRF in the BNST for a better understanding of how sex-specific characteristics of the brain may contribute to differences in anxiety- and stress-related psychological disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Conservatism and the neural circuitry of threat: economic conservatism predicts greater amygdala-BNST connectivity during periods of threat vs safety. (United States)

    Pedersen, Walker S; Muftuler, L Tugan; Larson, Christine L


    Political conservatism is associated with an increased negativity bias, including increased attention and reactivity toward negative and threatening stimuli. Although the human amygdala has been implicated in the response to threatening stimuli, no studies to date have investigated whether conservatism is associated with altered amygdala function toward threat. Furthermore, although an influential theory posits that connectivity between the amygdala and bed nucleus of the stria terminalis (BNST) is important in initiating the response to sustained or uncertain threat, whether individual differences in conservatism modulate this connectivity is unknown. To test whether conservatism is associated with increased reactivity in neural threat circuitry, we measured participants' self-reported social and economic conservatism and asked them to complete high-resolution fMRI scans while under threat of an unpredictable shock and while safe. We found that economic conservatism predicted greater connectivity between the BNST and a cluster of voxels in the left amygdala during threat vs safety. These results suggest that increased amygdala-BNST connectivity during threat may be a key neural correlate of the enhanced negativity bias found in conservatism. © The Author (2017). Published by Oxford University Press.

  13. Neuropeptide Y2 receptors in anteroventral BNST control remote fear memory depending on extinction training. (United States)

    Verma, Dilip; Tasan, Ramon; Sperk, Guenther; Pape, Hans-Christian


    The anterior bed nucleus of stria terminalis (BNST) is involved in reinstatement of extinguished fear, and neuropeptide Y2 receptors influence local synaptic signaling. Therefore, we hypothesized that Y2 receptors in anteroventral BNST (BNSTav) interfere with remote fear memory and that previous fear extinction is an important variable. C57BL/6NCrl mice were fear-conditioned, and a Y2 receptor-specific agonist (NPY 3-36 ) or antagonist (JNJ-5207787) was applied in BNSTav before fear retrieval at the following day. Remote fear memory was tested on day 16 in two groups of mice, which had (experiment 1) or had not (experiment 2) undergone extinction training after conditioning. In the group with extinction training, tests of remote fear memory revealed partial retrieval of extinction, which was prevented after blockade of Y2 receptors in BNSTav. No such effect was observed in the group with no extinction training, but stimulation of Y2 receptors in BNSTav mimicked the influence of extinction during tests of remote fear memory. Pharmacological manipulation of Y2 receptors in BNSTav before fear acquisition (experiment 3) had no effect on fear memory retrieval, extinction or remote fear memory. Furthermore, partial retrieval of extinction during tests of remote fear memory was associated with changes in number of c-Fos expressing neurons in BNSTav, which was prevented or mimicked upon Y2 blockade or stimulation in BNSTav. These results indicate that Y2 receptor manipulation in BNSTav interferes with fear memory and extinction retrieval at remote stages, likely through controlling neuronal activity in BNSTav during extinction training. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. The neurobiological basis of fear: a concise review

    African Journals Online (AJOL)


    5 Thus, activation of the LA results in disinhibition of the CeM, with a resultant fear response, as illustrated in Figure. 1. While the CeM is important for fear, the bed nucleus of the stria terminalis (BNST) is implicated in anxiety, ...

  15. No impact of deep brain stimulation on fear–potentiated startle in obsessive-compulsive disorder

    NARCIS (Netherlands)

    Baas, Johanna M P; Klumpers, Floris; Mantione, Mariska H.; Figee, Martijn; Vulink, Nienke C.; Richard Schuurman, P.; Mazaheri, Ali; Denys, Damiaan


    Deep brain stimulation (DBS) of the ventral internal capsule is effective in treating therapy refractory obsessive-compulsive disorder (OCD). Given the close proximity of the stimulation site to the stria terminalis (BNST), we hypothesized that the striking decrease in anxiety symptoms following DBS

  16. Coping with stress in rats and mice : Differential peptidergic modulation of the amygdala-lateral septum complex

    NARCIS (Netherlands)

    Koolhaas, J.M.; Everts, H.G J; de Ruiter, A.J.H.; de Boer, S.F.; Bohus, B.G J


    This chapter focuses on the parvicellular vasopressin (VP) system originating from the medial nucleus of the amygdala (MeA) and bed nucleus of the stria terminalis (BNST). The vasopressinergic fibers of these nuclei innervate a number of limbic brain areas including the septum-hippocampal complex.

  17. Tissue oxygen tension in the stria vascularis. (United States)

    Nagahara, K; Miyake, Y; Aoyama, T; Ogino, F


    Tissue oxygen tension in the stria vascularis was successfully measured in cats using the polarographic technique. A correlation study using the differential coefficient between oxygen tension in the stria vascularis and systemic blood pressure proved that vascular autoregulation is present in the mean systemic blood pressure range between 40 and 80 mmHg. The anatomical findings and the response patterns to different gas inhalations indicated that the type of vascular regulation present is more closely related to chemical control than to auto-regulation.

  18. Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST (United States)

    Alterations in hypothalamic–pituitary–adrenal axis function contribute to many of the adverse behavioral effects of chronic voluntary alcohol drinking, including alcohol dependence and mood disorders; limbic brain structures such as the bed nucleus of the stria termin...

  19. Development of stria gravidarum in pregnant women and associated factors

    Directory of Open Access Journals (Sweden)

    Arzu Kılıç


    Full Text Available Background and Design: Stria gravidarum is a cosmetically disfiguring condition that is commonly seen in pregnancy. Various parameters such as age of mother, genetical factors like family history, skin colour, various hormonal changes seen in pregnancy, weight gain and physical features of newborn are accused in the development. The studies reported primarily include primigravidas. In this study, the presence of stria gravidarum and associated risk factors are aimed to be investigated. Materials and methods: All attenders' gestastional week, prepregnancy and delivery weights, height, family history of stria, smoking habits and/or alcohol use during pregnancy, any use of cream and/or oil for preventing stria, delivery way, newborn's gender, height, weight and head circumference were recorded. In both primigravidas and multigravidas, factors that could be associated with stria gravidarum were investigated by Spearman'scorrelation analysis and risk factors in the development of stria gravidarum by logistic regression analysis. Results: Fifty of 128 pregnant women were primigravidas and 78 were multigravidas. In primigravidas, a correlation was detected between family history of stria, non-usage of cream and/or oil during pregnancy,head circumference of newborn and development of stria gravidarum while in multigravidas, a correlation is detected between prepregnancy weight, delivery weight, smoking during pregnancy, not using of any cream and/or oil during pregnancy, family history of stria, head circumference of newborn, weight of newborn and stria gravidarum development. Presence of family history of stria and not using of any cream and/or oil were found to be risk factors in development of stria gravidarum in all pregnant women by logistic regression analysis. Conclusion: Both genetical and physical factors are thought to play a role in development of stria gravidarum; however, further broad scale studies with larger samples including both

  20. Extrahypothalamic vasopressin and oxytocin in the human brain; presence of vasopressin cells in the bed nucleus of the stria terminalis

    NARCIS (Netherlands)

    Fliers, E.; Guldenaar, S. E.; van de Wal, N.; Swaab, D. F.


    In the present study, the distribution of extrahypothalamic vasopressin (VP) and oxytocin (OXT) in the human brain was investigated by means of immunocytochemistry. In the septum verum, few VP fibers were found in the nucleus septalis lateralis and medialis (NSL and NSM), and in the bed nucleus of

  1. Revalidation of Ceresa terminalis walker and its placement in Stictocephala Stål (Hemiptera, Membracidae Revalidação de Ceresa terminalis walker e sua alocação em Stictocephala Stål (Hemiptera, Membracidae

    Directory of Open Access Journals (Sweden)

    Gabriel S. de Andrade


    Full Text Available Ceresa terminalis Walker, 1851 is reinstated and transferred to Stictocephala Stål, 1869: Stictocephala terminalis (Walker, 1851 sp. rev., comb. nov.Ceresa terminalis Walker, 1851 é revalidada e transferida para Stictocephala Stål, 1869: Stictocephala terminalis (Walker, 1851 sp. rev., comb. nov.

  2. ESTEVE Terminali kiire arengu tagavad vanametall ja autod / Sirje Niitra

    Index Scriptorium Estoniae

    Niitra, Sirje, 1948-


    Ilmunud ka: Delovõje Vedomosti : Transport i logistika 25. mai lk. 7. Ülevaade Paldiski lõunasadamas tegutseva ESTEVE Terminali edukast tegevusest. Diagrammid: ESTEVE kasvab kiiresti. Vt. samas: Paldiski sadamal head arenguväljavaated. Kommenteerib Romet Kreek

  3. Socioterminologia da indÃstria madeireira


    Alcides Fernandes de Lima


    O trabalho Socioterminologia da IndÃstria Madeireira tem como objetivo fundamental a construÃÃo de um dicionÃrio terminolÃgico (ou dicionÃrio especializado) da madeira. Os fundamentos teÃricos e metodolÃgicos da pesquisa e do trabalho terminogrÃfico, para a elaboraÃÃo do dicionÃrio, se embasam na Teoria Comunicativa da Terminologia (CABRÃ, 2002) e, principalmente, na Socioterminologia (GAUDIN, 1993a e 1993b). Para a elaboraÃÃo do dicionÃrio foi usado um corpus com mais de 4 milhÃes de palavra...

  4. Congenital Generalized Hypertrichosis Terminalis with Gingival Hyperplasia and a Coarse Face: a Case Report

    Directory of Open Access Journals (Sweden)

    Kazandjieva Jana


    Full Text Available Congenital generalized hypertrichosis, in its most common form, is idiopathic. In the absence of underlying endocrine or metabolic disorders, congenital generalized hypertrichosis is rare in humans, affecting as few as one in a billion individuals and may be an isolated condition of the skin, or a component feature of other disorders or syndromes. Congenital generalized hypertrichosis terminalis is an extremely rare condition, a distinct subset of disorders with congenital hypertrichosis, presenting with excessive hair as the primary clinical feature. Congenital generalized hypertrichosis terminalis is characterized by universal excessive growth of pigmented terminal hair and often accompanied with gingival hyperplasia and/or a coarse face. Gingival hyperplasia may be delayed even until puberty. Its pathogenesis may be caused by one of the following mechanisms: conversion of vellus to terminal hairs and/or prolonged anagenetic stage, and/or increase in the number of hair follicles. Since the Middle Ages, less than 60 individuals with congenital hypertrichosis terminalis have been described, and, according to the most recent estimates, less than 40 cases were documented adequately and definitively in the literature. Recent articles identified congenital generalized hypertrichosis terminalis as a genomic disorder.

  5. Phytochemical composition of the root extract of Ichthyothere terminalis from two geographical regiones in Colombia

    Directory of Open Access Journals (Sweden)

    Luz Yineth Ortiz-Rojas


    Full Text Available The phytochemical analysis of two extracts from Ichthyothere terminalis root which were collected in the localities of Cumaral (Meta and Abrego (Norte de Santander, Colombia is reported. Extracts were obtained with ethanol using distillation under reduced pressure and were characterized by qualitative assays and by gas chromatography coupled to a mass spectrometery (GC-MS. GC-MS analysis revealed differences in Ichthyothere terminalis compounds according to locality. Plants from Cumaral contain saponins, coumarins, and tannins, while those from Abrego contains tannins, alkaloids, coumarins and flavoniods. Plants from Abrego contain octadecadien-1-ol (53.5%, caryophyllene oxide (30.8%, hexadecanol (24.0%, trans-β-caryophyllene (13.6%, cycloisolongifolene (11.6%, germacrene D (6.0%, and 9-octadecen-1-ol (8.0%. Plants from Cumaral have citronellal (46.4%, p-cymene (6.4%, geraniol (5.0%, and citronellol (4.6%. Among the chemical compounds found, several have repellent properties, according to ethnobotanics reports from Amazonian Region. Further studies may determine the effectiveness as repellent of extracts from I. Terminalis root.

  6. Stria vascularis and cochlear hair cell changes in syphilis: A human temporal bone study. (United States)

    Hızlı, Ömer; Kaya, Serdar; Hızlı, Pelin; Paparella, Michael M; Cureoglu, Sebahattin


    To observe any changes in stria vascularis and cochlear hair cells in patients with syphilis. We examined 13 human temporal bone samples from 8 patients with syphilis (our syphilis group), as well as 12 histopathologically normal samples from 9 age-matched patients without syphilis (our control group). We compared, between the two groups, the mean area of the stria vascularis (measured with conventional light microscopy connected to a personal computer) and the mean percentage of cochlear hair cell loss (obtained from cytocochleograms). In our syphilis group, only 1 (7.7%) of the 13 samples had precipitate in the endolymphatic or perilymphatic spaces; 8 (61.5%) of the samples revealed the presence of endolymphatic hydrops (4 cochlear, 4 saccular). The mean area of the stria vascularis did not significantly differ, in any turn of the cochlea, between the 2 groups (P>0.1). However, we did find significant differences between the 2 groups in the mean percentage of outer hair cells in the apical turn (Psyphilis group, we observed either complete loss of the organ of Corti or a flattened organ of Corti without any cells in addition to the absence of both outer and inner hair cells. In this study, syphilis led either to complete loss of the organ of Corti or to significant loss of cochlear hair cells, in addition to cochleosaccular hydrops. But the area of the stria vascularis did not change. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Prominent crista terminalis mimicking a right atrial mixoma: cardiac magnetic resonance aspects. (United States)

    Gaudio, C; Di Michele, S; Cera, M; Nguyen, B L; Pannarale, G; Alessandri, N


    A 68-year-old woman came to our observation with a clinical history of isolated systolic hypertension poorly controlled by the combination of ramipril 5 mg and hydrochlorothiazide 12.5 mg o.d. The ECG showed sinus rhythm with heart rate of 68 beats per minute and signs of left ventricular hypertrophy without strain. Further investigation included an echocardiogram that showed normal left and right cavities and normal cardiac valves. At the level of the posterior wall of the right atrial (RA) an apparent smooth, bean-like tumor, having a thin pedicle, was identified as a RA mixoma. Cardiac MRI was requested and showed in two sequential slices a muscular ridge, identified as a prominent crista terminalis. Some para-physiological structures sited in the RA may have the appearance of tumors, as crista terminalis, Eustachian valve extending into the RA chambers and Chiari network. The multiplain projections of MRI allow the cardiologist to identify the presence of intracardiac masses and to make a differential diagnosis between neoplasms and variant anatomic structures.

  8. Dynorphin Controls the Gain of an Amygdalar Anxiety Circuit

    Directory of Open Access Journals (Sweden)

    Nicole A. Crowley


    Full Text Available Kappa opioid receptors (KORs are involved in a variety of aversive behavioral states, including anxiety. To date, a circuit-based mechanism for KOR-driven anxiety has not been described. Here, we show that activation of KORs inhibits glutamate release from basolateral amygdala (BLA inputs to the bed nucleus of the stria terminalis (BNST and occludes the anxiolytic phenotype seen with optogenetic activation of BLA-BNST projections. In addition, deletion of KORs from amygdala neurons results in an anxiolytic phenotype. Furthermore, we identify a frequency-dependent, optically evoked local dynorphin-induced heterosynaptic plasticity of glutamate inputs in the BNST. We also find that there is cell type specificity to the KOR modulation of the BLA-BNST input with greater KOR-mediated inhibition of BLA dynorphin-expressing neurons. Collectively, these results provide support for a model in which local dynorphin release can inhibit an anxiolytic pathway, providing a discrete therapeutic target for the treatment of anxiety disorders.

  9. Monoaminergic innervation of the rat organum vasculosum laminae terminalis as revealed by radioautography

    International Nuclear Information System (INIS)

    Bosler, O.


    As revealed by radioautography after in vivo labelling with [ 3 H]monoamines, the organum vasculosum laminae terminalis (OVLT) is mostly supplied with serotonin (5-HT) fibres which terminate profusely throughout its thickness. Catecholamine, mostly dopamine (DA) afferents, are scarce and exhibit a mainly perivascular distribution. Some 25% of the 5-HT endings in the juxtaventricular zone are engaged in morphologically defined synaptic axo-dendritic contacts. In the juxtavascular zone, 5-HT and DA varicosities never show true synaptic junctional complexes but frequently establish synaptoid-like contacts with astrocytic and/or tanycytic processes. Occasionally, they can about onto the parenchymal basement membrane limiting the perivascular space. Monoamines might therefore be involved in the OVLT function through interactions with neural and non-neural elements. A morphological substratum also exists for a direct neurohormonal release of 5-HT and DA at the OVLT level. (author)

  10. "Cristal tachycardias": origin of right atrial tachycardias from the crista terminalis identified by intracardiac echocardiography. (United States)

    Kalman, J M; Olgin, J E; Karch, M R; Hamdan, M; Lee, R J; Lesh, M D


    We sought to use intracardiac echocardiography (ICE) to identify the anatomic origin of focal right atrial tachycardias and to define their relation with the crista terminalis (CT). Previous studies using ICE during mapping of atrial flutter and inappropriate sinus tachycardia have demonstrated an important relation between endocardial anatomy and electrophysiologic events. Recent studies have suggested that right atrial tachycardias may also have a characteristic anatomic distribution. Twenty-three consecutive patients with 27 right atrial tachycardias were included in the study. ICE was used to facilitate activation mapping in relation to endocardial structures. A 20-pole catheter was positioned along the CT under ICE guidance. ICE was also used to assist in guiding detailed mapping with the ablation catheter in the right atrium. Of 27 focal right atrial tachycardias, 18 (67%, 95% confidence interval [CI] 46% to 83%) were on the CT (2 high medial, 8 high lateral, 6 mid and 2 low). ICE identified the location of the tip of the ablation catheter in immediate relation to the CT in all 18 cases. The 20-pole mapping catheter together with echocardiographic visualization of the CT provided a guide to the site of tachycardia origin along this structure. Radiofrequency ablation was successful in 26 (96%) of 27 (95% CI 81% to 100%) right atrial tachycardias. This study demonstrates that approximately two thirds of focal right atrial tachycardias occurring in the absence of structural heart disease will arise along the CT. Recognition of this common distribution may potentially facilitate mapping and ablation of these tachycardias.

  11. Role of Oestrogen α Receptors in Sociosexual Behaviour in Female Rats Housed in a Seminatural Environment. (United States)

    Snoeren, E M S; Antonio-Cabrera, E; Spiteri, T; Musatov, S; Ogawa, S; Pfaff, D W; Ågmo, A


    The present study investigated the role of oestrogen receptor (ER)α in the ventromedial nucleus of the hypothalamus (VMN), the preoptic area (POA), the medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in sociosexual behaviour in female rats. This was conducted in two sets of experiments, with the VMN and POA investigated in the first set, and the MePD and BNST in the second set. The VMN and POA received intense projections from the MePD and BNST. We used a short hairpin RNA encoded within an adeno-associated viral vector directed against the gene for ERα to reduce the number of ERα in the VMN or POA (first set of experiments) or in the BNST or MePD (second set of experiments) in female rats. The rats were housed in groups of four ovariectomised females and three males in a seminatural environment for 8 days. Compared with traditional test set-ups, the seminatural environment provides an arena in which the rats can express their full behavioural repertoire, which allowed us to investigate multiple aspects of social and sexual behaviour in groups of rats. Behavioural observation was performed after oestrogen and progesterone injections. A reduction of ERα expression in the VMN or POA diminished the display of paracopulatory behaviours and lordosis responses compared to controls, whereas the lordosis quotient remained unaffected. This suggests that ERα in the VMN and POA play an important role in intrinsic sexual motivation. The reduction in ERα did not affect the social behaviour of the females, although the males sniffed and pursued the females with reduced ERα less than the controls. This suggests that the ERα in the VMN and POA is involved in the regulation of sexual attractiveness of females. The ERα in the MePD and BNST, on the other hand, plays no role in sociosexual behaviour. © 2015 British Society for Neuroendocrinology.

  12. Presbycusis: a human temporal bone study of individuals with flat audiometric patterns of hearing loss using a new method to quantify stria vascularis volume. (United States)

    Nelson, Erik G; Hinojosa, Raul


    The purpose of this study was to determine the prevalence of stria vascularis atrophy in individuals with presbycusis and flat audiometric patterns of hearing loss. Individuals with presbycusis have historically been categorized by the shape of their audiograms, and flat audiometric thresholds have been reported to be associated with atrophy of the stria vascularis. Stria vascularis volume was not measured in these studies. Retrospective case review. Archival human temporal bones from individuals with presbycusis were selected on the basis of strict audiometric criteria for flat audiometric thresholds. Six temporal bones that met these criteria were identified and compared with 10 temporal bones in individuals with normal hearing. A unique quantitative method was developed to measure the stria vascularis volume in these temporal bones. The hair cell and spiral ganglion cell populations also were quantitatively evaluated. Only one of the six individuals with presbycusis and flat audiometric thresholds had significant atrophy of the stria vascularis. This individual with stria vascularis atrophy also had reduced inner hair cell, outer hair cell, and ganglion cell populations. Three of the individuals with presbycusis had spiral ganglion cell loss, three individuals had inner hair cell loss, and all six individuals had outer hair cell loss. The results of this investigation suggest that individuals with presbycusis and flat audiometric patterns of hearing loss infrequently have stria vascularis atrophy. Outer hair cell loss alone or in combination with inner hair cell or ganglion cell loss may be the cause of flat audiometric thresholds in individuals with presbycusis.

  13. c-fos Changes following an aggressive encounter in female California mice: a synthesis of behavior, hormone changes and neural activity. (United States)

    Davis, E S; Marler, C A


    Although there has been growing interest in the neuroanatomical and physiological mechanisms underlying aggressive behavior, little work has focused on possible mechanisms controlling natural plasticity in aggression. In the current study, we used naturally occurring changes in aggression level displayed by female Peromyscus californicus across the estrous cycle and parallel changes in c-fos expression to examine possible brain regions involved in mediating this plasticity. We found that c-fos expression was increased in females exposed to a conspecific female intruder compared with control females in numerous brain regions thought to be involved in the control of aggression. More importantly, we found that c-fos increased in the bed nucleus of the stria terminalis (BNST) and ventral lateral septum (LSv) only in the more aggressive, diestrous females, and not in the less aggressive, proestrous and estrous females. Conversely, c-fos increased in the medial amygdala (MeA) across all stages of estrus compared with controls, suggesting the MeA is not involved in mediating changes in individual levels of aggression. Moreover, we found correlations between several measures of aggression and c-fos expression in the BNST and LSv but not the MeA, again suggesting a role in mediating aggression plasticity for the former two but not the latter brain region. We further hypothesize that the BNST and the LSv may be involved more generally in mediating natural changes in aggression, such as increases often observed after individuals win aggressive interactions against conspecifics.

  14. NPY Signaling Inhibits Extended Amygdala CRF Neurons to Suppress Binge Alcohol Drinking (United States)

    Pleil, Kristen E.; Rinker, Jennifer A.; Lowery-Gionta, Emily G.; Mazzone, Christopher M.; McCall, Nora M.; Kendra, Alexis M.; Olson, David P.; Lowell, Bradford B.; Grant, Kathleen A.; Thiele, Todd E.; Kash, Thomas L.


    Summary paragraph Binge alcohol drinking is a tremendous public health problem because it leads to the development of numerous pathologies including alcohol abuse, and anxiety1–4. It is thought to do so by hijacking brain systems that regulate stress and reward, including neuropeptide Y (NPY) and corticotropin–releasing factor (CRF). The central actions of NPY and CRF play opposing functional roles in the regulation of emotional and reward–seeking behaviors; therefore, dysfunctional interactions between these peptidergic systems could play a role in the development of these pathologies. Here, we used converging physiological, pharmacological, and chemogenetic approaches to identify a precise neural mechanism in the bed nucleus of the stria terminalis (BNST), a limbic brain region involved in pathological reward and anxiety behaviors, underlying the interactions between NPY and CRF in the regulation of binge alcohol drinking in both mice and monkeys. We found that NPY Y1 receptor (Y1R) activation in the BNST suppressed binge alcohol drinking by enhancing inhibitory synaptic transmission specifically in CRF neurons via a novel, Gi-mediated, PKA-dependent postsynaptic mechanism. Further, chronic alcohol drinking led to persistent alterations in Y1R function in the BNST of both mice and monkeys, highlighting the enduring, conserved nature of this effect across mammalian species. Together, these data provide both a cellular locus and signaling framework for the development of novel therapeutics for treatment of neuropsychiatric diseases, including alcohol use disorders. PMID:25751534

  15. Blocking oxytocin receptors inhibits vaginal marking to male odors in female Syrian hamsters. (United States)

    Martinez, Luis A; Albers, H Elliott; Petrulis, Aras


    In Syrian hamsters (Mesocricetus auratus), precopulatory behaviors such as vaginal scent marking are essential for attracting a suitable mate. Vaginal marking is dependent on forebrain areas implicated in the neural regulation of reproductive behaviors in rodents, including the medial preoptic/anterior hypothalamus (MPOA-AH). Within MPOA-AH, the neuropeptide oxytocin (OT) acts to facilitate copulation (lordosis), as well as ultrasonic vocalizations towards males. It is not known, however, if OT in this area also facilitates vaginal marking. In the present study, a specific oxytocin receptor antagonist (OTA) was injected into MPOA-AH of intact female Syrian hamsters to determine if oxytocin receptor-dependent signaling is critical for the normal expression of vaginal marking elicited by male, female, and clean odors. OTA injections significantly inhibited vaginal marking in response to male odors compared with vehicle injections. There was no effect of OTA on marking in response to either female or clean odors. When injected into the bed nucleus of the stria terminalis (BNST), a nearby region to MPOA-AH, OTA was equally effective in decreasing marking. Finally, the effects of OTA appear to be specific to vaginal marking, as OTA injections in MPOA-AH or BNST did not alter general locomotor activity, flank marking, or social odor investigation. Considered together, these results suggest that OT in MPOA-AH and/or BNST normally facilitates male odor-induced vaginal marking, providing further evidence that OT generally supports prosocial interactions among conspecifics. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Neudesin is involved in anxiety behavior: structural and neurochemical correlates

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    Ashley eNovais


    Full Text Available Neudesin (also known as neuron derived neurotrophic factor, Nenf is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional and cognitive dimensions of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze, light/dark box and novelty suppressed feeding tests, but not in the acoustic startle test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.

  17. The nervus terminalis in amphibians: anatomy, chemistry and relationship with the hypothalamic gonadotropin-releasing hormone system. (United States)

    Muske, L E; Moore, F L


    The nervus terminalis (TN), a component of the olfactory system, is found in most vertebrates. The TN of some fishes and mammals contains neurons immunoreactive (ir) to gonadotropin-releasing hormone (LHRH), and to several other neuropeptides and neurotransmitter systems, but there is little information on TN chemistry in other vertebrate taxa. Using immunocytochemical techniques, we found LHRH-ir neurons in amphibian TNs. In anurans, but not in a urodele, the TN was also found to contain Phe-Met-Arg-Phe-NH2 (FMRFamide) immunoreactivity. LHRH-ir neurons of the TN and those of the septal-hypothalamic system are morphologically homogeneous and form a distinct anatomical continuum in amphibians. Based upon topographical and cytological criteria, we hypothesize that LHRH-ir systems in vertebrates might derive embryonically from the TN.

  18. MR Imaging of Ventriculus Terminalis of The Conus Medullaris. A report of two operated patients and review of the literature

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    Dullerud, Reidar; Server, A. [Ullevaal Univ. Hospital, Oslo (Norway). Div. of Radiology; Berg-Johnsen, J. [The National Hospital, Oslo (Norway). Dept. of Neurosurgery


    We report on 2 patients in whom a cystic dilation of the conus medullaris was incidentally found at MR imaging carried out in the work-up for sciatica. The cysts were well circumscribed and had signal intensity identical to the CSF on both T1- and T2-weighted images. There was no evidence of contrast enhancement. None of the patients had specific symptoms related to the spinal cord. At surgery, no evidence of malignancy was seen in any of the patients. A benign cystic dilation, also called dilated ventriculus terminalis, occasionally can be seen in the conus medullaris as an incidental finding at thoracolumbar MR imaging. Unless the expansion per se indicates cyst drainage, these patients may be monitored by clinical and MR follow-up, avoiding surgery in a substantial number of cases.

  19. A Switch in Keystone Seed-Dispersing Ant Genera between Two Elevations for a Myrmecochorous Plant, Acacia terminalis. (United States)

    Thomson, Fiona J; Auld, Tony D; Ramp, Daniel; Kingsford, Richard T


    The dispersal capacity of plant species that rely on animals to disperse their seeds (biotic dispersal) can alter with changes to the populations of their keystone dispersal vectors. Knowledge on how biotic dispersal systems vary across landscapes allows better understanding of factors driving plant persistence. Myrmecochory, seed dispersal by ants, is a common method of biotic dispersal for many plant species throughout the world. We tested if the seed dispersal system of Acacia terminalis (Fabaceae), a known myrmecochore, differed between two elevations in the Greater Blue Mountains World Heritage Area, in southeastern Australia. We compared ant assemblages, seed removal rates of ants and other vertebrates (bird and mammal) and the dominant seed-dispersing ant genera. At low elevations (c. 200 m a.s.l) seed removal was predominantly by ants, however, at high elevation sites (c. 700 m a.s.l) vertebrate seed dispersers or seed predators were present, removing over 60% of seeds from experimental depots when ants were excluded. We found a switch in the keystone seed-dispersing ant genera from Rhytidoponera at low elevations sites to Aphaenogaster at high elevation sites. This resulted in more seeds being removed faster at low elevation sites compared to high elevation sites, however long-term seed removal rates were equal between elevations. Differences in the keystone seed removalist, and the addition of an alternate dispersal vector or seed predator at high elevations, will result in different dispersal and establishment patterns for A. terminalis at different elevations. These differences in dispersal concur with other global studies that report myrmecochorous dispersal systems alter with elevation.

  20. A Switch in Keystone Seed-Dispersing Ant Genera between Two Elevations for a Myrmecochorous Plant, Acacia terminalis.

    Directory of Open Access Journals (Sweden)

    Fiona J Thomson

    Full Text Available The dispersal capacity of plant species that rely on animals to disperse their seeds (biotic dispersal can alter with changes to the populations of their keystone dispersal vectors. Knowledge on how biotic dispersal systems vary across landscapes allows better understanding of factors driving plant persistence. Myrmecochory, seed dispersal by ants, is a common method of biotic dispersal for many plant species throughout the world. We tested if the seed dispersal system of Acacia terminalis (Fabaceae, a known myrmecochore, differed between two elevations in the Greater Blue Mountains World Heritage Area, in southeastern Australia. We compared ant assemblages, seed removal rates of ants and other vertebrates (bird and mammal and the dominant seed-dispersing ant genera. At low elevations (c. 200 m a.s.l seed removal was predominantly by ants, however, at high elevation sites (c. 700 m a.s.l vertebrate seed dispersers or seed predators were present, removing over 60% of seeds from experimental depots when ants were excluded. We found a switch in the keystone seed-dispersing ant genera from Rhytidoponera at low elevations sites to Aphaenogaster at high elevation sites. This resulted in more seeds being removed faster at low elevation sites compared to high elevation sites, however long-term seed removal rates were equal between elevations. Differences in the keystone seed removalist, and the addition of an alternate dispersal vector or seed predator at high elevations, will result in different dispersal and establishment patterns for A. terminalis at different elevations. These differences in dispersal concur with other global studies that report myrmecochorous dispersal systems alter with elevation.

  1. Phytophthora terminalis sp. nov. and Phytophthora occultans sp. nov., two invasive pathogens of ornamental plants in Europe. (United States)

    Man In 't Veld, Willem A; Rosendahl, Karin C H M; van Rijswick, Patricia C J; Meffert, Johan P; Westenberg, Marcel; van de Vossenberg, Bart T L H; Denton, Geoff; van Kuik, Fons A J


    In the past decade several Phytophthora strains were isolated from diseased Pachysandra terminalis plants suffering stem base and root rot, originating from the Netherlands and Belgium. All isolates were homothallic and had a felt-like colony pattern, produced semi-papillate sporangia, globose oogonia and had a maximum growth at ~ 27 C. Several additional Phytophthora strains were isolated from diseased Buxus sempervirens plants, originating from the Netherlands and Belgium, which had sustained stem base and root rot; similar strains also were isolated from Acer palmatum, Choisya ternata and Taxus in the United Kingdom. All isolates were homothallic and had a stellate colony pattern, produced larger semi-papillate sporangia and smaller globose oogonia than the isolates from Pa. terminalis and had a maximum growth temperature of ~ 30 C. Phylogenetic analyses of both species using the internal transcribed spacer region of the nuc rDNA (ITS), mt cytochrome oxidases subunit I gene (CoxI) and nuc translation elongation factor 1-α gene (TEF1α) revealed that all sequences of each species were identical at each locus and unique to that species, forming two distinct clusters in subclade 2a. Sequence analysis of partial β-tubulin genes showed that both taxa share an identical sequence that is identical to that of Ph. himalsilva, a species originating from Asia, suggesting a common Asian origin. Pathogenicity trials demonstrated disease symptoms on their respective hosts, and re-isolation and re-identification of the inoculated pathogens confirmed Koch's postulates. © 2015 by The Mycological Society of America.

  2. Epithelial cell stretching and luminal acidification lead to a retarded development of stria vascularis and deafness in mice lacking pendrin.

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    Hyoung-Mi Kim


    Full Text Available Loss-of-function mutations of SLC26A4/pendrin are among the most prevalent causes of deafness. Deafness and vestibular dysfunction in the corresponding mouse model, Slc26a4(-/-, are associated with an enlargement and acidification of the membranous labyrinth. Here we relate the onset of expression of the HCO(3 (- transporter pendrin to the luminal pH and to enlargement-associated epithelial cell stretching. We determined expression with immunocytochemistry, cell stretching by digital morphometry and pH with double-barreled ion-selective electrodes. Pendrin was first expressed in the endolymphatic sac at embryonic day (E 11.5, in the cochlear hook-region at E13.5, in the utricle and saccule at E14.5, in ampullae at E16.5, and in the upper turn of the cochlea at E17.5. Epithelial cell stretching in Slc26a4(-/- mice began at E14.5. pH changes occurred first in the cochlea at E15.5 and in the endolymphatic sac at E17.5. At postnatal day 2, stria vascularis, outer sulcus and Reissner's membrane epithelial cells, and utricular and saccular transitional cells were stretched, whereas sensory cells in the cochlea, utricle and saccule did not differ between Slc26a4(+/- and Slc26a4(-/- mice. Structural development of stria vascularis, including vascularization, was retarded in Slc26a4(-/- mice. In conclusion, the data demonstrate that the enlargement and stretching of non-sensory epithelial cells precedes luminal acidification in the cochlea and the endolymphatic sac. Stretching and luminal acidification may alter cell-to-cell communication and lead to the observed retarded development of stria vascularis, which may be an important step on the path to deafness in Slc26a4(-/- mice, and possibly in humans, lacking functional pendrin expression.

  3. Expression of aquaporins and vasopressin type 2 receptor in the stria vascularis of the cochlea. (United States)

    Nishioka, R; Takeda, T; Kakigi, A; Okada, T; Takebayashi, S; Taguchi, D; Nishimura, M; Hyodo, M


    Recently, considerable evidence has been accumulated to support the novel view that water homeostasis in the inner ear is regulated via the vasopressin-aquaporin 2 (VP-AQP2) system in the same fashion as in the kidney. Indeed, multiple subtypes of AQPs including AQP-2 are reported to be expressed in the cochlea. However, the mechanism that underlies VP-AQP-2 mediated water homeostasis remains to be elucidated. In the present study, the localizations of AQP-1, -2, -3, -4, -5, -7, -8, -9, and vasopressin type 2 receptor (V2-R) in the stria vascularis (SV) were molecular biologically and immunohistochemically examined to evaluate the role of the AQP water channel system in water homeostasis of the SV. A RT-PCR study revealed that AQPs and V2-R mRNA are expressed in the cochlea. As for their immunohistochemical localization, the AQP-2 protein is expressed on the basal side of the basal cells of the SV, and proteins of AQP-3 and V2-R are expressed on the apical side of the basal cells. AQP-7 and -9 proteins are expressed on the apical side of marginal cells. AQP-4, -5, and -8 protein expressions could not be detected in the lateral wall of the cochlea. From the present results, water flux in the SV is thought to be regulated at the level of the basal cells by vasopressin. Furthermore, such a distribution of AQP-2, -3, and V2-R suggests that VP-AQP-2 mediated water transport might work actively in the basal cells from perilymph towards endolymph containing AQP-1, -7 and -9. Copyright 2009 Elsevier B.V. All rights reserved.

  4. Sex differences in cells expressing green fluorescent protein under the control of the estrogen receptor-α promoter in the hypothalamus of mice. (United States)

    Kyi-Tha-Thu, Chaw; Okoshi, Kota; Ito, Hiroto; Matsuda, Ken-Ichi; Kawata, Mitsuhiro; Tsukahara, Shinji


    Estradiol that originates from testicular testosterone and binds to estrogen receptor-α (ERα) during developing period acts to organize the male-type brain in mice. Here, we examined transgenic mice expressing green fluorescent protein (GFP) under the control of the ERα promoter, in which ERα-expressing cells in the brain can be visualized by GFP. Fluorescence microscopy revealed the existence of many GFP-expressing cells in the medial preoptic area, medial preoptic nucleus (MPN), bed nucleus of the stria terminalis (BNST), and striohypothalamic nucleus (StHy) of adult transgenic mice. Neuronal nuclear antigen, a neuron marker, but not glial fibrillary acidic protein, an astrocyte marker, was mostly expressed by GFP-expressing cells. Analysis of GFP expression area showed that adult females had higher GFP expression in a region including the ventral part of the BNST, StHy, and dorsal part of the MPN than in adult males. Such female-biased sex difference was also found in transgenic pups on postnatal day 5 and 8. The GFP expression area of adult females was decreased by postnatal treatment with testosterone or estradiol. These results indicate that GFP visualizes a sex difference of ERα-expressing neurons. The transgenic mice may be useful for the analysis of the sexual differentiation of the brain. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  5. Monoamine innervation of the organum vasculosum laminae terminalis (OVLT): a high resolution radioautographic study in the rat

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    Bosler, O.; Descarries, L.


    The monoamine innervation of the organum vasculosum laminae terminalis (OVLT) was examined in the adult rat by light and electron microscope radioautography after intraventricular administration of tritiated serotonin (( 3H)5-HT) or dopamine (( 3H)DA). Radioautographic and biochemical controls after 5,7-dihydroxytryptamine or 6-hydroxydopamine lesioning established the respective serotonin (5-HT) and catecholamine (CA) identities of the axonal varicosities labeled under the conditions of the present experiments. For descriptive purposes, the OVLT was subdivided in three parts: two parenchymal zones, one juxtaventricular, the other juxtavascular, and the vascular core. Almost 10% of all axonal varicosities in the OVLT were found to be labeled with (3H)5-HT. This 5-HT innervation was most prominent in the rostrocaudal and ventrodorsal portions of the juxtaventricular zone and the dorsal aspect of the juxtavascular zone; there was none in the vascular core. (3H)DA-labeled varicosities were much less abundant and yet more numerous than earlier histofluorescent and immunohistochemical studies would have predicted. They predominated in the juxtavascular zone, where a majority presumably had a dopamine (DA) rather than a noradrenaline identity. Some were also found in the vascular core, where they most likely corresponded to peripheral autonomic noradrenaline endings. In the juxtaventricular zone of the OVLT, a significant proportion of the (3H)5-HT-labeled varicosity profiles could be observed to form axodendritic synapses, but in the juxtavascular zone no 5-HT or any (3H)DA-labeled ones were ever seen in synaptic junction. In the juxtavascular zone, the 5-HT and the presumed DA endings established close relationships with neurosecretory axons, and with astrocytic or tanycytic processes on which they occasionally formed synaptoid contacts.

  6. Structure and function of the amygdaloid NPY system: NPY Y2 receptors regulate excitatory and inhibitory synaptic transmission in the centromedial amygdala. (United States)

    Wood, J; Verma, D; Lach, G; Bonaventure, P; Herzog, H; Sperk, G; Tasan, R O


    The amygdala is essential for generating emotional-affective behaviors. It consists of several nuclei with highly selective, elaborate functions. In particular, the central extended amygdala, consisting of the central amygdala (CEA) and the bed nucleus of the stria terminalis (BNST) is an essential component actively controlling efferent connections to downstream effectors like hypothalamus and brain stem. Both, CEA and BNST contain high amounts of different neuropeptides that significantly contribute to synaptic transmission. Among these, neuropeptide Y (NPY) has emerged as an important anxiolytic and fear-reducing neuromodulator. Here, we characterized the expression, connectivity and electrophysiological function of NPY and Y2 receptors within the CEA. We identified several NPY-expressing neuronal populations, including somatostatin- and calretinin-expressing neurons. Furthermore, in the main intercalated nucleus, NPY is expressed primarily in dopamine D1 receptor-expressing neurons but also in interspersed somatostatin-expressing neurons. Interestingly, NPY neurons did not co-localize with the Y2 receptor. Retrograde tract tracing experiments revealed that NPY neurons reciprocally connect the CEA and BNST. Functionally, the Y2 receptor agonist PYY3-36, reduced both, inhibitory as well as excitatory synaptic transmission in the centromedial amygdala (CEm). However, we also provide evidence that lack of NPY or Y2 receptors results in increased GABA release specifically at inhibitory synapses in the CEm. Taken together, our findings suggest that NPY expressed by distinct populations of neurons can modulate afferent and efferent projections of the CEA via presynaptic Y2 receptors located at inhibitory and excitatory synapses.


    Münsterkötter, Anna Luisa; Notzon, Swantje; Redlich, Ronny; Grotegerd, Dominik; Dohm, Katharina; Arolt, Volker; Kugel, Harald; Zwanzger, Peter; Dannlowski, Udo


    Processes of phasic fear responses to threatening stimuli are thought to be distinct from sustained, anticipatory anxiety toward an unpredicted, potential threat. There is evidence for dissociable neural correlates of phasic fear and sustained anxiety. Whereas increased amygdala activity has been associated with phasic fear, sustained anxiety has been linked with activation of the bed nucleus of stria terminalis (BNST), anterior cingulate cortex (ACC), and the insula. So far, only a few studies have focused on the dissociation of neural processes related to both phasic and sustained fear in specific phobia. We suggested that first, conditions of phasic and sustained fear would involve different neural networks and, second, that overall neural activity would be enhanced in a sample of phobic compared to nonphobic participants. Pictures of spiders and neutral stimuli under conditions of either predicted (phasic) or unpredicted (sustained) fear were presented to 28 subjects with spider phobia and 28 nonphobic control subjects during functional magnetic resonance imaging (fMRI) scanning. Phobic patients revealed significantly higher amygdala activation than controls under conditions of phasic fear. Sustained fear processing was significantly related to activation in the insula and ACC, and phobic patients showed a stronger activation than controls of the BNST and the right ACC under conditions of sustained fear. Functional connectivity analysis revealed enhanced connectivity of the BNST and the amygdala in phobic subjects. Our findings support the idea of distinct neural correlates of phasic and sustained fear processes. Increased neural activity and functional connectivity in these networks might be crucial for the development and maintenance of anxiety disorders. © 2015 Wiley Periodicals, Inc.

  8. A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA exposure in a prosocial species, the prairie vole (Microtus ochrogaster). (United States)

    Sullivan, Alana W; Beach, Elsworth C; Stetzik, Lucas A; Perry, Amy; D'Addezio, Alyssa S; Cushing, Bruce S; Patisaul, Heather B


    Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-μg/kg body weight (bw)/d, 50-μg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8-14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50-mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated sex differences in PVN TH-ir neuron numbers and reversed this sex difference at the highest dose. Minimal behavioral effects were observed in BPA-exposed males. These data support the hypothesis that BPA alters affective behaviors, potentially via disruption of OT/AVP pathways.

  9. Deafness in Claudin 11-Null Mice Reveals the Critical Contribution of Basal Cell Tight Junctions to Stria Vascularis Function (United States)

    Gow, Alexander; Davies, Caroline; Southwood, Cherie M.; Frolenkov, Gregory; Chrustowski, Mark; Ng, Lily; Yamauchi, Daisuke; Marcus, Daniel C.; Kachar, Bechara


    Generation of a strong electrical potential in the cochlea is uniquely mammalian and may reflect recent evolutionary advances in cellular voltage-dependent amplifiers. This endocochlear potential is hypothesized to dramatically improve hearing sensitivity, a concept that is difficult to explore experimentally, because manipulating cochlear function frequently causes rapid degenerative changes early in development. Here, we examine the deafness phenotype in adult Claudin 11-null mice, which lack the basal cell tight junctions that give rise to the intrastrial compartment and find little evidence of cochlear pathology. Potassium ion recycling is normal in these mutants, but endocochlear potentials were below 30 mV and hearing thresholds were elevated 50 dB sound pressure level across the frequency spectrum. Together, these data demonstrate the central importance of basal cell tight junctions in the stria vascularis and directly verify the two-cell hypothesis for generation of endocochlear potential. Furthermore, these data indicate that endocochlear potential is an essential component of the power source for the mammalian cochlear amplifier. PMID:15306639

  10. La estria supranuclear de las células ciliadas en la rinitis alérgica Supranuclear stria of ciliated cells in allergic rhinitis

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    Ana Zerdiew


    Full Text Available Se estudiaron 80 pacientes adultos alérgicos, que cursaron con los siguientes cuadros clínicos: 16 casos de rinitis intermitente y 64 de rinitis persistente. Se realizó el recuento porcentual de la estría supranuclear de las células ciliadas, respecto de los leucocitos presentes en los extendidos obtenidos por toma endonasal. Con los datos obtenidos se clasificaron los extendidos en 4 grupos; Grupo A (N=23: predominio leucocitario eosinófilo con eosinofilia nasal >10%, Grupo B (N=15: abundantes leucocitos neutrófilos y eosinofilia nasal >10%, Grupo C (N=29: con escasos leucocitos, Grupo D (N=13: con abundantes leucocitos de predominio neutrófilo sin eosinofilia. Se observó que el incremento porcentual de estría supranuclear se correlacionó con eosinofilia nasal >10% y con las muestras que presentaron escasos leucocitos. Sin embargo se evidenció una marcada disminución del porcentaje de estría supranuclear en la leucocitosis neutrófila de etiología bacteriana.Nasal secretions were studied in 80 allergic adults patients: 16 with intermittent rhinitis and 64 with persistent rhinitis. The percentage of supranuclear stria of ciliated cells with regard to leucocytes was studied by nasal scraping. Four groups of patients were classified according to nasal leucocytic predominance: patients with eosinophilic predominance with eosinophils > 10% in Group A (N=23, patients with abundant neutrophils and eosinophils >10% in Group B (N=15, patients with scant leucocytes in Group C (N=29, patients with neutrophilic predominance without eosinophils in Group D (N=13. An increase of supranuclear stria percentage was correlated to eosinophils > 10% and also correlated to scant leucocytes. Nevertheless, a significant decrease of supranuclear stria percentage was observed in neutrophilic leukocytosis of bacterial etiology.

  11. Adenosine Triphosphate-sensitive Micro-reentrant Atrial Tachycardia Originating from the Crista Terminalis in a Patient with Chronic Renal Failure due to Thrombotic Thrombocytopenic Purpura

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    Shinya Sugiura, MD


    Full Text Available A 57-year-old woman with chronic renal failure due to the thrombotic thrombocytopenic purpura complained of palpitation. A 12-lead ECG showed supraventricular tachycardia with a cycle length of 375 ms. During the electrophysiological study, a tachycardia with a cycle length of 375 ms was reproducibly induced and terminated by atrial extrastimulation. The tachycardia exhibited an inverse relationship between the coupling interval of extrastimulus initiating the tachycardia, and the first postpacing return cycle, as well as an increasing pattern of resetting the tachycardia with an atrial extrastimulus. Ventricular burst pacing during tachycardia produced AV dissociation. Intravenous injections of a low dose (4 mg of adenosine triphosphate (ATP terminated the tachycardia without a preceding atrio-His bundle block. The tachycardia was diagnosed as an ATP-sensitive micro-reentrant atrial tachycardia. Real-time endocardial activation mapping using an electroanatomical mapping system revealed that the earliest activation site of the tachycardia was located at the midlateral portion of the crista terminalis. The tachycardia was abolished by focal ablation targeting the earliest activation site during tachycardia. This is the first reported case of an ATP-sensitive micro-reentrant atrial tachycardia associated with thrombotic thrombocytopenic purpura.

  12. Glucocorticoids regulation of FosB/ΔFosB expression induced by chronic opiate exposure in the brain stress system.

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    Daniel García-Pérez

    Full Text Available Chronic use of drugs of abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads to accumulation of the transcription factor ΔFosB, particularly in brain areas associated with reward and stress. The persistent effects of ΔFosB on target genes may play an important role in the plasticity induced by drugs of abuse. Recent evidence suggests that stress-related hormones (e.g., glucocorticoids, GC may induce adaptations in the brain stress system that is likely to involve alteration in gene expression and transcription factors. This study examined the role of GC in regulation of FosB/ΔFosB in both hypothalamic and extrahypothalamic brain stress systems during morphine dependence. For that, expression of FosB/ΔFosB was measured in control (sham-operated and adrenalectomized (ADX rats that were made opiate dependent after ten days of morphine treatment. In sham-operated rats, FosB/ΔFosB was induced after chronic morphine administration in all the brain stress areas investigated: nucleus accumbens(shell (NAc, bed nucleus of the stria terminalis (BNST, central amygdala (CeA, hypothalamic paraventricular nucleus (PVN and nucleus of the solitary tract noradrenergic cell group (NTS-A(2. Adrenalectomy attenuated the increased production of FosB/ΔFosB observed after chronic morphine exposure in NAc, CeA, and NTS. Furthermore, ADX decreased expression of FosB/ΔFosB within CRH-positive neurons of the BNST, PVN and CeA. Similar results were obtained in NTS-A(2 TH-positive neurons and NAc pro-dynorphin-positive neurons. These data suggest that neuroadaptation (estimated as accumulation of FosB/ΔFosB to opiates in brain areas associated with stress is modulated by GC, supporting the evidence of a link between brain stress hormones and addiction.

  13. Quantitative analysis of long-form aromatase mRNA in the male and female rat brain. (United States)

    Tabatadze, Nino; Sato, Satoru M; Woolley, Catherine S


    In vitro studies show that estrogens acutely modulate synaptic function in both sexes. These acute effects may be mediated in vivo by estrogens synthesized within the brain, which could fluctuate more rapidly than circulating estrogens. For this to be the case, brain regions that respond acutely to estrogens should be capable of synthesizing them. To investigate this question, we used quantitative real-time PCR to measure expression of mRNA for the estrogen-synthesizing enzyme, aromatase, in different brain regions of male and female rats. Importantly, because brain aromatase exists in two forms, a long form with aromatase activity and a short form with unknown function, we targeted a sequence found exclusively in long-form aromatase. With this approach, we found highest expression of aromatase mRNA in the amygdala followed closely by the bed nucleus of the stria terminalis (BNST) and preoptic area (POA); we found moderate levels of aromatase mRNA in the dorsal hippocampus and cingulate cortex; and aromatase mRNA was detectable in brainstem and cerebellum, but levels were very low. In the amygdala, gonadal/hormonal status regulated aromatase expression in both sexes; in the BNST and POA, castration of males down-regulated aromatase, whereas there was no effect of estradiol in ovariectomized females. In the dorsal hippocampus and cingulate cortex, there were no differences in aromatase levels between males and females or effects of gonadal/hormonal status. These findings demonstrate that long-form aromatase is expressed in brain regions that respond acutely to estrogens, such as the dorsal hippocampus, and that gonadal/hormonal regulation of aromatase differs among different brain regions.

  14. Binge Alcohol Drinking Elicits Persistent Negative Affect in Mice (United States)

    Lee, Kaziya M.; Coehlo, Michal; McGregor, Hadley A.; Waltermire, Ryan S.; Szumlinski, Karen K.


    Cessation from chronic alcohol abuse often produces a dysphoric state that can persist into protracted withdrawal. This dysphoric state is theorized to function as a negative reinforcer that maintains excessive alcohol consumption and/or precipitates relapse in those struggling to abstain from alcohol. However, we know relatively little regarding the impact of cessation from binge drinking on behavioral measures of negative affect and related neurobiology. Male C57BL/6J mice were given access to unsweetened 20% alcohol for 6 weeks under modified Drinking-in-the-Dark procedures, followed by behavioral testing beginning either 1 or 21 days into withdrawal. Mice were administered a behavioral test battery consisting of: the elevated plus maze, light/dark box, novel object test, marble burying test, Porsolt forced swim test and sucrose preference test to assess anxiogenic and depressive signs. Egr1 immunostaining was used to quantify cellular activity within the central nucleus of the amygdala (CEA), basolateral amygdala (BLA), bed nucleus of the stria terminalis (BNST), and the nucleus accumbens (Acb) shell (AcbSh) and core (AcbC). Compared to water controls, alcohol-drinking mice exhibited higher indices of emotionality in the majority of behavioral assays. The hyper-emotionality exhibited by binge drinking mice was apparent at both withdrawal time-points and correlated with higher Egr1+ cell counts in the CEA and BNST, compared to controls. These data show that affective symptoms emerge very early after cessation of binge drinking and persist into protracted withdrawal. A history of binge drinking is capable of producing enduring neuroadaptations within brain circuits mediating emotional arousal. PMID:26048424

  15. Estrogenic suppression of binge-like eating elicited by cyclic food restriction and frustrative-nonreward stress in female rats. (United States)

    Micioni Di Bonaventura, Maria Vittoria; Lutz, Thomas A; Romano, Adele; Pucci, Mariangela; Geary, Nori; Asarian, Lori; Cifani, Carlo


    Because binge eating and emotional eating vary through the menstrual cycle in human females, we investigated cyclic changes in binge-like eating in female rats and their control by estrogens. Binge-like eating was elicited by three cycles of 4 days of food restriction and 4 days of free feeding followed by a single frustrative nonreward-stress episode (15 min visual and olfactory exposure to a familiar palatable food) immediately before presentation of the palatable food. Intact rats showed binge-like eating during the diestrous and proestrous phases of the ovarian cycle, but not during the estrous (periovulatory) phase. Ovariectomized (OVX) rats not treated with estradiol (E2) displayed binge-like eating, whereas E2-treated OVX rats did not. The procedure did not increase signs of anxiety in an open-field test. OVX rats not treated with E2 that were subjected to food restriction and sacrificed immediately after frustrative nonreward had increased numbers of cells expressing phosphorylated extracellular signal-regulated kinases (ERK) in the central nucleus of the amygdala (CeA), paraventricular nucleus of hypothalamus (PVN), and dorsal and ventral bed nuclei of the stria terminalis (BNST) compared with nonrestricted or E2-treated rats. These data suggest that this female rat model is appropriate for mechanistic studies of some aspects of menstrual-cycle effects on emotional and binge eating in human females, that anxiety is not a sufficient cause of binge-like eating, and that the PVN, CeA, and BNST may contribute to information processing underlying binge-like eating. © 2017 Wiley Periodicals, Inc.

  16. Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo). (United States)

    Moeller, John F; Meredith, Michael


    The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks, the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RF-amide-like peptides. To define further the cell populations and connectivity, we used double-label immunocytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH-immunoreactive (ir) cell profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT)-negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH-immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Combined effects of dietary fructooligosaccharide and Bacillus licheniformis on innate immunity, antioxidant capability and disease resistance of triangular bream (Megalobrama terminalis). (United States)

    Zhang, Chun-Nuan; Li, Xiang-Fei; Xu, Wei-Na; Jiang, Guang-Zhen; Lu, Kang-Le; Wang, Li-Na; Liu, Wen-Bin


    This study was conducted to investigate the effects of fructooligosaccharide (FOS) and Bacillus licheniformis (B. licheniformis) and their interaction on innate immunity, antioxidant capability and disease resistance of triangular bream Megalobrama terminalis (average initial weight 30.5 ± 0.5 g). Nine experimental diets were formulated to contain three FOS levels (0, 0.3% and 0.6%) and three B. licheniformis levels (0, 1 × 10(7), 5 × 10(7) CFU g(-1)) according to a 3 × 3 factorial design. At the end of the 8-week feeding trial, fish were challenged by Aeromonas hydrophila (A. hydrophila) and survival rate was recorded for the next 7 days. The results showed that leucocyte counts, alternative complement activity as well as total serum protein and globulin contents all increased significantly (P licheniformis levels increased from 0 to 1 × 10(7) CFU g(-1), while little difference (P > 0.05) was observed in these parameters in terms of dietary FOS levels. Both plasma alkaline phosphatase and phenoloxidase activities were significantly (P 0.05) by both FOS and B. licheniformis. Liver catalase, glutathione peroxidase as well as plasma SOD activities of fish fed 1 × 10(7) CFU g(-1)B. licheniformis were all significantly (P 0.05) by either FOS levels or B. licheniformis contents, whereas a significant (P licheniformis. The results of this study indicated that dietary FOS and B. licheniformis could significantly enhance the innate immunity and antioxidant capability of triangular bream, as well as improve its disease resistance. The best combination of these two prebiotics and/or probiotics was 0.3% FOS and 1 × 10(7) CFU g(-1)B. licheniformis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. No impact of deep brain stimulation on fear-potentiated startle in obsessive-compulsive disorder

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    Johanna M.P. Baas


    Full Text Available Deep brain stimulation (DBS of the ventral internal capsule is effective in treating therapy refractory obsessive-compulsive disorder (OCD. Given the close proximity of the stimulation site to the stria terminalis (BNST, we hypothesized that the striking decrease in anxiety symptoms following DBS could be the result of the modulation of contextual anxiety. However, the effect of DBS in this region on contextual anxiety is as of yet unknown. Thus, the current study investigated the effect of DBS on contextual anxiety in an experimental threat of shock paradigm. Eight patients with DBS treatment for severe OCD were tested in a double-blind crossover design with randomly assigned two-week periods of active and sham stimulation. DBS resulted in significant decrease of obsessive-compulsive symptoms, anxiety and depression. However, even though the threat manipulation resulted in a clear context potentiated startle effect, none of the parameters derived from the startle recordings was modulated by the DBS. This suggests that DBS in the ventral internal capsule is effective in treating anxiety symptoms of obsessive-compulsive disorder without modulating the startle circuitry. We hypothesize that the anxiety symptoms present in OCD are likely distinct from the pathological brain circuits in defensive states of other anxiety disorders.

  19. Striatum on the anxiety map: Small detours into adolescence. (United States)

    Lago, Tiffany; Davis, Andrew; Grillon, Christian; Ernst, Monique


    Adolescence is the most sensitive period for the development of pathological anxiety. Moreover, specific neural changes associated with the striatum might be related to adolescent vulnerability to anxiety. Up to now, the study of anxiety has primarily focused on the amygdala, bed nucleus of the stria terminalis (BNST), hippocampus and ventromedial prefrontal cortex (vmPFC), while the striatum has typically not been considered as part of the anxiety system. This review proposes the addition of the striatum, a complex, multi-component structure, to the anxiety network by underscoring two lines of research. First, the co-occurrence of the adolescent striatal development with the peak vulnerability of adolescents to anxiety disorders might potentially reflect a causal relationship. Second, the recognition of the role of the striatum in fundamental behavioral processes that do affect anxiety supports the putative importance of the striatum in anxiety. These behavioral processes include (1) attention, (2) conditioning/prediction error, and (3) motivation. This review proposes a simplistic schematic representation of the anxiety circuitry that includes the striatum, and aims to promote further work in this direction, as the role of the striatum in shaping an anxiety phenotype during adolescence could have critical implications for understanding and preventing the peak onset of anxiety disorders during this period. This article is part of a Special Issue entitled SI: Adolescent plasticity. Published by Elsevier B.V.

  20. Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine fear responsiveness to unpredictable threat. (United States)

    Lange, M D; Daldrup, T; Remmers, F; Szkudlarek, H J; Lesting, J; Guggenhuber, S; Ruehle, S; Jüngling, K; Seidenbecher, T; Lutz, B; Pape, H C


    The brain circuits underlying behavioral fear have been extensively studied over the last decades. Although the vast majority of experimental studies assess fear as a transient state of apprehension in response to a discrete threat, such phasic states of fear can shift to a sustained anxious apprehension, particularly in face of diffuse cues with unpredictable environmental contingencies. Unpredictability, in turn, is considered an important variable contributing to anxiety disorders. The networks of the extended amygdala have been suggested keys to the control of phasic and sustained states of fear, although the underlying synaptic pathways and mechanisms remain poorly understood. Here, we show that the endocannabinoid system acting in synaptic circuits of the extended amygdala can explain the fear response profile during exposure to unpredictable threat. Using fear training with predictable or unpredictable cues in mice, combined with local and cell-type-specific deficiency and rescue of cannabinoid type 1 (CB1) receptors, we found that presynaptic CB1 receptors on distinct amygdala projections to bed nucleus of the stria terminalis (BNST) are both necessary and sufficient for the shift from phasic to sustained fear in response to an unpredictable threat. These results thereby identify the causal role of a defined protein in a distinct brain pathway for the temporal development of a sustained state of anxious apprehension during unpredictability of environmental influences, reminiscent of anxiety symptoms in humans.

  1. Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors. (United States)

    Bales, K L; Plotsky, P M; Young, L J; Lim, M M; Grotte, N; Ferrer, E; Carter, C S


    Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the long-lasting, developmental effects of exposure to neonatal OT or OTA might reflect changes in the expression of receptors for these peptides. On postnatal day 1, prairie voles were injected intraperitoneally with either OT (1 mg/kg), an OTA (0.1 mg/kg), saline vehicle, or were handled only. At approximately 60 days of age, vasopressin V1a receptors, OT receptors (OTR) and dopamine D2 receptor binding were quantified using receptor autoradiography in brain tissue taken from males and females. Significant treatment effects on V1a binding were found in the bed nucleus of the stria terminalis (BNST), cingulate cortex (CgCtx), mediodorsal thalamus (MdThal), medial preoptic area of the hypothalamus (MPOA), and lateral septum (LS). The CgCtx, MPOA, ventral pallidum, and LS also showed significant sex by treatment interactions on V1a binding. No significant treatment or sex differences were observed for D2 receptor binding. No significant treatment difference was observed for OTR receptor binding, and only a marginal sex difference. Changes in the neuropeptide receptor expression, especially the V1a receptor, may help to explain sexually dimorphic changes in behavior that follow comparable neonatal manipulations.

  2. Effect of acupuncture on adrenocortical hormone production in rabbits with a central lesion

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    Liao, Y.Y.; Seto, K.; Saitoh, H.; Kawakami, M.

    A study was made of adrenocortical hormone production under electroacupuncture stimulation of the Tsu-San-Li locus in rabbits with a lesion in the fornix, stria terminalis, ventromedial nucleus or arcuate nucleus. In rabbits with a lesion in the stria terminalis or ventromedial nucleus, electroacupuncture stimulation of Tsu-San-Li resulted in no increase in phase 1 but an increase in phase 2 of adrenocortical hormone production. In rabbits with a lesion in the fornix or arcuate nucleus electroacupuncture stimulation of Tsu-San-Li was followed by increased adrenocortical hormone production in the both phases. These results show that the stria terminalis and the ventromedial nucleus play a major role in the augmentation of adrenocortical hormone production by electroacupuncture stimulation of Tsu-San-Li.

  3. Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse (United States)

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P


    Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

  4. Acute and chronic effects of selective serotonin reuptake inhibitor treatment on fear conditioning: implications for underlying fear circuits. (United States)

    Burghardt, N S; Bauer, E P


    Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment of a spectrum of anxiety disorders, yet paradoxically they may increase symptoms of anxiety when treatment is first initiated. Despite extensive research over the past 30 years focused on SSRI treatment, the precise mechanisms by which SSRIs exert these opposing acute and chronic effects on anxiety remain unknown. By testing the behavioral effects of SSRI treatment on Pavlovian fear conditioning, a well characterized model of emotional learning, we have the opportunity to identify how SSRIs affect the functioning of specific brain regions, including the amygdala, bed nucleus of the stria terminalis (BNST) and hippocampus. In this review, we first define different stages of learning involved in cued and context fear conditioning and describe the neural circuits underlying these processes. We examine the results of numerous rodent studies investigating how acute SSRI treatment modulates fear learning and relate these effects to the known functions of serotonin in specific brain regions. With these findings, we propose a model by which acute SSRI administration, by altering neural activity in the extended amygdala and hippocampus, enhances both acquisition and expression of cued fear conditioning, but impairs the expression of contextual fear conditioning. Finally, we review the literature examining the effects of chronic SSRI treatment on fear conditioning in rodents and describe how downregulation of N-methyl-d-aspartate (NMDA) receptors in the amygdala and hippocampus may mediate the impairments in fear learning and memory that are reported. While long-term SSRI treatment effectively reduces symptoms of anxiety, their disruptive effects on fear learning should be kept in mind when combining chronic SSRI treatment and learning-based therapies, such as cognitive behavioral therapy. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Why may allopregnanolone help alleviate loneliness? (United States)

    Cacioppo, S; Cacioppo, J T


    Impaired biosynthesis of Allopregnanolone (ALLO), a brain endogenous neurosteroid, has been associated with numerous behavioral dysfunctions, which range from anxiety- and depressive-like behaviors to aggressive behavior and changes in responses to contextual fear conditioning in rodent models of emotional dysfunction. Recent animal research also demonstrates a critical role of ALLO in social isolation. Although there are likely aspects of perceived social isolation that are uniquely human, there is also continuity across species. Both human and animal research show that perceived social isolation (which can be defined behaviorally in animals and humans) has detrimental effects on physical health, such as increased hypothalamic pituitary adrenal (HPA) activity, decreased brain-derived neurotrophic factor (BDNF) expression, and increased depressive behavior. The similarities between animal and human research suggest that perceived social isolation (loneliness) may also be associated with a reduction in the synthesis of ALLO, potentially by reducing BDNF regulation and increasing HPA activity through the hippocampus, amygdala, and bed nucleus of the stria terminalis (BNST), especially during social threat processing. Accordingly, exogenous administration of ALLO (or ALLO precursor, such as pregnenolone), in humans may help alleviate loneliness. Congruent with our hypothesis, exogenous administration of ALLO (or ALLO precursors) in humans has been shown to improve various stress-related disorders that show similarities between animals and humans i.e., post-traumatic stress disorders, traumatic brain injuries. Because a growing body of evidence demonstrates the benefits of ALLO in socially isolated animals, we believe our ALLO hypothesis can be applied to loneliness in humans, as well. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Epigenetics and sex differences in the brain: A genome-wide comparison of histone-3 lysine-4 trimethylation (H3K4me3) in male and female mice. (United States)

    Shen, Erica Y; Ahern, Todd H; Cheung, Iris; Straubhaar, Juerg; Dincer, Aslihan; Houston, Isaac; de Vries, Geert J; Akbarian, Schahram; Forger, Nancy G


    Many neurological and psychiatric disorders exhibit gender disparities, and sex differences in the brain likely explain some of these effects. Recent work in rodents points to a role for epigenetics in the development or maintenance of neural sex differences, although genome-wide studies have so far been lacking. Here we review the existing literature on epigenetics and brain sexual differentiation and present preliminary analyses on the genome-wide distribution of histone-3 lysine-4 trimethylation in a sexually dimorphic brain region in male and female mice. H3K4me3 is a histone mark primarily organized as 'peaks' surrounding the transcription start site of active genes. We microdissected the bed nucleus of the stria terminalis and preoptic area (BNST/POA) in adult male and female mice and used ChIP-Seq to compare the distribution of H3K4me3 throughout the genome. We found 248 genes and loci with a significant sex difference in H3K4me3. Of these, the majority (71%) had larger H3K4me3 peaks in females. Comparisons with existing databases indicate that genes and loci with increased H3K4me3 in females are associated with synaptic function and with expression atlases from related brain areas. Based on RT-PCR, only a minority of genes with a sex difference in H3K4me3 has detectable sex differences in expression at baseline conditions. Together with previous findings, our data suggest that there may be sex biases in the use of epigenetic marks. Such biases could underlie sex differences in vulnerabilities to drugs or diseases that disrupt specific epigenetic processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Sex-Dependent Effects of Prenatal Stress on Social Memory in Rats: A Role for Differential Expression of Central Vasopressin-1a Receptors. (United States)

    Grundwald, N J; Benítez, D P; Brunton, P J


    Prenatal stress (PNS) affects a number of traits in the offspring, including stress axis regulation, emotionality and cognition; however, much less is known about the effects of PNS on social memory and the underlying central mechanisms. In the present study, we investigated social preference, social memory under basal and stress conditions and olfactory memory for social and nonsocial odours in the adult offspring of dams exposed to social stress during late pregnancy. Given the key roles that the central oxytocin and vasopressin systems play in facilitating social memory, we further investigated the effects of PNS on the central expression of mRNA for oxytocin (Oxtr) and vasopressin-1a (Avpr1a) receptors. PNS did not affect social preference in either sex; however, social memory was impaired under basal conditions in PNS females but not PNS males. Accordingly, Avpr1a mRNA expression in the lateral septum and bed nucleus of stria terminalis (BNST) was unaltered in males but was significantly lower in PNS females compared to controls. No differences in Oxtr mRNA expression were detected between control and PNS offspring in either sex in any of the brain regions examined. Social memory deficits in PNS females persisted when social odours were used; however, this does not appear to be a result of impaired olfaction because memory for nonsocial odours was similar in control and PNS females. Under acute stress conditions, deficits in social memory were observed in both male and female control offspring; however, PNS males were unaffected. Moreover, acute stress facilitated social memory in PNS females and this was associated with an up-regulation of Avpr1a mRNA in the lateral septum and BNST. Our data support a role for altered signalling via central Avpr1a in PNS-induced sex-dependent changes in social memory and may have implications for understanding the aetiology of neurodevelopmental disorders characterised by social behaviour deficits in humans. © 2015 The

  8. Sexual behavior reduces hypothalamic androgen receptor immunoreactivity

    NARCIS (Netherlands)

    Fernandez-Guasti, Alonso; Swaab, Dick; Rodríguez-Manzo, Gabriela


    Male sexual behavior is regulated by limbic areas like the medial preoptic nucleus (MPN), the bed nucleus of the stria terminalis (BST), the nucleus accumbens (nAcc) and the ventromedial hypothalamic nucleus (VMN). Neurons in these brain areas are rich in androgen receptors (AR) and express

  9. Fornix transection: Discrimination between neuropeptide effects on attention and memory

    NARCIS (Netherlands)

    Wimersma Greidanus, T.B. van; Croiset, G.; Schuiling, G.A.


    Transection of the fornix and the stria terminalis completely blocks the inhibitory action of ACTH 4–10 on extinction of a conditioned avoidance response (CAR), whereas this effect of the vasopressin analogue des-glycinamide-lysine-vasopressin (DG-LVP) is not affected. These data indicate that the



    Araújo, Raffaelle Andressa dos Santos; Utta, Bergson Pereira


    Foi na década de 40 que os renomados filósofos Theodor Adorno e Max Horkheimer reverberaram sobre a cultura, mais precisamente acerca da inclusão dos meios técnicos aos bens culturais, assumindo uma posição crítica sobre a relação entre industrialização e arte, acreditando que toda expressão cultural seria transformada em produto, numa indústria cultural. Na obra Dialética do Esclarecimento, eles defendem a tese de que mito e esclarecimento mantêm entre si uma relação dialética, com o mito já...

  11. Photoperiod reverses the effects of estrogens on male aggression via genomic and nongenomic pathways


    Trainor, Brian C.; Lin, Shili; Finy*, M. Sima; Rowland, Michael R.; Nelson, Randy J.


    Despite recent discoveries of the specific contributions of genes to behavior, the molecular mechanisms mediating contributions of the environment are understudied. We demonstrate that the behavioral effects of estrogens on aggression are completely reversed by a discrete environmental signal, day length. Selective activation of either estrogen receptor α or β decreases aggression in long days and increases aggression in short days. In the bed nucleus of the stria terminalis, one of several n...

  12. Neurobiology of Learning and Memory: Modulation and Mechanisms (United States)


    memory through influences invol- ving noradrenergic receptors in the amygdala. , .. . .... C-Qc- u , Y\\ o C r z A-, - r V r a ,, ~ Epinephrine Effects...epinephrine affects memory through influences involving the amygdala is supported by the finding that lesions of the stria terminalis (ST), a major...interpreted these findings as indicating that peripherally- administered naloxone influences memory by blocking opioid peptide recep- tors located within

  13. Biochemical evidence for glutamate as a transmitter in hippocampal efferents to the basal forebrain and hypothalamus in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I.; Fonnum, F.


    The effects of bilateral transection of the fornix bundle on the high affinity uptake of glutamate and on the amino acid content in several nuclei of rat forebrain and hypothalamus were studied in order to investigate the possible role of glutamate as a transmitter of these fibres. This lesion decreased the high affinity uptake of L-glutamate by 60 to 70% in the mammillary body and lateral septum, and by 40 to 50% in the anterior diagonal band nucleus, the bed nucleus of the stria terminalis, the mediobasal hypothalamus and the nucleus accumbens. The content of endogenous glutamate in samples dissected from freeze-dried tissue also decreased significantly in these regions. Endogenous aspartate was slightly decreased in the anterior diagonal band nucleus and the mammillary body, but unchanged in the other regions. No significant changes were seen in the levels of serine, ..gamma..-aminobutyric acid, glutamine and taurine, except for an increase in glutamine and taurine in the bed nucleus of the stria terminalis. The high affinity uptake of ..gamma..-aminobutyric acid, tested in the bed nucleus of the stria terminalis, the mediobasal hypothalamus and the mammillary body, was unchanged after the lesion. The results indicate that allocortical efferents innervating subcortial nuclei through the fornix might use glutamate as a transmitter. The study further supports the concept that glutamate plays an important role as transmitter of several different corticofugal fibre systems in mammalian brain.

  14. Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography (United States)

    Koller, Kristin; Bultitude, Janet H.; Mullins, Paul; Ward, Robert; Mitchell, Anna S.; Bell, Andrew H.


    It has been suggested that some cortically blind patients can process the emotional valence of visual stimuli via a fast, subcortical pathway from the superior colliculus (SC) that reaches the amygdala via the pulvinar. We provide in vivo evidence for connectivity between the SC and the amygdala via the pulvinar in both humans and rhesus macaques. Probabilistic diffusion tensor imaging tractography revealed a streamlined path that passes dorsolaterally through the pulvinar before arcing rostrally to traverse above the temporal horn of the lateral ventricle and connect to the lateral amygdala. To obviate artifactual connectivity with crossing fibers of the stria terminalis, the stria was also dissected. The putative streamline between the SC and amygdala traverses above the temporal horn dorsal to the stria terminalis and is positioned medial to it in humans and lateral to it in monkeys. The topography of the streamline was examined in relation to lesion anatomy in five patients who had previously participated in behavioral experiments studying the processing of emotionally valenced visual stimuli. The pulvinar lesion interrupted the streamline in two patients who had exhibited contralesional processing deficits and spared the streamline in three patients who had no deficit. Although not definitive, this evidence supports the existence of a subcortical pathway linking the SC with the amygdala in primates. It also provides a necessary bridge between behavioral data obtained in future studies of neurological patients, and any forthcoming evidence from more invasive techniques, such as anatomical tracing studies and electrophysiological investigations only possible in nonhuman species. PMID:26224780


    Directory of Open Access Journals (Sweden)

    Edmara Menezes


    Full Text Available A criatividade é um valor existente em qualquer sociedade. É um recurso inato do ser humano e provavelmente, o mais potente, porque a criatividade desafia e questiona as formas, estruturas e hierarquias. O termo indústrias criativas surgiu nos anos 90, para designar setores nos quais a criatividade é uma dimensão essencial do negócio. As Indústrias Criativas, portanto, são aquelas que têm sua origem na criatividade, habilidade e talento individuais, e possuem o potencial para a criação de riqueza e empregos através da geração e da exploração da propriedade intelectual, compreendem, entre outras, as atividades relacionadas ao cinema, ao teatro, à música e às artes plásticas. O presente artigo traça um painel de discussões sobre as indústrias criativas trazendo visões, definições sobre o tema e mapeamento das indústrias.


    Directory of Open Access Journals (Sweden)

    Karl Heinz Luersen


    Full Text Available Com o objetivo de avaliar a possibilidade de reúso do efluente líquido tratado de uma indústria curtidora, foi realizada esta pesquisa. O procedimento experimental comparou a produção de couros confeccionados com água potável, extraída de poços artesianos, com couros produzidos a partir do efluente líquido final tratado. Para alcançar este objetivo, foram realizados testes físicos e químicos através de análises em laboratório (análises químicas e de resistências físicas e avaliações organolépticas executadas por profissionais do setor de couro (quanto a cor, firmeza de flor, enchimento e toque. A avaliação analítica e a das características organolépticas não indicam diferenças representativas quando comparadas aos padrões de referência da ABNT de couros produzidos, permitindo, assim, concluir que o reúso de efluente tratado não altera a aparência dos artigos de couro.

  17. Extending the amygdala in theories of threat processing (United States)

    Fox, Andrew S.; Oler, Jonathan A.; Tromp, Do P.M.; Fudge, Julie L.; Kalin, Ned H.


    The central extended amygdala is an evolutionarily conserved set of interconnected brain regions that play an important role in threat processing to promote survival. Two core components of the central extended amygdala, the central nucleus of the amygdala (Ce) and the lateral bed nucleus of the stria terminalis (BST) are highly similar regions that serve complimentary roles by integrating fear- and anxiety-relevant information. Survival depends on the central extended amygdala's ability to rapidly integrate and respond to threats that vary in their immediacy, proximity, and characteristics. Future studies will benefit from understanding alterations in central extended amygdala function in relation to stress-related psychopathology. PMID:25851307

  18. Psychobiology of the acute stress response and its relationship to the psychobiology of post-traumatic stress disorder. (United States)

    Marshall, Randall D; Garakani, Amir


    PTSD that distinguishes the disorder from a simple trauma-induced phobia. The bed nucleus of the stria terminalis (BNST) is specifically implicated from preclinical research in the mediation of context-dependent cues [1]. Treatments that result in down-regulation of the BNST are therefore of particular interest in therapeutic models of prevention after trauma. The fact that a number of vulnerability factors associated with increased risk for developing PTSD are also likely to be biologically based (e.g., a genetic component, prior psychiatric history, prior family of history of psychiatric disorder), provides further evidence in support of a role for psychobiological factors in producing PTSD. Nevertheless, the considerable overlap on these measures between those who will develop PTSD, and those who eventually recover spontaneously, belies any attempt to identify any single or pathognomonic biological marker for risk. For now, the standard of care in predicting level of symptomatology and prognosis in the acute setting continues to be based on careful, informed, serial assessments of symptoms and functioning. Because the capacity to learn from and adapt to adverse conditions are essential to the survival of any species, understanding the neurobiological pathways that mediate learning from traumatic experiences in an adaptive way is as important as understanding the etiology of PTSD and other trauma-related maladaptive consequences. Biological models that trace the causal cascade of post-traumatic events in the brain and neuroendocrine systems may offer a multiplicity of possibilities for intervention. It is well established that conditioned responses are robust and persistent. Moreover, the primary mechanism of habituation is overlearning rather than extinction. Interventions that promote overlearning may therefore prove to be the most powerful and efficient preventative treatments. The therapeutics literature supports this hypothesis, in that brief psychosocial

  19. Effects of pelvic, pudendal, or hypogastric nerve cuts on Fos induction in the rat brain following vaginocervical stimulation. (United States)

    Pfaus, James G; Manitt, Colleen; Coopersmith, Carol B


    In the female rat, genitosensory input is conveyed to the central nervous system predominantly through the pelvic, pudendal, and hypogastric nerves. The present study examined the relative contribution of those three nerves in the expression of Fos immunoreactivity within brain regions previously shown to be activated by vaginocervical stimulation (VCS). Bilateral transection of those nerves, or sham neurectomy, was conducted in separate groups of ovariectomized, sexually-experienced females. After recovery, females were primed with estrogen and progesterone and given either 50 manual VCSs with a lubricated glass rod over the course of 1 h. VCS increased the number of neurons expressing Fos immunoreactivity in the medial preoptic area, lateral septum, bed nucleus of the stria terminalis, ventromedial hypothalamus, and medial amygdala of sham neurectomized females. Transection of the pelvic nerve reduced Fos immunoreactivity in the medial preoptic area, bed nucleus of the stria terminalis, ventromedial hypothalamus, and medial amygdala, whereas transection of the pudendal nerve had no effect. In contrast, transection of the hypogastric nerve increased Fos immunoreactivity in the medial preoptic area and lateral septum, whereas transaction of the pelvic nerve increased Fos immunoreactivity in the lateral septum, following VCS. All females given VCS, except those with pelvic neurectomy, displayed a characteristic immobility during each application. These data confirm that the pelvic nerve is largely responsible for the neural and behavioral effects of VCS, and support a separate function for the hypogastric nerve.

  20. Callous-unemotional traits drive reduced white-matter integrity in youths with conduct problems. (United States)

    Breeden, A L; Cardinale, E M; Lozier, L M; VanMeter, J W; Marsh, A A


    Callous-unemotional (CU) traits represent a significant risk factor for severe and persistent conduct problems in children and adolescents. Extensive neuroimaging research links CU traits to structural and functional abnormalities in the amygdala and ventromedial prefrontal cortex. In addition, adults with psychopathy (a disorder for which CU traits are a developmental precursor) exhibit reduced integrity in uncinate fasciculus, a white-matter (WM) tract that connects prefrontal and temporal regions. However, research in adolescents has not yet yielded similarly consistent findings. We simultaneously modeled CU traits and externalizing behaviors as continuous traits, while controlling for age and IQ, in order to identify the unique relationship of each variable with WM microstructural integrity, assessed using diffusion tensor imaging. We used tract-based spatial statistics to evaluate fractional anisotropy, an index of WM integrity, in uncinate fasciculus and stria terminalis in 47 youths aged 10-17 years, of whom 26 exhibited conduct problems and varying levels of CU traits. Whereas both CU traits and externalizing behaviors were negatively correlated with WM integrity in bilateral uncinate fasciculus and stria terminalis/fornix, simultaneously modeling both variables revealed that these effects were driven by CU traits; the severity of externalizing behavior was not related to WM integrity after controlling for CU traits. These results indicate that WM abnormalities similar to those observed in adult populations with psychopathy may emerge in late childhood or early adolescence, and may be critical to understanding the social and affective deficits observed in this population.

  1. Tallinna Lennujaama vana terminali renoveerimine = Renovation of Tallinn Airport's old terminal / Epp Lankots

    Index Scriptorium Estoniae

    Lankots, Epp, 1976-


    Arhitektid: Andres Põime, Reet Põime, Tiiu Truus. Tallinna Lennujaama reisijateterminali projekteerisid 1939. a. arhitektid Roman Koolmar ja Artur Jürvetson, hoone valmis Paula Koido rekonstrueerimisprojekti järgi. Ill.: 2 värv. sisevaadet, välisvaade

  2. Muuga terminal 2 - panus Vene Raudteele. Konkurent tooks terminali teenuste odavnemise / Jaroslav Tavgen

    Index Scriptorium Estoniae

    Tavgen, Jaroslav


    Muuga konteinerterminali operaatori konkursi kaotanud Muuga CT omanik AS Transiidikeskus ei ole Tallinna Sadama otsusega rahul ja leiab, et selle konkursi võitnud Rail Garant ei suuda kaubavedu suurendada


    Directory of Open Access Journals (Sweden)

    silvia novaes zilber


    Full Text Available O objetivo desse trabalho foi descrever o modelo de negócio dos criadores e distribuidores de conteúdo da indústria fonográfica a partir do uso da Internet, entendida como inovação.. O método empregado foi o estudo de casos múltiplos, com quatro criadores de conteúdo (artistas e dois distribuidores de conteúdo (uma major- Sony- e uma indie.Os resultados mostraram transformações no produto (digital ao invés de suporte físico, distribuição- feita por lojas virtuais, ocorrendo a desintermediação, possibilitando artistas conectarem-se diretamente a seus clientes, e faturamento aumentado para artistas e distribuidores indie, que se beneficiaram da divulgação pela Internet, enquanto que distribuidoras major não perceberam esse aumento, talvez devido à pirataria.

  4. NPBWR1 and NPBWR2: implications in energy homeostasis, pain, and emotion

    Directory of Open Access Journals (Sweden)

    Takeshi eSakurai


    Full Text Available Neuropeptide B/W receptor 1 (NPBWR1 and NPBWR2 had been known as orphan receptors GPR7 and 8, respectively. Endogenous peptide ligands of these receptors, neuropeptide B and neuropeptide W, were identified in 2002 and 2003 (1-3. These peptides have been implicated in regulation of feeding behavior, energy homeostasis, neuroendocrine function, and modulating inflammatory pain. In addition, strong and discrete expression of their receptors in the extended amygdala and bed nucleus of the stria terminalis suggests a potential role in regulating stress responses, emotion, anxiety and fear. Recent studies of NPB/NPW using both pharmacological and phenotypic analyses of genetically engineered mice as well as a human study support this hypothesis.

  5. Photoperiod reverses the effects of estrogens on male aggression via genomic and nongenomic pathways. (United States)

    Trainor, Brian C; Lin, Shili; Finy, M Sima; Rowland, Michael R; Nelson, Randy J


    Despite recent discoveries of the specific contributions of genes to behavior, the molecular mechanisms mediating contributions of the environment are understudied. We demonstrate that the behavioral effects of estrogens on aggression are completely reversed by a discrete environmental signal, day length. Selective activation of either estrogen receptor alpha or beta decreases aggression in long days and increases aggression in short days. In the bed nucleus of the stria terminalis, one of several nuclei in a neural circuit that controls aggression, estrogen-dependent gene expression is increased in long days but not in short days, suggesting that estrogens decrease aggression by driving estrogen-dependent gene expression. Estradiol injections increased aggression within 15 min in short days but not in long days, suggesting that estrogens increase aggression in short days primarily via nongenomic pathways. These data demonstrate that the environment can dictate how hormones affect a complex behavior by altering the molecular pathways targeted by steroid receptors.

  6. Receptors for GRP/bombesin-like peptides in the rat forebrain

    International Nuclear Information System (INIS)

    Wolf, S.S.; Moody, T.W.


    Binding sites in the rat forebrain were characterized using ( 125 I-Tyr4)bombesin as a receptor probe. Pharmacology experiments indicate that gastrin releasing peptide (GRP) and the GRP fragments GRP as well as Ac-GRP inhibited radiolabeled (Tyr4)bombesin binding with high affinity. Biochemistry experiments indicated that heat, N-ethyl maleimide or trypsin greatly reduced radiolabeled (Tyr4)bombesin binding. Also, autoradiographic studies indicated that highest grain densities were present in the stria terminalis, periventricular and suprachiasmatic nucleus of the hypothalamus, dorsomedial and rhomboid thalamus, dentate gyrus, hippocampus and medial amygdaloid nucleus. The data suggest that CNS protein receptors, which are discretely distributed in the rat forebrain, may mediate the action of endogenous GRP/bombesin-like peptides



    Pedroso, Larissa Batisti; Isoppo, Anelise; Bitencourt, Jaqueline; Pacheco, Diego Augusto de Jesus


    Este estudo tem por objetivo analisar o impacto ao se realizar o mapeamento do fluxo de valor atual e projetar o estado futuro em uma indústria de equipamentos de limpeza. O foco do estudo é a redução do lead time de produção utilizando práticas da manufatura enxuta. Para conduzir a pesquisa foram realizadas pesquisas em documentos da empresa para obtenção de dados históricos, revisão bibliográfica e a aplicação de estudo de caso. Os principais resultados da pesquisa demonstram que a aplicaçã...


    Directory of Open Access Journals (Sweden)

    Emiliane Andrade ARAÚJO


    Full Text Available

    A contaminação de superfícies por microrganismos deterioradores e patogênicos é causa de preocupação na indústria de alimentos. Desenvolvimento de biofilmes em ambientes de processamento de alimentos resulta na deterioração do produto e em possíveis riscos para a saúde pública, além de criar sérios problemas nas operações de processamento do fl uido. A adesão da bactéria à superfície é um dos primeiros passos para a formação do biofilme e propriedades físico-químicas da interface bacteriana infl uenciam o processo de adesão microbiana e, consequentemente, os procedimentos operacionais de higienização. A estrutura do biofilme e as características fisiológicas do microrganismo podem conferir resistência aos agentes antimicrobianos, como por exemplo, aos sanitizantes usados no procedimento de higienização. Dentre os fatores que infl uenciam o processo de adesão, as características de hidrofobicidade do microrganismo e da superfície apresentam grande importância nos mecanismos de adesão. As técnicas da medição do ângulo de contato e da coluna de interação hidrofóbica, para determinação da hidrofobicidade de superfícies de ribotipos de Bacillus cereus isolados de indústria de laticínios, foram avaliadas. Observou-se que as quatro superfícies dos ribotipos avaliados apresentaram a mesma classificação quanto à hidrofobicidade tanto pela medida do ângulo de contato com a água quanto pela determinação da energia livre de interação hidrofóbica (ΔGsas TOT. Três ribotipos foram considerados hidrofílicos e um hidrofóbico. Já a técnica da coluna de interação hidrofóbica não mostrou diferença (p>0,05 no percentual de células retidas na coluna, sugerindo que as superfícies dos ribotipos apresentam as mesmas características quanto à hidrofobicidade. Os resultados indicam que a técnica da medição do ângulo de contato é a mais indicada para avaliar a hidrofobicidade de superfícies celulares. A determinação da hidrofobicidade da superfície celular é relevante, uma vez que quando se conhece também a hidrofobicidade da superfície de processamento é possível predizer se a adesão bacteriana é termodinamicamente favorável, a fim de adotar métodos eficientes para reduzir a contaminação de B.cereus e conseqüente adesão e formação de biofilmes.


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    Reynaldo Cavalheiro Marcondes


    Full Text Available Este artigo tem como objetivo identificar o nível de alinhamento das dimensões da informação entre dois elos da cadeia de suprimentos, a indústria de medicamentos e as farmácias e drogarias segundo a abordagem da gestão da cadeia de suprimentos. Para tanto, foi utilizada uma amostra de 85 empresas, sendo 51 delas varejistas de farmácias e drogarias e 34 fabricantes de medicamentos, localizadas na região metropolitana da cidade de São Paulo, SP. A pesquisa é de natureza exploratória descritiva, com aporte quantitativo, tendo os dados sidos coletados por meio de um questionário estruturado com questões fechadas. Os resultados evidenciaram que ocorre o alinhamento em padrões pouco significativos entre as dimensões da informação quando comparados os dados informacionais desses dois elos pesquisados. Como essa evidência contrasta com a literatura que defende que a gestão da cadeia de suprimentos deve apresentar elevado alinhamento estratégico das informações com seus parceiros, foram formuladas algumas hipóteses sobre essa constatação.


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    Denise Medeiros Ribeiro Salles


    Full Text Available This article explores the influence of the confined work system on the organizational environment representations and social behaviors, inside and outside the workplace. Confinement may be referred to as a total experience in the workplace, imposing special work and life regimes over workers. The study, based on Bourdieu´s and on Moscovici’s Social Representations Theory, explored how confined workers construct meanings and representations of their work through free evocation and discourse analysis. Forty interviews were conducted in two large companies in the oil industry, with head offices in the cities of Rio de Janeiro and Duque de Caxias (RJ. The results presented confirmed the influence of confined work environments in the formation of beliefs and the consolidation of specific behaviors, based on defense mechanisms designed to maintain psychological stability of workers, essential to survival in such environments.


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    Full Text Available

    RESUMO: O xilitol é um açúcar-álcool de grande valor econômico e social, devido à sua ampla utilização em vários segmentos industriais. Esta revisão pretende mostrar algumas das aplicações mais significativas do xilitol nas indústrias de alimentos, odontológica e farmacêutica. PALAVRAS – CHAVE: Xilitol; adoçante.



    Silvio Silvério da SILVA; Michele VITOLO; Ismael Maciel de MANCILHA; Inês Conceição ROBERTO; Maria das Graças Almeida FELIPE


    RESUMO: O xilitol é um açúcar-álcool de grande valor econômico e social, devido à sua ampla utilização em vários segmentos industriais. Esta revisão pretende mostrar algumas das aplicações mais significativas do xilitol nas indústrias de alimentos, odontológica e farmacêutica. PALAVRAS – CHAVE: Xilitol; adoçante.





    RESUMO: O xilitol é um açúcar-álcool de grande valor econômico e social, devido à sua ampla utilização em vários segmentos industriais. Esta revisão pretende mostrar algumas das aplicações mais significativas do xilitol nas indústrias de alimentos, odontológica e farmacêutica. PALAVRAS – CHAVE: Xilitol; adoçante.


    Directory of Open Access Journals (Sweden)

    Celso Edmundo Bochetti Foelkel


    Full Text Available Este trabalho procurou avaliar a eficiência de tratamento floculante com sulfato de alumínio ou cloreto férrico para o efluente bruto neutralizado de uma indústria de celulose e papel. A filtração do efluente, removendo fibras, finos, macromoléculas e flocos naturais, permitiu expressivas reduções da cor aparente, cor real e DQO do mesmo. Enquanto o sulfato de alumínio mostrou excelentes resultados, o cloreto férrico não teve bom desempenho. Deve-se otimizar as concentrações, as formas de agitação e a decantação dos flocos. Para as amostras testadas, na primeira seqüência de testes, concentrações com cerca de 2500 ppm de sulfato de alumínio (com 14 moléculas de água de hidratação mostraram ótimos resultados para redução de cor aparente, cor real, DQO e cloretos. Conforme o previsto, na segunda seqüência de testes as concentrações de [Al2(SO43 . 14 H2O] diminuíram para todos os índices físico-químicos testados. A melhor concentração para pH, cor aparente e cor real foi de 1000 ppm filtrado, enquanto que para cloretos foi de 2000 ppm não filtrado, com o tempo de agitação de 1 minuto com alta velocidade e 15 minutos à baixa velocidade, com exceção da cor real que foi de 10 minutos à baixa velocidade. Como recomendação, sugere-se avaliar uma etapa seqüencial de filtração após clarifloculação/decantação. Com isso, o desempenho de um tratamento físico-químico de efluentes desse tipo será eficiente, apesar do custo envolvido na aquisição do insumo sulfato de alumínio.


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    Roberto Giro Moori


    Full Text Available Este artigo tem como objetivo identificar o nível de alinhamento das dimensões da informação entre dois elos da cadeia de suprimentos, a indústria de medicamentos e as farmácias e drogarias segundo a abordagem da gestão da cadeia de suprimentos. Para tanto, foi utilizada uma amostra de 85 empresas, sendo 51 delas varejistas de farmácias e drogarias e 34 fabricantes de medicamentos, localizadas na região metropolitana da cidade de São Paulo, SP. A pesquisa é de natureza exploratória descritiva, com aporte quantitativo, tendo os dados sidos coletados por meio de um questionário estruturado com questões fechadas. Os resultados evidenciaram que ocorre o alinhamento em padrões pouco significativos entre as dimensões da informação quando comparados os dados informacionais desses dois elos pesquisados. Como essa evidência contrasta com a literatura que defende que a gestão da cadeia de suprimentos deve apresentar elevado alinhamento estratégico das informações com seus parceiros, foram formuladas algumas hipóteses sobre essa constatação.


    Directory of Open Access Journals (Sweden)

    João Batista Sarmento dos Santos Neto


    Full Text Available O desenvolvimento sustentável associado à solução de problemas que prejudicam de alguma maneira a sociedade é um assunto que merece destaque e abordagem ampla em pesquisas acadêmicas. A utilização de materiais alternativos buscando soluções para os problemas ocasionados pelo ruído procura, ao mesmo tempo, oferecer conforto e comodidade para o meio urbano, além de ser uma alternativa para destinação final de resíduos sólidos produzidos por demais setores da economia. Desta forma, o presente estudo tem o objetivo de desenvolver enchimento alternativo para drywall utilizando fibra residual do setor sucroalcooleiro com a finalidade de buscar condicionamento acústico. Após produção do material pesquisado, foi realizado o ensaio para a determinação do desempenho acústico por meio da Perda de Transmissão Sonora (TL, onde foram comparados os valores obtidos de TL do painel de drywall com o enchimento pesquisado, com painéis drywall com enchimentos de lã de vidro e ar. Ao fim dos ensaios, pode-se concluir que o painel com enchimento pesquisado obteve resultados superiores aos comparados quando analisado em baixas frequências.


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    Antonio Thomaz Jr.


    Full Text Available As novas formas de controle do processo de trabalho e de gestão territorial do capital sobre a ctrabalhadora é o que estamos nos dedicando. Questões como superexploração do trabalho, incrementoconcentração da propriedade da terra, articulada ou não com a centralização e concentração de capfortalecimento das relações de assalariamento por um lado, e de relações não assalariadas por outro - como nodos produtores camponeses, integrados, em bases familiares, com a explicitação das diferentes formaapropriação da renda da terra e do excedente, é o substrato em que o agronegócio está implementando seu prode expansão e ganhos com base em diferentes ações simultâneas. Assim, a efetivação dos investimentostecnologia associadas às formas de gestão e controle do processo de trabalho colocam ao mesmo tempo, ndesafios ao movimento sindical. Desde os controles microprocessados na planta fabril, passando pela intensificdo corte mecanizado da cana, à sofisticação dos mecanismos de gestão e controle do processo de produçãoforça de trabalho, incluindo-se a ampliação do processo de terceirização e da participação das cooperativas de mde-obra, bem como as reais possibilidades que se abrem para a constituição de cadeias produtivas (comobagaço e da sucroalcoolquímica, ultrapassam, os limites do ramo agroindustrial sucroalcooleiro e, aindrecrudescimento da concentração e centralização de capital. Temos que considerar também o novo ceninstitucional, que por um lado, remete ao culto à negociação, às reminiscências das câmaras setoriais, permanecos trabalhadores imersos na roda viva dos desígnios do capital.



    Fabiane Barili; Juliano Varella de Carvalho; Marta Rosecler Bez


    Este artigo se propõe a demonstrar um panorama atualizado dos setores criativos do I Congresso de Indústrias Criativas, realizado na Universidade Feevale em 2015. Ele identifica como os trabalhos do congresso se relacionam com o modelo de Economia Criativa apresentado pela UNESCO, em sua edição de 2013. Este estudo apresenta uma fundamentação teórica sobre os conceitos de Indústria Criativa, Economia Criativa e Indústria Cultural, com o auxílio dos principais teóricos da área. Metodologicamen...


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    Fabiane Barili


    Full Text Available Este artigo se propõe a demonstrar um panorama atualizado dos setores criativos do I Congresso de Indústrias Criativas, realizado na Universidade Feevale em 2015. Ele identifica como os trabalhos do congresso se relacionam com o modelo de Economia Criativa apresentado pela UNESCO, em sua edição de 2013. Este estudo apresenta uma fundamentação teórica sobre os conceitos de Indústria Criativa, Economia Criativa e Indústria Cultural, com o auxílio dos principais teóricos da área. Metodologicamente, este trabalho se realiza com a técnica da bibliometria, leitura e análise dos dados coletados. Sendo assim, este trabalho demonstra um panorama atualizado dos setores criativos, observando quais deles estão em maior crescimento a partir dos trabalhos analisados. O estudo revelou uma pulverização de estudos na área e que o setor da Indústria Criativa em maior evidência é aquele relacionado com áreas de publicidade, televisão e moda. Também se destacam a interdisciplinaridade e as mais diferentes áreas de formação dos profissionais que atuam na Indústria Criativa. Palavras-chave: Indústria Criativa. Economia Criativa. Economia Cultural.


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    Renan Felinto de Farias Aires


    Full Text Available O setor da construção civil é um dos mais dinâmicos setores da economia brasileira, impactando toda a complexa cadeia de atividades ligadas à construção, como, por exemplo, a produção de cimento. Assim, todas as indústrias ligadas à produção desse material necessitam tomar decisões da melhor maneira de forma a competirem no acirrado mercado brasileiro de cimento - quarto maior produtor do mundo. Por conta disso, o objetivo deste estudo é desenvolver um modelo multicritério para apoiar a compra de uma linha de ensacamento e paletização de pós para uma indústria de cimentos e derivados. Para isso, este estudo de caso exploratório empregou o método ELECTRE II ao problema a partir de quatro critérios. O resultado é apresentado por meio de um ranking das alternativas estudadas e as implicações deste. Concluiu-se que os resultados apresentados foram satisfatórios devido à robustez e a implicação prática dos mesmos.

  1. Genoarchitecture of the extended amygdala in zebra finch, and expression of FoxP2 in cell corridors of different genetic profile. (United States)

    Vicario, Alba; Mendoza, Ezequiel; Abellán, Antonio; Scharff, Constance; Medina, Loreta


    We used a battery of genes encoding transcription factors (Pax6, Islet1, Nkx2.1, Lhx6, Lhx5, Lhx9, FoxP2) and neuropeptides to study the extended amygdala in developing zebra finches. We identified different components of the central extended amygdala comparable to those found in mice and chickens, including the intercalated amygdalar cells, the central amygdala, and the lateral bed nucleus of the stria terminalis. Many cells likely originate in the dorsal striatal domain, ventral striatal domain, or the pallidal domain, as is the case in mice and chickens. Moreover, a cell subpopulation of the central extended amygdala appears to originate in the prethalamic eminence. As a general principle, these different cells with specific genetic profiles and embryonic origin form separate or partially intermingled cell corridors along the extended amygdala, which may be involved in different functional pathways. In addition, we identified the medial amygdala of the zebra finch. Like in the chickens and mice, it is located in the subpallium and is rich in cells of pallido-preoptic origin, containing minor subpopulations of immigrant cells from the ventral pallium, alar hypothalamus and prethalamic eminence. We also proposed that the medial bed nucleus of the stria terminalis is composed of several parallel cell corridors with different genetic profile and embryonic origin: preoptic, pallidal, hypothalamic, and prethalamic. Several of these cell corridors with distinct origin express FoxP2, a transcription factor implicated in synaptic plasticity. Our results pave the way for studies using zebra finches to understand the neural basis of social behavior, in which the extended amygdala is involved.

  2. Sex-Specific Effects of Stress on Oxytocin Neurons Correspond With Responses to Intranasal Oxytocin. (United States)

    Steinman, Michael Q; Duque-Wilckens, Natalia; Greenberg, Gian D; Hao, Rebecca; Campi, Katharine L; Laredo, Sarah A; Laman-Maharg, Abigail; Manning, Claire E; Doig, Ian E; Lopez, Eduardo M; Walch, Keenan; Bales, Karen L; Trainor, Brian C


    Oxytocin (OT) is considered to be a stress-buffering hormone, dampening the physiologic effects of stress. However, OT can also be anxiogenic. We examined acute and long-lasting effects of social defeat on OT neurons in male and female California mice. We used immunohistochemistry for OT and c-fos cells to examine OT neuron activity immediately after defeat (n = 6-9) and 2 weeks (n = 6-9) and 10 weeks (n = 4-5) later. We quantified Oxt messenger RNA with quantitative polymerase chain reaction (n = 5-9). Intranasal OT was administered to naïve and stressed mice tested in social interaction and resident-intruder tests (n = 8-14). Acute exposure to a third episode of defeat increased OT/c-fos colocalizations in the paraventricular nucleus of both sexes. In the medioventral bed nucleus of the stria terminalis, defeat increased Oxt messenger RNA, total OT neurons, and OT/c-fos colocalizations in female mice but not male mice. Intranasal OT failed to reverse stress-induced social withdrawal in female mice and reduced social interaction behavior in female mice naïve to defeat. In contrast, intranasal OT increased social interaction in stressed male mice and reduced freezing in the resident-intruder test. Social defeat induces long-lasting increases in OT production and OT/c-fos cells in the medioventral bed nucleus of the stria terminalis of female mice but not male mice. Intranasal OT largely reversed the effects of stress on behavior in male mice, but effects were mixed in female mice. These results suggest that changes in OT-sensitive networks contribute to sex differences in behavioral responses to stress. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Connections of the corticomedial amygdala in the golden hamster. I. Efferents of the ''vomeronasal amygdala''

    International Nuclear Information System (INIS)

    Kevetter, G.A.; Winans, S.S.


    The medial (M) an posteromedial cortical (C3) amygdaloid nuclei and the nucleus of the accessory olfactory tract (NAOT) are designated the ''vomeronasal amygdala'' because they are the only components of the amygdala to receive a direct projection from the accessory olfactory bulb (AOB). The efferents of M and C3 were traced after injections of 3 H-proline into the amygdala in male golden hamsters. Frozen sections of the brains were processed for autoradiography. The efferents of the ''vomeronasal amygdala'' are largely to areas which are primary and secondary terminal areas along the vomeronasal pathway, although the efferents from C3 and M terminate in different layers in these areas than do the projections from the vomeronasal nerve or the AOB. Specifically, C3 projects ipsilaterally to the internal granule cell layer of the AOB, the cellular layer of NAOT, and layer Ib of M. Additional fibers from C3 terminate in a retrocommissural component of the bed nucleus of the strain terminalis (BNST) bilaterally, and in the cellular layers of the contralateral C3. The medial nucleus projects to the cellular layer of the ipsilateral NAOT, layer Ib of C3, and bilaterally to the medial component of BNST. Projections from M to non-vomeronasal areas terminate in the medial preoptic area-anterior hypothalamic junction, ventromedial nucleus of the hypothalamus, ventral premammillary nucleus and possibly in the ventral subiculum. These results demonstrate reciprocal connections between primary and secondary vomeronasal areas between the secondary areas themselves. They suggest that M, but not C3, projects to areas outside this vomeronasal network. The medial amygdaloid nucleus is therefore an important link between the vomeronasal organ and areas of the brain not receiving direct vomeronasal input

  4. The extended amygdala and salt appetite (United States)

    Johnson, A. K.; de Olmos, J.; Pastuskovas, C. V.; Zardetto-Smith, A. M.; Vivas, L.


    Both chemo- and mechanosensitive receptors are involved in detecting changes in the signals that reflect the status of body fluids and of blood pressure. These receptors are located in the systemic circulatory system and in the sensory circumventricular organs of the brain. Under conditions of body fluid deficit or of marked changes in fluid distribution, multiple inputs derived from these humoral and neural receptors converge on key areas of the brain where the information is integrated. The result of this central processing is the mobilization of homeostatic behaviors (thirst and salt appetite), hormone release, autonomic changes, and cardiovascular adjustments. This review discusses the current understanding of the nature and role of the central and systemic receptors involved in the facilitation and inhibition of thirst and salt appetite and on particular components of the central neural network that receive and process input derived from fluid- and cardiovascular-related sensory systems. Special attention is paid to the structures of the lamina terminalis, the area postrema, the lateral parabrachial nucleus, and their association with the central nucleus of the amygdala and the bed nucleus of the stria terminalis in controlling the behaviors that participate in maintaining body fluid and cardiovascular homeostasis.

  5. Phytophtora terminalis sp. nov. and Phytophthora occultans sp. nov., two invasive pathogens of ornamental plants in Europe

    NARCIS (Netherlands)

    Man in 't Veld, W.A.; Rosendahl, K.C.H.M.; Rijswick, van P.C.J.; Meffert, J.P.; Westenberg, M.; Vossenberg, van de B.T.L.H.; Denton, G.; Kuik, van A.J.


    To evaluate, among the elderly, the association of self-rated health (SRH) with mortality, and to identify determinants of self-rating health as “at-least-good”.

    Study Design
    Individual data on SRH and important covariates were obtained for 424,791 European and Unites


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    Caroline Glier


    Full Text Available Alterações no perfil lipídico estão relacionados ao estilo de vida e comumente são tratadas com estatinas. Desta forma, esta pesquisa objetiva caracterizar trabalhadores da agroindústria e produtores rurais quanto à presença de dislipidemia e uso de estatinas, associado a variáveis demográficas. Estudo transversal e analítico, com 127 sujeitos da região do Conselho Regional de Desenvolvimento do Vale do Rio Pardo, avaliados em 2012-2013. O uso de estatinas bem como as variáveis demográficas (sexo, faixa etária, estado civil, classe econômico e escolaridade foram obtidas por questionários. A definição da presença ou ausência de dislipidemia foi definida pelos marcadores bioquímicos, obtidos através de coleta sanguínea, após 12 horas de jejum. Os dados foram analisados com medidas de frequência e percentual, além do teste Exato de Fisher (p < 0,05. Constatou-se que 61,4% dos sujeitos eram dislipidêmicos, dos quais 89,7% não usavam estatinas. Houveram diferenças demográficas quanto a faixa etária entre aqueles que usam ou não estatinas tanto na presença de dislipidemia (p = 0,006 quanto em sua ausência (p=0,022. Verificou-se o desconhecimento e falta de controle dos níveis do perfil lipídico por alguns indivíduos.



    Cánepa, Daniela; Ludwig, Vanelli Salati


    This article seeks to discuss the relevance of the performance indicators in the process of business management, and to indicate the importance of the alignment of these indicators with the business strategy. In a competitive environment, companies face increasing difficulties in order to keep their market competitiveness. In this sense, the financial indicators turn out to be insufficient to assess the business performance, and the utilization of non-financial indicators gets more importance...


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    Carlos Otávio Zamberlan


    Full Text Available O arroz é considerado um importante produto na economia mundial, pois é consumido em vários países e continentes. Todavia, a maior parte dos países consumidores são também produtores e as empresas que o beneficiam enfrentam uma grande concorrência. Para ganhar em competitividade a inovação deve se fazer presente. Este artigo tem como objetivo analisar as inovações em produto por parte das empresas beneficiadoras do Rio Grande do Sul, maior produtor nacional. Para isso, utilizou-se de métodos qualitativos baseados em análise lexical e de conteúdo. Concluiu-se que ocorrem inovações tanto incrementais em produtos existentes, bem como no lançamento de novos produtos visando, também, o fortalecimento de marca, o aumento de opções para o cliente, entre outros motivos.


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    Luiz Célio Souza Rocha


    Full Text Available Quando se analisa o setor de lácteos brasileiro, constata-se que muitas empresas ainda estão distantes da implementação de estratégias que possibilitem o alcance de diferenciais competitivos. O presente trabalho buscou quantificar as perdas operacionais em uma fábrica de queijo localizada no Município de Rio Pomba/MG considerando o não uso de um programa de garantia da qualidade que refletisse na melhoria da matéria-prima. Como resultado, obteve-se que o rendimento foi significativamente afetado pelo tempo de armazenamento. Por fim, conclui-se que a implementação da gestão da qualidade na indústria queijeira analisada melhoraria seu desempenho operacional e econômico.


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    Diogo Del Fiori


    Full Text Available O presente trabalho se propõe a fazer uma análise das características setoriais do Brasil desde a segunda metade do século XIX até a data presente, com o objetivo de mostrar que embora tenham ocorrido intervenções do Estado para a realização do processo de industrialização ao longo da história brasileira, nota-se que elas foram de certa forma ineficiente, e acabaram influenciando a trajetória dos setores econômicos de tal forma que na data presente, o Brasil possui a predominância de exportação dos setores básicos, sendo uma verdadeira contradição para as metas que o Brasil almeja alcançar nas próximas décadas. Este trabalho sugere que o Brasil necessita rever suas políticas e escolher algum setor líder no mercado mundial e o setor da Agroindústria poderia ser o segmento econômico líder do país, conforme será abordado neste trabalho. Palavras-Chave: Indústrias, Estado, Setores Abstract: This work intends to make an analysis of industry characteristics in Brazil since the mid-nineteenth century to the present date in order to show that although there were state interventions to the achievement of industrialization throughout history Brazilian note that they were somewhat inefficient, and ultimately influencing the trajectory of economic sectors so that at the present time, Brazil has the predominance of the basic sectors of export, being a real contradiction to the goals that Brazil intends to reach the coming decades. This work suggests that Brazil needs to review its policies and choose a sector leader in the world market and agribusiness sector could be the key economic sector in Brazil, according to his approach in this work. Key Words: Industries, State, Sectors



    Oliveira Junior, Antonio Martins de; Universidade Federal de Sergipe; Oliveira, Gardenia Rocha; Universidade Federal de Sergipe; Santos, Jéssica Teles Siqueira; Universidade Federal de Sergipe; Campos, Ananda Fontes Pinheiro; Universidade Federal de Sergipe; Nunes, Tatiana Pacheco; Universidade Federal de Sergipe; Russo, Suzana Leitão; Universidade Federal de Sergipe


    O processo de liofilização ou secagem pelo frio “freeze drying” ou “lyophilization”, apresenta uma série de vantagens quanto à manutenção das características originais dos produtos, pelo fato de não submetê-lo a elevadas temperaturas conforme outros processos de desidratação. Preservação do sabor e aroma, aumento da estabilidade através da diminuição da atividade de água, que minimiza a deterioração do alimento durante o armazenamento, são vantagens deste processo. A aplicação da liofilização...


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    Antonio Martins de Oliveira Junior


    Full Text Available O processo de liofilização ou secagem pelo frio “freeze drying” ou “lyophilization”, apresenta uma série de vantagens quanto à manutenção das características originais dos produtos, pelo fato de não submetê-lo a elevadas temperaturas conforme outros processos de desidratação. Preservação do sabor e aroma, aumento da estabilidade através da diminuição da atividade de água, que minimiza a deterioração do alimento durante o armazenamento, são vantagens deste processo. A aplicação da liofilização em produtos alimentícios ainda é cara, sendo empregada com maior frequência, na fabricação de produtos nobres que necessitam de reidratação rápida e completa. O objetivo deste trabalho foi avaliar as perspectivas e a evolução das competências tecnológicas traduzidas através dos depósitos de patentes referentes à aplicação da liofilização na indústria alimentícia, bem como mapear as pesquisas desenvolvidas. A prospecção foi realizada no Banco Europeu de Patente, no Banco de Dados do Instituto Nacional de Propriedade Intelectual do Brasil, no Banco da Organização Mundial de Propriedade Intelectual e no Banco Americano de Marcas e Patentes. A classificação internacional mais frequente nessa prospecção foi Subseção A23 e principalmente na Subclasse A23L. Com a palavra chave freeze-drying e CIP A23L a República da Coreia, apresentou-se como o maior depositante. Os dados permitem concluir que se trata de uma área promissora, com crescimento de patentes depositadas.


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    Full Text Available El Agronegocio es uno de los sectores más importantes de la economía brasileña y su segmento industrial tiene un papel significativo. Debido a esa relevancia, cuestiones técnicas y gerenciales merecen atención especial. Este artículo procura promover una discusión sobre el desempeño organizacional de empresas brasileñas de papel y celulosa, desde informaciones contables -financieras. Por medio de la aplicación del Análisis Envolvente de Datos (DEA, se busca identificar un índice de desempeño multicriterial para cada empresa y hacer un análisis de benchmarking para mostrar lo que las empresas ineficientes necesitan hacer para hacerse eficientes. Los resultados muestran que las mejores empresas son aquéllas que mejor com - binan sus inputs (índices del tipo cuanto menor mejor a los outputs que buscan (índices del tipo cuanto mayor mejor. Además, las peores empresas son aquéllas que necesitan cambios radicales en sus niveles de input y/o output para que alcancen el desempeño máximo.


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    Williani Fabíola GRANDO


    Full Text Available

    O objetivo deste trabalho foi isolar Staphylococcus aureus de manipuladores de alimentos de um lacticínio e determinar sua suscetibilidade a diversos antimicrobianos. Para tal, coletaram-se amostras a partir das mãos e cavidade nasal de 29 manipuladores. Foram obtidos 58 cultivos suspeitos, os quais foram submetidos a testes bioquímicos e ao teste de suscetibilidade aos antimicrobianos ciprofloxacina, oxacilina, penicilina G, clindamicina, tetraciclina, eritromicina, nitrofurantoína, sulfazotrim, rifampicina e vancomicina através da técnica de difusão em disco. Foram isoladas 19 cepas de S. aureus, sendo 42,10% provenientes das mãos e 57,90% da cavidade nasal dos indivíduos avaliados. O maior índice de resistência foi encontrado para penicilina G (78,95%, seguido pela tetraciclina (26,31%, enquanto que o maior índice de sensibilidade foi observado para nitrofurantoína, sulfazotrim, rifampicina e vancomicina (100%, seguido da oxacilina (94,73% e ciprofloxacina (89,47%. De modo geral, as cepas apresentaram baixos níveis de resistência, entretanto, a presença de S. aureus nas mãos e cavidades nasais dos manipuladores desempenham papel importante na disseminação do micro-organismo.


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    Bruno Chaves Correia Lima


    Full Text Available O estudo objetiva analisar a cultura organizacional quanto aos estilos de funcionamentoe aos mecanismos de aprendizagem em uma indústria de criação funcional. Trata-se deuma pesquisa quantitativa, descritiva, com uso de questionários estruturados. Utilizou-seestatísticas descritivas de médias, desvio-padrão e correlação mediante informações damaior empresa de publicidade e propaganda do Ceará. A cultura da organização é formadapela presença moderada e simultânea dos estilos empreendedor, afiliativo, burocrático eindividualista, predominando o primeiro. O único mecanismo de aprendizagem com nível altode ocorrência foi codificação e controle de conhecimento, evidenciando fraca correlação entreimportância atribuída e ocorrência desses mecanismos.


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    Roberto Naime


    Full Text Available A preocupação com a preservação ambiental é relativamente recente na história das sociedades humanas, tendo nascido do grande desenvolvimento, com paralela produção de impactos ambientais decorrentes da aceleração do processo industrial. Este trabalho apresenta um estudo de caso de implantação de um sistema de Gestão Ambiental em uma empresa do setor automotivo. Sistematiza questões referentes à metodologia de implantação e em relação aos benefícios produzidos na produção em função do SGA. Aborda também as melhorias de qualidade de vida obtidas por funcionários e colaboradores. E finaliza qualificando os ganhos com a percepção da comunidade sobre a nova visão socioambiental que a empresa assume a partir da implantação de um Sistema de Gestão Ambiental. O trabalho objetiva estimular a reflexão de outras empresas e organizações sobre as vantagens globais da implantação de Sistemas de Gestão Ambiental. Palavras-chave: Gestão. Meio ambiente. Sistemas.


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    Luciel Henrique de Oliveira


    Full Text Available Tubaína is the generic name of a tutti-frutti flavored soft drink, produced by Brazilian industries, with many regional variations. These soft drinks are generally popular, very sweet, withlower price and local brand. This research aimed to describe the economic importance of the Brazilian soft drinks, from the point of view of small and medium manufacturers. What strategies used by theseindustries to face the big companies competition? How can these companies survive and grow in such a competitive market? The study had three objectives: (1 know and understand the popular soft drinkindustry, highlighting the participation of regional industries, (2 raise the popular soft drink industries of São Paulo State, highlighting the most relevant cases, (3 analyze prominent cases, relating them to theories of strategy envisaged. We found that the main strategy of small and mid-sized companies is to prioritize and focus their strength in regional markets where their factories are located. Producers invest in production vertical integration, modern equipment similar to those used by large enterprises, and innovation to reduce costs and gain a competitive advantage. Always they try to follow the trends set by big players hit the market. Combining the lower prices and a quality product to the local tradition of consuming these soft drinks, these companies can compete and annoy the major sector’s industries.


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    André Rafael Weyermüller


    Full Text Available A inovação oriunda da criatividade e é o elemento chave para promover o adequado encaminhamento de diversas problemáticas da sociedade atual. A Indústria Criativa Verde é a fonte do desenvolvimento de produtos e serviços diferenciados, os quais conciliam aplicações no mercado com a necessidade de preservação ambiental. A legislação que se propõe a viabilizar ações inovadoras como na área do turismo, são representativas de uma proposta adaptativa que supera a sustentabilidade. Palavras-chave: Inovação. Adaptação. Direito. Turismo. Indústria Criativa.



    André Rafael Weyermüller; Pedro Ernesto Neubarth Jung; Maria Eduarda Lima da Rosa; Lucas Rodrigo Kehl


    A inovação oriunda da criatividade e é o elemento chave para promover o adequado encaminhamento de diversas problemáticas da sociedade atual. A Indústria Criativa Verde é a fonte do desenvolvimento de produtos e serviços diferenciados, os quais conciliam aplicações no mercado com a necessidade de preservação ambiental. A legislação que se propõe a viabilizar ações inovadoras como na área do turismo, são representativas de uma proposta adaptativa que supera a sustentabilidade. Palavras-cha...



    Maciel, Cristiano Oliveira; Augusto, Paulo Otávio Mussi


    RESUMO No presente artigo, tentou-se ir além das explicações tradicionais sobre as modas gerenciais que configuram a indústria do management. Para tanto, foi adotada uma perspectiva praxeológica ao examinar as bases de sustentação dessa indústria. Os dados foram coletados durante um período de sete meses via observação, pesquisa documental e entrevistas em uma organização do emergente setor dos sites de vendas de cupons de desconto. A análise do processo de construção social dos praticantes d...


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    Taise Gross


    Full Text Available This article presents a case study of a Brazilian company, operating in the footwear sector, located in Parobé city, in the Valley of Paranhana, in the state of Rio Grande do Sul. The process analyzed showed high failure rates of manufactured batches and by quality analysis tools, the Statistical Process Control tools were applied to analyze the variability. The tools applied were the control charts, process capacity and capability analysis, histogram, Pareto chart and cause and effect analysis. The main results of the study were the reduction of the rejection indices of the process to zero and improvement in the capacity index from 0,424 to 1,52, demonstrating the reduction of the sources of variation of the production process and reaching the objectives The research. This research can be used by academics and professionals to improve the competitive performance of footwear companies.


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    Valdemar Valente Junior


    Full Text Available Uma visão panorâmica do samba a partir de sua inserção como produto cultural no Brasil do século XX. Sua configuração de gênero musical moderno e sua ascensão de manifestação periférica e marginal à condição de música definidora de um sentido de nacionalidade. A influência dos gêneros estrangeiros e o papel da indústria do rádio, do disco e mais tarde da televisão como multiplicadora de sua importância como música de consumo.


    Directory of Open Access Journals (Sweden)

    Alex Volnei Teixeira


    Full Text Available The global picture of the twenty-first century presents the knowledge management as a strategy in the use of their practices to enhance intangible assets focusing better systematic processes and reach a higher performance of the organization. This article seeks to describe the importance of knowledge management practices Paraná industries. Data collection was done through a questionnaire, and as a result we sought to identify which practices are most important in this scenario knowledge management for the development of the organization to support the local industry.


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    Wilian Gatti Junior

    Full Text Available A economia criativa tem recebido pouca atenção da comunidade acadêmica, a despeito de sua importância econômica e cultural. Este artigo procura contribuir com a literatura sobre o tema com foco na indústria de animação, mais precisamente na produção de animações para a TV, pois recentemente o país produziu animações de sucesso na TV paga exibidas não só no Brasil, mas também em vários países. Este artigo procura analisar como as produtoras nacionais construíram vantagens competitivas que as possibilitaram obter êxito em suas produções em um mercado dominado por estúdios internacionais. Para atingir esse propósito foi conduzida uma pesquisa exploratório-descritiva analisando três produtoras (Flamma, TV PinGuim e 2DLab que exibem seu produto no canal Discovery Kids, voltado ao público préescolar. Foram entrevistados todos os sócios das produtoras (em um total de seis, dois de cada produtora, mais uma representante da indústria de animação para o cinema. Além das entrevistas, foram utilizados dados secundários, basicamente coletados na mídia (jornais, revistas e internet. O trabalho revelou a convergência de duas fontes de vantagens competitivas. A primeira ligada a fatores internos às produtoras estudadas (conhecimento técnico e visão do negócio e a segunda fonte ligada a fatores ambientais, criados pela cadeia produtiva dessa indústria (criação de novos canais de TV, interesse de parceiros internacionais e linhas de financiamento para a produção.


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    Alano De La Torre Silva


    Full Text Available Este trabalho foi realizado pelo meio de um estudo de caso em uma indústria frigorífica de bovinos. O plano de manutenção preventiva da empresa estudada possuía deficiências na parte de lubrificação dos equipamentos. Desta forma, este trabalho tem a finalidade de mostrar como é a implantação de um plano de lubrificação na empresa estudada. Foi implantado um plano de lubrificação destinado a cinco maquinas diferentes. Foram necessários três meses para a implantação do plano. Comparando-se o número de ordens de serviço de manutenções corretivas relacionadas à falta de lubrificação antes e três meses após a implantação do plano de lubrificação nas máquinas citadas, obteve-se um resultado satisfatório, pois houve uma redução de cerca de 50% das ordens de serviços para manutenção corretivas dos equipamentos,

  6. Betahistine exerts a dose-dependent effect on cochlear stria vascularis blood flow in guinea pigs in vivo.

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    Fritz Ihler

    Full Text Available Betahistine is a histamine H(1-receptor agonist and H(3-receptor antagonist that is administered to treat Menière's disease. Despite widespread use, its pharmacological mode of action has not been entirely elucidated. This study investigated the effect of betahistine on guinea pigs at dosages corresponding to clinically used doses for cochlear microcirculation.Thirty healthy Dunkin-Hartley guinea pigs were randomly assigned to five groups to receive betahistine dihydrochloride in a dose of 1,000 mg/kg b. w. (milligram per kilogram body weight, 0.100 mg/kg b. w., 0.010 mg/kg b. w., 0.001 mg/kg b. w. in NaCl 0.9% or NaCl 0.9% alone as placebo. Cochlear blood flow and mean arterial pressure were continuously monitored by intravital fluorescence microscopy and invasive blood pressure measurements 3 minutes before and 15 minutes after administration of betahistine.When betahistine was administered in a dose of 1.000 mg/kg b. w. cochlear blood flow was increased to a peak value of 1.340 arbitrary units (SD: 0.246; range: 0.933-1.546 arb. units compared to baseline (p<0.05; Two Way Repeated Measures ANOVA/Bonferroni t-test. The lowest dosage of 0.001 mg/kg b. w. betahistine or NaCl 0.9% had the same effect as placebo. Nonlinear regression revealed that there was a sigmoid correlation between increase in blood flow and dosages.Betahistine has a dose-dependent effect on the increase of blood flow in cochlear capillaries. The effects of the dosage range of betahistine on cochlear microcirculation corresponded well to clinically used single dosages to treat Menière's disease. Our data suggest that the improved effects of higher doses of betahistine in the treatment of Menière's disease might be due to a corresponding increase of cochlear blood flow.


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    Leonardo F. Santos

    Full Text Available In various industrial processes, such as the process of obtaining potassium by solution mining or in the oil industry, fuels are burnt concurrently to the formation of saline effluents. The opportunity to sequester carbon through capturing the CO2 from the flue gas by carbonation of these effluents and reducing the potential of scaling of the water is evident. The use of saline industrial effluent from electrodialysis for carbon sequestration by mineralization of carbon dioxide is the focus of this work. The carbonation reaction of saline effluent of reverse electrodialysis, of low ionic strength and higher CO2 solubility, was simulated through OLI®. Precipitation tests were performed by bubbling 10-20 NL h-1 CO2 in a glass reactor containing the brine and pH adjusted to 8.9. The solid was characterized and the results from the simulation and the experiments were compared. The removal of calcium and strontium in the form of carbonates reach out up to 98% and 75%. The simulation results were in line with the experimental results for the calcium behavior, but not for strontium. The OLI® simulation was powerful to represent the calcium carbonate formation, however, comparisons between predicted Sr removal and testwork results presented differences and must be investigated.


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    Waldir Nagel Schirmer


    Full Text Available O caráter odorante de compostos reduzidos de enxofre (TRS, tipicamente emitidos na indústria papeleira, tem gerado grande interesse por parte dessas indústrias em predizer a qualidade do ar nas proximidades de suas fontes emissoras. Desse modo, o presente trabalho tem por objetivo avaliar o impacto na atmosfera resultante das emissões de TRS de uma fabricante de papel e celulose de grande porte, por meio da modelagem dos compostos gasosos emitidos a partir de duas fontes pontuais (tomadas como as maiores contribuidoras. Para tanto, foi utilizado o “software” AID (Avaliação Instantânea de Dispersão baseado no modelo de Gauss para determinação das concentrações (no ar resultantes dessas emissões. Nessa determinação, foram abordados os principais parâmetros meteorológicos (dos últimos 3 anos e cinéticos de emissão necessários à modelagem. A máxima concentração de TRS obtida após a modelagem foi de 3,84 ppb (somatório das duas fontes avaliadas, ficando bem abaixo dos limites de percepção odorífera (LPO recomendado por órgãos internacionais (o Brasil não possui leis específicas para esse caso. Como os limites de toxicidade quase sempre estão bem acima dos LPO, é seguro afirmar que, no caso avaliado, a concentração máxima estimada não apresenta riscos de toxicidade à população exposta, uma vez, pelo valor obtido, nem o odor pode ser percebido.


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    Wuili Roberto Vela Ocaña


    Full Text Available Este estudo tem como finalidade, analisar a formação e a estruturação do campo organizacional da indústria pesqueira na região do Callao, Peru, apoiando-se nos pressupostos da teoria institucional. Utilizar o conceito de campo organizacional e aplicá-lo na indústria pesqueira permitirá determinar como estão se comportando as organizações que fazem parte do mesmo. Os resultados aqui apresentados, bem como a análise, foram elaborados a partir dos dados coletados em documentos assim, como em uma série de entrevistas semi-estruturadas com representantes das principais organizações que compõem o campo. O atual grau de estruturação do campo é moderado, por esta atividade centrar-se quase exclusivamente na produção de farinha de pescado e, descuidar os outros tipos de empresas existentes, mas também devido a fragilidade com a qual alguns indicadores se apresentaram no campo. A influência do setor privado é determinante dessa situação.

  10. Circuit and synaptic mechanisms of repeated stress: Perspectives from differing contexts, duration, and development

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    Kevin G. Bath


    Full Text Available The current review is meant to synthesize research presented as part of a symposium at the 2016 Neurobiology of Stress workshop in Irvine California. The focus of the symposium was “Stress and the Synapse: New Concepts and Methods” and featured the work of several junior investigators. The presentations focused on the impact of various forms of stress (altered maternal care, binge alcohol drinking, chronic social defeat, and chronic unpredictable stress on synaptic function, neurodevelopment, and behavioral outcomes. One of the goals of the symposium was to highlight the mechanisms accounting for how the nervous system responds to stress and their impact on outcome measures with converging effects on the development of pathological behavior. Dr. Kevin Bath's presentation focused on the impact of disruptions in early maternal care and its impact on the timing of hippocampus maturation in mice, finding that this form of stress drove accelerated synaptic and behavioral maturation, and contributed to the later emergence of risk for cognitive and emotional disturbance. Dr. Scott Russo highlighted the impact of chronic social defeat stress in adolescent mice on the development and plasticity of reward circuity, with a focus on glutamatergic development in the nucleus accumbens and mesolimbic dopamine system, and the implications of these changes for disruptions in social and hedonic response, key processes disturbed in depressive pathology. Dr. Kristen Pleil described synaptic changes in the bed nuclei of the stria terminalis that underlie the behavioral consequences of allostatic load produced by repeated cycles of alcohol binge drinking and withdrawal. Dr. Eric Wohleb and Dr. Ron Duman provided new data associating decreased mammalian target of rapamycin (mTOR signaling and neurobiological changes in the synapses in response to chronic unpredictable stress, and highlighted the potential for the novel antidepressant ketamine to rescue

  11. Circuits regulating pleasure and happiness: the evolution of the amygdalar-hippocampal-habenular connectivity in vertebrates.

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    Anton J.M. Loonen


    Full Text Available Appetitive-searching (reward-seeking and distress-avoiding (misery-fleeing behavior are essential for all free moving animals to stay alive and to have offspring. Therefore, even the oldest ocean-dwelling animal creatures, living about 560 million years ago and human ancestors, must have been capable of generating these behaviors. The current article describes the evolution of the forebrain with special reference to the development of the misery-fleeing system. Although the earliest vertebrate ancestor already possessed a dorsal pallium, which corresponds to the human neocortex, the structure and function of the neocortex was acquired quite recently within the mammalian evolutionary line. Up to, and including, amphibians, the dorsal pallium can be considered to be an extension of the medial pallium, which later develops into the hippocampus. The ventral and lateral pallium largely go up into the corticoid part of the amygdala. The striatopallidum of these early vertebrates becomes extended amygdala, consisting of centromedial amygdala (striatum connected with the bed nucleus of the stria terminalis (pallidum. This amygdaloid system gives output to hypothalamus and brainstem, but also a connection with the cerebral cortex exists, which in part was created after the development of the more recent cerebral neocortex. Apart from bidirectional connectivity with the hippocampal complex, this route can also be considered to be an output channel as the fornix connects the hippocampus with the medial septum, which is the most important input structure of the medial habenula. The medial habenula regulates the activity of midbrain structures adjusting the intensity of the misery-fleeing response. Within the bed nucleus of the stria terminalis the human homologue of the ancient lateral habenula-projecting globus pallidus may exist; this structure is important for the evaluation of efficacy of the reward-seeking response. The described organization offers a

  12. The Endocannabinoid System and Anxiety. (United States)

    Lisboa, S F; Gomes, F V; Terzian, A L B; Aguiar, D C; Moreira, F A; Resstel, L B M; Guimarães, F S


    The medical properties of Cannabis sativa is known for centuries. Since the discovery and characterization of the endogenous cannabinoid system, several studies have evaluated how cannabinoid compounds and, particularly, how the modulation of the endocannabinoid (eCB) system influences a wide range of functions, from metabolic to mental disorders. Cannabinoids and eCB system often exert opposite effects on several functions, such as anxiety. Although the mechanisms are not completely understood, evidence points to different factors influencing those effects. In this chapter, the recent advances in research about the relationship between eCB system and anxiety disorders in humans, as well as in animal models, will be discussed. The recent data addressing modulation of the eCBs in specific brain areas, such as the medial prefrontal cortex, amygdaloid complex, bed nucleus of stria terminalis, hippocampus, and dorsal periaqueductal gray, will be summarized. Finally, data from animal models addressing the mechanisms through which the eCB system modulates anxiety-related behavior dependent on stressful situations, such as the involvement of different receptors, distinct eCBs, modulation of neurotransmitters release, HPA axis and immune system activation, and plastic mechanisms, will also be discussed. © 2017 Elsevier Inc. All rights reserved.

  13. Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women. (United States)

    Borg, Charmaine; de Jong, Peter J; Georgiadis, Janniko R


    Lifetime experiences shape people's attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile-vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-'hot' vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-'hot') associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli.

  14. Chronic social isolation enhances reproduction in the monogamous prairie vole (Microtus ochrogaster). (United States)

    Perry, Adam N; Carter, C Sue; Cushing, Bruce S


    Chronic stressors are generally considered to disrupt reproduction and inhibit mating. Here we test the hypothesis that a chronic stressor, specifically social isolation, can facilitate adaptive changes that enhance/accelerate reproductive effort. In general, monogamous species display high levels of prosociality, delayed sexual maturation, and greater parental investment in fewer, higher quality offspring compared with closely related polygynous species. We predicted that chronic social isolation would promote behavioral and neurochemical patterns in prairie voles associated with polygyny. Male and female prairie voles were isolated for four weeks and changes in mating behavior, alloparental care, estrogen receptor (ER) α expression and tyrosine hydroxylase (TH) expression in brain regions regulating sociosexual behavior were examined. In males, isolation accelerated copulation, increased ERα in the medial amygdala (MEApd) and bed nucleus of the stria terminalis (BSTpm), and reduced TH expression in the MEApd and BSTpm, but had no effect on alloparental behavior. In females, isolation resulted in more rapid estrus induction and reduced TH expression in the MEApd and BSTpm, but had no effect on estradiol sensitivity or ERα expression. The results support the hypothesis that ERα expression in the MEApd and BSTpm is a critical determinant of male copulatory behavior and/or mating system. The lack of change in alloparental behavior suggests that changes in prosocial behavior are selective and regulated by different mechanisms. The results also suggest that TH in the MEApd and BSTpm may play a critical role in determining mating behavior in both sexes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Imaging of aromatase distribution in rat and rhesus monkey brains with [{sup 11}C]vorozole

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    Takahashi, Kayo [Division of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala SE-75124 (Sweden); Uppsala Imanet, Uppsala SE-75109 (Sweden)]. E-mail:; Bergstroem, Mats [Uppsala Imanet, Uppsala SE-75109 (Sweden); Department of Pharmaceutical Biosciences, Uppsala University, Uppsala SE-75124 (Sweden); Fraendberg, Pernilla [Uppsala Imanet, Uppsala SE-75109 (Sweden); Vesstroem, Eva-Lotta [Uppsala Imanet, Uppsala SE-75109 (Sweden); Watanabe, Yasuyoshi [Department of Physiology, Osaka City University Graduate School of Medicine, Osaka 545-8585 (Japan); Langstroem, Bengt [Uppsala Imanet, Uppsala SE-75109 (Sweden)


    Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [{sup 11}C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K {sub d} of [{sup 11}C]vorozole binding to aromatase in MA was determined to be 0.60{+-}0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [{sup 11}C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons.

  16. Effects of estrous cycle and xenoestrogens expositions on mice nitric oxide producing system. (United States)

    Gotti, Stefano; Martini, Mariangela; Viglietti-Panzica, Carla; Miceli, Desiree; Panzica, GianCarlo


    Nitric oxide (NO)-containing neurons are widely distributed within the central nervous system, including regions involved in the control of reproduction and sexual behavior. Nitrergic neurons may co-localize with gonadal hormone receptors and gonadal hormones may influence neuronal NO synthase expression in adulthood as well as during development. In rodents, the female, in physiological conditions, is exposed to short-term changes of gonadal hormones levels (estrous cycle). Our studies, performed in mouse hypothalamic and limbic systems, reveal that the expression of neuronal NO synthase may vary according to the rapid variations of hormonal levels that take place during the estrous cycle. This is in accordance with the hypothesis that gonadal hormone activation of NO-cGMP pathway is important for mating behavior. NO-producing system appears particularly sensitive to alterations of endocrine balance during development, as demonstrated by our experiments utilizing perinatal exposure to bisphenol A, an endocrine disrupting chemical. In fact, significant effects were detected in adulthood in the medial preoptic nucleus and in the ventromedial subdivision of the bed nucleus of the stria terminalis. Therefore, alteration of the neuronal NO synthase expression may be one of the causes of the important behavioral alterations observed in bisphenol-exposed animals.

  17. Behavioural and biochemical evidence for interactions between Δ9-tetrahydrocannabinol and nicotine (United States)

    Valjent, Emmanuel; Mitchell, Jennifer M; Besson, Marie-Jo; Caboche, Jocelyne; Maldonado, Rafael


    Behavioural and pharmacological effects of Δ9-tetrahydrocannabinol (THC) and nicotine are well known. However, the possible interactions between these two drugs of abuse remain unclear in spite of the current association of cannabis and tobacco in humans. The present study was designed to analyse the consequences of nicotine administration on THC-induced acute behavioural and biochemical responses, tolerance and physical dependence. Nicotine strongly facilitated hypothermia, antinociception and hypolocomotion induced by the acute administration of THC. Furthermore, the co-administration of sub-threshold doses of THC and nicotine produced an anxiolytic-like response in the light–dark box and in the open-field test as well as a significant conditioned place preference. Animals co-treated with nicotine and THC displayed an attenuation in THC tolerance and an enhancement in the somatic expression of cannabinoid antagonist-precipitated THC withdrawal. THC and nicotine administration induced c-Fos expression in several brain structures. Co-administration of both compounds enhanced c-Fos expression in the shell of the nucleus accumbens, central and basolateral nucleus of the amygdala, dorso-lateral bed nucleus of the stria terminalis, cingular and piriform cortex, and paraventricular nucleus of the hypothalamus. These results clearly demonstrate the existence of a functional interaction between THC and nicotine. The facilitation of THC-induced acute pharmacological and biochemical responses, tolerance and physical dependence by nicotine could play an important role in the development of addictive processes. PMID:11815392

  18. Physical interaction is not necessary for the induction of housing-type social buffering of conditioned hyperthermia in male rats. (United States)

    Kiyokawa, Yasushi; Kodama, Yuka; Takeuchi, Yukari; Mori, Yuji


    In social animals, housing with conspecific animals after a stressful event attenuates the subsequent adverse outcomes due to the event, and this has been called housing-type social buffering. We have previously found that housing-type social buffering attenuates the enhancement of hyperthermia and Fos expression in the paraventricular nucleus of the hypothalamus that occurs in response to an aversive conditioned stimulus in male rats. Here, we analyzed the role of physical interactions during social housing in the induction of housing-type social buffering. When a fear-conditioned subject was alone after the conditioning and then exposed to the conditioned stimulus, it showed behavioral, autonomic, and neural stress responses. However, social housing, during which physical interactions were prevented by wire mesh, attenuated these autonomic and neural stress responses, as has been seen in previous studies. These results suggested that physical interaction was not necessary for the induction of housing-type social buffering. With this social cohabitation model, we then found that social cohabitation increased Fos expression in the posterior complex of the anterior olfactory nucleus of the fear-conditioned subject. Social cohabitation also increased Fos expression in 11 brain regions, including the prefrontal cortex, the nucleus accumbens, the bed nucleus of the stria terminalis, and the medial, lateral, basal, and cortical amygdala. These results provide information about the neural mechanisms that induce housing-type social buffering. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Autoradiographic distribution of /sup 125/I-galanin binding sites in the rat central nervous system

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    Skofitsch, G.; Sills, M.A.; Jacobowitz, D.M.


    Galanin (GAL) binding sites in coronal sections of the rat brain were demonstrated using autoradiographic methods. Scatchard analysis of /sup 125/I-GAL binding to slide-mounted tissue sections revealed saturable binding to a single class of receptors with a Kd of approximately 0.2 nM. /sup 125/I-GAL binding sites were demonstrated throughout the rat central nervous system. Dense binding was observed in the following areas: prefrontal cortex, the anterior nuclei of the olfactory bulb, several nuclei of the amygdaloid complex, the dorsal septal area, dorsal bed nucleus of the stria terminalis, the ventral pallidum, the internal medullary laminae of the thalamus, medial pretectal nucleus, nucleus of the medial optic tract, borderline area of the caudal spinal trigeminal nucleus adjacent to the spinal trigeminal tract, the substantia gelatinosa and the superficial layers of the dorsal spinal cord. Moderate binding was observed in the piriform, periamygdaloid, entorhinal, insular cortex and the subiculum, the nucleus accumbens, medial forebrain bundle, anterior hypothalamic, ventromedial, dorsal premamillary, lateral and periventricular thalamic nuclei, the subzona incerta, Forel's field H1 and H2, periventricular gray matter, medial and superficial gray strata of the superior colliculus, dorsal parts of the central gray, peripeduncular area, the interpeduncular nucleus, substantia nigra zona compacta, ventral tegmental area, the dorsal and ventral parabrachial and parvocellular reticular nuclei. The preponderance of GAL-binding in somatosensory as well as in limbic areas suggests a possible involvement of GAL in a variety of brain functions.

  20. Statistical modeling implicates neuroanatomical circuit mediating stress relief by 'comfort' food. (United States)

    Ulrich-Lai, Yvonne M; Christiansen, Anne M; Wang, Xia; Song, Seongho; Herman, James P


    A history of eating highly palatable foods reduces physiological and emotional responses to stress. For instance, we have previously shown that limited sucrose intake (4 ml of 30 % sucrose twice daily for 14 days) reduces hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. However, the neural mechanisms underlying stress relief by such 'comfort' foods are unclear, and could reveal an endogenous brain pathway for stress mitigation. As such, the present work assessed the expression of several proteins related to neuronal activation and/or plasticity in multiple stress- and reward-regulatory brain regions of rats after limited sucrose (vs. water control) intake. These data were then subjected to a series of statistical analyses, including Bayesian modeling, to identify the most likely neurocircuit mediating stress relief by sucrose. The analyses suggest that sucrose reduces HPA activation by dampening an excitatory basolateral amygdala-medial amygdala circuit, while also potentiating an inhibitory bed nucleus of the stria terminalis principle subdivision-mediated circuit, resulting in reduced HPA activation after stress. Collectively, the results support the hypothesis that sucrose limits stress responses via plastic changes to the structure and function of stress-regulatory neural circuits. The work also illustrates that advanced statistical methods are useful approaches to identify potentially novel and important underlying relationships in biological datasets.

  1. Neural correlates underlying naloxone-induced amelioration of sexual behavior deterioration due to an alarm pheromone

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    Tatsuya eKobayashi


    Full Text Available Sexual behavior is suppressed by various types of stressors. We previously demonstrated that an alarm pheromone released by stressed male Wistar rats is a stressor to other rats, increases the number of mounts needed for ejaculation, and decreases the hit rate (described as the number of intromissions/sum of the mounts and intromissions. This deterioration in sexual behavior was ameliorated by pretreatment with the opioid receptor antagonist naloxone. However, the neural mechanism underlying this remains to be elucidated. Here, we examined Fos expression in 31 brain regions of pheromone-exposed rats and naloxone-pretreated pheromone-exposed rats 60 min after 10 intromissions. As previously reported, the alarm pheromone increased the number of mounts and decreased the hit rate. In addition, Fos expression was increases in the anterior medial division, anterior lateral division and posterior division of the bed nucleus of the stria terminalis, parvocellular part of the paraventricular nucleus of the hypothalamus, arcuate nucleus, dorsolateral and ventrolateral periaqueductal gray, and nucleus paragigantocellularis. Fos expression decreased in the magnocellular part of the paraventricular nucleus of the hypothalamus. Pretreatment with naloxone blocked the pheromone-induced changes in Fos expression in the magnocellular part of the paraventricular nucleus of the hypothalamus, ventrolateral periaqueductal gray, and nucleus paragigantocellularis. Based on these results, we hypothesize that the alarm pheromone deteriorated sexual behavior by activating the ventrolateral periaqueductal gray-nucleus paragigantocellularis cluster and suppressing the magnocellular part of the paraventricular nucleus of the hypothalamus via the opioidergic pathway.

  2. Behavioral transition from attack to parenting in male mice: a crucial role of the vomeronasal system. (United States)

    Tachikawa, Kashiko S; Yoshihara, Yoshihiro; Kuroda, Kumi O


    Sexually naive male mice show robust aggressive behavior toward pups. However, the proportion of male mice exhibiting pup-directed aggression declines after cohabitation with a pregnant female for 2 weeks after mating. Subsequently, on becoming fathers, they show parental behavior toward pups, similar to maternal behavior by mothers. To elucidate the neural mechanisms underlying this behavioral transition, we examined brain regions differentially activated in sexually naive males and fathers after exposure to pups, using c-Fos expression as a neuronal activation marker. We found that, after pup exposure, subsets of neurons along the vomeronasal neural pathway-including the vomeronasal sensory neurons, the accessory olfactory bulb, the posterior medial amygdala, the medioposterior division of the bed nucleus of stria terminalis, and the anterior hypothalamic area-were more strongly activated in sexually naive males than in fathers. Notably, c-Fos induction was not observed in the vomeronasal sensory neurons of fathers after pup exposure. Surgical ablation of the vomeronasal organ in sexually naive males resulted in the abrogation of pup-directed aggression and simultaneous induction of parental behavior. These results suggest that chemical cues evoking pup-directed aggression are received by the vomeronasal sensory neurons and activate the vomeronasal neural pathway in sexually naive male mice but not in fathers. Thus, the downregulation of pup pheromone-induced activation of the vomeronasal system might be important for the behavioral transition from attack to parenting in male mice.

  3. Brain structures and neurotransmitters regulating aggression in cats: implications for human aggression. (United States)

    Gregg, T R; Siegel, A


    1. Violence and aggression are major public health problems. 2. The authors have used techniques of electrical brain stimulation, anatomical-immunohistochemical techniques, and behavioral pharmacology to investigate the neural systems and circuits underlying aggressive behavior in the cat. 3. The medial hypothalamus and midbrain periaqueductal gray are the most important structures mediating defensive rage behavior, and the perifornical lateral hypothalamus clearly mediates predatory attack behavior. The hippocampus, amygdala, bed nucleus of the stria terminalis, septal area, cingulate gyrus, and prefrontal cortex project to these structures directly or indirectly and thus can modulate the intensity of attack and rage. 4. Evidence suggests that several neurotransmitters facilitate defensive rage within the PAG and medial hypothalamus, including glutamate, Substance P, and cholecystokinin, and that opioid peptides suppress it; these effects usually depend on the subtype of receptor that is activated. 5. A key recent discovery was a GABAergic projection that may underlie the often-observed reciprocally inhibitory relationship between these two forms of aggression. 6. Recently, Substance P has come under scrutiny as a possible key neurotransmitter involved in defensive rage, and the mechanism by which it plays a role in aggression and rage is under investigation. 7. It is hoped that this line of research will provide a better understanding of the neural mechanisms and substrates regulating aggression and rage and thus establish a rational basis for treatment of disorders associated with these forms of aggression.

  4. Contributions of the Central Extended Amygdala to Fear and Anxiety. (United States)

    Shackman, Alexander J; Fox, Andrew S


    It is widely thought that phasic and sustained responses to threat reflect dissociable circuits centered on the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), the two major subdivisions of the central extended amygdala. Early versions of this hypothesis remain highly influential and have been incorporated into the National Institute of Mental Health Research Research Domain Criteria framework. However, new observations encourage a different perspective. Anatomical studies show that the Ce and BST form a tightly interconnected unit, where different kinds of threat-relevant information can be integrated and used to assemble states of fear and anxiety. Imaging studies in humans and monkeys show that the Ce and BST exhibit similar functional profiles. Both regions are sensitive to a range of aversive challenges, including uncertain or temporally remote threat; both covary with concurrent signs and symptoms of fear and anxiety; both show phasic responses to short-lived threat; and both show heightened activity during sustained exposure to diffusely threatening contexts. Mechanistic studies demonstrate that both regions can control the expression of fear and anxiety during sustained exposure to diffuse threat. These observations compel a reconsideration of the central extended amygdala's contributions to fear and anxiety and its role in neuropsychiatric disease. Copyright © 2016 the authors 0270-6474/16/368050-14$15.00/0.

  5. Mapping the co-localization of the circadian proteins PER2 and BMAL1 with enkephalin and substance P throughout the rodent forebrain.

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    Ariana Frederick

    Full Text Available Despite rhythmic expression of clock genes being found throughout the central nervous system, very little is known about their function outside of the suprachiasmatic nucleus. Determining the pattern of clock gene expression across neuronal subpopulations is a key step in understanding their regulation and how they may influence the functions of various brain structures. Using immunofluorescence and confocal microscopy, we quantified the co-expression of the clock proteins BMAL1 and PER2 with two neuropeptides, Substance P (SubP and Enkephalin (Enk, expressed in distinct neuronal populations throughout the forebrain. Regions examined included the limbic forebrain (dorsal striatum, nucleus accumbens, amygdala, stria terminalis, thalamus medial habenula of the thalamus, paraventricular nucleus and arcuate nucleus of the hypothalamus and the olfactory bulb. In most regions examined, BMAL1 was homogeneously expressed in nearly all neurons (~90%, and PER2 was expressed in a slightly lower proportion of cells. There was no specific correlation to SubP- or Enk- expressing subpopulations. The olfactory bulb was unique in that PER2 and BMAL1 were expressed in a much smaller percentage of cells, and Enk was rarely found in the same cells that expressed the clock proteins (SubP was undetectable. These results indicate that clock genes are not unique to specific cell types, and further studies will be required to determine the factors that contribute to the regulation of clock gene expression throughout the brain.

  6. Autoradiographic localization of (125I-Tyr4)bombesin-binding sites in rat brain

    International Nuclear Information System (INIS)

    Zarbin, M.A.; Kuhar, M.J.; O'Donohue, T.L.; Wolf, S.S.; Moody, T.W.


    The binding of ( 125 I-Tyr 4 )bombesin to rat brain slices was investigated. Radiolabeled (Tyr 4 )bombesin bound with high affinity (K/sub d/ . 4 nM) to a single class of sites (B/sub max/ . 130 fmol/mg of protein); the ratio of specific to nonspecific binding was 6/1. Also, pharmacology studies indicated that the C-terminal of bombesin was important for the high affinity binding activity. Autoradiographic studies indicated that the ( 125 I-Tyr4)bombesin-binding sites were discretely distributed in certain gray but not white matter regions of rat brain. Highest grain densities were present in the olfactory bulb and tubercle, nucleus accumbens, suprachiasmatic and periventricular nuclei of the hypothalamus, central medial thalamic nucleus, medial amygdaloid nucleus, hippocampus, dentate gyrus, subiculum, nucleus of the solitary tract, and substantia gelatinosa. Moderate grain densities were present in the parietal cortex, deep layers of the neocortex, rhinal cortex, caudate putamen, stria terminalis, locus ceruleus, parabrachial nucleus, and facial nucleus. Low grain densities were present in the globus pallidus, lateral thalamus, and midbrain. Negligible grain densities were present in the cerebellum, corpus callosum, and all regions treated with 1 microM unlabeled bombesin. The discrete regional distribution of binding suggests that endogenous bombesin-like peptides may function as important regulatory agents in certain brain loci

  7. Effects of perinatal daidzein exposure on subsequent behavior and central estrogen receptor α expression in the adult male mouse. (United States)

    Yu, Chengjun; Tai, Fadao; Zeng, Shuangyan; Zhang, Xia


    Daidzein is one of the most important isoflavones present in soy and it is unique as it can be further metabolized to equol, a compound with greater estrogenic activity than other isoflavones. The potential role of daidzein in the prevention of some chronic diseases has drawn public attention and increased its consumption in human, including in pregnant women and adolescent. It is unclear whether perinatal exposure to daidzein through maternal diets affects subsequent behavior and central estrogen receptor α (ERα) expression in male adults. Following developmental exposure to daidzein through maternal diets during perinatal period, subsequent anxiety-like behavior, social behavior, spatial learning and memory of male mice at adulthood were assessed using a series of tests. The levels of central ER α expression were also examined using immunocytochemistry. Compared with the controls, adult male mice exposed to daidzein during the perinatal period showed significantly less exploration, higher levels of anxiety and aggression. They also displayed more social investigation for females and a tendency to improve spatial learning and memory. The mice with this early daidzein treatment demonstrated significantly higher levels of ERα expression in several brain regions such as the bed nucleus of the stria terminalis, medial preoptic, arcuate hypothalamic nucleus and central amygdaloid mucleus, but decreased it in the lateral septum. Our results indicated that perinatal exposure to daidzein enhanced masculinization on male behaviors which is assocciated with alterations in ERα expression levels led by perinatal daidzein exposure. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity. (United States)

    Garcia-Falgueras, Alicia; Swaab, Dick F


    Transsexuality is an individual's unshakable conviction of belonging to the opposite sex, resulting in a request for sex-reassignment surgery. We have shown previously that the bed nucleus of the stria terminalis (BSTc) is female in size and neuron number in male-to-female transsexual people. In the present study we investigated the hypothalamic uncinate nucleus, which is composed of two subnuclei, namely interstitial nucleus of the anterior hypothalamus (INAH) 3 and 4. Post-mortem brain material was used from 42 subjects: 14 control males, 11 control females, 11 male-to-female transsexual people, 1 female-to-male transsexual subject and 5 non-transsexual subjects who were castrated because of prostate cancer. To identify and delineate the nuclei and determine their volume and shape we used three different stainings throughout the nuclei in every 15th section, i.e. thionin, neuropeptide Y and synaptophysin, using an image analysis system. The most pronounced differences were found in the INAH3 subnucleus. Its volume in thionin sections was 1.9 times larger in control males than in females (P 0.117) and females (volume P > 0.245 and number of neurons P > 0.341). There was no difference in INAH3 between pre-and post-menopausal women, either in the volume (P > 0.84) or in the number of neurons (P gender identity.

  9. Involvement of the amygdala in memory storage: Interaction with other brain systems (United States)

    McGaugh, James L.; Cahill, Larry; Roozendaal, Benno


    There is extensive evidence that the amygdala is involved in affectively influenced memory. The central hypothesis guiding the research reviewed in this paper is that emotional arousal activates the amygdala and that such activation results in the modulation of memory storage occurring in other brain regions. Several lines of evidence support this view. First, the effects of stress-related hormones (epinephrine and glucocorticoids) are mediated by influences involving the amygdala. In rats, lesions of the amygdala and the stria terminalis block the effects of posttraining administration of epinephrine and glucocorticoids on memory. Furthermore, memory is enhanced by posttraining intra-amygdala infusions of drugs that activate β-adrenergic and glucocorticoid receptors. Additionally, infusion of β-adrenergic blockers into the amygdala blocks the memory-modulating effects of epinephrine and glucocorticoids, as well as those of drugs affecting opiate and GABAergic systems. Second, an intact amygdala is not required for expression of retention. Inactivation of the amygdala prior to retention testing (by posttraining lesions or drug infusions) does not block retention performance. Third, findings of studies using human subjects are consistent with those of animal experiments. β-Blockers and amygdala lesions attenuate the effects of emotional arousal on memory. Additionally, 3-week recall of emotional material is highly correlated with positron-emission tomography activation (cerebral glucose metabolism) of the right amygdala during encoding. These findings provide strong evidence supporting the hypothesis that the amygdala is involved in modulating long-term memory storage. PMID:8942964

  10. Cocaine-associated odor cue re-exposure increases blood oxygenation level dependent signal in memory and reward regions of the maternal rat brain. (United States)

    Caffrey, Martha K; Febo, Marcelo


    Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and -Cue). The BOLD response to +Cue and -Cue was measured in dams on postpartum days 2-4. Odor cues were delivered to dams in the absence and then the presence of pups. Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus -Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. The hypothalamic neuropeptide FF network is impaired in hypertensive patients. (United States)

    Goncharuk, Valeri D; Buijs, Ruud M; Jhamandas, Jack H; Swaab, Dick F


    The human hypothalamus contains the neuropeptide FF (NPFF) neurochemical network. Animal experiments demonstrated that NPFF is implicated in the central cardiovascular regulation. We therefore studied expression of this peptide in the hypothalamus of individuals who suffered from essential hypertension (n = 8) and died suddenly due to acute myocardial infarction (AMI), and compared to that of healthy individuals (controls) (n = 6) who died abruptly due to mechanical trauma of the chest. The frozen right part of the hypothalamus was cut coronally into serial sections of 20 μm thickness, and each tenth section was stained immunohistochemically using antibody against NPFF. The central section through each hypothalamic nucleus was characterized by the highest intensity of NPFF immunostaining and thus was chosen for quantitative densitometry. In hypertensive patients, the area occupied by NPFF immunostained neuronal elements in the central sections through the suprachiasmatic nucleus (SCh), paraventricular hypothalamic nucleus (Pa), bed nucleus of the stria terminalis (BST), perinuclear zone (PNZ) of the supraoptic nucleus (SON), dorso- (DMH), ventromedial (VMH) nuclei, and perifornical nucleus (PeF) was dramatically decreased compared to controls, ranging about six times less in the VMH to 15 times less in the central part of the BST (BSTC). The NPFF innervation of both nonstained neuronal profiles and microvasculature was extremely poor in hypertensive patients compared to control. The decreased NPFF expression in the hypothalamus of hypertensive patients might be a cause of impairment of its interaction with other neurochemical systems, and thereby might be involved in the pathogenesis of the disease.

  12. Anatomical and electrophysiological characterization of presumed dopamine-containing neurons within the supramammillary region of the rat. (United States)

    Shepard, P D; Mihailoff, G A; German, D C


    A combination of immunocytochemical, electrophysiological and pharmacological techniques were employed to study the properties of neurons within the supramammillary (SUM) complex of the rat. The SUM region contains a small, but dense, population of tyrosine hydroxylase immunoreactive neurons. Following injection of the orthograde neuroanatomical tracer, Phaseolus Vulgaris leucoagglutinin, into the SUM region, heavy terminal labeling was observed in the lateral septal nucleus, diagonal band of Broca and bed nucleus of the stria terminalis. The electrophysiological and pharmacological properties of antidromically-activated SUM neurons revealed evidence of two neuronal populations. Both groups of neurons exhibited long duration action potentials (greater than 2 msec) and slow conduction velocities (less than 0.5 m/sec). However, cells in one group were characterized by slow and erratic firing rates and insensitivity to dopamine (DA) autoreceptor agonists. Cells in the other group typically exhibited no spontaneous activity but could be induced to discharge by iontophoretic application of glutamate. These latter cells were sensitive to DA autoreceptor stimulation. Of the two populations of mammilloseptal SUM neurons, the silent population exhibited several properties similar to those of midbrain DA neurons.

  13. Estrous cycle influences the expression of neuronal nitric oxide synthase in the hypothalamus and limbic system of female mice

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    Viglietti-Panzica Carla


    Full Text Available Abstract Background Nitric oxide plays an important role in the regulation of male and female sexual behavior in rodents, and the expression of the nitric oxide synthase (NOS is influenced by testosterone in the male rat, and by estrogens in the female. We have here quantitatively investigated the distribution of nNOS immunoreactive (ir neurons in the limbic hypothalamic region of intact female mice sacrificed during different phases of estrous cycle. Results Changes were observed in the medial preoptic area (MPA (significantly higher number in estrus and in the arcuate nucleus (Arc (significantly higher number in proestrus. In the ventrolateral part of the ventromedial nucleus (VMHvl and in the bed nucleus of the stria terminalis (BST no significant changes have been observed. In addition, by comparing males and females, we observed a stable sex dimorphism (males have a higher number of nNOS-ir cells in comparison to almost all the different phases of the estrous cycle in the VMHvl and in the BST (when considering only the less intensely stained elements. In the MPA and in the Arc sex differences were detected only comparing some phases of the cycle. Conclusion These data demonstrate that, in mice, the expression of nNOS in some hypothalamic regions involved in the control of reproduction and characterized by a large number of estrogen receptors is under the control of gonadal hormones and may vary according to the rapid variations of hormonal levels that take place during the estrous cycle.

  14. Oxytocin Reduces Cocaine Seeking and Reverses Chronic Cocaine-Induced Changes in Glutamate Receptor Function (United States)

    Zhou, Luyi; Sun, Wei-Lun; Young, Amy B.; Lee, Kunhee; McGinty, Jacqueline F.


    Background: Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown. Methods: In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level. Results: Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus. Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment. Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner. Conclusions: These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions. PMID:25539504

  15. Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the Four Core Genotype mouse model. (United States)

    Corre, Christina; Friedel, Miriam; Vousden, Dulcie A; Metcalf, Ariane; Spring, Shoshana; Qiu, Lily R; Lerch, Jason P; Palmert, Mark R


    Males and females exhibit several differences in brain structure and function. To examine the basis for these sex differences, we investigated the influences of sex hormones and sex chromosomes on brain structure and function in mice. We used the Four Core Genotype (4CG) mice, which can generate both male and female mice with XX or XY sex chromosome complement, allowing the decoupling of sex chromosomes from hormonal milieu. To examine whole brain structure, high-resolution ex vivo MRI was performed, and to assess differences in cognitive function, mice were trained on a radial arm maze. Voxel-wise and volumetric analyses of MRI data uncovered a striking independence of hormonal versus chromosomal influences in 30 sexually dimorphic brain regions. For example, the bed nucleus of the stria terminalis and the parieto-temporal lobe of the cerebral cortex displayed steroid-dependence while the cerebellar cortex, corpus callosum, and olfactory bulbs were influenced by sex chromosomes. Spatial learning and memory demonstrated strict hormone-dependency with no apparent influence of sex chromosomes. Understanding the influences of chromosomes and hormones on brain structure and function is important for understanding sex differences in brain structure and function, an endeavor that has eventual implications for understanding sex biases observed in the prevalence of psychiatric disorders.

  16. Differential visualization of dopamine and norepinephrine uptake sites in rat brain using [3H]mazindol autoradiography

    International Nuclear Information System (INIS)

    Javitch, J.A.; Strittmatter, S.M.; Snyder, S.H.


    Mazindol is a potent inhibitor of neuronal dopamine (DA) and norepinephrine (NE) uptake. DA and NE uptake sites in rat brain have been differentially visualized using [ 3 H]mazindol autoradiography. At appropriate concentrations, desipramine (DMI) selectively inhibits [ 3 H]mazindol binding to NE uptake sites without significantly affecting binding to DA uptake sites. The localization of DMI-insensitive specific [ 3 H] mazindol binding, reflecting DA uptake sites, is densest in the caudate-putamen, the nucleus accumbens, the olfactory tubercle, the subthalamic nucleus, the ventral tegmental area, the substantia nigra (SN) pars compacta, and the anterior olfactory nuclei. In contrast, the localization of DMI-sensitive specific [ 3 H]mazindol binding, representing NE uptake sites, is densest in the locus coeruleus, the nucleus of the solitary tract, the bed nucleus of the stria terminalis, the paraventricular and periventricular nuclei of the hypothalamus, and the anteroventral thalamus. The distribution of DMI-insensitive specific [ 3 H]mazindol binding closely parallels that of dopaminergic terminal and somatodendritic regions, while the distribution of DMI-sensitive specific [ 3 H]mazindol binding correlates well with the regional localization of noradrenergic terminals and cell bodies. Injection of 6-hydroxydopamine, ibotenic acid, or colchicine into the SN decreases [ 3 H]mazindol binding to DA uptake sites in the ipsilateral caudate-putamen by 85%. In contrast, ibotenic acid lesions of the caudate-putamen do not reduce [ 3 H]mazindol binding to either the ipsilateral or contralateral caudate-putamen

  17. Personality is Tightly Coupled to Vasopressin-Oxytocin Neuron Activity in a Gregarious Finch

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    Aubrey M Kelly


    Full Text Available Nonapeptides of the vasopressin-oxytocin family modulate social processes differentially in relation to sex, species, behavioral phenotype, and human personality. However, the mechanistic bases for these differences are not well understood, in part because multidimensional personality structures remain to be described for common laboratory animals. Based upon principal components (PC analysis of extensive behavioral measures in social and nonsocial contexts, we now describe three complex dimensions of phenotype (personality for the zebra finch, a species that exhibits a human-like social organization that is based upon biparental nuclear families embedded within larger social groups. These dimensions can be characterized as Social competence/dominance, Gregariousness, and Anxiety. We further demonstrate that the phasic Fos response of nonapeptide neurons in the paraventricular nucleus of the hypothalamus and medial bed nucleus of the stria terminalis are significantly predicted by personality, sex, social context, and their interactions. Furthermore the behavioral PCs are each associated with a distinct suite of neural PCs that incorporate both peptide cell numbers and their phasic Fos responses, indicating that personality is reflected in complex patterns of neuromodulation arising from multiple peptide cell groups. These findings provide novel insights into the mechanisms underlying sex- and phenotype-specific modulation of behavior, and should be broadly relevant, given that vasopressin-oxytocin systems are strongly conserved across vertebrates.

  18. Vasotocin neurons and septal V1a-like receptors potently modulate songbird flocking and responses to novelty. (United States)

    Kelly, Aubrey M; Kingsbury, Marcy A; Hoffbuhr, Kristin; Schrock, Sara E; Waxman, Brandon; Kabelik, David; Thompson, Richmond R; Goodson, James L


    Previous comparisons of territorial and gregarious finches (family Estrildidae) suggest the hypothesis that arginine vasotocin (VT) neurons in the medial bed nucleus of the stria terminalis (BSTm) and V(1a)-like receptors in the lateral septum (LS) promote flocking behavior. Consistent with this hypothesis, we now show that intraseptal infusions of a V(1a) antagonist in male zebra finches (Taeniopygia guttata) reduce gregariousness (preference for a group of 10 versus 2 conspecific males), but have no effect on the amount of time that subjects spend in close proximity to other birds ("contact time"). The antagonist also produces a profound increase in anxiety-like behavior, as exhibited by an increased latency to feed in a novelty-suppressed feeding test. Bilateral knockdown of VT production in the BSTm using LNA-modified antisense oligonucleotides likewise produces increases in anxiety-like behavior and a potent reduction in gregariousness, relative to subjects receiving scrambled oligonucleotides. The antisense oligonucleotides also produced a modest increase in contact time, irrespective of group size. Together, these combined experiments provide clear evidence that endogenous VT promotes preferences for larger flock sizes, and does so in a manner that is coupled to general anxiolysis. Given that homologous peptide circuitry of the BSTm-LS is found across all tetrapod vertebrate classes, these findings may be predictive for other highly gregarious species. Published by Elsevier Inc.

  19. Behavioral Relevance of Species-Specific Vasotocin Anatomy in Gregarious Finches

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    Aubrey M Kelly


    Full Text Available Despite substantial species differences in the vasotocin/vasopressin (VT/VP circuitry of the medial bed nucleus of the stria terminalis (BSTm and lateral septum (LS; a primary projection target of BSTm VT/VP cells, functional consequences of this variation are poorly known. Previous experiments in the highly gregarious zebra finch (Estrildidae: Taeniopygia guttata demonstrate that BSTm VT neurons promote gregariousness in a male-specific manner and reduce anxiety in both sexes. However, in contrast to the zebra finch, the less gregarious Angolan blue waxbill (Estrildidae: Uraeginthus angolensis exhibits fewer VT-immunoreactive cells in the BSTm as well as differences in receptor distribution across the LS subnuclei, suggesting that knockdown of VT production in the BSTm would produce behavioral effects in Angolan blue waxbills that are distinct from zebra finches. Thus, we here quantified social contact, gregariousness (i.e. preference for the larger of two groups, and anxiety-like behavior following bilateral antisense knockdown of VT production in the BSTm of male and female Angolan blue waxbills. We find that BSTm VT neurons promote social contact, but not gregariousness (as in male zebra finches, and that antisense effects on social contact are significantly stronger in male waxbills than in females. Knockdown of BSTm VT production has no effect on anxiety-like behavior. These data provide novel evidence that species differences in the VT/VP circuitry arising in the BSTm are accompanied by species-specific effects on affiliation behaviors.

  20. Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain (United States)

    Auger, Catherine J.; Coss, Dylan; Auger, Anthony P.; Forbes-Lorman, Robin M.


    Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor α (ERα) mRNA expression and decreased ERα promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. The maintenance of methylated or demethylated states of some genes in the adult brain by the presence of steroid hormones may play a role in the homeostatic regulation of behaviorally relevant systems. PMID:21368111

  1. The avian subpallium: new insights into structural and functional subdivisions occupying the lateral subpallial wall and their embryological origins (United States)

    Kuenzel, Wayne J.; Medina, Loreta; Csillag, Andras; Perkel, David J.; Reiner, Anton


    The subpallial region of the avian telencephalon contains neural systems whose functions are critical to the survival of individual vertebrates and their species. The subpallial neural structures can be grouped into five major functional systems, namely the dorsal somatomotor basal ganglia; ventral viscerolimbic basal ganglia; subpallial extended amygdala including the central and medial extended amygdala and bed nuclei of the stria terminalis; basal telencephalic cholinergic and non-cholinergic corticopetal systems; and septum. The paper provides an overview of the major developmental, neuroanatomical and functional characteristics of the first four of these neural systems, all of which belong to the lateral telencephalic wall. The review particularly focuses on new findings that have emerged since the identity, extent and terminology for the regions was considered by the Avian Brain Nomenclature Forum. New terminology is introduced as appropriate based on the new findings. The paper also addresses regional similarities and differences between birds and mammals, and notes areas where gaps in knowledge occur for birds. PMID:22015350

  2. Sexually dimorphic effects of a prenatal immune challenge on social play and vasopressin expression in juvenile rats

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    Taylor Patrick V


    Full Text Available Abstract Background Infectious diseases and inflammation during pregnancy increase the offspring’s risk for behavioral disorders. However, how immune stress affects neural circuitry during development is not well known. We tested whether a prenatal immune challenge interferes with the development of social play and with neural circuits implicated in social behavior. Methods Pregnant rats were given intraperitoneal injections of the bacterial endotoxin lipopolysaccharide (LPS – 100 μg /kg or saline on the 15th day of pregnancy. Offspring were tested for social play behaviors between postnatal days 26–40. Brains were harvested on postnatal day 45 and processed for arginine vasopressin (AVP mRNA in situ hybridization. Results In males, LPS treatment reduced the frequency of juvenile play behavior and reduced AVP mRNA expression in the medial amygdala and bed nucleus of the stria terminalis. These effects were not found in females. LPS treatment did not change AVP mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, or supraoptic nucleus of either sex, nor did it affect the sex difference in the size of the sexually dimorphic nucleus of the preoptic area. Conclusions Given AVP’s central role in regulating social behavior, the sexually dimorphic effects of prenatal LPS treatment on male AVP mRNA expression may contribute to the sexually dimorphic effect of LPS on male social play and may, therefore, increase understanding of factors that contribute to sex differences in social psychopathology.

  3. In vivo magnetic resonance imaging of the human limbic white matter

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    Susumu eMori


    Full Text Available The limbic system mediates memory, behavior, and emotional output in the human brain, and is implicated in the pathology of Alzheimer’s disease and a wide spectrum of related neurological disorders. In vivo magnetic resonance imaging (MRI of structural components comprising the limbic system and their interconnections via white matter pathways in the human brain has helped define current understanding of the limbic model based on the classical circuit proposed by Papez. MRI techniques, including diffusion MR imaging, provide a non-invasive method to characterize white matter tracts of the limbic system, and investigate pathological changes that affect these pathways in clinical settings. This review focuses on delineation of the anatomy of major limbic tracts in the human brain, namely, the cingulum, the fornix and fimbria, and the stria terminalis, based on in vivo MRI contrasts. The detailed morphology and intricate trajectories of these pathways that can be identified using relaxometry-based and diffusion-weighted MRI provide an important anatomical reference for evaluation of clinical disorders commonly associated with limbic pathology.

  4. Influence of lesions in the limbic-hypothalamic system on adrenocortical responses to daily repeated exposures to immobilization stress in rabbits

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    Seto, K.; Saito, H.; Kaba, H.; Kawakami, M.


    The influences of daily repeated exposures of immobilization stress on the adrenocorticoid formation in adrenal slices of rabbits with lesions of various sites of the hypothalamus and limbic structures had been investigated. The experimental results obtained were as follows: (1) Lesions in periventricular arcuate nucleus (ARC) and ventromedial hypothalamus (VMH) decreased the rates of adrenocortical responses to the 1st immobilization exposure (exposure on the 1st day), but did not alter the rates of adrenocortical responses to the 4th immobilization exposure (exposure on the 4th day). (2) Lesions in stria-terminalis (ST) and dorsal fornix (FX) did not alter the rates of adrenocortical responses to the 1st immobilization exposure, but increased the rates of adrenocortical responses to the 4th immobilization exposure. (3) The adrenocortical responses to immobilization stress were completely abolished by the seven times repetition of exposures in each sham-operated group and in the animals with lesions of ARC and VMH, but in the rabbits with lesions of ST and FX the adrenocortical responses to immobilization stress were not abolished by the seven times repetition of exposures. (4) These results suggested that such basal medial hypothalamus participated in the mechanisms of adrenocortical responses to the 1st exposure of immobilization stress, but did not participate in the disappearance process of adrenocortical responses to immobilization stress by the seven times repetition of exposures.

  5. AGROINDÚSTRIAS RURAIS FAMILIARES: Estratégias de mercado na região do COREDE Jacuí Centro/RS

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    Chaiane Leal Agne


    Full Text Available Resumo: As Agroindústrias Rurais Familiares destacam-se pelo desenvolvimento de produtos diferenciados. Assim, o presente trabalho teve como objetivo descrever as características que estão diferenciando os produtos agroindustriais nos mercados de proximidade, na região do Corede Jacuí Centro. O estudo caracterizou-se como exploratório-descritivo, com a coleta de informações secundárias e primárias. Foram realizadas 41 entrevistas, com o auxílio de um formulário semiestruturado e diários de campo. Utilizou-se de metodologia qualitativa (análise de conteúdo e quantitativa (média aritmética simples para a análise dos dados. A diferenciação destaca-se como um conjunto de aspectos pertinentes para entender a consolidação de mercados para os produtos da agroindústria rural familiar. Para os agricultores, as características que diferenciam seus produtos nos mercados são: o natural, o jeito de fazer, o sabor, o trabalho do agricultor para produzir, o preço, a certificação SIM e a produção ecológica. Palavras-chave: Agroindústria. Agricultura Familiar. Produtos Diferenciados. Rio Grande do Sul



    Correia de Araujo, Wanderbeg; Elisa Fontana, Marcele


    O presente estudo tem como objetivo, analisar à forma de gerenciamento dos resíduos sólidos, com foco em restos de tecidos, das micro e pequenas empresas de confecções do Agreste de Pernambuco, bem como propor formas de prevenção de resíduos na fonte e melhorias em seu gerenciamento. Para isso, foram realizadas entrevistas e aplicação de questionário para identificar o perfil das empresas e as práticas de gerenciamento de seus resíduos de tecidos. Através desta pesquisa, constatou-se que a ma...



    Luis Gilberto Scherer; Marcelo Alexandre Borges


    Tem se verificado que as operações industriais aplicam, cada vez mais, esforços e recursos no sentido de promover a melhoria contínua de seus processos e assim garantir uma sólida posição no mercado. Este artigo visa a identificar oportunidades de redução das perdas do processo de manufatura, através da utilização da ferramenta de mapeamento de fluxo de valor e a aplicação de Kaizen. Trata-se de um estudo de caso na indústria de motosserras, em que há um levantamento detalhado de dados de tod...


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    Silvia Bohrer Oliva


    Full Text Available RESUMO: Objetivo: identificar o conhecimento dos trabalhadores da indústria metalmecânica em relação aos fatores de risco para doença arterial coronariana (DAC e às atitudes voltadas a sua prevenção. Métodos: estudo com delineamento transversal, realizado com um grupo de trabalhadores da indústria metal-mecânica do sul do Brasil. A amostra foi por conveniência. Os dados foram coletados por meio de um questionário e verificação de medidas antropométricas. Análise descritiva. Resultados: foram incluídos 100 trabalhadores, com idade média de 29,0+10,16 anos, 66% homens. A obesidade foi considerada como fator de risco para DAC por 94% dos trabalhadores, a hipertensão arterial por 88% e hipercolesterolemia por 80%. Em relação às atitudes para prevenção da DAC, 51% da amostra referiram praticar atividade física. Conclusão: a maioria dos entrevistados conhece os principais fatores de risco para DAC. Contudo, as atitudes voltadas à prevenção ainda são limitadas.


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    João Guilherme de Camargo Ferraz Machado


    Full Text Available O objetivo desse trabalho foi analisar as estratégias de marketing e comunicação dos frigoríficos na região de Presidente Prudente-SP, visando melhorar a competitividade do setor e de toda a cadeia produtiva, identificando as principais estratégias relacionadas ao composto mercadológico. A coleta de dados se deu por meio de entrevistas semi-estruturadas, aplicadas em dois frigoríficos da região de Presidente Prudente-SP. Observou-se que as estratégias do composto mercadológico das empresas do setor sofrem poucas variações, em função das características dos produtos e do público-alvo dessas empresas. Também foi verificado um distanciamento entre as empresas e o consumidor final, no que diz respeito às práticas de marketing e comunicação, podendo ser responsável por um desconhecimento, por parte das empresas, das necessidades e dos hábitos de consumo do consumidor final.


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    Michelle Cristine Silveira Meireles


    Full Text Available


    O presente artigo aborda questões relacionadas a estratégias de planejamento, negociação e marketing utilizadas por uma empresa na área têxtil. A realização da pesquisa pautou-se em um estudo de caso, a partir de entrevistas semi-estruturadas e consultas a materiais institucionais. As abordagens teóricas utilizadas no corpo da pesquisa são aplicadas no estudo no intuito de embasar a compreensão do fenômeno estudado. A empresa trabalha com produto de qualidade, bons preços, tendo seu maior problema localizado no capital de giro. Na realização de uma análise organizacional mais detalhada, pesquisa direta com clientes e arrolamento de novas táticas de atuação, percebeu-se que houve por parte da empresa pesquisada uma ampliação à visão de mercado abrindo caminhos e potenciais possibilidades para uma nova atuação de mercado. Assim, o estudo revelou que a empresa deve implantar um conjunto de políticas empresariais de modo agressivo e interativo dentro de suas possibilidades e limitações tanto com os consumidores/clientes quanto no mercado em que atua. 


    Palavras-chave: Estratégia; Indústria Têxtil; Negociação.



    The present paper approach questions related to planning, negotiation and marketing strategies carried by a textile industry enterprise. The search was based in a study of case, by semi-structured interviews and institutional document analyses. The theoric base utilized in the search was applied in sense to embased the comprehension of studied phenomenon. The enterprise play with quality product, low prices, and the major problem was in turnover capital. In the realization of a detailed organizational analyses, costumers direct search and inventore of new tatics of atuation, was perceived the occurrence of a market sense improve, leading the enterprise to new market perspectives. By this way, the study show that the organization should implant a conjoint of enterprise policies by intense and interactive way considering yours possibilities and limitations about consumers/costumers as in your market.


    Keywords: Strategy; Textile Industry; Negotiation.


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    Rosana Beatriz Baptista Haddad


    Full Text Available Este trabalho apresenta um estudo de caso para problemas de seqüenciamento de lotes numa indústria de autopeças. Nele é proposta a adição de um módulo de Capacitação a um software de ERP de forma que o Módulo de MRP deste passe a respeitar os limites de capacidade de recursos considerados críticos. Para isso, o problema de seqüenciamento de produção nos recursos críticos é modelado como problema de fluxos em redes com restrições adicionais. A grande vantagem do método está na "visão temporal" do sistema, que permite antecipações ou atrasos de lotes de fabricação - desde que exista capacidade disponível - sempre que houver sobrecarga. O método permite ainda a análise de diferentes objetivos. Ao final é apresentado um estudo de caso realizado com dados reais da empresa.


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    Lília Calheiros de Oliveira Barretto


    Full Text Available A biotecnologia continua a oferecer muitas alternativas para elaboração de produtos exclusivos. A indústria de laticínios vem contribuindo para o desenvolvimento e aplicação de processos inovadores, com destaque para os alimentos funcionais. O objetivo deste trabalho foi identificar as principais tendências sobre a biotecnologia aplicada no desenvolvimento de produtos lácteos a partir da análise de patentes, pela base Derwent, e de artigos científicos, pela base Scopus. Houve uma maior concentração de documentos de patentes entre os anos de 2003 e 2009. A Rússia foi o país líder em termos de patentes concedidas, com predominância de 73,4 % dos documentos analisados. Dentre as tecnologias, destacaram-se a produção de fermentados probióticos e a extração de oligossacarídeos do leite humano. Os países asiáticos e os europeus foram os maiores contribuidores no tocante desenvolvimento de pesquisas científicas sobre biotecnologia aplicada à indústria de laticínios, totalizando 91 % das publicações reportadas entre 2010 e 2016. Observou-se uma tendência de busca por suporte à propriedade intelectual superior às publicações científicas das biotecnologias associadas à indústria láctea.


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    Claudia Viegas


    Full Text Available O presente artigo está dividido em duas partes. Na primeira, atualiza informações sobre a geração de resíduos industriais por parte de empresas do setor coureiro-calçadista do Vale do Sinos, a partir de uma seleção crítica de informações com base em levantamento recente, realizado pela Fundação Estadual de Proteção Ambiental (Fepam/RS, e de entrevistas junto a administradores de centrais de gerenciamento de resíduos industriais da região. Ainda na primeira parte, constata a evolução quantitativa dessas centrais. Na segunda parte, o artigo propõe a realização de um estudo de avaliação da capacidade tecnológica dos consórcios que gerenciam os referidos resíduos, tendo como base pesquisa semelhante, com método já desenvolvido, amparada em teoria de Lall (1992. Palavras-chave: resíduos industriais; gestão de resíduos; consórcios de gestão de resíduos; capacidade tecnológica.



    Vaz, Elisangela Carvalho


    Esta dissertação discute a geopolítica internacional a partir da inserção da indústria farmacêutica no Brasil, Índia e China. O segmento farmacêutico consolidou-se internacionalmente a partir da Segunda Grande Guerra, com a comercialização da penicilina. Foi a partir de 1945 que houve a reconfiguração deste setor em nível internacional com a presença dos Estados Unidos, a partir de alianças estratégicas entre a indústria farmacêutica, as universidades e novos centros de pesquis...


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    Felipe Crisóstomo Gadelha


    Full Text Available O presente trabalho apresenta o estudo de uma alteração de layout, de funcional para celular, motivado pelos fundamentos da manufatura enxuta. Tendo como objetivo verificar os benefícios de se utilizar a manufatura celular com fluxo enxuto (contínuo, apresenta como metodologia um estudo de caso, pós-fato, em uma indústria de transformadores, onde a mudança foi realizada. Para fundamentar o estudo, apresenta revisão dos temas: Sistema de Manufatura Enxuta e layout industrial, para, em seguida, trazer os dados apresentados por esta indústria, ainda em um arranjo físico funcional, antes da alteração, e, em seguida, nas células de manufatura com um fluxo enxuto, após a alteração, e realizar uma comparação entre ambos. Os resultados obtidos desta comparação apresentam ganhos como aumento de produção, em 20%, e produtividade, em 56%, redução de lead time, em 67%, mão de obra direta, em 30%, tempo de processamento, em 20%, e área fabril, em 24%, dentre outros, evidenciando os benefícios que a utilização de um layout celular e Manufatura Enxuta proporcionam.


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    Maria C. M. Silva


    Full Text Available No ramo de papel e celulose os efluentes são um dos principais problemas e o consumo de água é crítico. Os circuitos internos estão sendo fechados e as fontes de contaminação precisam ser conhecidas. Uma das fontes de contaminação destes efluentes são os minerais da madeira, matéria-prima neste tipo de indústria. Neste trabalho foi avaliada a quantidade de alumínio, cálcio, cobre, ferro, potássio, magnésio, manganês, sódio, níquel e silício em madeiras de cinco espécies florestais, plantadas na região de Guaíba, RS, compreendendo Acacia mearnsii, Eucalyptus dunnii, Eucalyptus globulus, Eucalyptus grandis, Eucalyptus saligna. As amostras de madeira foram tratadas com digestão ácida e com carbonização em mufla, solubilizando em ácido para serem analisadas por ICP (Inductively Coupled Plasm. Foi observado que a quantidade de elementos é considerável e os principais elementos encontrados foram K, Ca, Na, Al, Mn, e Si. As espécies Eucalyptus grandis e Eucalyptus saligna mostraram melhor crescimento. Por outro lado, Eucalyptus globulus e Eucalyptus dunnii mostraram menor crescimento e maior teor de elementos. Pelo fato dessas espécies introduzirem maiores quantidades de elementos no processo de fabricação, devem conduzir a maiores problemas industriais. A Acacia mearnsii mostrou o menor nível para ferro, manganês e níquel, sendo uma boa opção para uso em branqueamento com oxigênio, ozônio e peróxido. O silício observado estava em baixa quantidade, o que leva a afirmar que há, na prática industrial, muita contaminação da madeira explorada com solo já que se encontram altos valores de sílica nos circuitos de licores. A entrada dos elementos minerais estudados em uma fábrica de celulose via madeira varia de 4 a 6 kg por tonelada de polpa não-branqueada produzida. Cuidados especiais devem ser tomados com as espécies com madeiras mais ricas em cinzas e elementos minerais e mais baixas eficiências nutricionais, como foi o caso de Eucalyptus dunnii e Eucalyptus globulus.


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    Luis Gilberto Scherer


    Full Text Available Tem se verificado que as operações industriais aplicam, cada vez mais, esforços e recursos no sentido de promover a melhoria contínua de seus processos e assim garantir uma sólida posição no mercado. Este artigo visa a identificar oportunidades de redução das perdas do processo de manufatura, através da utilização da ferramenta de mapeamento de fluxo de valor e a aplicação de Kaizen. Trata-se de um estudo de caso na indústria de motosserras, em que há um levantamento detalhado de dados de todo o processo produtivo através do mapeamento da cadeia de valor, desde o recebimento da matéria-prima até os clientes. A partir da análise desses dados, demonstra-se o aumento de produtividade e outros ganhos em termos de resposta rápida e flexibilidade. Palavras-Chave: Mapeamento do Fluxo de Valor. Kaizen. Produtividade.


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    Full Text Available O segmento de moda é compreendido por várias redes de empresas, que atuam em conjunto, de forma interdependente, visando o sucesso da cadeia produtiva. Utilizando grande capilaridade, essas redes são formadas por empresas que interagem com diversos ramos de negócios e de produção de vários produtos. São também várias as formas de distribuição utilizadas nesta rede. Esta pesquisa objetivou investigar a aplicação de conceitos de sustentabilidade na cadeia de produção e de distribuição de vestuário de moda. A pesquisa foi elaborada a partir de um estudo exploratório e um estudo de caso, totalizando cinco entrevistas. A compreensão do tema sustentabilidade nos diversos segmentos que compõem as redes de empresas de moda é apresentado e discutido, sendo proposto o algodão colorido para sustentabilidade do setor.



    Gadelha, Diego


    O município de Sobral, no Estado do Ceará, Brasil, foi selecionado na década de 1990 pela capital industrial nacional para cumprir uma função específica no circuito espacial da produção calçadista. Essa inserção, fruto da reestruturação produtiva e da redefinição da divisão espacial do trabalho por qual passou o setor, no final da década de 1980, incorporou novos municípios no circuito produtivo, em especial do nordeste brasileiro. As transformações decorrentes da apropriação de Sobral para d...


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    Simara Netto Martins Cunha


    Full Text Available Este trabalho tem a finalidade de avaliar a carreira profissional dos técnicos formados nas áreas de: eletromecânica, eletrônica, automação e eletrotécnica, que atuam em empresas do ramo petrolífero e, a partir deste levantamento, avaliar o curso técnico que oferece as melhores condições de empregabilidade na Região Norte do Estado do Rio de Janeiro. A coleta de dados foi realizada com aplicação de 86 questionários entre os profissionais técnicos que atuam em empresas petrolíferas sediadas em Macaé, RJ. O método AHP (Analytic Hierarchy Process foi utilizado para seleção da melhor carreira com base nos seguintes critérios de seleção: salário, ascensão profissional, satisfação profissional, tempo para primeira contratação, duração do curso, estabilidade e periculosidade. Os técnicos formados em Eletrônica tem maior tempo de empresa, satisfação profissional, salário e conseguiram seu primeiro emprego mais rápido que os demais técnicos entrevistados. Situação oposta ocorre com os técnicos em Eletrotécnica, apesar de terem maior estabilidade no emprego. Todos os técnicos entrevistados se mostraram insatisfeitos com a ascensão profissional e aplicam parcialmente os conhecimentos adquiridos durante sua formação no ambiente de trabalho. O profissional formado em Eletromecânica julga que sua profissão apresenta periculosidade mediana, maior que os demais entrevistados. O método AHP apontou o curso de Eletromecânica como a melhor alternativa atual. Este trabalho pode auxiliar estudantes na seleção de suas carreiras, baseados na opinião de profissionais que atuam no setor petrolífero regional. O método AHP pode ser usado para tomada de decisões pessoais e oferecer uma resposta objetiva para uma decisão extremamente importante na vida dos jovens que buscam qualificação profissional para atuar na indústria do petróleo.



    Ferreira, Mábele de Cássia; Costa, Samara Maria Lopes; Pasin, Liliana Auxiliadora Avelar


    O presente trabalho objetivou avaliar a utilização do resíduo orgânico da agroindústria processadora de bananas na composição de substratos em comparação com outros substratos para produção de mudas de Platycyamus regnellii Benth. O experimento foi realizado em casa de vegetação, avaliando-se seis substratos dispostos em blocos casualizados, constando de: solo, areia e compostagem da casca de banana (S1); solo, areia e compostagem de cascas de vegetais diversos sem adição de banana (S2); solo...


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    José Roberto Nunes de Azevedo


    Full Text Available Vimos por meio deste texto trazer alguns elementos fundamentais para o entendimentoda configuração da agroindústria canavieira, associado, pois, à ação metabólica do capital quealicerça a sua consubstanciação no território paulista, bem como, a trama que marca o conflitocapital x trabalho nesse setor produtivo.


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    G. Barbirato


    Full Text Available Este trabalho descreve um estudo sobre o potencial de utilização de um forro ecológico constituído de subprodutos da agroindústria (partículas de madeira de maravalha de Pinus sp. e bagaço de cana-de-açúcar - Saccharum officinarum L. associado a placas de poliestireno expandido (isopor® e de poliuretano à base de óleo de mamona (PU-mamona, quando aplicados em bezerreiros cobertos com telha de fibrocimento. Nesse estudo foi aferida a temperatura interna, umidade relativa e o índice de temperatura e umidade (ITU, no período do verão, durante 21 dias. Os resultados obtidos indicaram que o ITU e temperatura ambiente interna das instalações com forro ecológico associado a placas de isopor® e PU-mamona foram inferiores àquelas aferidas em bezerreiros sem forro. As imagens captadas por câmera termográfica indicam que os materiais empregados como forro amorteceram a transferência de calor e radiação para o interior dos bezerreiros, ocasionando menores temperaturas internas nesses ambientes.


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    Juliano Franco e Silva Amaral


    Full Text Available Uma característica da sociedade contemporânea é a crescente inquietação com a qualidade do ambiente natural. Grupos de pressão, cientistas, consumidores, políticos e empresas estão mais conscientes do meio ambiente e cada vez mais influentes. Na década de 1990, temas e conceitos importantes foram estudados: a teoria dos stakeholders, a ética nos negócios, a gestão ambiental, a cidadania empresarial, o desenvolvimento sustentável e a governança corporativa. Para Freeman apud Kreitlon (2003, os stakeholders podem ser definidos como qualquer grupo ou indivíduo capaz de afetar ou ser afetado pela organização. Em sentido estrito, são aqueles grupos vitais para o negócio da empresa. Segundo Moreira (2001, a organização que tem gestão ambiental é aquela que possui um departamento de meio ambiente responsável por atender às exigências dos órgãos ambientais e indicar equipamentos e dispositivos de controle ambiental apropriados à realidade do negócio e aos impactos ambientais. Por outro lado, o sistema de gestão ambiental adquire uma visão estratégica do meio ambiente. A organização deixa de agir apenas em função dos riscos e passa a perceber também as oportunidades de acordo com orientações de inserção da variável ambiental na gestão do negócio. Este artigo tem como objetivo descrever a influência da implantação do sistema de gestão ambiental na imagem de uma indústria têxtil de Minas Gerais frente aos stakeholders. A metodologia utilizada foi a revisão bibliográfica sobre sistema de gestão ambiental, a análise de documentos da Empresa Alfa e entrevistas não estruturadas com os responsáveis pela implantação da ISO 14001 e pela área de relação com investidores


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    Katiane Crotti

    Full Text Available RESUMO Aliar as necessidades dos negócios às ambientais, trata-se de um desafio para as organizações. Os sistemas de gestão ambiental certificados pela NBR ISO 14001:2004 visam facilitar este processo, além de propiciar visibilidade positiva às organizações. No entanto, para adotar tal certificação, exige-se o atendimento de diversos requisitos e o desenvolvimento de estratégias de ecoinovação. Sob tal enfoque, esta pesquisa levantou os seguintes questionamentos: como a indústria de papel atendeu as exigências da NBR ISO 14001:2004? Quais estratégias de ecoinovação foram realizadas para a indústria conquistar a certificação? O objetivo geral buscou identificar e analisar as ações realizadas para a implantação da certificação ISO 14001:2004 em uma indústria de papel da região Centro-Sul do Paraná. Para isso utilizou-se do estudo de caso, no contexto da abordagem qualitativa, por meio de entrevistas, observação e pesquisa documental, e o tratamento destes se deu pela análise de conteúdo. Os principais resultados apontam que essa indústria atendeu aos requisitos de maneira satisfatória, demonstrando sua capacidade de adequar-se à norma. Observou-se também que as estratégias de ecoinovação desenvolvidas contribuíram para o alcance da certificação, o que exigiu da empresa adotar um processo de inovação capaz de subsidiar o atendimento de requisitos fundamentais de gestão ambiental.


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    Juliano Franco e Silva Amaral


    Full Text Available Uma característica da sociedade contemporânea é a crescente inquietação com a qualidade do ambiente natural. Grupos de pressão, cientistas, consumidores, políticos e empresas estão mais conscientes do meio ambiente e cada vez mais influentes. Na década de 1990, temas e conceitos importantes foram estudados: a teoria dos stakeholders, a ética nos negócios, a gestão ambiental, a cidadania empresarial, o desenvolvimento sustentável e a governança corporativa. Para Freeman apud Kreitlon (2003, os stakeholders podem ser definidos como qualquer grupo ou indivíduo capaz de afetar ou ser afetado pela organização. Em sentido estrito, são aqueles grupos vitais para o negócio da empresa. Segundo Moreira (2001, a organização que tem gestão ambiental é aquela que possui um departamento de meio ambiente responsável por atender às exigências dos órgãos ambientais e indicar equipamentos e dispositivos de controle ambiental apropriados à realidade do negócio e aos impactos ambientais. Por outro lado, o sistema de gestão ambiental adquire uma visão estratégica do meio ambiente. A organização deixa de agir apenas em função dos riscos e passa a perceber também as oportunidades de acordo com orientações de inserção da variável ambiental na gestão do negócio. Este artigo tem como objetivo descrever a influência da implantação do sistema de gestão ambiental na imagem de uma indústria têxtil de Minas Gerais frente aos stakeholders. A metodologia utilizada foi a revisão bibliográfica sobre sistema de gestão ambiental, a análise de documentos da Empresa Alfa e entrevistas não estruturadas com os responsáveis pela implantação da ISO 14001 e pela área de relação com investidores.


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    Lilian Pugliese


    Full Text Available Este trabalho tem como objetivo compilar e apresentar conjuntamente os principais impactos ambientais causados pela produção agrícola e industrial da produção de etanol, assim como apontar medidas de mitigação que têm sido apresentadas na literatura. O delineamento do estudo foi realizado pela análise qualitativa do material obtido em revisão bibliográfica. Durante a produção agrícola, os principais impactos ambientais encontrados foram a compactação dos solos por tratores e implementos agrícolas, a contaminação de corpos d’água e solos pelo uso intensivo de fertilizantes e agrotóxicos, aplicação não controlada de vinhaça, torta de filtro ou escórias de siderurgia e poluição do ar por queimadas da palha da cana-de-açúcar. Durante a produção industrial, os principais impactos ambientais apontados relacionam-se com a poluição de ar proveniente da queima do bagaço e palhada excedente para geração de energia elétrica e cinzas dessa queima, com o descarte inadequados da água de lavagem da cana e de equipamentos, das águas residuais de condensadores e multijatos e das águas residuais domésticas. As discussões apresentadas demonstram que a produção de etanol pode gerar impactos desconhecidos pela maior parte da população, tanto na produção agrícola, quanto na produção industrial, podendo ocasionar poluição atmosférica e dos recursos hídricos. Medidas de mitigação, como biodegradação da vinhaça e produção de gases para geração de energia, diminuição do consumo e reúso da água, também são apontadas.


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    Vívian Flores Costa

    Full Text Available RESUMO Este estudo tem o objetivo central identificar os comportamentos de cidadania organizacional (CCO predominantes no contexto organizacional, a partir da visão de colaboradores e de gestores de uma indústria de eletrodomésticos. Para tanto, realizou-se uma pesquisa descritiva, de natureza quantitativa e qualitativa, concretizada por meio de um estudo de caso em uma empresa fabricante de eletrodomésticos. Inicialmente, na etapa quantitativa, participaram 302 colaboradores pertencentes a diversas posições hierárquicas da empresa pesquisada, os quais responderam um questionário elaborado a partir do modelo Escala de Civismo nas Organizações (ECO de Porto e Tamayo (2003. Em um segundo momento, na etapa qualitativa, participaram 10 gestores da empresa investigada, com os quais se efetivaram entrevistas semiestruturadas, sendo o protocolo elaborado à luz do modelo de Porto e Tamayo (2003. Os principais resultados encontrados expõem que, no que tange aos CCO, os comportamentos de Proteção ao sistema e de Cooperação com os colegas foram os indicados pelos colaboradores e gestores como os mais presentes no contexto organizacional investigado. Em contrapartida, na visão dos colaboradores, o autotreinamento e o comportamento de sugestão à gestão organizacional são os menos praticados no ambiente de trabalho. Contudo, a visão dos gestores apresentou algumas dissensões, visto que apontaram esses comportamentos como recorrentes nos membros da organização.



    Almeida, Marly Mizue Kaibara de; Marins, Fernando Augusto Silva; Tramarico, Claudemir Leif


    O aumento da competição, a globalização e a necessidade de redução do ciclo de produção e níveis de estoques criou a necessidade de processos baseados em alianças eficazes na cadeia de suprimentos. Estas pressões têm levado os gestores a reverem suas empresas individualmente e analisar sua posição na cadeia de suprimentos. O Gerenciamento da Cadeia de Suprimentos representa uma importante evolução nas práticas de relacionamento entre clientes e fornecedores participantes de um mesmo canal de ...


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    Adriana de Fátima Gomes Gouvêa


    Full Text Available In order to improve global effectiveness of energy production, a strategy is the model of bio-refineries in which all the components of biomass are totally used to produce a range of products with aggregated value. The kraft lignin is one of the products originated in the process of cellulose production that can be used in making densified products. The objective of this work was to evaluate the behavior of the addition of extracted kraft lignin of black kraft liquor in briquette manufactures with furniture industry waste, in the form of shavings and panel particles in different proportions. The briquettes were produced in laboratory briquetting, using the temperatures of 60, 75 and 90 o C. The pressing and cooling time was 5 minutes and pressure 68,9 x 10 5 N.m -2 (1000 PSI. The briquette quality was evaluated through determining the mechanical properties. The kraft lignin in adequate proportions and temperature showed advantages in the increase of resistance and the durability of the briquettes. The kraft lignin presented advantages such as agglutinative in briquette productions from wood waste at a pressing temperature of 90 o C with addition of 20% of kraft lignin, and at pressing temperatures of 60 and 75 o C at a proportion of addition of 40 and 60% of kraft lignin to wood waste, respectively.



    Hajjar Júnior, Georges


    Este trabalho teve como objetivo construir um modelo de gerência de projetos para o lançamento de novos produtos na indústria farmacêutica de medicamentos genéricos. O foco da pesquisa voltou-se ao desenvolvimento de técnicas e ferramentas de trabalho que possibilitam um maior controle sobre o processo de desenvolvimento de um novo produto a ser lançado no mercado e sirvam como base para planejamento, implantação, controle e avaliação do processo como um todo, fornecendo uma vi...



    Pinheiro, Selma Sotelo; Troccoli, Irene Raguenet


    Esta investigación cualitativa sobre el mercado de reseguros brasileño tuvo el objetivo de rescatar la manera como cinco reseguradoras locales en funcionamiento en Brasil se configuraran estratégicamente después de la apertura de este mercado. Por el método utilizado hubo la formación de dos grupos estratégicos (GE): un formado por las reseguradoras locales con actuación endógena, y otro formado por el Instituto de Resseguros do Brasil (IRB) conjuntamente con las reseguradoras locales de actu...


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    Jean Pierre Ludwig


    Full Text Available O presente artigo apresenta a revisão sistemática da literatura sobre ferramentas da qualidade enfatizando os modelos integrados entre FMEA (Failure Mode and Effect Analysis e MASP (Method of Analysis and Solving Problems. Como resultado, foram identificados 209 trabalhos. Destes, foram selecionados 40 considerados relevantes a pesquisa. O período usado para a pesquisa foi de 2005 a 2015. A partir da análise dos artigos publicados sobre a integração das duas ferramentas, foi possível concluir sobre a inexistência de um modelo integrado que contemple os requisitos particulares das empresas fabricantes de móveis sob encomenda. Dessa maneira, a presente pesquisa se torna relevante no contexto da gestão de operações industriais, pois permitiu a proposição de um conjunto de requisitos que devem ser considerados para a elaboração de um modelo integrado de gestão da qualidade que contemple FMEA e MASP para visando estruturar os processos de melhoria contínua e gestão da qualidade de empresas fabricantes de móveis sob encomenda.


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    Full Text Available Algunos microorganismos útiles y bacterias patógenas como por ejemplo Pseudomonas, Vibrio, Escherichia, Salmonella, Listeria, Streptococcus, Staphylococcus, Mycobacteria, tienen la capacidad de adherirse y crecer en los alimentos y/o en las superficies que están en contacto con ellos formando biopelículas. Estas son significativamente importantes en el campo alimentario porgue causan serios problemas que dificultan y perjudican las operaciones y los procesos al generar pérdidas de energía, reducción del flujo (en tuberías y transferencia de calor, y taponamiento de poros de membranas, entre otros. Este documento considera los aspectos biológicos y fisicoquímicos relacionados con la formación y desarrollo de las biopelículas, lo cual, unido al desarrollo de metodologías de diagnóstico e identificación, permitirán desarrollar estrategias gue faciliten la prevención y control de la contaminación en la industria de alimentos para mantener los sistemas libres de biopelículas y favorecer la calidad y seguridad de los alimentos.Alguns microorganismos úteis e bactérias patogênicas, como Pseudomonas, Vibrio, Escherichia, Salmonella, Listeria, Streptococcus, Staphylococcus, Micobactéria, têm a capacidade de aderir e crescer em alimentos e/ou as superfícies em contato com eles. Neste contexto, os biofilmes são significativamente importantes na alimentação, porque podem causar problemas graves que impedem e dificultam as operações e processos para gerar perdas de energia, fluxo reduzido (tubos e transferência de calor, e entupimento de poros da membrana, entre outros. Este documento considera a aspectos biológicos e físico-químicas relacionadas à formação e desenvolvimento de biofilmes, que, juntamente com o desenvolvimento de métodos para o diagnóstico e identificação, ajudará a desenvolver estratégias de prevenção e controle da poluição na indústria de alimentos para manter os sistemas de biofilme livre e promover a qualidade e segurança alimentar.Some useful microorganisms and pathogenic bacteria such as Pseudomonas, Vibrio, Escherichia, Salmonella, Listeria, Streptococcus, Staphylococcus, Mycobacterium, have the ability to adhere and grow in food and/or surfaces in contact with them. In this context, the biofilms are significantly important in the food industry because they cause serious problems that impede and impair the operations and processes to generate energy losses, reduced flow (in pipes and heat transfer, and plugging of membrane pores, among others. This document considers the biological and physicochemical aspects related to training and development of biofilms, which, together with the development of methods for diagnosis and identification, will help develop strategies for prevention and control of pollution in the food industry to maintain biofilm-free systems and promote the quality and food safety


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    Juliane Luchese


    Full Text Available O objetivo deste artigo é analisar os impactos da implantação do TPC (Tambor-Pulmão-Corda, descrevendo as desvantagens observadas antes desta modificação, bem como os benefícios obtidos após as mudanças. O método de pesquisa foi o estudo de caso único, efetuado em uma empresa pertencente ao polo moveleiro de Bento Gonçalves localizado no Rio Grande do Sul. Entre os resultados obtidos com a pesquisa, evidenciaram-se os processos da empresa, o espaço físico, o transporte de peças entre setores e o sequenciamento da produção, prévios a aplicação da metodologia. Constatou-se que a implantação de um sistema TPC foi essencial para que a melhoria dos processos fosse alcançada.


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    Mauricio Farias Cardoso


    Full Text Available O objetivo deste estudo é analisar o impacto da rotatividade e absenteísmo de pessoal sobre o custo do produto em uma indústria gaúcha.  Para tanto, realizou-se um estudo de caso, que envolveu a participação de uma empresa multinacional, com unidade produtiva no estado do Rio Grande do Sul. Os dados foram coletados no período de 2011, por meio de entrevista semiestruturada com a responsável pelo setor de recursos humanos e também com supervisora de controladoria da empresa. Além das entrevistas foram analisados documentos contábeis e relatórios gerenciais de custos e de recursos humanos. O estudo limitou-se a analisar o produto de maior giro e o setor com maior índice de rotatividade e absenteísmo na empresa. Neste estudo foi possível demonstrar que a rotatividade e o absenteísmo apresentados pelo setor tiveram impacto relevante sobre o custo do produto analisado, diminuindo os resultados proporcionados pela venda deste produto nos períodos em que o custo apresentou maior elevação. 



    Joel Fiegenbaum


    O presente estudo visaanalisar a organização e a localização da agroindústria de leite no estado do Rio Grande do Sul entre os anos de 1990 a 2010. Busca-se neste estudo avaliar a evolução da agroindústria do leite, nos aspectos de estrutura industrial, de volume de produção e de localização do processamento fabril e da captação in natura. As referências teóricas perpassam pela utilização do Commodity System Approach, o modelo de estruturaconduta- desempenho (ECD) dinâmico, as ...


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    Mauricio Uriona Maldonado


    Full Text Available A representação do conhecimento apoia as técnicas e ferramentas de gestão e deve possuir uma compreensão substancial do negócio em que está inserido. A identificação e análise do negócio onde estão embutidos os aspectos de conhecimento são fundamentais para o sucesso da gestão do conhecimento nas organizações. Este artigo descreve a construção da primeira fase de um sistema de conhecimento para o serviço de atendimento ao usuário de uma software-house no Brasil. A metodología empregada é a engenharia do conhecimento e mais específicamente os modelos da camada contextual do CommonKADS. Inicialmente é apresentada uma revisão sobre o framework metodológico CommonKADS, com foco nos modelos de organização, tarefa e agente. Em seguida são descritas as etapas de construção do sistema de conhecimento e apresentado o local de aplicação. Conclui com as implicações do sistema de conhecimento para a software-house analizada bem como as recomendações dos próximos passos de aplicação do CommonKADS.Knowledge representation supports management tools and techniques and must possess a substantial comprehension of the business in which is inserted. This paper describes the first phase construction of a knowledge system for a Brazilian software-house´s customer service. The method applied is knowledge engineering and specifically the context-layer models of CommonKADS. First, a literature review is presented regarding the CommonKADS Methodology, focusing in the Organization, Tasks and Agent Models. Next, the development phases for the knowledge system are described as well as the company where the study was made. It concludes with the business implications of the knowledge system for the software-house as well as the next steps of application for CommonKADS.


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    Guilherme Zim Zaniol


    Full Text Available O presente artigo tem como objetivo analisar a evolução da concentração na indústria brasileira de produção de cerveja no período de 1989 a 2011, segregando-o entre dois períodos: antes e depois da fusão que originou a AmBev. O estudo procura mostrar os antecedentes à criação da AmBev, bem como o comportamento do setor depois da sua criação. A análise permitiu a conclusão de que houve aumento da concentração durante o período referido, como também houve significativo impacto do surgimento da AmBev no mercado.


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    Alexandre Shigunov Neto


    Full Text Available RESUMO O objetivo deste texto é analisar as implicações que a introdução da maquinaria trouxe para os trabalhadores das fábricas, tomando como ponto de partida o período inicial da Revolução Industrial. Nossa hipótese de trabalho sugere que a maquinaria em si, como instrumento auxiliar do progresso, é benéfica para a sociedade e, até mesmo, para o trabalhador, no entanto, a aplicação dada pelo capitalista é que poderá ser prejudicial para os mesmos, em especial para o trabalhador e suas condições de trabalho.


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    Marcus Alexandre de Pádua Cavalcanti


    Full Text Available Marcus Alexandre de Pádua Cavalcanti DOI: 10.12957/periferia.2013.15326O presente artigo propõe uma reflexão sobre as relações e os processos de comunicação promovidos pelas redes digitais e os meios de comunicação de massas, no sentido de perceber, na contemporaneidade, como ambos se integram e se complementam em suas práticas. No decorrer desta apresentação, serão abordados os conceitos de indústria cultural, cibercultura, hegemonia, contra-hegemonia e rizoma. Tais conceitos serão utilizados para analisar e apontar as dinâmicas e configurações das formas verticais/centralizadas e horizontais/descentralizadas de comunicação. As metáforas das ramificações arborescentes e rizomáticas serão utilizadas nesse contexto para visualizar e comunicar melhor o funcionamento desses dois sistemas. Discutem-se as características desses dois paradigmas, como eles convivem e se agenciam de maneira colaborativa e concomitante, potencializando e ampliando as práticas comunicacionais.


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    Carlos Bruno Barreto Luna


    Full Text Available O reaproveitamento de borrachas tem sido bastante explorado, por meio de misturas com polímeros virgens, para gerar compostos utilizados em diversas aplicações. O objetivo deste trabalho foi produzir blendas poliméricas a partir de uma matriz de poliamida 6 com resíduos de borracha reciclada (SBR-R. Foram realizados estudos sobre reologia, temperatura de deflexão térmica (HDT, análise térmica dinâmico-mecânica (DMTA e espectroscopia na região do infravermelho com transformada de Fourier (FTIR. As blendas de poliamida 6/resíduo de borracha reciclada foram preparadas em uma extrusora de rosca dupla corrotacional e os grânulos extrusados foram moldados por injeção. Os resultados obtidos com o estudo reológico mostraram que quanto maior a percentagem de SBR-R adicionado, maiores os valores de torque. As temperaturas de deflexão térmica das blendas reduziram pouco, quando comparadas à da poliamida 6. No ensaio de DMTA, as blendas binárias e ternárias tiveram deslocamento dos picos para, aproximadamente, -10°C e o deslocamento da relaxação α da PA6, para valores maiores. Os resultados do FTIR evidenciaram que as bandas características da PA6 não foram modificadas pela presença do SBR-R e nem pelo aumento da percentagem nas blendas binárias e pela presença de PE-g-MA nas blendas ternárias, mostrando que os seus grupamentos químicos não foram afetados.

  3. Mürgilaeva maaletoojad / Sulev Vedler, Tarmo Vahter

    Index Scriptorium Estoniae

    Vedler, Sulev, 1970-


    Paldiskis kinni peetud mürgilaeva Probo Koalat rentiv Madalmaade naftakaubanduskompanii Trafigura Beheer on Alexela Terminali suurim aktsionär. Keskkonnakaitsjate surve, laeva kinnipidamise põhjused ja süüdistused. Lisa: Alexela terminali omanikud

  4. Pattern of distribution of serotonergic fibers to the amygdala and extended amygdala in the rat. (United States)

    Linley, Stephanie B; Olucha-Bordonau, Francisco; Vertes, Robert P


    As is well recognized, serotonergic (5-HT) fibers distribute widely throughout the forebrain, including the amygdala. Although a few reports have examined the 5-HT innervation of select nuclei of the amygdala in the rat, no previous report has described overall 5-HT projections to the amygdala in the rat. Using immunostaining for the serotonin transporter, SERT, we describe the complete pattern of distribution of 5-HT fibers to the amygdala (proper) and to the extended amygdala in the rat. Based on its ontogenetic origins, the amygdala was subdivided into two major parts, pallial and subpallial components, with the pallial component further divided into superficial and deep nuclei (Olucha-Bordonau et al. 2015). SERT + fibers were shown to distributed moderately to densely to the deep and cortical pallial nuclei, but, by contrast, lightly to the subpallial nuclei. Specifically, 1) of the deep pallial nuclei, the lateral, basolateral, and basomedial nuclei contained a very dense concentration of 5-HT fibers; 2) of the cortical pallial nuclei, the anterior cortical and amygdala-cortical transition zone rostrally and the posteromedial and posterolateral nuclei caudally contained a moderate concentration of 5-HT fibers; and 3) of the subpallial nuclei, the anterior nuclei and the rostral part of the medial (Me) nuclei contained a moderate concentration of 5-HT fibers, whereas caudal regions of Me as well as the central nuclei and the intercalated nuclei contained a sparse/light concentration of 5-HT fibers. With regard to the extended amygdala (primarily the bed nucleus of stria terminalis; BST), on the whole, the BST contained moderate numbers of 5-HT fibers, spread fairly uniformly throughout BST. The findings are discussed with respect to a critical serotonergic influence on the amygdala, particularly on the basal complex, and on the extended amygdala in the control of states of fear and anxiety. J. Comp. Neurol. 525:116-139, 2017. © 2016 Wiley Periodicals, Inc.

  5. Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia. (United States)

    Huang, Chi-Wei; Tsai, Meng-Han; Chen, Nai-Ching; Chen, Wei-Hsi; Lu, Yan-Ting; Lui, Chun-Chung; Chang, Ya-Ting; Chang, Wen-Neng; Chang, Alice Y W; Chang, Chiung-Chih


    Endothelial dysfunction leads to worse cognitive performance in Alzheimer's dementia (AD). While both cerebrovascular risk factors and endothelial dysfunction lead to activation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, it is not known whether these biomarkers extend the diagnostic repertoire in reflecting intracerebral structural damage or cognitive performance. A total of 110 AD patients and 50 age-matched controls were enrolled. Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured and correlated with the cognitive performance, white matter macro-structural changes, and major tract-specific fractional anisotropy quantification. The AD patients were further stratified by clinical dementia rating score (mild dementia, n=60; moderate-to-severe dementia, n=50). Compared with the controls, plasma levels of VCAM-1 (p< 0.001), ICAM-1 (p=0.028) and E-selectin (p=0.016) were significantly higher in the patients, but only VCAM-1 levels significantly reflected the severity of dementia (p< 0.001). In addition, only VCAM-1 levels showed an association with macro- and micro- white matter changes especially in the superior longitudinal fasciculus (p< 0.001), posterior thalamic radiation (p=0.002), stria terminalis (p=0.002) and corpus callosum (p=0.009), and were independent of, age and cortical volume. These tracts show significant association with MMSE, short term memory and visuospatial function. Meanwhile, while VCAM-1 level correlated significantly with short-term memory (p=0.026) and drawing (p=0.025) scores in the AD patients after adjusting for age and education, the significance disappeared after adjusting for global FA. Endothelial activation, especially VCAM-1, was of clinical significance in AD that reflects macro- and micro-structural changes and poor short term memory and visuospatial function.

  6. Distinct BOLD activation profiles following central and peripheral oxytocin administration in awake rats

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    Craig F Ferris


    Full Text Available A growing body of literature has suggested that intranasal oxytocin (OT or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain-barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level dependent (BOLD signal intensity in response to peripheral OT injections (0.1, 0.5 or 2.5 mg/kg during functional magnetic resonance (fMRI in awake rats imaged at 7.0 tesla. These data were compared to OT (1ug/5 µl given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

  7. Increased STAT5 signaling in the ring dove brain in response to prolactin administration and spontaneous elevations in prolactin during the breeding cycle (United States)

    Buntin, John D.; Buntin, Linda


    Prolactin acts on target cells in the central nervous system (CNS) to stimulate behavioral changes associated with parental care in birds, but the signaling mechanisms that mediate these actions have not been characterized. In mammals, the Janus Kinase 2-Signal Transducer and Activator of Transcription 5 (JAK2-STAT5) signaling pathway mediates many of the actions of prolactin. To assess the importance of this pathway in prolactin-sensitive target cells in the avian brain, we measured changes in activated (phosphorylated) STAT5 (pSTAT5) in the forebrain of female ring doves sampled as plasma prolactin levels change during the breeding cycle and in prolactin-treated, non-breeding females. The anatomical distribution of cells exhibiting pSTAT5 immunoreactivity in dove brain closely paralleled the distribution of prolactin receptors in this species. The density of pSTAT5 immunoreactive (pSTAT5-ir) cells were highest in the preoptic area, the suprachiasmatic, paraventricular, ventromedial hypothalamic nuclei, the lateral and tuberal hypothalamic regions, the lateral bed nucleus of the stria terminalis, and the lateral septum. Mean pSTAT5-ir cell densities in these eight brain areas were several fold higher in breeding females during late incubation/early post-hatching when plasma prolactin levels have been observed to peak than in non-breeding females or breeding females sampled at earlier stages when prolactin titers have been reported to be lower. Similar differences were observed between prolactin-treated and vehicle-treated females in all three of the forebrain regions that were compared. We conclude that JAK2-STAT5 signaling is strongly activated in response to prolactin stimulation in the ring dove brain and could potentially mediate some of the centrally-mediated behavioral effects of this hormone. PMID:24530808

  8. Tuning the brain for motherhood: prolactin-like central signalling in virgin, pregnant, and lactating female mice. (United States)

    Salais-López, Hugo; Lanuza, Enrique; Agustín-Pavón, Carmen; Martínez-García, Fernando


    Prolactin is fundamental for the expression of maternal behaviour. In virgin female rats, prolactin administered upon steroid hormone priming accelerates the onset of maternal care. By contrast, the role of prolactin in mice maternal behaviour remains unclear. This study aims at characterizing central prolactin activity patterns in female mice and their variation through pregnancy and lactation. This was revealed by immunoreactivity of phosphorylated (active) signal transducer and activator of transcription 5 (pSTAT5-ir), a key molecule in the signalling cascade of prolactin receptors. We also evaluated non-hypophyseal lactogenic activity during pregnancy by administering bromocriptine, which suppresses hypophyseal prolactin release. Late-pregnant and lactating females showed significantly increased pSTAT5-ir resulting in a widespread pattern of immunostaining with minor variations between pregnant and lactating animals, which comprises nuclei of the sociosexual and maternal brain, including telencephalic (septum, nucleus of the stria terminalis, and amygdala), hypothalamic (preoptic, paraventricular, supraoptic, and ventromedial), and midbrain (periaqueductal grey) regions. During late pregnancy, this pattern was not affected by the administration of bromocriptine, suggesting it to be elicited mostly by non-hypophyseal lactogenic agents, likely placental lactogens. Virgin females displayed, instead, a variable pattern of pSTAT5-ir restricted to a subset of the brain nuclei labelled in pregnant and lactating mice. A hormonal substitution experiment confirmed that estradiol and progesterone contribute to the variability found in virgin females. Our results reflect how the shaping of the maternal brain takes place prior to parturition and suggest that lactogenic agents are important candidates in the development of maternal behaviours already during pregnancy.

  9. Differential efferent projections of the anterior, posteroventral and posterodorsal subdivisions of the medial amygdala in mice

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    Cecília ePardo-Bellver


    Full Text Available The medial amygdaloid nucleus (Me is a key structure in the control of sociosexual behaviour in mice. It receives direct projections from the main and accessory olfactory bulbs, as well as an important hormonal input. To better understand its behavioural role, in this work we investigate the structures receiving information from the Me, by analysing the efferent projections from its anterior (MeA, posterodorsal (MePD and posteroventral (MePV subdivisions, using anterograde neuronal tracing with biotinylated and tetrametylrhodamine-conjugated dextranamines.The Me is strongly interconnected with the rest of the chemosensory amygdala, but shows only moderate projections to the central nucleus and light projections to the associative nuclei of the basolateral amygdaloid complex. In addition, the MeA originates a strong feedback projection to the deep mitral cell layer of the accessory olfactory bulb, whereas the MePV projects to its granule cell layer. The medial amygdaloid nucleus (especially the MeA has also moderate projections to different olfactory structures, including the piriform cortex. The densest outputs of the Me target the bed nucleus of the stria terminalis (BST and the hypothalamus. The MeA and MePV project to key structures of the circuit involved in the defensive response against predators (medial posterointermediate BST, anterior hypothalamic area, dorsomedial aspect of the ventromedial hypothalamic nucleus, although less dense projections also innervate reproductive-related nuclei. In contrast, the MePD projects mainly to structures that control reproductive behaviours (medial posteromedial BST, medial preoptic nucleus, and ventrolateral aspect of the ventromedial hypothalamic nucleus, although less dense projections to defensive-related nuclei also exist. These results confirm and extend previous results in other rodents and suggest that the medial amygdala is anatomically and functionally compartmentalized.

  10. Somatostatin receptor subtype 4 activation is involved in anxiety and depression-like behavior in mouse models. (United States)

    Scheich, Bálint; Gaszner, Balázs; Kormos, Viktória; László, Kristóf; Ádori, Csaba; Borbély, Éva; Hajna, Zsófia; Tékus, Valéria; Bölcskei, Kata; Ábrahám, István; Pintér, Erika; Szolcsányi, János; Helyes, Zsuzsanna


    Somatostatin regulates stress-related behavior and its expression is altered in mood disorders. However, little is known about the underlying mechanisms, especially about the importance of its receptors (sst1-sst5) in anxiety and depression-like behavior. Here we analyzed the potential role of sst4 receptor in these processes, since sst4 is present in stress-related brain regions, but there are no data about its functional relevance. Genetic deletion of sst4 (Sstr4(-/-)) and its pharmacological activation with the newly developed selective non-peptide agonist J-2156 were used. Anxiety was examined in the elevated plus maze (EPM) and depression-like behavior in the forced swim (FST) and tail suspension tests (TST). Neuronal activation during the TST was monitored by Fos immunohistochemistry, receptor expression was identified by sst4(LacZ) immunostaining in several brain regions. Sstr4(-/-) mice showed increased anxiety in the EPM and enhanced depression-like behavior in the FST. J-2156 (100 μg/kg i.p.) exhibited anxiolytic effect in the EPM and decreased immobility in the TST. J-2156 alone did not influence Fos immunoreactivity in intact mice, but significantly increased the stress-induced Fos response in the dorsal raphe nucleus, central projecting Edinger-Westphal nucleus, periaqueductal gray matter, the magnocellular, but not the parvocellular part of the hypothalamic paraventricular nucleus, lateral septum, bed nucleus of the stria terminalis and the amygdala. Notably, sst4(LacZ) immunoreactivity occurred in the central and basolateral amygdala. Together, these studies reveal that sst4 mediates anxiolytic and antidepressant-like effects by enhancing the stress-responsiveness of several brain regions with special emphasis on the amygdala. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Characterization of Aromatase Expression in the Adult Male and Female Mouse Brain. I. Coexistence with Oestrogen Receptors α and β, and Androgen Receptors (United States)

    Stanić, Davor; Dubois, Sydney; Chua, Hui Kheng; Tonge, Bruce; Rinehart, Nicole; Horne, Malcolm K.; Boon, Wah Chin


    Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, including the bed nucleus of the stria terminalis, olfactory tubercle, medial amygdaloid nucleus and medial preoptic area, with the densest distributions of EGFP-positive cell bodies in the bed nucleus and medial amygdala. Differences between male and female mice were apparent, with the density of EGFP-positive cell bodies and fibres being lower in some brain regions of female mice, including the bed nucleus and medial amygdala. EGFP-positive cell bodies in the bed nucleus, lateral septum, medial amygdala and hypothalamus co-expressed oestrogen receptor (ER) α and β, or the androgen receptor (AR), although single-labelled EGFP-positive cells were also identified. Additionally, single-labelled ERα−, ERβ- or AR-positive cell bodies often appeared to be surrounded by EGFP-immunoreactive nerve fibres/terminals. The widespread distribution of EGFP-positive cell bodies and fibres suggests that aromatase signalling is common in the mouse brain, and that locally synthesised brain oestrogens could mediate biological effects by activating pre- and post-synaptic oestrogen α and β receptors, and androgen receptors. The higher number of EGFP-positive cells in male mice may indicate that the autocrine and paracrine effects of oestrogens are more prominent in males than females. PMID:24646567

  12. Chronic intermittent hypoxia sensitizes acute hypothalamic-pituitary-adrenal stress reactivity and Fos induction in the rat locus coeruleus in response to subsequent immobilization stress. (United States)

    Ma, S; Mifflin, S W; Cunningham, J T; Morilak, D A


    Obstructive sleep apnea (OSA) is associated with several pathophysiological conditions, including hypertension, obesity, insulin resistance, hypothalamic-pituitary-adrenal (HPA) dysregulation, and other endocrine and metabolic disturbances comprising the "metabolic syndrome." Repeated episodes of hypoxia in OSA may represent a chronic intermittent stress, leading to HPA dysregulation. Alterations in HPA reactivity could then contribute to or exacerbate other pathophysiological processes. We showed previously that another metabolic stressor, chronic intermittent cold stress, enhanced noradrenergic facilitation of acute HPA stress reactivity. In this study, we investigated whether chronic intermittent hypoxia (CIH), a rat model for the arterial hypoxemia that accompanies OSA, similarly sensitizes the HPA response to novel acute stress. Rats were exposed to CIH (alternating cycles of normoxia [3 min at 21% O(2)] and hypoxia [3 min at 10% O(2)], repeated continuously for 8 h/day during the light portion of the cycle for 7 days). On the day after the final CIH exposure, there were no differences in baseline plasma adrenocorticotropic hormone (ACTH), but the peak ACTH response to 30 min acute immobilization stress was greater in CIH-stressed rats than in controls. Induction of Fos expression by acute immobilization stress was comparable following CIH in several HPA-modulatory brain regions, including the paraventricular nucleus, bed nucleus of the stria terminalis, and amygdala. Fos induction was attenuated in lateral hypothalamus, an HPA-inhibitory region. By contrast, acute Fos induction was enhanced in noradrenergic neurons in the locus coeruleus following CIH exposure. Thus, similar to chronic cold stress, CIH sensitized acute HPA and noradrenergic stress reactivity. Plasticity in the acute stress response is important for long-term adaptation, but may also contribute to pathophysiological conditions associated with states of chronic or repeated stress, such as OSA

  13. Knowledge synthesis with maps of neural connectivity

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    Marcelo eTallis


    Full Text Available This paper describes software for neuroanatomical knowledge synthesis based on high-quality neural connectivity data. This software supports a mature neuroanatomical methodology developed since the early 1990s. Over this time, the Swanson laboratory at USC has generated an account of the neural connectivity of the sub-structures of the hypothalamus, amygdala, septum, hippocampus and bed nucleus of the stria terminalis. This is based on neuroanatomical data maps drawn into a standard brain atlas by experts. In earlier work, we presented an application for visualizing and comparing anatomical macroconnections using the Swanson 3rd edition atlas as a framework for accurate registration. Here we describe major improvements to the NeuARt application based on the incorporation of a knowledge representation of experimental design. We also present improvements in the interface and features of the neuroanatomical data mapping components within a unified web-application. As a step towards developing an accurate sub-regional account of neural connectivity, we provide navigational access between the neuroanatomical data maps and a semantic representation of area-to-area connections that they support. We do so based on an approach called ’Knowledge Engineering from Experimental Design’ (KEfED model that is based on experimental variables. We have extended the underlying KEfED representation of tract-tracing experiments by incorporating the definition of a neuronanatomical data map as a measurement variable in the study design. This paper describes the software design of a web application that allows anatomical data sets to be described within a standard experimental context and thus incorporated with non-spatial data sets.

  14. Evaluating the relationship between white matter integrity, cognition, and varieties of video game learning. (United States)

    Ray, Nicholas R; O'Connell, Margaret A; Nashiro, Kaoru; Smith, Evan T; Qin, Shuo; Basak, Chandramallika


    Many studies are currently researching the effects of video games, particularly in the domain of cognitive training. Great variability exists among video games however, and few studies have attempted to compare different types of video games. Little is known, for instance, about the cognitive processes or brain structures that underlie learning of different genres of video games. To examine the cognitive and neural underpinnings of two different types of game learning in order to evaluate their common and separate correlates, with the hopes of informing future intervention research. Participants (31 younger adults and 31 older adults) completed an extensive cognitive battery and played two different genres of video games, one action game and one strategy game, for 1.5 hours each. DTI scans were acquired for each participant, and regional fractional anisotropy (FA) values were extracted using the JHU atlas. Behavioral results indicated that better performance on tasks of working memory and perceptual discrimination was related to enhanced learning in both games, even after controlling for age, whereas better performance on a perceptual speed task was uniquely related with enhanced learning of the strategy game. DTI results indicated that white matter FA in the right fornix/stria terminalis was correlated with action game learning, whereas white matter FA in the left cingulum/hippocampus was correlated with strategy game learning, even after controlling for age. Although cognition, to a large extent, was a common predictor of both types of game learning, regional white matter FA could separately predict action and strategy game learning. Given the neural and cognitive correlates of strategy game learning, strategy games may provide a more beneficial training tool for adults suffering from memory-related disorders or declines in processing speed, particularly older adults.

  15. Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study. (United States)

    Takiguchi, Kazuo; Uezato, Akihito; Itasaka, Michio; Atsuta, Hidenori; Narushima, Kenji; Yamamoto, Naoki; Kurumaji, Akeo; Tomita, Makoto; Oshima, Kazunari; Shoda, Kosaku; Tamaru, Mai; Nakataki, Masahito; Okazaki, Mitsutoshi; Ishiwata, Sayuri; Ishiwata, Yasuyoshi; Yasuhara, Masato; Arima, Kunimasa; Ohmori, Tetsuro; Nishikawa, Toru


    It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.

  16. The underestimated role of olfaction in avian reproduction ? (United States)

    Balthazart, Jacques; Taziaux, Mélanie


    Until the second half of the 20th century, it was broadly accepted that most birds are microsmatic if not anosmic and unable to detect and use olfactory information. Exceptions were eventually conceded for species like procellariiforms, vultures or kiwis that detect their food at least in part based on olfactory signals. During the past 20–30 years, many publications have appeared indicating that this view is definitely erroneous. We briefly review here anatomical, electrophysiological and behavioral data demonstrating that birds in general possess a functional olfactory system and are able to use olfactory information in a variety of ethological contexts, including reproduction. Recent work also indicates that brain activation induced by sexual interactions with a female is significantly affected by olfactory deprivation in Japanese quail. Brain activation was measured via immunocytochemical detection of the protein product of the immediate early gene c-fos. Changes observed concerned two brain areas that play a key role in the control of male sexual behavior, the medial preoptic nucleus and the bed nucleus of the stria terminalis therefore suggesting a potential role of olfaction in the control of reproduction. The widespread idea that birds are anosmic or microsmatic is thus not supported by the available experimental data and presumably originates in our anthropomorphic view that leads us to think that birds do not smell because they have a rigid beak and nostrils and do not obviously sniff. Experimental analysis of this phenomenon is thus warranted and should lead to a significant change in our understanding of avian biology. PMID:18804490

  17. Orexin 1 receptors are a novel target to modulate panic responses and the panic brain network. (United States)

    Johnson, Philip L; Samuels, Brian C; Fitz, Stephanie D; Federici, Lauren M; Hammes, Nathan; Early, Maureen C; Truitt, William; Lowry, Christopher A; Shekhar, Anantha


    Although the hypothalamic orexin system is known to regulate appetitive behaviors and promote wakefulness and arousal (Sakurai, 2007 [56]), this system may also be important in adaptive and pathological anxiety/stress responses (Suzuki et al., 2005 [4]). In a recent study, we demonstrated that CSF orexin levels were significantly higher in patients experiencing panic attacks compared to non-panicking depressed subjects (Johnson et al., 2010 [9]). Furthermore, genetically silencing orexin synthesis or blocking orexin 1 receptors attenuated lactate-induced panic in an animal model of panic disorder. Therefore, in the present study, we tested if orexin (ORX) modulates panic responses and brain pathways activated by two different panicogenic drugs. We conducted a series of pharmacological, behavioral, physiological and immunohistochemical experiments to study the modulation by the orexinergic inputs of anxiety behaviors, autonomic responses, and activation of brain pathways elicited by systemic injections of anxiogenic/panicogenic drugs in rats. We show that systemic injections of two different anxiogenic/panicogenic drugs (FG-7142, an inverse agonist at the benzodiazepine site of the GABA(A) receptor, and caffeine, a nonselective competitive adenosine receptor antagonist) increased c-Fos induction in a specific subset of orexin neurons located in the dorsomedial/perifornical (DMH/PeF) but not the lateral hypothalamus. Pretreating rats with an orexin 1 receptor antagonist attenuated the FG-7142-induced anxiety-like behaviors, increased heart rate, and neuronal activation in key panic pathways, including subregions of the central nucleus of the amygdala, bed nucleus of the stria terminalis, periaqueductal gray and in the rostroventrolateral medulla. Overall, the data here suggest that the ORX neurons in the DMH/PeF region are critical to eliciting coordinated panic responses and that ORX1 receptor antagonists constitute a potential novel treatment strategy for panic and

  18. Estrogen Receptor Alpha Distribution and Expression in the Social Neural Network of Monogamous and Polygynous Peromyscus.

    Directory of Open Access Journals (Sweden)

    Bruce S Cushing

    Full Text Available In microtine and dwarf hamsters low levels of estrogen receptor alpha (ERα in the bed nucleus of the stria terminalis (BST and medial amygdala (MeA play a critical role in the expression of social monogamy in males, which is characterized by high levels of affiliation and low levels of aggression. In contrast, monogamous Peromyscus males display high levels of aggression and affiliative behavior with high levels of testosterone and aromatase activity. Suggesting the hypothesis that in Peromyscus ERα expression will be positively correlated with high levels of male prosocial behavior and aggression. ERα expression was compared within the social neural network, including the posterior medial BST, MeA posterodorsal, medial preoptic area (MPOA, ventromedial hypothalamus (VMH, and arcuate nucleus in two monogamous species, P. californicus and P. polionotus, and two polygynous species, P. leucopus and P. maniculatus. The results supported the prediction, with male P. polionotus and P. californicus expressing higher levels of ERα in the BST than their polygynous counter parts, and ERα expression was sexually dimorphic in the polygynous species, with females expressing significantly more than males in the BST in both polygynous species and in the MeA in P. leucopus. Peromyscus ERα expression also differed from rats, mice and microtines as in neither the MPOA nor the VMH was ERα sexually dimorphic. The results supported the hypothesis that higher levels of ERα are associated with monogamy in Peromyscus and that differential expression of ERα occurs in the same regions of the brains regardless of whether high or low expression is associated with social monogamy. Also discussed are possible mechanisms regulating this differential relationship.

  19. cFOS and pCREB activation and maternal aggression in mice. (United States)

    Gammie, S C; Nelson, R J


    Lactating mice exhibit a dramatic increase in aggression, termed maternal aggression, only in association with the rearing and protection of their offspring. Previous work indicates that the neural mechanisms underlying maternal and male aggression are different in rodents. In this study, we sought to examine possible neural regions involved in the control of maternal aggression by combining behavioral testing with immunohistochemistry for both cFOS and pCREB, two indirect markers of neuronal activity. All lactating female mice were exposed to a male intruder for 20 min and those exhibiting maternal aggression were placed in one group and those that were non-aggressive were placed in a second group. Thus, the sensory stimuli were similar and the main difference between the two groups was the behavior. cFOS expression increased significantly in the claustrum, bed nucleus of the stria terminalis, medial preoptic nucleus, paraventricular nucleus, medial amygdala, and cortical amygdala in association with maternal aggression. In contrast, the number of pCREB-positive cells significantly increased only in the ventrolateral portion of the caudal periaqueductal gray and in the lateral septum in aggressive lactating mice. Due to large variance in the counts of pCREB-positive cells, the data were log transformed prior to statistical analysis. Thus, the sites of cFOS and pCREB increases do not overlap, but provide complementary indirect information on neural regions active during maternal aggression. These results complement previous studies of nitric oxide release during maternal aggression to create a possible map of the functional neural circuitry underlying maternal aggression.

  20. Dopaminergic regulation of mate competition aggression and aromatase-Fos colocalization in vasotocin neurons. (United States)

    Kabelik, David; Kelly, Aubrey M; Goodson, James L


    Recent experiments demonstrate that aggressive competition for potential mates involves different neural mechanisms than does territorial, resident-intruder aggression. However, despite the obvious importance of mate competition aggression, we know little about its regulation. Immediate early gene experiments show that in contrast to territorial aggression, mate competition in finches is accompanied by the activation of neural populations associated with affiliation and motivation, including vasotocin (VT) neurons in the medial bed nucleus of the stria terminalis (BSTm) and midbrain dopamine (DA) neurons that project to the BSTm. Although VT is known to facilitate mate competition aggression, the role of DA has not previously been examined. We now show that in male zebra finches (Taeniopygia guttata), mate competition aggression is inhibited by the D(2) agonist quinpirole, though not the D(1) agonist SKF-38393 or the D(4) agonist PD168077. The D(3) agonist 7-OH-DPAT also inhibited aggression, but only following high dose treatment that may affect aggression via nonspecific binding to D(2) receptors. Central VT infusion failed to restore D(2) agonist-inhibited aggression in a subsequent experiment, demonstrating that D(2) does not suppress aggression by inhibiting VT release from BSTm neurons. In a final experiment, we detected D(2) agonist-induced increases in immunofluorescent colocalization of the product of the immediate early gene c-fos and the steroid-converting enzyme aromatase (ARO) within VT neurons of the BSTm. Thus, although VT and DA appear to influence mate competition aggression independently, BSTm VT neurons are clearly influenced by the activation of D(2) receptors, which may modify future behaviors.

  1. The Multifaceted Role of the Ventromedial Prefrontal Cortex in Emotion, Decision Making, Social Cognition, and Psychopathology. (United States)

    Hiser, Jaryd; Koenigs, Michael


    The ventromedial prefrontal cortex (vmPFC) has been implicated in a variety of social, cognitive, and affective functions that are commonly disrupted in mental illness. In this review, we summarize data from a diverse array of human and animal studies demonstrating that the vmPFC is a key node of cortical and subcortical networks that subserve at least three broad domains of psychological function linked to psychopathology. One track of research indicates that the vmPFC is critical for the representation of reward- and value-based decision making, through interactions with the ventral striatum and amygdala. A second track of research demonstrates that the vmPFC is critical for the generation and regulation of negative emotion, through its interactions with the amygdala, bed nucleus of the stria terminalis, periaqueductal gray, hippocampus, and dorsal anterior cingulate cortex. A third track of research shows the importance of the vmPFC in multiple aspects of social cognition, such as facial emotion recognition, theory-of-mind ability, and processing self-relevant information, through its interactions with the posterior cingulate cortex, precuneus, dorsomedial PFC, and amygdala. We then present meta-analytic data revealing distinct subregions within the vmPFC that correspond to each of these three functions, as well as the associations between these subregions and specific psychiatric disorders (depression, posttraumatic stress disorder, addiction, social anxiety disorder, bipolar disorder, schizophrenia, and attention-deficit/hyperactivity disorder). We conclude by describing several translational possibilities for clinical studies of vmPFC-based circuits, including neuropsychological assessment of transdiagnostic functions, anatomical targets for intervention, predictors of treatment response, markers of treatment efficacy, and subtyping within disorders. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Distribution of vasopressin in the brain of the eusocial naked mole-rat. (United States)

    Rosen, Greta J; De Vries, Geert J; Goldman, Sharry L; Goldman, Bruce D; Forger, Nancy G


    Naked mole-rats are eusocial rodents that live in large subterranean colonies in which one queen breeds with one to three males. All other animals are nonbreeding subordinates. The external features of male and female subordinates, including their genitalia, are remarkably monomorphic, as is their behavior. Because vasopressin (VP) is associated with social behaviors and sex differences in other species, its distribution in naked mole-rats was of interest. We used immunohistochemistry to examine VP in the brains of subordinate and breeding naked mole-rats of both sexes. As in other mammals, VP-immunoreactive (-ir) somata were found in the paraventricular (PVN) and supraoptic nuclei (SON) and VP-ir projections from these nuclei ran through the internal and external zone of the median eminence. However, naked mole-rats had very few VP-ir cells in the bed nucleus of the stria terminalis (BST) and none in the suprachiasmatic nucleus (SCN); the extensive network of fine-caliber VP-ir fibers usually seen in projection sites of the BST and SCN were also absent. Equally unexpected was the abundance of large-caliber VP-ir fibers in the dorsomedial septum. VP immunoreactivity was generally similar in all groups, with the exception of VP-ir cell number in the dorsomedial hypothalamus (DMH). Breeders had a population of labeled cells in the DMH that was absent, or nearly absent, in subordinates. Future studies on the function of VP in these areas are needed to determine how the atypical distribution of VP immunoreactivity relates to eusociality and the unusual physiology of naked mole-rats.

  3. Social status and sex effects on neural morphology in Damaraland mole-rats, Fukomys damarensis. (United States)

    Anyan, Jeff J; Seney, Marianne L; Holley, Amanda; Bengston, Lynn; Goldman, Bruce D; Forger, Nancy G; Holmes, Melissa M


    We previously reported that in a eusocial rodent, the naked mole-rat (Heterocephalus glaber), traditional neural sex differences were absent; instead, neural dimorphisms were associated with breeding status. Here we examined the same neural regions previously studied in naked mole-rats in a second eusocial species, the Damaraland mole-rat (Fukomys damarensis). Damaraland mole-rats live in social groups with breeding restricted to a small number of animals. However, colony sizes are much smaller in Damaraland mole-rats than in naked mole-rats and there is consequently less reproductive skew. In this sense, Damaraland mole-rats may be considered intermediate in social organization between naked mole-rats and more traditional laboratory rodents. We report that, as in naked mole-rats, breeding Damaraland mole-rats have larger volumes of the principal nucleus of the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus than do subordinates, with no effect of sex on these measures. Thus, these structures may play special roles in breeders of eusocial species. However, in contrast to what was seen in naked mole-rats, we also found sex differences in Damaraland mole-rats: volume of the medial amygdala and motoneuron number in Onuf's nucleus were both greater in males than in females, with no significant effect of breeding status. Thus, both sex and breeding status influence neural morphology in Damaraland mole-rats. These findings are in accord with the observed sex differences in body weight and genitalia in Damaraland but not naked mole-rats. We hypothesize that the increased sexual dimorphism in Damaraland mole-rats relative to naked mole-rats is related to reduced reproductive skew. 2011 S. Karger AG, Basel.

  4. Social status and sex independently influence androgen receptor expression in the eusocial naked mole-rat brain. (United States)

    Holmes, Melissa M; Goldman, Bruce D; Forger, Nancy G


    Naked mole-rats (Heterocephalus glaber) are eusocial rodents that live in large subterranean colonies including a single breeding female and 1-3 breeding males; all other members of the colony, known as subordinates, are reproductively suppressed. We recently found that naked mole-rats lack many of the sex differences in the brain and spinal cord commonly found in other rodents. Instead, neural morphology is influenced by breeding status, such that breeders, regardless of sex, have more neurons than subordinates in the ventromedial nucleus of the hypothalamus (VMH), and larger overall volumes of the bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN) and medial amygdala (MeA). To begin to understand how breeding status influences brain morphology, we examined the distribution of androgen receptor (AR) immunoreactivity in gonadally intact breeders and subordinates of both sexes. All animals had AR+ nuclei in many of the same regions positive for AR in other mammals, including the VMH, BST, PVN, MeA, and the ventral portion of the premammillary nucleus (PMv). We also observed diffuse labeling throughout the preoptic area, demonstrating that distribution of the AR protein in presumptive reproductive brain nuclei is well-conserved, even in a species that exhibits remarkably little sexual dimorphism. In contrast to other rodents, however, naked mole-rats lacked AR+ nuclei in the suprachiasmatic nucleus and hippocampus. Males had more AR+ nuclei in the MeA, VMH, and PMv than did females. Surprisingly, breeders had significantly fewer AR+ nuclei than subordinates in all brain regions examined (VMH, BST, PVN, MeA, and PMv). Thus, social status is strongly correlated with AR immunoreactivity in this eusocial species.

  5. Sociality and the telencephalic distribution of corticotrophin-releasing factor, urocortin 3, and binding sites for CRF type 1 and type 2 receptors: A comparative study of eusocial naked mole-rats and solitary Cape mole-rats. (United States)

    Coen, Clive W; Kalamatianos, Theodosis; Oosthuizen, Maria K; Poorun, Ravi; Faulkes, Christopher G; Bennett, Nigel C


    Various aspects of social behavior are influenced by the highly conserved corticotrophin-releasing factor (CRF) family of peptides and receptors in the mammalian telencephalon. This study has mapped and compared the telencephalic distribution of the CRF receptors, CRF1 and CRF2 , and two of their ligands, CRF and urocortin 3, respectively, in African mole-rat species with diametrically opposed social behavior. Naked mole-rats live in large eusocial colonies that are characterized by exceptional levels of social cohesion, tolerance, and cooperation in burrowing, foraging, defense, and alloparental care for the offspring of the single reproductive female. Cape mole-rats are solitary; they tolerate conspecifics only fleetingly during the breeding season. The telencephalic sites at which the level of CRF1 binding in naked mole-rats exceeds that in Cape mole-rats include the basolateral amygdaloid nucleus, hippocampal CA3 subfield, and dentate gyrus; in contrast, the level is greater in Cape mole-rats in the shell of the nucleus accumbens and medial habenular nucleus. For CRF2 binding, the sites with a greater level in naked mole-rats include the basolateral amygdaloid nucleus and dentate gyrus, but the septohippocampal nucleus, lateral septal nuclei, amygdalostriatal transition area, bed nucleus of the stria terminalis, and medial habenular nucleus display a greater level in Cape mole-rats. The results are discussed with reference to neuroanatomical and behavioral studies of various species, including monogamous and promiscuous voles. By analogy with findings in those species, we speculate that the abundance of CRF1 binding in the nucleus accumbens of Cape mole-rats reflects their lack of affiliative behavior. © 2015 Wiley Periodicals, Inc.

  6. Neuropeptide Y attenuates anxiety- and depression-like effects of cholecystokinin-4 in mice. (United States)

    Desai, S J; Borkar, C D; Nakhate, K T; Subhedar, N K; Kokare, D M


    We investigated the involvement of neuropeptide Y (NPY) in the modulation of cholecystokinin-4 (CCK-4)-evoked anxiety and depression. Adult male mice were injected with vehicle, CCK-4, NPY, NPY Y1 receptor agonist [Leu(31), Pro(34)]-NPY or antagonist BIBP3226, via intracerebroventricular route, and subjected to social interaction or forced swim test (FST) for the evaluation of anxiety- and depression-like phenotypes, respectively. To assess the interactions between the two systems, if any, NPYergic agents were administered prior to CCK-4 and the animals were subjected to these behavioral tests. Treatment with CCK-4 or BIBP3226 dose-dependently reduced social interaction time, while NPY or [Leu(31), Pro(34)]-NPY produced opposite effect. CCK-4 treatment increased immobility time in FST. This effect was reversed by NPY and [Leu(31), Pro(34)]-NPY, although BIBP3226 per se did not alter the immobility time. In a combination study, the anxiogenic or depressive effects of CCK-4 were attenuated by NPY or [Leu(31), Pro(34)]-NPY and potentiated by BIBP3226. The brains of CCK-4 treated rats were processed for NPY immunohistochemistry. Following CCK-4 treatment, the nucleus accumbens shell (AcbSh), ventral part of lateral division of the bed nucleus of stria terminalis (BSTLV), hypothalamic paraventricular nucleus and locus coeruleus showed a reduction in NPY-immunoreactive fibers. Population of NPY-immunopositive cells was also decreased in the AcbSh, BSTLV, prefrontal cortex and hypothalamic arcuate nucleus (ARC). However, NPY-immunoreaction in the fibers of the ARC and cells of the central nucleus of amygdala was unchanged. We conclude that, inhibition of NPY signaling in the brain by CCK-4 might be causal to anxiety- and depression-like behaviors. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Impaired white matter connections of the limbic system networks associated with impaired emotional memory in Alzheimer's disease

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    Xiaoshu Li


    Full Text Available Background: Discrepancies persist regarding retainment of emotional enhancement of memory (EEM in mild cognitive impairment (MCI and early Alzheimer’s disease (AD patients. In addition, the neural mechanisms are still poorly understood, little is known about emotional memory related changes in white matter (WM.Objective: To observe whether EEM is absent in amnestic MCI (aMCI and AD patients, and to investigate if emotional memory is associated with WM connections and gray matters (GM of the limbic system networks. Methods: Twenty-one AD patients, 20 aMCI patients and 25 normal controls participated in emotional picture recognition tests and MRI scanning. Tract-based spatial statistics (TBSS and voxel-based morphometry (VBM methods were used to determine white and gray matter changes of patients. Fourteen regions of interest (ROI of WM and 20 ROIs of GM were then selected for the correlation analyses with behavioral scores. Results: The EEM effect was lost in AD patients. Both white and gray matter of the limbic system networks were impaired in AD patients. Significant correlations or tendencies between the bilateral uncinate fasciculus, corpus callosum (genu and body, left cingulum bundle, left parahippocampal WM and the recognition sensitivity of emotional valence pictures, and significant correlations or tendencies between the splenium of corpus callosum, left cingulum bundle, left crus of fornix and stria terminalis and the recognition sensitivity of EEM were found. The volume of left amygdala, bilateral insula, medial frontal lobe, anterior and middle cingulum gyrus were positively correlated with the recognition sensitivity of emotional photos, and the right precuneus was positively correlated with the negative EEM effect. However, the affected brain areas of aMCI patients were more localized, and aMCI patients benefited only from positive stimuli. Conclusion: There are impairments of the limbic system networks of AD patients. Damaged WM

  8. Effects of VRK2 (rs2312147 on white matter connectivity in patients with schizophrenia.

    Directory of Open Access Journals (Sweden)

    Hoyoung Sohn

    Full Text Available Recent genome-wide association studies of schizophrenia reported a novel risk variant, rs2312147 at vaccinia-related kinase 2 gene (VRK2, in multiple Asian and European samples. However, its effect on the brain structure in schizophrenia is little known. We analyzed the brain structure of 36 schizophrenia patients and 18 healthy subjects with regard to rs2312147 genotype groups. Brain magnetic resonance scans for gray matter (GM and white matter (WM analysis, and genotype analysis for VRK2 rs2312147, were conducted. The Positive and Negative Syndrome Scale and the Digit Symbol Test were assessed for schizophrenia patients. There was no significant difference in either GM volume or WM connectivity with regard to rs2312147 genotype in healthy subjects. In contrast, we found significant differences in the WM connectivity between rs2312147 CC and CT/TT genotype groups of schizophrenia patients. The related brain areas included the splenium of corpus callosum, the left occipital lobe WM, the internal capsule (left anterior limb and right retrolenticular part, the bilateral temporal lobe WM, the left fornix/stria terminalis, the left cingulate gyrus WM, and the left parietal lobe WM. Voxelwise correlation analysis revealed that the Digit Symbol Test scores (age corrected correlated with the fractional anisotropy in WM tracts that previously showed significant group differences between the CT/TT and CC genotypes in the rs2312147 CT/TT genotype group, while no significant correlation was found in the CC genotype group. Our data may provide evidence for the effect of VRK2 on WM connectivity in patients with schizophrenia.

  9. Olfactory systems and neural circuits that modulate predator odor fear

    Directory of Open Access Journals (Sweden)

    Lorey K. Takahashi


    Full Text Available When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS and accessory olfactory systems (AOS detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray, paraventricular nucleus of the hypothalamus, and the medial amygdala appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal stress hormone secretion. The medial amygdala also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus appear prominently involve in predator odor fear behavior. The basolateral amygdala, medial hypothalamic nuclei, and medial prefrontal cortex are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator odors activate

  10. Subdivisions of the turtle Pseudemys scripta subpallium based on the expression of regulatory genes and neuronal markers. (United States)

    Moreno, Nerea; Morona, Ruth; López, Jesús M; González, Agustín


    The patterns of distribution of a set of conserved brain developmental regulatory transcription factors and neuronal markers were analyzed in the subpallium of the juvenile turtle, Pseudemys scripta. Immunohistochemical techniques were used with a combination of primary antibodies for the identification of the main boundaries and subdivisions in the basal telencephalon. In the basal ganglia, the combinatorial expression on Pax6, Nkx2.1, and GABA was a powerful tool for the identification of the nucleus accumbens, the dorsal portion of the striatum, and the pallidal regions. It was also possible to suggest migratory streams of neurons from the pallidum into the striatal regions. On the basis of GABA, Pax6, Tbr1, tyrosine hydroxylase, Darpp32, and Nkx2.1 combinatorial expression patterns, the boundaries of the septal subdivisions and their embryological origin were assessed. In particular, the bed nucleus of the stria terminalis was identified. Within the amygdaloid complex, the striatal central amygdala was characterized by Pax6 expression, whereas Orthopedia gene expression highlighted, at least, a subdivision of the medial amygdala. A newly identified preoptic commissural area and the boundaries of the preoptic area were assessed, mainly by the localization of Nkx2.1 expression. Finally, additional data were obtained by combining immunohistochemistry and tracing techniques on the interneuronal nature of the cholinerginergic, nitrergic, and Nkx2.1-positive striatal cells. Taken together, all the results of the present study allowed recognizing main features in the organization of the subpallium in reptiles that, in most cases, are shared with other amniotes and amphibians. © 2010 Wiley-Liss, Inc.

  11. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders (United States)

    Campos, Alline Cristina; Moreira, Fabricio Araújo; Gomes, Felipe Villela; Del Bel, Elaine Aparecida; Guimarães, Francisco Silveira


    Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound Δ9-tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARγ receptors agonism, intracellular (Ca2+) increase, etc.), on CBD behavioural effects. PMID:23108553

  12. Connections of the juxtaventromedial region of the lateral hypothalamic area in the male rat.

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    Joel D Hahn


    Full Text Available Evolutionary conservation of the hypothalamus attests to its critical role in the control of fundamental behaviors. However, our knowledge of hypothalamic connections is incomplete, particularly for the lateral hypothalamic area (LHA. Here we present the results of neuronal pathway-tracing experiments to investigate connections of the LHA juxtaventromedial region, which is parceled into dorsal (LHAjvd and ventral (LHAjvv zones. Phaseolus vulgaris leucoagglutinin (PHAL, for outputs and cholera toxin B subunit (CTB, for inputs coinjections were targeted stereotaxically to the LHAjvd/v. RESULTS: LHAjvd/v connections overlapped highly but not uniformly. Major joint outputs included: Bed nuc. stria terminalis (BST, interfascicular nuc. (BSTif and BST anteromedial area, rostral lateral septal (LSr- and ventromedial hypothalamic (VMH nuc., and periaqueductal gray. Prominent joint LHAjvd/v input sources included: BSTif, BST principal nuc., LSr, VMH, anterior hypothalamic-, ventral premammillary-, and medial amygdalar nuc., and hippocampal formation (HPF field CA1. However, LHAjvd HPF retrograde labeling was markedly more abundant than from the LHAjvv; in the LSr this was reversed. Furthermore, robust LHAjvv (but not LHAjvd targets included posterior- and basomedial amygdalar nuc., whereas the midbrain reticular nuc. received a dense input from the LHAjvd alone. Our analyses indicate the existence of about 500 LHAjvd and LHAjvv connections with about 200 distinct regions of the cerebral cortex, cerebral nuclei, and cerebrospinal trunk. Several highly LHAjvd/v-connected regions have a prominent role in reproductive behavior. These findings contrast with those from our previous pathway-tracing studies of other LHA medial and perifornical tier regions, with different connectional behavioral relations. The emerging picture is of a highly differentiated LHA with extensive and far-reaching connections that point to a role as a central coordinator of behavioral

  13. Organizing effects of sex steroids on brain aromatase activity in quail.

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    Charlotte A Cornil


    Full Text Available Preoptic/hypothalamic aromatase activity (AA is sexually differentiated in birds and mammals but the mechanisms controlling this sex difference remain unclear. We determined here (1 brain sites where AA is sexually differentiated and (2 whether this sex difference results from organizing effects of estrogens during ontogeny or activating effects of testosterone in adulthood. In the first experiment we measured AA in brain regions micropunched in adult male and female Japanese quail utilizing the novel strategy of basing the microdissections on the distribution of aromatase-immunoreactive cells. The largest sex difference was found in the medial bed nucleus of the stria terminalis (mBST followed by the medial preoptic nucleus (POM and the tuberal hypothalamic region. A second experiment tested the effect of embryonic treatments known to sex-reverse male copulatory behavior (i.e., estradiol benzoate [EB] or the aromatase inhibitor, Vorozole on brain AA in gonadectomized adult males and females chronically treated as adults with testosterone. Embryonic EB demasculinized male copulatory behavior, while vorozole blocked demasculinization of behavior in females as previously demonstrated in birds. Interestingly, these treatments did not affect a measure of appetitive sexual behavior. In parallel, embryonic vorozole increased, while EB decreased AA in pooled POM and mBST, but the same effect was observed in both sexes. Together, these data indicate that the early action of estrogens demasculinizes AA. However, this organizational action of estrogens on AA does not explain the behavioral sex difference in copulatory behavior since AA is similar in testosterone-treated males and females that were or were not exposed to embryonic treatments with estrogens.

  14. Trait-like brain activity during adolescence predicts anxious temperament in primates.

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    Andrew S Fox


    Full Text Available Early theorists (Freud and Darwin speculated that extremely shy children, or those with anxious temperament, were likely to have anxiety problems as adults. More recent studies demonstrate that these children have heightened responses to potentially threatening situations reacting with intense defensive responses that are characterized by behavioral inhibition (BI (inhibited motor behavior and decreased vocalizations and physiological arousal. Confirming the earlier impressions, data now demonstrate that children with this disposition are at increased risk to develop anxiety, depression, and comorbid substance abuse. Additional key features of anxious temperament are that it appears at a young age, it is a stable characteristic of individuals, and even in non-threatening environments it is associated with increased psychic anxiety and somatic tension. To understand the neural underpinnings of anxious temperament, we performed imaging studies with 18-fluoro-deoxyglucose (FDG high-resolution Positron Emission Tomography (PET in young rhesus monkeys. Rhesus monkeys were used because they provide a well validated model of anxious temperament for studies that cannot be performed in human children. Imaging the same animal in stressful and secure contexts, we examined the relation between regional metabolic brain activity and a trait-like measure of anxious temperament that encompasses measures of BI and pituitary-adrenal reactivity. Regardless of context, results demonstrated a trait-like pattern of brain activity (amygdala, bed nucleus of stria terminalis, hippocampus, and periaqueductal gray that is predictive of individual phenotypic differences. Importantly, individuals with extreme anxious temperament also displayed increased activity of this circuit when assessed in the security of their home environment. These findings suggest that increased activity of this circuit early in life mediates the childhood temperamental risk to develop anxiety and

  15. Diffusion tensor imaging in male premutation carriers of the fragile X mental retardation gene. (United States)

    Hashimoto, Ryu-ichiro; Srivastava, Siddharth; Tassone, Flora; Hagerman, Randi J; Rivera, Susan M


    Older male premutation carriers of the FMR1 gene are associated with the risk of developing a late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome. Although previous postmortem and in vivo magnetic resonance imaging studies have indicated white matter pathology, the regional selectivity of abnormalities, as well as their relationship with molecular variables of the FMR1 gene, has not been investigated. In this study, we used diffusion tensor imaging to study male premutation carriers with and without fragile X-associated tremor/ataxia syndrome and healthy sex-matched controls. We performed a tract of interest analysis for fractional anisotropy and axial and radial diffusivities of major white matter tracts in the cerebellar-brain stem and limbic systems. Compared with healthy controls, patients with fragile X-associated tremor/ataxia syndrome showed significant reductions of fractional anisotropy in multiple white matter tracts, including the middle cerebellar peduncle, superior cerebellar peduncle, cerebral peduncle, and the fornix and stria terminalis. Significant reduction of fractional anisotropy in these tracts was confirmed by voxel-wise analysis using tract-based spatial statistics. Analysis of axial and radial diffusivities showed significant elevation of these measures in middle cerebellar peduncle, even among premutation carriers without fragile X-associated tremor/ataxia syndrome. Furthermore, regression analyses demonstrated a clear inverted U-shaped relationship between CGG-repeat size and axial and radial diffusivities in middle cerebellar peduncle. These results provide new evidence from diffusion tensor imaging for white matter abnormalities in the cerebellar-brain stem and limbic systems among individuals with the fragile X premutation and suggest the involvement of molecular mechanisms related to the FMR1 gene in their white matter pathology. Copyright © 2011 Movement Disorder Society.

  16. Characterization of aromatase expression in the adult male and female mouse brain. I. Coexistence with oestrogen receptors α and β, and androgen receptors. (United States)

    Stanić, Davor; Dubois, Sydney; Chua, Hui Kheng; Tonge, Bruce; Rinehart, Nicole; Horne, Malcolm K; Boon, Wah Chin


    Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, including the bed nucleus of the stria terminalis, olfactory tubercle, medial amygdaloid nucleus and medial preoptic area, with the densest distributions of EGFP-positive cell bodies in the bed nucleus and medial amygdala. Differences between male and female mice were apparent, with the density of EGFP-positive cell bodies and fibres being lower in some brain regions of female mice, including the bed nucleus and medial amygdala. EGFP-positive cell bodies in the bed nucleus, lateral septum, medial amygdala and hypothalamus co-expressed oestrogen receptor (ER) α and β, or the androgen receptor (AR), although single-labelled EGFP-positive cells were also identified. Additionally, single-labelled ERα-, ERβ- or AR-positive cell bodies often appeared to be surrounded by EGFP-immunoreactive nerve fibres/terminals. The widespread distribution of EGFP-positive cell bodies and fibres suggests that aromatase signalling is common in the mouse brain, and that locally synthesised brain oestrogens could mediate biological effects by activating pre- and post-synaptic oestrogen α and β receptors, and androgen receptors. The higher number of EGFP-positive cells in male mice may indicate that the autocrine and paracrine effects of oestrogens are more prominent in males than females.

  17. Relationships between rapid changes in local aromatase activity and estradiol concentrations in male and female quail brain. (United States)

    Dickens, M J; de Bournonville, C; Balthazart, J; Cornil, C A


    Estradiol-17β (E2) synthesized in the brain plays a critical role in the activation of sexual behavior in many vertebrate species. Because E2 concentrations depend on aromatization of testosterone, changes in aromatase enzymatic activity (AA) are often utilized as a proxy to describe E2 concentrations. Utilizing two types of stimuli (sexual interactions and acute restraint stress) that have been demonstrated to reliably alter AA within minutes in opposite directions (sexual interactions=decrease, stress=increase), we tested in Japanese quail whether rapid changes in AA are paralleled by changes in E2 concentrations in discrete brain areas. In males, E2 in the pooled medial preoptic nucleus/medial portion of the bed nucleus of the stria terminalis (POM/BST) positively correlated with AA following sexual interactions. However, following acute stress, E2 decreased significantly (approximately 2-fold) in the male POM/BST despite a significant increase in AA. In females, AA positively correlated with E2 in both the POM/BST and mediobasal hypothalamus supporting a role for local, as opposed to ovarian, production regulating brain E2 concentrations. In addition, correlations of individual E2 in POM/BST and measurements of female sexual behavior suggested a role for local E2 synthesis in female receptivity. These data demonstrate that local E2 in the male brain changes in response to stimuli on a time course suggestive of potential non-genomic effects on brain and behavior. Overall, this study highlights the complex mechanisms regulating local E2 concentrations including rapid stimulus-driven changes in production and stress-induced changes in catabolism. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Female mice deficient in alpha-fetoprotein show female-typical neural responses to conspecific-derived pheromones.

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    Olivier Brock

    Full Text Available The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO and which lack the protective actions of AFP against maternal estradiol, that exposure to prenatal estradiol completely defeminized the potential to show lordosis behavior in adulthood. Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male. In the present study, we asked whether neural responses to male- and female-derived odors are also affected in AFP-KO female mice. Therefore, we compared patterns of Fos, the protein product of the immediate early gene, c-fos, commonly used as a marker of neuronal activation, between wild-type (WT and AFP-KO female mice following exposure to male or estrous female urine. We also tested WT males to confirm the previously observed sex differences in neural responses to male urinary odors. Interestingly, AFP-KO females showed normal, female-like Fos responses, i.e. exposure to urinary odors from male but not estrous female mice induced equivalent levels of Fos protein in the accessory olfactory pathways (e.g. the medial part of the preoptic nucleus, the bed nucleus of the stria terminalis, the amygdala, and the lateral part of the ventromedial hypothalamic nucleus as well as in the main olfactory pathways (e.g. the piriform cortex and the anterior cortical amygdaloid nucleus, as WT females. By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors. These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

  19. Olfactory systems and neural circuits that modulate predator odor fear. (United States)

    Takahashi, Lorey K


    When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS) and accessory olfactory systems (AOS) detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray (DPAG), paraventricular nucleus (PVN) of the hypothalamus, and the medial amygdala (MeA) appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal (HPA) stress hormone secretion. The MeA also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus (VHC) appear prominently involved in predator odor fear behavior. The basolateral amygdala (BLA), medial hypothalamic nuclei, and medial prefrontal cortex (mPFC) are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator

  20. Sex differences in circuits activated by corticotropin releasing factor in rats. (United States)

    Salvatore, Madeleine; Wiersielis, Kimberly R; Luz, Sandra; Waxler, David E; Bhatnagar, Seema; Bangasser, Debra A


    Women are more likely than men to suffer from psychiatric disorders characterized by corticotropin releasing factor (CRF) hypersecretion, suggesting sex differences in CRF sensitivity. In rodents, sex differences in the sensitivity of specific brain regions to CRF have been identified. However, regions do not work in isolation, but rather form circuits to coordinate distinct responses to stressful events. Here we examined whether CRF activates different circuits in male and female rats. Following central administration of CRF or artificial cerebrospinal fluid (aCSF), neuronal activation in stress-related areas was assessed using cFOS. Functional connectivity was gauged by correlating the number of cFOS-positive cells between regions and then identifying differences within each sex in correlations for aCSF-treated and CRF-treated groups. This analysis revealed that CRF altered different circuits in males and females. As an example, CRF altered correlations involving the dorsal raphe in males and the bed nucleus of the stria terminalis in females, suggesting sex differences in stress-activated circuits controlling mood and anxiety. Next, plasma estradiol and progesterone levels were correlated with cFOS counts in females. Negative correlations between estradiol and neuronal activation in the regions within the extended amygdala were found in CRF-treated, but not aCSF-treated females. This result suggests that estrogens and CRF together modulate the fear and anxiety responses mediated by these regions. Collectively, these studies reveal sex differences in the way brain regions work together in response to CRF. These differences could drive different stress coping strategies in males and females, perhaps contributing to sex biases in psychopathology. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The dynamics of stress: a longitudinal MRI study of rat brain structure and connectome. (United States)

    Magalhães, R; Barrière, D A; Novais, A; Marques, F; Marques, P; Cerqueira, J; Sousa, J C; Cachia, A; Boumezbeur, F; Bottlaender, M; Jay, T M; Mériaux, S; Sousa, N


    Stress is a well-established trigger for a number of neuropsychiatric disorders, as it alters both structure and function of several brain regions and its networks. Herein, we conduct a longitudinal neuroimaging study to assess how a chronic unpredictable stress protocol impacts the structure of the rat brain and its functional connectome in both high and low responders to stress. Our results reveal the changes that stress triggers in the brain, with structural atrophy affecting key regions such as the prelimbic, cingulate, insular and retrosplenial, somatosensory, motor, auditory and perirhinal/entorhinal cortices, the hippocampus, the dorsomedial striatum, nucleus accumbens, the septum, the bed nucleus of the stria terminalis, the thalamus and several brain stem nuclei. These structural changes are associated with increasing functional connectivity within a network composed by these regions. Moreover, using a clustering based on endocrine and behavioural outcomes, animals were classified as high and low responders to stress. We reveal that susceptible animals (high responders) develop local atrophy of the ventral tegmental area and an increase in functional connectivity between this area and the thalamus, further spreading to other areas that link the cognitive system with the fight-or-flight system. Through a longitudinal approach we were able to establish two distinct patterns, with functional changes occurring during the exposure to stress, but with an inflection point after the first week of stress when more prominent changes were seen. Finally, our study revealed differences in functional connectivity in a brainstem-limbic network that distinguishes resistant and susceptible responders before any exposure to stress, providing the first potential imaging-based predictive biomarkers of an individual's resilience/vulnerability to stressful conditions.Molecular Psychiatry advance online publication, 5 December 2017; doi:10.1038/mp.2017.244.

  2. Distribution and densitometry mapping of L1-CAM Immunoreactivity in the adult mouse brain – light microscopic observation

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    Yamasaki Hironobu


    Full Text Available Abstract Background The importance of L1 expression in the matured brain is suggested by physiological and behavioral studies showing that L1 is related to hippocampal plasticity and fear conditioning. The distribution of L1 in mouse brain might provide a basis for understanding its role in the brain. Results We examined the overall distribution of L1 in the adult mouse brain by immunohistochemistry using two polyclonal antibodies against different epitopes for L1. Immunoreactive L1 was widely but unevenly distributed from the olfactory bulb to the upper cervical cord. The accumulation of immunoreactive L1 was greatest in a non-neuronal element of the major fibre bundles, i.e. the lateral olfactory tract, olfactory and temporal limb of the anterior commissure, corpus callosum, stria terminalis, globus pallidus, fornix, mammillothalamic tract, solitary tract, and spinal tract of the trigeminal nerve. High to highest levels of non-neuronal and neuronal L1 were found in the grey matter; i.e. the piriform and entorhinal cortices, hypothalamus, reticular part of the substantia nigra, periaqueductal grey, trigeminal spinal nucleus etc. High to moderate density of neuronal L1 was found in the olfactory bulb, layer V of the cerebral cortex, amygdala, pontine grey, superior colliculi, cerebellar cortex, solitary tract nucleus etc. Only low to lowest levels of neuronal L1 were found in the hippocampus, grey matter in the caudate-putamen, thalamus, cerebellar nuclei etc. Conclusion L1 is widely and unevenly distributed in the matured mouse brain, where immunoreactivity was present not only in neuronal elements; axons, synapses and cell soma, but also in non-neuronal elements.

  3. The role of intrinsically photosensitive retinal ganglion cells in nonimage-forming responses to light

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    Warthen DM


    Full Text Available Daniel M Warthen,1,2 Ignacio Provencio11Department of Biology, University of Virginia, Charlottesville, VA, USA; 2Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USAAbstract: Light exerts many effects on behavior and physiology. These effects can be characterized as either image-forming or nonimage-forming (NIF visual processes. Image-forming vision refers to the process of detecting objects and organisms in the environment and distinguishing their physical characteristics, such as size, shape, and direction of motion. NIF vision, in contrast, refers to effects of light that are independent of fine spatiotemporal vision. NIF effects are many and varied, ranging from modulation of basal physiology, such as heart rate and body temperature, to changes in higher functions, such as mood and cognitive performance. In mammals, many NIF effects of light are dependent upon the inner retinal photopigment melanopsin and the cells in which melanopsin is expressed, the intrinsically photosensitive retinal ganglion cells (ipRGCs. The ipRGCs project broadly throughout the brain. Many of these projections terminate in areas known to mediate NIF effects, while others terminate in regions whose link to photoreception remains to be established. Additionally, the presence of ipRGC projections to areas of the brain with no known link to photoreception suggests the existence of additional ipRGC-mediated NIF effects. This review summarizes the known NIF effects of light and the role of melanopsin and ipRGCs in driving these effects, with an eye toward stimulating further investigation of the many and varied effects of light on physiology and behavior.Keywords: amygdala, bed nucleus of the stria terminalis, melanopsin, opsin, optic nerve, retina

  4. Differential effects of cocaine on extracellular signal-regulated kinase phosphorylation in nuclei of the extended amygdala and prefrontal cortex of psychogenetically selected Roman high- and low-avoidance rats. (United States)

    Giorgi, Osvaldo; Corda, Maria G; Sabariego, Marta; Giugliano, Valentina; Piludu, Maria A; Rosas, Michela; Acquas, Elio


    Roman high (RHA)- and low (RLA)-avoidance rats are selectively bred for rapid vs. poor acquisition of active avoidance, respectively, and differ markedly in emotional reactivity, coping style, and behavioral and neurochemical responses to morphine and psychostimulants. Accordingly, acute cocaine induces more robust increments in locomotion and dopamine output in the nucleus accumbens shell (AcbSh) of RHA than of RLA rats. Cocaine induces short- and long-term neuronal plasticity via activation of the extracellular signal-regulated kinase (ERK) pathway. This study compares the effects of acute cocaine on ERK phosphorylation (pERK) in limbic brain areas of Roman rats. In RHA but not RLA rats, cocaine (5 mg/kg) increased pERK in the infralimbic prefrontal cortex and AcbSh, two areas involved in its acute effects, but did not modify pERK in the prelimbic prefrontal cortex and Acb core, which mediate the chronic effects of cocaine. Moreover, cocaine failed to affect pERK immunolabeling in the bed nucleus of stria terminalis pars lateralis and central amygdala of either line but increased it in the basolateral amygdala of RLA rats. These results extend to pERK expression previous findings on the greater sensitivity to acute cocaine of RHA vs. RLA rats and confirm the notion that genetic factors influence the differential responses of the Roman lines to addictive drugs. Moreover, they support the view that the Roman lines are a useful tool to investigate the molecular underpinnings of individual vulnerability to drug addiction. © 2014 Wiley Periodicals, Inc.

  5. Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats. (United States)

    Micioni Di Bonaventura, Maria Vittoria; Ubaldi, Massimo; Liberati, Sonia; Ciccocioppo, Roberto; Massi, Maurizio; Cifani, Carlo


    Nociceptin/orphanin FQ (N/OFQ) is a functional antagonist of corticotrophin-releasing factor, the main mediator of the stress response. Stress represents a key determinant of binge eating (BE) for highly palatable food (HPF). In relation to the antistress properties of N/OFQ, we evaluated its effect on BE. After the observation that episodes of food restriction increase the sensitivity to its hyperphagic effects, the function of NOP receptor and N/OFQ was investigated after cycles of food restrictions. In BE experiments, four groups were used: rats fed normally and not stressed or stressed, rats exposed to cycles of restriction/refeeding and then stressed, or not stressed. In the other experiments, two groups were used: rats exposed or not to food restriction. Only restricted and stressed rats exhibited BE for HPF (containing chocolate cream). Intracerebroventricular injections of N/OFQ of 0.5 nmol/rat significantly reduced BE. N/OFQ 1 nmol/rat did not reduce BE but significantly increased HPF intake following food restrictions. Cycles of food restriction increased animals' sensitivity to the hyperphagic effect of N/OFQ for HPF. In situ hybridization studies following food restrictions showed decreased ppN/OFQ mRNA expression in the bed nucleus of the stria terminalis and increased expression of ppN/OFQ and NOP receptor mRNA in the ventral tegmental area and in the ventromedial hypothalamus, respectively. These findings indicate that N/OFQ slightly reduces BE at low doses, while higher doses increase HPF intake, due to increased sensitivity to its hyperphagic effect following a history of caloric restrictions.

  6. Differential visualization of dopamine and norepinephrine uptake sites in rat brain using [3H]mazindol autoradiography. (United States)

    Javitch, J A; Strittmatter, S M; Snyder, S H


    Mazindol is a potent inhibitor of neuronal dopamine (DA) and norepinephrine (NE) uptake. DA and NE uptake sites in rat brain have been differentially visualized using [3H]mazindol autoradiography. At appropriate concentrations, desipramine (DMI) selectively inhibits [3H]mazindol binding to NE uptake sites without significantly affecting binding to DA uptake sites. The localization of DMI-insensitive specific [3H] mazindol binding, reflecting DA uptake sites, is densest in the caudate-putamen, the nucleus accumbens, the olfactory tubercle, the subthalamic nucleus, the ventral tegmental area, the substantia nigra (SN) pars compacta, and the anterior olfactory nuclei. In contrast, the localization of DMI-sensitive specific [3H]mazindol binding, representing NE uptake sites, is densest in the locus coeruleus, the nucleus of the solitary tract, the bed nucleus of the stria terminalis, the paraventricular and periventricular nuclei of the hypothalamus, and the anteroventral thalamus. The distribution of DMI-insensitive specific [3H]mazindol binding closely parallels that of dopaminergic terminal and somatodendritic regions, while the distribution of DMI-sensitive specific [3H]mazindol binding correlates well with the regional localization of noradrenergic terminals and cell bodies. Injection of 6-hydroxydopamine, ibotenic acid, or colchicine into the SN decreases [3H]mazindol binding to DA uptake sites in the ipsilateral caudate-putamen by 85%. In contrast, ibotenic acid lesions of the caudate-putamen do not reduce [3H]mazindol binding to either the ipsilateral or contralateral caudate-putamen. Thus, the DA uptake sites in the caudate-putamen are located on the presynaptic terminals of dopaminergic axons originating from the SN.

  7. Differential visualization of dopamine and norepinephrine uptake sites in rat brain using (/sup 3/H)mazindol autoradiography

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    Javitch, J.A.; Strittmatter, S.M.; Snyder, S.H.


    Mazindol is a potent inhibitor of neuronal dopamine (DA) and norepinephrine (NE) uptake. DA and NE uptake sites in rat brain have been differentially visualized using (/sup 3/H)mazindol autoradiography. At appropriate concentrations, desipramine (DMI) selectively inhibits (/sup 3/H)mazindol binding to NE uptake sites without significantly affecting binding to DA uptake sites. The localization of DMI-insensitive specific (/sup 3/H) mazindol binding, reflecting DA uptake sites, is densest in the caudate-putamen, the nucleus accumbens, the olfactory tubercle, the subthalamic nucleus, the ventral tegmental area, the substantia nigra (SN) pars compacta, and the anterior olfactory nuclei. In contrast, the localization of DMI-sensitive specific (/sup 3/H)mazindol binding, representing NE uptake sites, is densest in the locus coeruleus, the nucleus of the solitary tract, the bed nucleus of the stria terminalis, the paraventricular and periventricular nuclei of the hypothalamus, and the anteroventral thalamus. The distribution of DMI-insensitive specific (/sup 3/H)mazindol binding closely parallels that of dopaminergic terminal and somatodendritic regions, while the distribution of DMI-sensitive specific (/sup 3/H)mazindol binding correlates well with the regional localization of noradrenergic terminals and cell bodies. Injection of 6-hydroxydopamine, ibotenic acid, or colchicine into the SN decreases (/sup 3/H)mazindol binding to DA uptake sites in the ipsilateral caudate-putamen by 85%. In contrast, ibotenic acid lesions of the caudate-putamen do not reduce (/sup 3/H)mazindol binding to either the ipsilateral or contralateral caudate-putamen.

  8. Increased potency and binding of mazindol to putative brain anorectic receptors in obesity-prone rats. (United States)

    Levin, B E; Brown, K L; Vincent, G


    A class of sodium-sensitive, low affinity binding sites in the brain recognizes [3H]mazindol (MAZ). Competition for [3H]MAZ binding at these sites correlates with the anorectic potency of various phenethylamine drugs suggesting that these might be anorectic binding sites. Here [3H]MAZ binding, in the absence of sodium, was assessed by quantitative receptor autoradiography in rat brain. Binding was saturable, widespread and heterogenous with Kd = 3-229 microM and Bmax = 0.64-21.9 nmol/mg protein in various brain areas. By saturation studies, highest binding was in the somatosensory cortex, central amygdalar nucleus and bed nucleus of the stria terminalis. Hypothalamic subnuclei had intermediate and the piriform cortex had low binding. Rats were identified as prone to develop (DIO-prone) or resist (DR-prone) diet-induced obesity by their low vs. high 24 h urine norepinephrine excretion, respectively. While similar in body weight and basal 30 min intake of 4% sucrose, DIO-prone rats had 28% greater inhibition of sucrose intake by 3 mg/kg MAZ, i.p. (86 +/- 5%) than DR-prone rats (67 +/- 6%; P = 0.05). DIO-prone rats also had 23-55% higher levels of 10 nM [3H]MAZ binding in various hypothalamic and amygdalar nuclei, the somatosensory, piriform and gustatory cortices and thalamus. Given their greater sensitivity the highest dose of MAZ used and their higher binding of MAZ to putative brain anorectic receptors, DIO-prone rats might have a deficiency of an endogenous satiety factor which could predispose them to develop obesity when challenged with high energy, high sucrose diets.

  9. Lipopolysaccharide-induced neuronal activation in the paraventricular and dorsomedial hypothalamus depends on ambient temperature.

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    Samuel P Wanner

    Full Text Available Systemic inflammatory response syndrome is associated with either fever or hypothermia, but the mechanisms responsible for switching from one to the other are unknown. In experimental animals, systemic inflammation is often induced by bacterial lipopolysaccharide (LPS. To identify the diencephalic and brainstem structures involved in the fever-hypothermia switch, we studied the expression of c-Fos protein, a marker of neuronal activation, in rats treated with the same high dose of LPS (0.5 mg/kg, intravenously either in a thermoneutral (30 °C or cool (24 °C environment. At 30 °C, LPS caused fever; at 24 °C, the same dose caused profound hypothermia. Both fever and hypothermia were associated with the induction of c-Fos in many brain areas, including several structures of the anterior preoptic, paraventricular, lateral, and dorsal hypothalamus, the bed nucleus of the stria terminalis, the posterior pretectal nucleus, ventrolateral periaqueductal gray, lateral parabrachial nucleus, area postrema, and nucleus of the solitary tract. Every brain area studied showed a comparable response to LPS at the two different ambient temperatures used, with the exception of two areas: the dorsomedial hypothalamic nucleus (DMH, which we studied together with the adjacent dorsal hypothalamic area (DA, and the paraventricular hypothalamic nucleus (PVH. Both structures had much stronger c-Fos expression during LPS hypothermia than during fever. We propose that PVH and DMH/DA neurons are involved in a circuit, which - depending on the ambient temperature - determines whether the thermoregulatory response to bacterial LPS will be fever or hypothermia.

  10. Chemical anatomy of the human ventral striatum and adjacent basal forebrain structures. (United States)

    Prensa, Lucía; Richard, Sandra; Parent, André


    Calbindin D-28k (CB), calretinin (CR), substance P (SP), limbic system-associated membrane protein (LAMP), choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) were used as chemical markers to investigate the organization of the ventral striatum (VST) and adjacent structures in healthy human individuals. No clear boundary could be established between the dorsal striatum and the VST, and the core/shell subdivisions of nucleus accumbens (Acb) could be distinguished only at the midrostrocaudal level of the VST. The CB-poor shell displayed intense immunostaining for SP and CR but only weak staining for LAMP. By contrast, the core was weakly stained for SP and CR and moderately stained for LAMP and CB. There was no difference between shell and core with regard to the cholinergic markers. The Acb harbored numerous ChAT- and CR-immunoreactive cell bodies, the latter being distributed according to a marked, mediolaterally increasing gradient. The size of the ChAT- and CR-immunoreactive perikarya in the Acb varied according to their location in the core and shell. The VST was surrounded by a chemically heterogeneous group of cell clusters referred to as interface islands. The CR-rich caudal portion of the VST merged with the bed nucleus of the stria terminalis dorsally and the diagonal band of Broca ventromedially, the latter two structures displaying complex immunostaining patterns. The claustrum was markedly enriched in LAMP and harbored different types of CR- and CB-immunopositive neurons. These results demonstrate that the neurochemical organization of the human VST is strikingly complex and exhibits a greater heterogeneity than the dorsal striatum. Copyright 2003 Wiley-Liss, Inc.

  11. Oxytocin-Oxytocin Receptor Systems Facilitate Social Defeat Posture in Male Mice. (United States)

    Nasanbuyan, Naranbat; Yoshida, Masahide; Takayanagi, Yuki; Inutsuka, Ayumu; Nishimori, Katsuhiko; Yamanaka, Akihiro; Onaka, Tatsushi


    Social stress has deteriorating effects on various psychiatric diseases. In animal models, exposure to socially dominant conspecifics (i.e., social defeat stress) evokes a species-specific defeat posture via unknown mechanisms. Oxytocin neurons have been shown to be activated by stressful stimuli and to have prosocial and anxiolytic actions. The roles of oxytocin during social defeat stress remain unclear. Expression of c-Fos, a marker of neuronal activation, in oxytocin neurons and in oxytocin receptor‒expressing neurons was investigated in mice. The projection of oxytocin neurons was examined with an anterograde viral tracer, which induces selective expression of membrane-targeted palmitoylated green fluorescent protein in oxytocin neurons. Defensive behaviors during double exposure to social defeat stress in oxytocin receptor‒deficient mice were analyzed. After social defeat stress, expression of c-Fos protein was increased in oxytocin neurons of the bed nucleus of the stria terminalis, supraoptic nucleus, and paraventricular hypothalamic nucleus. Expression of c-Fos protein was also increased in oxytocin receptor‒expressing neurons of brain regions, including the ventrolateral part of the ventromedial hypothalamus and ventrolateral periaqueductal gray. Projecting fibers from paraventricular hypothalamic oxytocin neurons were found in the ventrolateral part of the ventromedial hypothalamus and in the ventrolateral periaqueductal gray. Oxytocin receptor‒deficient mice showed reduced defeat posture during the second social defeat stress. These findings suggest that social defeat stress activates oxytocin-oxytocin receptor systems, and the findings are consistent with the view that activation of the oxytocin receptor in brain regions, including the ventrolateral part of the ventromedial hypothalamus and the ventrolateral periaqueductal gray, facilitates social defeat posture.

  12. Manganese-enhanced magnetic resonance imaging (MEMRI) reveals brain circuitry involved in responding to an acute novel stress in rats with a history of repeated social stress. (United States)

    Bangasser, Debra A; Lee, Catherine S; Cook, Philip A; Gee, James C; Bhatnagar, Seema; Valentino, Rita J


    Responses to acute stressors are determined in part by stress history. For example, a history of chronic stress results in facilitated responses to a novel stressor and this facilitation is considered to be adaptive. We previously demonstrated that repeated exposure of rats to the resident-intruder model of social stress results in the emergence of two subpopulations that are characterized by different coping responses to stress. The submissive subpopulation failed to show facilitation to a novel stressor and developed a passive strategy in the Porsolt forced swim test. Because a passive stress coping response has been implicated in the propensity to develop certain psychiatric disorders, understanding the unique circuitry engaged by exposure to a novel stressor in these subpopulations would advance our understanding of the etiology of stress-related pathology. An ex vivo functional imaging technique, manganese-enhanced magnetic resonance imaging (MEMRI), was used to identify and distinguish brain regions that are differentially activated by an acute swim stress (15 min) in rats with a history of social stress compared to controls. Specifically, Mn(2+) was administered intracerebroventricularly prior to swim stress and brains were later imaged ex vivo to reveal activated structures. When compared to controls, all rats with a history of social stress showed greater activation in specific striatal, hippocampal, hypothalamic, and midbrain regions. The submissive subpopulation of rats was further distinguished by significantly greater activation in amygdala, bed nucleus of the stria terminalis, and septum, suggesting that these regions may form a circuit mediating responses to novel stress in individuals that adopt passive coping strategies. The finding that different circuits are engaged by a novel stressor in the two subpopulations of rats exposed to social stress implicates a role for these circuits in determining individual strategies for responding to stressors

  13. Differential brain-derived neurotrophic factor expression in limbic brain regions following social defeat or territorial aggression. (United States)

    Taylor, Stacie L; Stanek, Lisa M; Ressler, Kerry J; Huhman, Kim L


    Syrian hamsters readily form dominant-subordinate relationships under laboratory conditions. Winning or losing in agonistic encounters can have striking, long-term effects on social behavior, but the mechanisms underlying this experience-induced behavioral plasticity are unclear. The present study tested the hypothesis that changes in brain-derived neurotrophic factor (BDNF) may at least in part mediate this plasticity. Male hamsters were paired for 15-min using a resident-intruder model, and individuals were identified as winners or losers on the basis of their behavior. BDNF was examined with in situ hybridization 2 hr after treatment during the consolidation period of emotional learning. Losing animals had significantly more BDNF mRNA in the basolateral (BLA) and medial (MeA) nuclei of the amygdala when compared with winning animals as well as novel cage and home cage controls. Interestingly, winning animals had significantly more BDNF mRNA in the dentate gyrus of the dorsal hippocampus than did losing animals, novel, and home cage controls. No conflict-related changes in BDNF mRNA were observed in several other regions including the bed nucleus of the stria terminalis and central amygdala. Next, we demonstrated that K252a, a Trk receptor antagonist, significantly reduced the acquisition of conditioned defeat when administered within the BLA. These data support a model in which BDNF-mediated plasticity within the BLA supports learning of submission or subordinate social status in losing animals, whereas BDNF-mediated plasticity within the hippocampus may instantiate aspects of winning such as control of a territory in dominant animals. PsycINFO Database Record (c) 2011 APA, all rights reserved.

  14. Stress-induced changes in the expression of the clock protein PERIOD1 in the rat limbic forebrain and hypothalamus: role of stress type, time of day, and predictability.

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    Sherin Al-Safadi

    Full Text Available Stressful events can disrupt circadian rhythms in mammals but mechanisms underlying this disruption remain largely unknown. One hypothesis is that stress alters circadian protein expression in the forebrain, leading to functional dysregulation of the brain circadian network and consequent disruption of circadian physiological and behavioral rhythms. Here we characterized the effects of several different stressors on the expression of the core clock protein, PER1 and the activity marker, FOS in select forebrain and hypothalamic nuclei in rats. We found that acute exposure to processive stressors, restraint and forced swim, elevated PER1 and FOS expression in the paraventricular and dorsomedial hypothalamic nuclei and piriform cortex but suppressed PER1 and FOS levels exclusively in the central nucleus of the amygdala (CEAl and oval nucleus of the bed nucleus of the stria terminalis (BNSTov. Conversely, systemic stressors, interleukin-1β and 2-Deoxy-D-glucose, increased PER1 and FOS levels in all regions studied, including the CEAl and BNSTov. PER1 levels in the suprachiasmatic nucleus (SCN, the master pacemaker, were unaffected by any of the stress manipulations. The effect of stress on PER1 and FOS was modulated by time of day and, in the case of daily restraint, by predictability. These results demonstrate that the expression of PER1 in the forebrain is modulated by stress, consistent with the hypothesis that PER1 serves as a link between stress and the brain circadian network. Furthermore, the results show that the mechanisms that control PER1 and FOS expression in CEAl and BNSTov are uniquely sensitive to differences in the type of stressor. Finally, the finding that the effect of stress on PER1 parallels its effect on FOS supports the idea that Per1 functions as an immediate-early gene. Our observations point to a novel role for PER1 as a key player in the interface between stress and circadian rhythms.

  15. The organizational effects of oxytocin on the central expression of estrogen receptor α and oxytocin in adulthood

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    Papademetriou Eros


    Full Text Available Abstract Background Previous studies have demonstrated that neonatal manipulation of oxytocin (OT has effects on the expression of estrogen receptor α (ERα and the central production of oxytocin observed in juveniles (at weaning, 21 days of age. The goal of this study was to determine whether the effects of neonatal manipulation of OT last into adulthood, and if the effects differ from those observed during the early postnatal period. On the first day of life, prairie voles (Microtus ochrogaster received one of three doses of OT (High, 3 μg; Med, 0.3 μg; Low, 0.03 μg, an OT antagonist, or isotonic saline. Another group was handled, but not injected. Then as adults, brains were collected, sectioned, and stained for ERα or OT using immunocytochemistry. Results In females, treatment with OT increased the expression of ERα immunoreactivity in the ventral lateral septum (0.03 μg and the ventromedial nucleus of the hypothalamus and central amygdala (0.3 μg. In males, OT antagonist increased ERα expression in the bed nucleus of the stria terminalis. There was no apparent effect of OT on the number of cells producing OT in the paraventricular nucleus of the hypothalamus. Conclusion The current results suggest that neonatal manipulation of OT has long-term organizational effects on the expression of ERα in both males and females. The lack of effect on OT neurons in the paraventricular nucleus suggests that some developmental effects of OT previously observed in weanlings do not persist into adulthood. Developmental effects of OT on ERα patterns were sexually dimorphic, dose-dependent, and site-specific.

  16. Are behavioral effects of early experience mediated by oxytocin?

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    Karen Lisa Bales


    Full Text Available Early experiences can alter adaptive emotional responses necessary for social behavior as well as physiological reactivity in the face of challenge. In the highly social prairie vole (Microtus ochrogaster, manipulations in early life or hormonal treatments specifically targeted at the neuropeptides oxytocin (OT and arginine vasopressin (AVP, have long-lasting, often sexually-dimorphic, consequences for social behavior. Here we examine the hypothesis that behavioral changes associated with differential early experience, in this case handling the family during the first week of life, may be mediated by changes in OT or AVP or their brain receptors. Four early treatment groups were used, differing only in the amount of manipulation received during the first week of life. MAN1 animals were handled once on post-natal day 1; MAN1 treatment produces a pattern of behavior usually considered typical of this species, against which other groups were compared. MAN 1-7 animals were handled once a day for post-natal days 1-7, MAN 7 animals were handled once on post-natal day 7, and MAN0 animals received no handling during the first week of life. When tested following weaning, males in groups that had received manipulation during the first few days of life (MAN1 and MAN1-7 displayed higher alloparenting than other groups. Neuroendocrine measures, including OT receptor binding and OT and AVP immunoreactivity, varied by early treatment. In brain areas including the nucleus accumbens, bed nucleus of stria terminalis and lateral septum, MAN0 females showed increased OT receptor binding. MAN1 animals also displayed higher numbers of immunoreactive OT cell bodies in the supraoptic nucleus. Taken together these findings support the broader hypothesis that experiences in the first few days of life, mediated in part by sexually-dimorphic changes in neuropeptides, especially in the receptor for OT, may have adaptive consequences for sociality and emotion regulation.

  17. Alcohol consumption increases locomotion in an open field and induces Fos-immunoreactivity in reward and approach/withdrawal-related neurocircuitries. (United States)

    Wscieklica, Tatiana; de Barros Viana, Milena; Le Sueur Maluf, Luciana; Pouza, Kathlein Cristiny Peres; Spadari, Regina Célia; Céspedes, Isabel Cristina


    Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take the drug, loss of control in limiting intake and, eventually, the emergence of a negative emotional state when access to the drug is prevented. Both dopamine and corticotropin-releasing factor (CRF)-mediated systems seem to play important roles in the modulation of alcohol abuse and dependence. The present study investigated the effects of alcohol consumption on anxiety and locomotor parameters and on the activation of dopamine and CRF-innervated brain regions. Male Wistar rats were given a choice of two bottles for 31 days, one containing water and the other a solution of saccharin + alcohol. Control animals only received water and a solution of 0.2% saccharin. On the 31st day, animals were tested in the elevated plus-maze and open field, and euthanized immediately after the behavioral tests. An independent group of animals was treated with ethanol and used to measure blood ethanol concentration. Results showed that alcohol intake did not alter behavioral measurements in the plus-maze, but increased the number of crossings in the open field, an index of locomotor activity. Additionally, alcohol intake increased Fos-immunoreactivity (Fos-ir) in the prefrontal cortex, in the shell region of the nucleus accumbens, in the medial and central amygdala, in the bed nucleus of the stria terminalis, in the septal region, and in the paraventricular and dorsomedial hypothalamus, structures that have been linked to reward and to approach/withdrawal behavior. These observations might be relevant to a better understanding of the behavioral and physiological alterations that follow alcohol consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Collating and Curating Neuroanatomical Nomenclatures: Principles and Use of the Brain Architecture Knowledge Management System (BAMS). (United States)

    Bota, Mihail; Swanson, Larry W


    Terms used to describe nervous system parts and their interconnections are rife with synonyms, partial correspondences, and even homonyms, making effective scientific communication unnecessarily difficult. To address this problem a new Topological Relations schema for the Relations module of BAMS (Brain Architecture Knowledge Management System) was created. It includes a representation of the qualitative spatial relations between nervous system parts defined in different neuroanatomical nomenclatures or atlases and is general enough to record data and metadata from the literature, regardless of description level or species. Based on this foundation a Projections Translations inference engine was developed for the BAMS interface that automatically translates neuroanatomical projection (axonal inputs and outputs) reports across nomenclatures from translated information. To make BAMS more useful to the neuroscience community three things were done. First, we implemented a simple schema for validation of the translated neuroanatomical projections. Second, more than 1,000 topological relations between brain gray matter regions for the rat were inserted, along with associated details. Finally, a case study was performed to enter all historical or legacy published information about terminology related to one relatively complex gray matter region of the rat. The bed nuclei of the stria terminalis (BST) were chosen and 21 different nomenclatures from 1923 to present were collated, along with 284 terms for parts (gray matter differentiations), 360 qualitative topological relations between parts, and more than 7,000 details about spatial relations between parts, all of which was annotated with appropriate metadata. This information was used to construct a graphical "knowledge map" of relations used in the literature to describe subdivisions of the rat BST.

  19. Conditioned fear inhibits c-fos mRNA expression in the central extended amygdala. (United States)

    Day, Heidi E W; Kryskow, Elisa M; Nyhuis, Tara J; Herlihy, Lauren; Campeau, Serge


    We have shown previously that unconditioned stressors inhibit neurons of the lateral/capsular division of the central nucleus of the amygdala (CEAl/c) and oval division of the bed nucleus of the stria terminalis (BSTov), which form part of the central extended amygdala. The current study investigated whether conditioned fear inhibits c-fos mRNA expression in these regions. Male rats were trained either to associate a visual stimulus (light) with footshock or were exposed to the light alone. After training, animals were replaced in the apparatus, and 2 h later injected remotely, via a catheter, with amphetamine (2 mg/kg i.p.), to induce c-fos mRNA and allow inhibition of expression to be measured. The rats were then presented with 15 visual stimuli over a 30 minute period. As expected, fear conditioned animals that were not injected with amphetamine, had extremely low levels of c-fos mRNA in the central extended amygdala. In contrast, animals that were trained with the light alone (no fear conditioning) and were injected with amphetamine had high levels of c-fos mRNA in the CEAl/c and BSTov. Animals that underwent fear conditioning, and were re-exposed to the conditioned stimulus after amphetamine injection had significantly reduced levels of c-fos mRNA in both the BSTov and CEAl/c, compared to the non-conditioned animals. These data suggest that conditioned fear can inhibit neurons of the central extended amygdala. Because these neurons are GABAergic, and project to the medial CEA (an amygdaloid output region), this may be a novel mechanism whereby conditioned fear potentiates amygdaloid output.

  20. [Exploring life-experience of the staff and volunteers assisting pediatric patients in end-of-life situations] [Article in Italian] • I vissuti dello staff e dei volontari che assistono pazienti pediatrici terminali

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    Rosapia Lauro Grotto


    Full Text Available The development of guidelines for palliative care in the paediatric settings is judged to be still incomplete and characterized by many controversial issues; in order to explore the life-experience of individual health care professionals, we proposed a semi-structured questionnaire with open questions on end-of-life procedures to the staff members of the Paediatric Onco-hematology Ward of the University of Padua, of the Oncology Ward and in the Home Assistance Module of the Giannetta Gaslini Hospital, Genoa, both in Italy. This paper will focus on the responses provided to the third question: “In your opinion, can inducing the suspension of the state of consciousness be counted among end-of-life procedures? If so, how and when?”. Staff members were found to face challenging interactions at at least three levels: within the professional team, with respect to the parents and with respect to the adolescent patients. Among the most complex issues raised by the participants we found the moral distress sometimes experienced by nurses with respect to the decisions assumed by doctors, as stated by a nurse: “Everything is subjective in those 24 hours  (… and you are to do or not do certain things and it makes you feel distressed”. Second, it emerged that the relationship with the parents becomes very challenging when the two are not in agreement: “The father wants to give the morphine, but the mother secretly closes the drip”. Finally, the relationship of trust with the adolescent patients is under threat when they ‘want to know’ while parents seem to be unable to tolerate this degree of painful but essential self-consciousness in their ‘child’: “He locked me in the room and asked, ‘Am I dying?’, and I wanted to die at that point…”. Our study shows that health care professionals require not just guidelines but a tailor-made training and support which integrate much deeply the therapeutic as well as the moral and philosophical approaches to the issues raised by palliative care in paediatric settings.Articoli Selezionati del Congresso “Medicina Narrativa e Comunicazione nella Pratica Clinica” ·  Cagliari · 14 Aprile 2014 Guest Editors: Massimiliano Zonza, Vassilios Fanos, Gian Paolo Donzelli


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    Kathyana Vanessa Diniz Santos


    Full Text Available Existem nuances no conceito de arranjos produtivos locais (APL’s que nem sempre são percebidas e compreendidas quando da aplicação prática. Neste trabalho, foram apresentadas e analisadas as nuances existentes com o objetivo de verificar se a utilização do termo APL adotado pelo Sebrae em seus projetos é congruente com a literatura acadêmica. Como método tem-se um estudo de caso, visto que registrado no órgão existe um único projeto de APL ativo e em gestão (em maio de 2015 de acordo com o SIGEOR (Sistema de Informação da Gestão Estratégica Orientada para Resultados do próprio Sebrae/PB. O APL analisado foi o da Indústria de Calçados do Estado da Paraíba, com base nos elementos cruciais constituintes de um APL e concluiu-se que este arranjo não apresenta todos os elementos necessários para ser considerado um APL e assim, o Sebrae necessita rever o termo utilizado, não só para corrigir uma divergência conceitual em relação a literatura da academia, mas também para otimizar os processos existentes na própria organização.


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    Miguel Maurício Isoni


    Full Text Available Este artigo procura mostrar a pertinência de parâmetros e atributos de gestão reputacional percebidos pelos consumidores das marcas Fiat e Volks da indústria automobilística brasileira, através de quatro dimensões: (1 imagem, reputação e credibilidade; (2 relação com a comunidade; (3 ética e sustentabilidade; (4 decisão de compra ou recompra. Reputação corporativa tem sido tema mundialmente estudado e de grande importância para empresas e para a academia. Visando a mensurar a reputação corporativa, este estudo desenvolve uma escala de reputação baseada em Fombrun, Gardberg e Sever (2001 e King (2000. Com uma amostra de 316 respondentes de dois Estados brasileiros, buscando verificar a reputação da indústria automobilística, foi verificada a confiabilidade da escala, bem como traçados mapas perceptuais para análise dos resultados. Assim, este trabalho contribui para o desenvolvimento de uma escala brasileira de reputação corporativa e para a utilização de mapas perceptuais como instrumento gerencial e analítico.


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    Michelle Cristine Silveira Meireles


    Full Text Available Normal 0 21 false false false PT-BR X-NONE X-NONE MicrosoftInternetExplorer4 Resumo O presente artigo aborda questões relacionadas a estratégias de planejamento, negociação e marketing utilizadas por uma empresa na área têxtil. A realização da pesquisa pautou-se em um estudo de caso, a partir de entrevistas semi-estruturadas e consultas a materiais institucionais. As abordagens teóricas utilizadas no corpo da pesquisa são aplicadas no estudo no intuito de embasar a compreensão do fenômeno estudado. A empresa trabalha com produto de qualidade, bons preços, tendo seu maior problema localizado no capital de giro. Na realização de uma análise organizacional mais detalhada, pesquisa direta com clientes e arrolamento de novas táticas de atuação, percebeu-se que houve por parte da empresa pesquisada uma ampliação à visão de mercado abrindo caminhos e potenciais possibilidades para uma nova atuação de mercado. Assim, o estudo revelou que a empresa deve implantar um conjunto de políticas empresariais de modo agressivo e interativo dentro de suas possibilidades e limitações tanto com os consumidores/clientes quanto no mercado em que atua.    Palavras-chave: Estratégia; Indústria Têxtil; Negociação.   Abstract The present paper approach questions related to planning, negotiation and marketing strategies carried by a textile industry enterprise. The search was based in a study of case, by semi-structured interviews and institutional document analyses. The theoric base utilized in the search was applied in sense to embased the comprehension of studied phenomenon. The enterprise play with quality product, low prices, and the major problem was in turnover capital. In the realization of a detailed organizational analyses, costumers direct search and inventore of new tatics of atuation, was perceived the occurrence of a market sense improve, leading the enterprise to new market perspectives. By this way, the study show that the organization should implant a conjoint of enterprise policies by intense and interactive way considering yours possibilities and limitations about consumers/costumers as in your market.   Keywords: Strategy; Textile Industry; Negotiation.


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    Glayce Cassaro Pereira


    Full Text Available Nos últimos anos houve um grande avanço tecnológico no desenvolvimento de materiais compósitos reforçados com fibras naturais. Esse aumento do interesse das indústrias e grupos de pesquisa em desenvolver e utilizar materiais feitos a partir de matérias primas renováveis se deu principalmente pelo grande apelo mundial para a utilização de produtos naturais e pela preservação do meio ambiente. O presente trabalho visou a caracterização de compósitos reforçados com bagaço de cana em matriz de poliestireno de alto impacto (HIPS, tendo como objetivo uma possível substituição dos materiais utilizados atualmente na indústria de produtos para pet shop. Foram caracterizadas três famílias de compósitos, nas proporções de 10, 20 e 30% (m/m. Os resultados da dureza Shore A indicaram que a adição da fibra de bagaço ao HIPS não acarretou alterações nos valores da dureza nos compósitos quando comparados ao HIPS puro. E os resultados de resistência ao impacto foi possível constatar que a adição da fibra de bagaço ao HIPS acarretou uma diminuição na resistência ao impacto, quando comparados ao HIPS puro.


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    Gabriela Teixeira


    Full Text Available The apparel industry and their production processes generate serious impacts on the environment. This paper proposes a methodology to measure environmental impacts in a garment industry midsize Recife / PE. There are guidelines which the Design for Sustainability and Systems and Tools for Environmental Management were relevant to the search. This allowed mapping production processes and to analyze and measure the impacts generated by the creation and production of designitems. The aim is thus to encourage designers to seek to minimize the degradation caused by the production of Fashion Design.



    Gilmara Brandão Pereira; Glayce Cassaro Pereira; Márcio Alves de Lima; Sérgio Roberto Montoro


    Existe uma tendência mundial em buscar recursos naturais alternativos em substituição às fibras sintéticas. Diante deste cenário, as fibras naturais vegetais, como por exemplo, a fibra da casca do coco verde, é uma excelente alternativa por possuírem boas propriedades mecânicas e térmicas. Essas fibras, além de seu baixo custo, são biodegradáveis e de fonte renovável. No presente trabalho foram caracterizados compósitos poliméricos de HIPS reforçados com fibras naturais provenientes da casca ...


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    Gilmara Brandão Pereira


    Full Text Available Existe uma tendência mundial em buscar recursos naturais alternativos em substituição às fibras sintéticas. Diante deste cenário, as fibras naturais vegetais, como por exemplo, a fibra da casca do coco verde, é uma excelente alternativa por possuírem boas propriedades mecânicas e térmicas. Essas fibras, além de seu baixo custo, são biodegradáveis e de fonte renovável. No presente trabalho foram caracterizados compósitos poliméricos de HIPS reforçados com fibras naturais provenientes da casca do coco verde. Foram caracterizadas três famílias de compósitos, nas proporções de 10, 20 e 30% (m/m. Foi possível constatar que a adição da fibra de coco ao HIPS acarretou uma diminuição na resistência ao impacto, quando comparados ao HIPS puro. Dessa forma, com a adição de fibras de coco verde no HIPS obteve-se um material com até 30% menos polímero e com propriedades mecânicas viáveis para determinadas aplicações do HIPS.


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    Ana Carolina RITTER


    Full Text Available

    Embora a presença de bactérias seja esperada em águas minerais naturais, contaminações elevadas podem ocorrer e comprometer sua qualidade e segurança. O objetivo deste trabalho foi avaliar a qualidade microbiológica de amostras de água mineral natural e de tampas plásticas utilizadas em uma indústria localizada na grande Porto Alegre/RS. Foram analisadas 152 amostras de água do poço e 15 amostras de água envasada em garrafões de 20 litros, utilizando-se as técnicas de membrana fi ltrante e “pour plate”. Os microrganismos pesquisados foram aqueles preconizados pela RDC 275/2005, da ANVISA, além da contagem total de microrganismos heterotrófi cos. O número de microrganismos heterotrófi cos também foi analisado em 22 tampas plásticas de garrafões de 20 litros. Os resultados demonstraram que em nenhuma amostra foi detectada a presença de coliformes totais, coliformes fecais/ Escherichia coli, Enterococcus spp., Pseudomonas aeruginosa e Clostridium perfringens. Todas as amostras analisadas continham microrganismos viáveis, sendo que as contagens de microrganismos heterotrófi cos variaram de 1,0x10¹UFC/mL a 7,0x103UFC/mL. As tampas plásticas apresentaram contagens que variaram de 6,0x10¹UFC/ mL a 1,2x10²UFC/mL e essa contaminação representou aproximadamente 0,003 a 0,006% das contagens totais obtidas nos garrafões analisados. Os resultados indicaram que a água mineral natural estava dentro dos padrões exigidos pela legislação brasileira, além de demonstrar que a avaliação microbiológica foi importante como ferramenta para a melhoria dos processos empregados pela indústria em questão.


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    Jose Dutra Oliveira Neto


    Full Text Available O investimento para implementação de um sistema ERP é muito alto e a satisfação do usuário pode ser usada como um substituto para o sucesso da implementação do ERP. A satisfação do usuário é uma das formas de mensuração mais comuns encontradas na literatura para medir o sucesso do ERP. Um instrumento (escala de 5 pontos tipo Likert para mensurar a satisfação do usuário foi desenvolvido com 33 itens e 12 dimensões. Uma amostra de 81 respondentes, coletada por meio de um levantamento, em uma empresa farmacêutica no Brasil foi utilizada nesta pesquisa. Usando análise multivariada, os resultados desta pesquisa indicam a importância da satisfação do usuário, em todas as áreas da pesquisa, para o sucesso do ERP. Sugere ainda que a satisfação do usuário, quando desmembrada em 12 dimensões, pode ser base para um diagnóstica eficaz para implementação de um ERP. Os respondentes identificaram que em algumas áreas, como a Fiscal, não estão satisfeitos com ao menos uma dimensão relativos ao sistema ERP. Este resultado pode ajudar os gestores a realizarem ajustes localizados no ERP e/ou treinamentos específicos em algumas áreas, aumentando as chances de sucesso do sistema ERP.


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    Duvan Emilio Ramírez Ospina


    Full Text Available En este escrito se analiza el manejo de la emocionalidad en las estrategias de mercadeo en empresas del sector funerario, destacando el carácter contextual y ambiental del marketing dentro de la cultura como base permeable de la sociedad, sus hábitos, costumbres y rituales. Se partió de un estudio cualitativo usando entrevistas en profundidad y observación; se hizo un acercamiento teórico al marketing emocional y se muestran las relaciones encontradas entre este y las estrategias de mercadeo que están siendo usadas por las empresas funerarias.  Identificando el manejo de la emocionalidad implementado en el sector funerario por medio de “talleres de duelo”; eventos post-mortem de carácter masivo, donde los dolientes asisten a charlas programadas cada tres meses. Este tipo de eventos  por su periodicidad, asisten un número elevado de personas, dificultando que la experiencia sea individual, detallada y que facilite un contacto directo entre el cliente y la empresa.


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    Antonio S BREJÃO


    Full Text Available esfera da ecologia industrial. A proposta deste trabalho é analisar as características deste resíduo, objetivando o fechamento do ciclo de produção. O pó de silício obtido através do processo do corte das lâminas de silício foi caracterizado por ensaios físicos e por microscopia ótica. Após a separação, o resíduo foi adicionado ao cimento comum formando corpos de prova e com isso, avaliou-se o possível ganho na resistência à compressão comparada ao cimento comum, comprovando a viabilidade técnica da utilização deste tipo de resíduo na fabricação de produtos de cimento.


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    Juliane Ruffatto


    Full Text Available A inovação tem ganhado ênfase no cenário empresarial nos últimos anos, haja vista a sobrevivência no mercado. As empresas têm investido cada vez mais nessa área e na capacitação de pessoal para o desenvolvimento de novos produtos. Desse modo, este artigo trata-se de um estudo de caso realizado em uma indústria metal mecânica da região norte do Rio Grande do Sul que inovou o seu portfólio de produtos nos últimos anos. Essa inovação foi bastante motivada pelas ideias criativas e audaciosas de seus colaboradores, que, majoritariamente, são jovens, alguns deles em cargos de gestão. Assim, o objetivo é identificar as características da gestão da geração Y que contribuem para a inovação de produto, bem como a sua importância para a performance organizacional. Para cumprir com o objetivo proposto, utilizou-se o método qualitativo. Os dados foram coletados a partir de entrevistas, do tipo semiestruturada, com questões abertas, voltadas à identificação das características da Geração Y e como elas contribuem para a inovação na empresa em estudo. As entrevistas foram realizadas no mês de junho de 2015 e analisadas pela técnica de análise de conteúdo. Os resultados evidenciam que o perfil da empresa é bastante inovador e que é unânime a importância dada para o investimento em tecnologia e o desenvolvimento de novos produtos. As características mais importantes dos jovens da geração Y que contribuem para a inovação de produto na empresa é a criatividade, o espírito inventivo, a ambição e o dinamismo.


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    Leandro Kappes


    Full Text Available Tendo em vista que, com a globalização, as tecnologias de produção tornaram-se acessíveis à grande maioria das empresas, estas, para permanecerem no mercado e apresentar um diferencial competitivo, tiveram que investir fortemente no "talento humano", ou seja, na capacitação e desenvolvimento de seus funcionários. Neste sentido, o presente trabalho tem como objetivo relatar o processo de capacitação de um Fundidor de Barbotina, tendo como base o desenvolvimento das competências essenciais para desempenho desta função. Trata-se de um estudo de caso desenvolvido com uma metodologia qualitativa, no qual se pesquisou uma indústria de cerâmica triaxial. Através da análise dos resultados, demonstra-se a eficácia do processo de capacitação, bem como a colaboração deste nos resultados da empresa, evidenciados pelo aumento de produtividade e qualidade. É possível verificar, ainda, que, na empresa em estudo, há um alinhamento entre a teoria e a prática sobre o assunto, tendo em vista que o projeto Centro de Formação promoveu mudanças significativas no comportamento das pessoas. Palavras-chave: Conhecimento. Habilidade. Atitude. Competência. Capacitação.



    Priscila Cembranel


    Este trabalho busca conhecer as tendências da gestão participativa para redução de falhas no nível operacional nos sistemas produtivos em indústrias metalúrgicas. Para identificar as tendências da gestão participativa nas indústrias metalúrgicas objetivou-se levantar as estratégias de gestão participativa de acordo com gestores de produção, relacionar as práticas adotadas frente à redução de falhas inerentes aos processos produtivos e analisar os desafios em estratégias de gest...



    Franco, Letícia; Bilotta, Patrícia


    A água para fabricação de fármacos demanda qualidade rigorosa, por isso requer sucessivas etapas de purificação para atender as determinações da legislação brasileira. Da mesma forma, o efluente gerado no processo produtivo também exige tratamento antes do seu descarte em corpos d'água. O monitoramento da qualidade da água e do efluente industrial é realizado por meio de análises laboratoriais, em muitos casos, por laboratórios terceirizadas a um custo elevado. O objetivo deste artigo é ident...



    Luciano Daniel de Souza BARBOSA; João Guilherme de Camargo Ferraz MACHADO


    O objetivo da pesquisa foi analisar as ações realizadas pelas empresas de defensivos, visando fomentar o uso de EPI por parte dos agricultores. Buscou-se descrever e analisar os programas de três empresas fabricantes de defensivos agrícolas para fomentar o uso dos equipamentos de proteção individual (EPI), e compará-los. As empresas, multinacionais de defensivos agrícolas, foram selecionadas com base no faturamento. Os resultados foram obtidos a partir de material disponibilizado nos sites da...



    Alexsandra Matos Romio


    Com a necessidade de conhecer os estoques de forma cada vez mais precisa, a fim de planejar as vendas e a produção com o dinamismo que o mercado exige, mais empresas têm buscado ferramentas de controle de estoque, como sistemas informatizados, almejando resultados com alta precisão e confiabilidade. A incerteza de resultados positivos, nesse tipo de investimento, especialmente para metalúrgicas de pequeno porte, é uma incógnita, já que os recursos de pessoal e financeiro são ...


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    Marilise Dorneles Spat


    Full Text Available O objetivo desse artigo é descrever o comportamento da indústria de máquinas e implementos agrícolas (IMA no Brasil e nos principais pólos produtores, sendo eles Rio Grande do Sul (RS e São Paulo (SP, após a liberalização econômica e a estabilização monetária a partir de meados da década de 1990. A metodologia empregada foi a análise dos indicadores técnicos e econômicos da indústria, como: MCO (margem de custo de operação, MCM (margem de custo de matéria-prima, MCT (margem de custo do trabalho, MCP (margem de custo da produção, PT (produtividade do trabalho, MOE (margem operacional do excedente, LP (lucro da produção e mark-up. As fontes bibliográficas empregadas foram publicações especializadas da indústria, dados da FEE (Fundação de Economia e Estatística, da PIA (Pesquisa Industrial Anual do IBGE (Instituto Brasileiro de Geografia e Estatística, entre outros. Utilizou-se a classificação 29.3 do CNAE (Código Nacional de Atividade Econômica, correspondente à IMA. Como conclusões, observou-se que a indústria em questão passou por fortes oscilações e por mudanças no período analisado, além da sua elevada integração e competitividade, especialmente com os mercados dos Estados Unidos e da Europa.


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    Juliano BARRETO


    Full Text Available Este trabalho procurou avaliar a eficácia da aplicação da Análise de Perigos e Pontos Críticos de Controle (APPCC como ferramenta de qualidade na prevenção de contaminação por mofos e leveduras, em um processo produtivo em escala industrial de doce de leite. Essa ferramenta que a princípio foi desenvolvida pelo setor privado, atualmente faz parte da legislação de diversos países. Para isso foram avaliados dados da produção de uma fábrica de laticínio de Bom Jesus do Itabapoana, Noroeste do estado Rio de Janeiro, que processa em média cinquenta mil litros de leite por dia. Realizou-se uma pesquisa bibliográfica a respeito do APPCC e de sua implantação como ferramenta de qualidade que garantiu o suporte teórico. O estudo mostra a eficácia dessa ferramenta de qualidade na prevenção de contaminação por mofos e leveduras, para isso, foi realizada uma análise qualitativa e quantitativa nos registros de acompanhamento microbiológico do laticínio.


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    Mariana Provedel Martins


    Full Text Available RESUMO Este trabalho teve por objetivo avaliar briquetes produzidos a partir de finos de carvão vegetal compactados com resíduo celulósico gerado na decantação dos efluentes da indústria de papel e celulose. Foram realizados os seguintes tratamentos: briquetes produzidos com fino de carvão vegetal e resíduo celulósico nas proporções de 25% (T1, 30% (T2, 35% (T3, 40% (T4 e 45% (T5 e briquetes produzidos com finos de carvão vegetal com 10% de amido e resíduo celulósico nas proporções de 0% (T6, 5% (T7, 10% (T8, 15% (T9, 20% (T10 e 25% (T11. A caracterização dos briquetes foi realizada por meio de ensaios de análise química imediata, determinação do poder calorífico superior, densidade aparente e avaliação da resistência mecânica após a secagem dos briquetes em estufa ou ao ar livre. Observou-se que os briquetes com resíduo celulósico e amido em sua composição apresentaram maior densidade e resistência mecânica à compressão, concluindo-se, assim, que a presença do amido favoreceu a compactação e estabilidade dos briquetes. Observou-se, também, que o processo de secagem em estufa prejudicou a qualidade dos briquetes, de modo que a secagem ao ar livre forneceu briquetes mais resistentes e estáveis.



    Duvan Emilio Ramírez Ospina; Lina María Toro Gonzales; Carolina Duarte Pareja


    En este escrito se analiza el manejo de la emocionalidad en las estrategias de mercadeo en empresas del sector funerario, destacando el carácter contextual y ambiental del marketing dentro de la cultura como base permeable de la sociedad, sus hábitos, costumbres y rituales. Se partió de un estudio cualitativo usando entrevistas en profundidad y observación; se hizo un acercamiento teórico al marketing emocional y se muestran las relaciones encontradas entre este y las estrategias de mercadeo ...


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    Pedro Paulo Silva Leite


    Full Text Available O presente trabalho teve como objetivo geral analisar os benefícios ambientais e econômicos obtidos através da implementação da Produção mais Limpa (P+L em uma indústria de móveis localizada em Natal-RN. Trata-se de um estudo de caso que contou com uma revisão bibliográfica sobre o setor e a P+L e uma pesquisa de campo que contemplou as seguintes etapas: diagnóstico ambiental e operacional da empresa (estudo de arranjo físico, levantamento de métodos, fluxograma especifico do processo produtivo, levantamento de aspectos e impactos; levantamento de desperdícios; estudo de oportunidades de melhorias; implementação e monitoramento. Os resultados do diagnostico mostram desperdícios representativos de insumos (MDF, cola, lixa, etc, além da desorganização do espaço físico da empresa, insalubridade do galpão de produção. Assim, foram implementadas algumas medidas de otimização do uso de MDF, cola, lixa, além da implementação de um sistema de coleta de serragem e sistematização da produção, além do reaproveitamento de aparas de MDF para fabricação de chapas recicladas. Nesse contexto, as oportunidades de melhoria ambiental contemplaram os níveis 1 (redução na fonte e nível 2 (reciclagem interna acarretando na otimização do uso de recursos e a diminuição da poluição gerada, trazendo um alavancar uma receita anual para empresa aproximadamente em R$ 3.600 a partir de um investimento de R$ 4311, tendo um período de retorno não superior à 2 anos em cada estudo. Por fim, verifica-se que com a implementação das atividades vislumbradas é possível alcançar uma economia significativa nos gastos da empresa além dos benefícios operacionais como melhoria do ambiente de trabalho e mudanças benéficas no quesito meio ambiente através da diminuição do consumo de matéria prima e da geração de resíduos.


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    Jean Cristhiano Franco


    Full Text Available O desenvolvimento de novos projetos na industria automotiva apresenta-se como um projeto de grande porte, regido por metodologias, guias e ferramentas estruturadas que visam garantir a eficácia do projeto. Esta pesquisa foi desenvolvida com o intuito de contribuir para um maior entendimento entre a ferramenta APQP, de grande aplicação na industria automotiva, e o guia PMBOK, considerado referência no gerenciamento de projetos. Neste âmbito, este estudo realiza uma análise comparativa entre suas principais características, identificando suas semelhanças e divergências. Dentre os diversos resultados do estudo, é possível identificar que o guia PMBOK é mais completo que a ferramenta APQP utilizada no setor automobilístico, uma vez que traz de forma mais detalhada as etapas e as técnicas que são indicadas nas atividades, segundo as boas práticas dos PMPs (Project Management Professional.


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    Maique Antônio Rodrigues


    Full Text Available Esta pesquisa possui como principal foco a gestão de projetos associada ao desenvolvimento de novos produtos da indústria aeronáutica, destacando-se em especial a importância e eficiência dos processos de manufatura. A análise realizada tomou por base um questionário com os 47 processos disseminados pelo PMBOK, uma coleção de processos e conhecimentos aceitos como melhores práticas na área de gerenciamento de projetos. 20 profissionais com larga experiência no setor aeronáutico responderam à pesquisa e os dados foram tratados estatisticamente por meio das técnicas de Escalonamento Multidimensional e Análise Fatorial Exploratória para um único fator. Os resultados evidenciaram que os dez processos de maior importância estão associados às seguintes temáticas: 1º Desenvolver a equipe do projeto, 2º Controlar a qualidade, 3º Determinar o orçamento, 4º Conduzir as aquisições, 5º Controlar os riscos, 6º Identificar os riscos, 7º Planejar o gerenciamento de custos, 8º Gerenciar a equipe do projeto, 9º Planejar o gerenciamento das aquisições e 10º Planejar o gerenciamento de riscos. Apesar de bons resultados globais para os níveis de eficiência para os processos anteriores, observam-se ainda possibilidades de melhoria para a empresa estudada.


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    CATÃO Raïssa Mayer Ramalho


    Full Text Available Investigou-se a qualidade microbiológica do leite in natura e na linha de produção (leite recém-pasteurizado e leite ensacado, de uma usina de beneficiamento em Campina Grande-PB. Foi pesquisada a presença de Listeria spp. e sua diversidade de espécies, os níveis de coliformes totais (CT, coliformes fecais (CF e Escherichia coli. Analisou-se um total de 75 amostras de leite, sendo 45 de leite cru, 15 de leite recém-pasteurizado e 15 de leite ensacado. Os resultados foram reunidos em dois grupos segundo o período de monitoramento: antes e após mudanças no processo de higienização da usina. Foi evidenciada elevada contaminação nas amostras de leite cru nas duas épocas. Na primeira (março-abril/1998, todas as amostras de leite beneficiado estiveram fora dos padrões da legislação vigente para CT e CF; na segunda (maio-agosto/1998, houve acentuada redução dos níveis destas bactérias indicadoras, porém as melhorias na higienização não foram suficientes para solucionar este problema, visto que 11,1% das amostras recém-pasteurizadas estavam fora dos padrões para CT e 33,3% para CF. Das amostras ensacadas, 22,2% estavam fora dos padrões para CT e 44,4% para CF. Comparando-se os resultados de CT, CF, e E.coli nas amostras de leite recém-pasteurizado e não ensacado com as amostras de leite ensacado, foi verificado que as amostras após serem pasteurizadas e ensacadas apresentaram valores de CT e CF levemente mais elevados, sugerindo contaminação durante o processo de ensacamento ou falhas na armazenagem. Observou-se que 33 (73,3% das amostras de leite cru e 9 (30% das de leite pasteurizado estavam contaminadas com Listeria spp., sendo identificadas L. monocytogenes em 17 (51,5% amostras de leite cru e em 9 (100% de leite beneficiado (4 recém-pasteurizadas e 5 ensacadas. Em relação à diversidade de espécies, nas amostras de leite cru foram encontradas: L. monocytogenes (66,6%, L. innocua (25,3%, L. ivanovii (3,9%, L. welshimeri (2,5% e L. grayi (1,5%. Nas amostras de leite pasteurizado isolaram-se: L. monocyogenes e L. innocua. O conjunto dos resultados evidenciou deficiências higiênico-sanitárias no leite in natura e ao longo do processo de produção, resultando em porcentagens elevadas de amostras que ultrapassaram os valores padrões de CT e CF além de apresentarem-se contaminadas por Listeria spp., com predominância de L. monocytogenes, sugerindo a existência de uma relação direta entre os altos índices de coliformes e a presença de Listeria spp.

  6. Gazprom tõrjub võimalikku konkurenti / Vahur Koorits

    Index Scriptorium Estoniae

    Koorits, Vahur, 1981-


    Eesti põhjarannikule kavandatud veeldatud maagaasi ehk LNG terminali ees seisab rida takistusi, suurimaks probleemiks on Gazprom. Vt. samas: Veeldatud maagaasi terminal annaks sõltumatuse Gazpromist

  7. Перемещение частных пространств = Transporting private spaces / Тоомас Паавер ; интервьюировал Владимир Фролов

    Index Scriptorium Estoniae

    Паавер, Тоомас, 1976-


    Tallinna linna tasuta ühistranspordist, transpordisüsteemi puudustest ja arengusuundadest. PAIK Arhitektide (Toomas Paaver, Jaak-Adam Looveer, Lauri Saar) Kristiine terminali projektist, jalgrattateedest

  8. Patterns of Brain Activation and Meal Reduction Induced by Abdominal Surgery in Mice and Modulation by Rikkunshito.

    Directory of Open Access Journals (Sweden)

    Lixin Wang

    Full Text Available Abdominal surgery inhibits food intake and induces c-Fos expression in the hypothalamic and medullary nuclei in rats. Rikkunshito (RKT, a Kampo medicine improves anorexia. We assessed the alterations in meal microstructure and c-Fos expression in brain nuclei induced by abdominal surgery and the modulation by RKT in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access to food for 6-7 h and were treated twice with RKT or vehicle. Abdominal surgery (laparotomy-cecum palpation was performed 1-2 h before the dark phase. The food intake and meal structures were monitored using an automated monitoring system for mice. Brain sections were processed for c-Fos immunoreactivity (ir 2-h after abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency, size and duration, and time spent on meals, and increased inter-meal interval and satiety ratio resulting in 92-86% suppression of food intake at 2-24 h post-surgery compared with control group (no surgery. RKT significantly increased bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and autonomic nuclei, such as the bed nucleus of the stria terminalis, central amygdala, hypothalamic supraoptic (SON, paraventricular and arcuate nuclei, Edinger-Westphal nucleus (E-W, lateral periaqueduct gray (PAG, lateral parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius (NTS. RKT induced a small increase in c-Fos-ir neurons in the SON and E-W of control mice, and in mice with surgery there was an increase in the lateral PAG and a decrease in the NTS. These findings indicate that abdominal surgery inhibits food intake by increasing both satiation (meal duration and satiety (meal interval and activates brain circuits involved in pain, feeding behavior and stress that may underlie the alterations of meal pattern and food intake inhibition

  9. The effects of stimulation of substantia innominata and sensory receiving areas of the forebrain upon the activity of neurons within the amygdala of the anesthetized cat. (United States)

    Femano, P A; Edinger, H M; Siegel, A


    The present study investigated the response characteristics of individual neurons in the amygdala following stimulation of the substantia innominata (SI), and compared these responses with those elicited by stimulation of insular and temporal polar cortices and the lateral olfactory tract (LOT). Recordings were made from single units within the medial, central, basal, and lateral amygdaloid nuclei of anesthetized, male cats. Stimulating electrodes were located in the SI, LOT, and sylvian cortex (SG). Unit responses were classified as either excitation or inhibition. Excitatory responses were further divided into fixed latency excitation (FLE) and variable latency excitation (VLE) based on the variability of the onset latency of the response. The majority of responses to SI stimulation were of the FLE type, implying a direct orthodromic, monosynaptic activation of amygdaloid units. Proportionally more FLE responses were recorded laterally, especially in the magnocellular basal nucleus, compared to VLE responses which were more common in the medial and central nuclei. SI stimulation consistently affected the activity of many more units than did SG or LOT stimulation. The onset latencies of the population of cells exhibiting excitatory responses elicited by SI stimulation were distributed bimodally, and this may reflect a dual projection pathway of amygdaloid afferents from this basal forebrain region. This correlates with anatomical descriptions indicating that SI projections to amygdala pass via the ventral amygdalofugal pathway as well as in the stria terminalis. Excitatory onset latencies of responses to SI stimulation were the shortest in the lateral and magnocellular basal nuclei and the longest in the parvocellular basal nucleus. Amygdaloid units exhibited convergent input from the stimulus sites. A clear topographical distribution of units was not demonstrated. The data suggests that units receiving a convergent input were rarely driven monosynaptically by

  10. Core and paracores; some new chemoarchitectural entities in the mammalian neuraxis. (United States)

    Nieuwenhuys, R; Veening, J G; van Domburg, P

    nucleus and the catecholaminergic cell groups A1, A2, A5, A7 and C1 and C2. It harbours a large bundle of loosely arranged, thin fibres, which forms a direct caudal continuation of the hypothalamic medial forebrain bundle. This lateral paracore bundle contains numerous catecholaminergic and peptidergic fibres. Three typical core centres, viz. the nucleus centralis amygdalae, the bed nucleus of the stria terminalis and the lateral hypothalamic area contribute substantially to this bundle. The lateral paracore contains, just like the core region, a large number of functionally defined centres related to integrated somatomotor and visceromotor responses. It is postulated that non-synaptic interneuron

  11. Two Neural Measures Differ between Urban and Rural Song Sparrows after Conspecific Song Playback

    Directory of Open Access Journals (Sweden)

    Kendra B. Sewall


    Full Text Available Urbanization is a critical form of environmental change that can affect the physiology and behavior of wild animals and, notably, birds. One behavioral difference between birds living in urban and rural habitats is that urban males show elevated boldness or territorial aggression in response to simulated social challenge. This pattern has been described in several populations of song sparrow, Melospiza melodia. Such behavioral differences must be underpinned by differences in the brain, yet little work has explored how urbanization and neural function may be interrelated. We explored the relationship between urbanization and neural activation within a network of brain regions, collectively called the social behavior network, which contributes to the regulation of territorial aggression. Specifically, we captured free-living, territorial male song sparrows by playing them conspecific songs for 6–11 min, and then collected their brains. We estimated recent neural activation, as indicated by the immediate early gene FOS, and measured levels of a neuropeptide, arginine vasotocin (AVT, which is involved in the regulation of social behavior. Based on previous studies we expected urban males, which are generally more territorially aggressive, to have lower FOS expression in a node of the social behavior network implicated in regulating territoriality, the lateral septum (LS. Additionally, we expected urban males to have lower AVT expression in a brain region involved in the regulation of sociality, the medial bed nucleus of the stria terminalis (BSTm. We found that, compared to rural males, urban male song sparrows did have lower FOS expression in the LS. This pattern suggests that lower neural activation in the LS could contribute to behavioral adjustments to urbanization in male song sparrows. Additionally, counter to our predictions, urban male song sparrows had higher AVT-like immunoreactivity in the BSTm. Future work building upon these findings

  12. Early life stress elicits visceral hyperalgesia and functional reorganization of pain circuits in adult rats

    Directory of Open Access Journals (Sweden)

    D.P. Holschneider


    Full Text Available Early life stress (ELS is a risk factor for developing functional gastrointestinal disorders, and has been proposed to be related to a central amplification of sensory input and resultant visceral hyperalgesia. We sought to characterize ELS-related changes in functional brain responses during acute noxious visceral stimulation. Neonatal rats (males/females were exposed to limited bedding (ELS or standard bedding (controls on postnatal days 2–9. Age 10–11 weeks, animals were implanted with venous cannulas and transmitters for abdominal electromyography (EMG. Cerebral blood flow (rCBF was mapped during colorectal distension (CRD using [14C]-iodoantipyrine autoradiography, and analyzed in three-dimensionally reconstructed brains by statistical parametric mapping and functional connectivity. EMG responses to CRD were increased after ELS, with no evidence of a sex difference. ELS rats compared to controls showed a greater significant positive correlation of EMG with amygdalar rCBF. Factorial analysis revealed a significant main effect of ‘ELS’ on functional activation of nodes within the pain pathway (somatosensory, insular, cingulate and prefrontal cortices, locus coeruleus/lateral parabrachial n. [LC/LPB], periaqueductal gray, sensory thalamus, as well as in the amygdala, hippocampus and hypothalamus. In addition, ELS resulted in an increase in the number of significant functional connections (i.e. degree centrality between regions within the pain circuit, including the amygdala, LC/LPB, insula, anterior ventral cingulate, posterior cingulate (retrosplenium, and stria terminalis, with decreases noted in the sensory thalamus and the hippocampus. Sex differences in rCBF were less broadly expressed, with significant differences noted at the level of the cortex, amygdala, dorsal hippocampus, raphe, sensory thalamus, and caudate-putamen. ELS showed a sexually dimorphic effect (‘Sex x ELS’ interaction at the LC/LPB complex, globus pallidus

  13. White matter correlates of anxiety sensitivity in panic disorder. (United States)

    Kim, Min-Kyoung; Kim, Borah; Kiu Choi, Tai; Lee, Sang-Hyuk


    Anxiety sensitivity (AS) refers to a fear of anxiety-related sensations and is a dispositional variable especially elevated in patients with panic disorder (PD). Although several functional imaging studies of AS in patients with PD have suggested the presence of altered neural activity in paralimbic areas such as the insula, no study has investigated white matter (WM) alterations in patients with PD in relation to AS. The objective of this study was to investigate the WM correlates of AS in patients with PD. One-hundred and twelve right-handed patients with PD and 48 healthy control (HC) subjects were enrolled in this study. The Anxiety Sensitivity Inventory-Revised (ASI-R), the Panic Disorder Severity Scale (PDSS), the Albany Panic and Phobia Questionnaire (APPQ), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) were administered. Tract-based spatial statistics were used for diffusion tensor magnetic resonance imaging analysis. Among the patients with PD, the ASI-R total scores were significantly correlated with the fractional anisotropy values of the WM regions near the insula, the splenium of the corpus callosum, the tapetum, the fornix/stria terminalis, the posterior limb of the internal capsule, the retrolenticular part of the internal capsule, the posterior thalamic radiation, the sagittal striatum, and the posterior corona radiata located in temporo-parieto-limbic regions and are involved in interoceptive processing (p<0.01; threshold-free cluster enhancement [TFCE]-corrected). These WM regions were also significantly correlated with the APPQ interoceptive avoidance subscale and BDI scores in patients with PD (p<0.01, TFCE-corrected). Correlation analysis among the HC subjects revealed no significant findings. There has been no comparative study on the structural neural correlates of AS in PD. The current study suggests that the WM correlates of AS in patients with PD may be associated with the insula and the adjacent temporo

  14. Deep brain stimulation for severe treatment-resistant obsessive-compulsive disorder: An open-label case series. (United States)

    Farrand, Sarah; Evans, Andrew H; Mangelsdorf, Simone; Loi, Samantha M; Mocellin, Ramon; Borham, Adam; Bevilacqua, JoAnne; Blair-West, Scott; Walterfang, Mark A; Bittar, Richard G; Velakoulis, Dennis


    Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8-54 months). The sample included four females and three males, with a mean age of 46 years (range, 37-59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15-38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Deep

  15. Cocaine accumulates in dopamine-rich regions of primate brain after i.v. administration: comparison with mazindol distribution. (United States)

    Madras, B K; Kaufman, M J


    Pharmacological and neurochemical evidence suggest that brain dopamine systems, and the dopamine transporter in particular, contribute significantly to the behavioral effects and reinforcing properties of cocaine. The first objective of this study was to determine whether the brain distribution of cocaine supports these conclusions. A high resolution neuroanatomical map of cocaine disposition in brain after i.v. administration was developed. [3H]Cocaine ([3H](-)-cocaine) was administered to squirrel monkeys (Saimiri sciureus) at a trace dose (0.001 mg/kg) and at doses at or above the threshold for producing behavioral effects (0.1 mg/kg, 0.3 mg/kg). After 15 min, ex vivo autoradiography revealed the highest accumulation of [3H]cocaine in dopamine-rich brain regions, including the caudate nucleus, putamen, and nucleus accumbens/olfactory tubercle. The norepinephrine-rich locus coeruleus, the hippocampus, and amygdala also accumulated large quantities of [3H]cocaine. Moderately high levels were found in the stria terminalis, medial septum, substantia nigra, and other regions. Lowest levels were found in the cerebellum. A high and positive correlation was established for the brain distribution of [3H]cocaine administered at trace or at behaviorally relevant doses (r: 0.94; P mazindol, a potent norepinephrine and dopamine transport inhibitor with low abuse liability in humans. The disposition of intravenously administered [3H]mazindol in brain (0.001 mg/kg, 0.007 mg/kg) was surveyed by ex vivo autoradiography. In sharp contrast to [3H]cocaine distribution, the highest accumulation of [3H]mazindol was localized in the norepinephrine-rich pineal gland, discrete regions of the hypothalamus (paraventricular nucleus, supraoptic nucleus), and the locus coeruleus. Moderately high levels were detected in the caudate-putamen, nucleus accumbens, and other regions. The following conclusions were drawn: (1) Although dopamine-rich brain regions are principal targets of cocaine

  16. Comparative distribution of relaxin-3 inputs and calcium-binding protein-positive neurons in rat amygdala

    Directory of Open Access Journals (Sweden)

    Fabio N Santos


    Full Text Available The neural circuits involved in mediating complex behaviors are being rapidly elucidated using various newly developed and powerful anatomical and molecular techniques, providing insights into the neural basis for anxiety disorders, depression, addiction, and dysfunctional social behaviors. Many of these behaviors and associated physiological processes involve the activation of the amygdala in conjunction with cortical and hippocampal circuits. Ascending subcortical projections provide modulatory inputs to the extended amygdala and its related nodes (or ‘hubs’ within these key circuits. One such input arises from the nucleus incertus (NI in the tegmentum, which sends amino acid- and peptide-containing projections throughout the forebrain. Notably, a distinct population of GABAergic NI neurons expresses the highly-conserved neuropeptide, relaxin-3, and relaxin-3 signaling has been implicated in the modulation of reward/motivation and anxiety- and depressive-like behaviors in rodents via actions within the extended amygdala. Thus, a detailed description of the relaxin-3 innervation of the extended amygdala would provide an anatomical framework for an improved understanding of NI and relaxin-3 modulation of these and other specific amygdala-related functions. Therefore, in this study, we examined the distribution of NI projections and relaxin-3-positive elements (axons/fibers/terminals within the amygdala, relative to the distribution of neurons expressing the calcium-binding proteins, parvalbumin, calretinin and/or calbindin. Anterograde tracer injections into the NI revealed a topographic distribution of NI efferents within the amygdala that was near identical to the distribution of relaxin-3-immunoreactive fibers. Highest densities of anterogradely-labeled elements and relaxin-3-immunoreactive fibers were observed in the medial nucleus of the amygdala, medial divisions of the bed nucleus of the stria terminalis (BST and in the endopiriform

  17. Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors. (United States)

    Wang, Lei; de Kloet, Annette D; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A; Pioquinto, David J; Ludin, Jacob A; Oh, S Paul; Katovich, Michael J; Frazier, Charles J; Raizada, Mohan K; Krause, Eric G


    Over-activation of the brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme 2 (ACE2) inhibits RAS activity by converting angiotensin-II, the effector peptide of RAS, to angiotensin-(1-7), which activates the Mas receptor (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ∼62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the

  18. Untitled

    Indian Academy of Sciences (India)

    Name of the pathogens Name of the hosts other susceptible viability plants. Months. P. bauhiniae . . ... Bauhinia purpurea * * 11. Callistemon indica . . . 12. Dracaena terminalis 14%. P. carica-papayae ... Carica papaya # 4. 10. Bauhinia purpurea 114 . Eriobotrya japonica 15. P. dracaenae . . . Dracaena terminalis * - - - 11.

  19. LNG terminal võib tulla ka igasse Balti riiki. Arutlused esialgu jätkuvad / Sirje Rank

    Index Scriptorium Estoniae

    Rank, Sirje, 1966-


    Balti peaministrid pole üksmeelel, kas ja kuhu rajada veeldatud gaasi terminal. Lepiti kokku, et kõik kolm riiki teevad vedelgaasi terminali tasuvusuuringu. Leedu kavatseb rajada oma riigi vajadusteks LNG ujuvterminali, kuid see ei välista osalemist suurema terminali projektis

  20. As bases neuroanatômicas do comportamento: histórico e contribuições recentes Neuroanatomical basis of behavior: history and recent contributions

    Directory of Open Access Journals (Sweden)

    Guilherme Carvalhal Ribas


    conjunto com o núcleo basal de Meynert e com o sistema septo-banda diagonal, constituem as principais estruturas e sistemas que possuem conexões com as áreas corticais límbicas e que, em conjunto com estas, atuam sobre o hipotálamo e o tronco encefálico que, por sua vez, geram os componentes autonômicos, endócrinos e somatomotores das experiências emocionais e que regulam as atividades básicas de beber, comer e pertinentes ao comportamento sexual.Considering the most recent contributions, the limbic cortical areas, originally known as the greater limbic lobe, besides the cingulated and the parahippocampal gyri also includes the insula and the posterior orbital cortex. In contrast to the nonlimbic cortical areas that project to the basal ganglia (particularly over the dorsal aspects of the striatum, constituted by the caudate nucleus and by the putamen, the limbic cortical areas are characterized by projecting to the hypothalamus and also to the ventral striatum (particularly to the nucleus accumbens. Once all the striatum projects to the globus pallidus which projects to the thalamus and then to the cortex, generating cortical-subcortical reentrant circuits, while the dorsal striatum and pallidum related cortico-subcortical loops are involved with motor activities, the ventral cortical-striatal-pallidal system is particularly related with behavior functions. The extended amygdala (central medial amygdala, stria terminalis or dorsal component, ventral component, and bed nucleus of stria terminalis receives inputs primarily from the limbic cortical areas, is particularly modulated by the prefrontal cortex, and receives also direct connections from the thalamus that enables the amygdala to generate nonspecific and quick responses through its projections to the hypothalamus and to the brainstem. The ventral striatal-pallidal and the extended amygdala are then two basal forebrain macro-anatomical systems, that together with the basal nucleus of Meynert and with the

  1. Ärimehed lennukitüüri taga / Küllike Rooväli

    Index Scriptorium Estoniae

    Rooväli, Küllike, 1969-


    Copterline Eesti terminali juht Tõnis Lepp ja Eesti Esimese Aeronautikaklubi juht Johan Pender lendamisest, lennuõpetusest. Lisad: Eralenduri õpe Eestis; Erapiloodi kursus. Vt. samas: Kooliõpetajast saab vaheajal lendur [intervjuu Eesti Era- ja Harrastuspilootide Liidu esimehe Hendrik Aguriga

  2. Balti riigid asutavad Rail Balticu raudteefirma / Raimo Poom

    Index Scriptorium Estoniae

    Poom, Raimo


    Baltimaade peaministrite kohtumisel Tallinnas jõuti üksmeelele Euroopa rööpalaiusega Rail Balticu ehitamises. Projekti elluviimiseks luuakse ühisettevõte. Veeldatud maagaasi terminali asukohas üksmeel puudub

  3. Dombrovskis: toetus Rail Balticule sõltub Siim Kallasest / Valdis Dombrovskis ; intervjueerinud Andres Reimer

    Index Scriptorium Estoniae

    Dombrovskis, Valdis, 1971-


    Intervjuu Läti peaministriga Swedbankiga seotud sularahapaanikast, LNG terminali asukohast, Läti ettepanekust peatada Baltimaade eletrkisüsteemide Euroopaga sünkroniseerimise projekt, Poola väljumisest kavandatavast Visaginase tuumajaama projektist, Rail Balticust

  4. Kak zhit v Jevropeiskom Sojuze? : AO DBT = What will the life in the European Union be like? : AO DBT / Vladimir Volohhonski

    Index Scriptorium Estoniae

    Volohhonski, Vladimir, 1948-2013


    DBT (Dry Bulk Terminal) AS-i juhatuse esimees räägib kuivainete terminali tegevusest tollivabas tsoonis, võrdleb Baltimaade ja Venemaa sadamate olukorda ning prognoosib Euroopa Liiduga liitumise mõju Eesti transiitkaubandusele

  5. Kelle süül ikkagi nurjus Baskimaa rahuprotsess? / Anna-Maria Penu

    Index Scriptorium Estoniae

    Penu, Anna-Maria, 1978-


    Madridi lennujaama terminalis plahvatas pomm, riigi siseministri sõnul lõpetas see rahuprotsessi. Autori hinnangul eksis peaminister Jose Luis Rodriguez Zapatero, uskudes, et Baskimaa probleem on küpseks dialoogiks valmis. Lisa: Rahuvahendaja tekitas segadust

  6. Dlja kompanii "Bega" ne nuzhen shljus v Jevrosojuz! = BEGA does not need any sluice to the EU / Aloizas Kuzmarskis

    Index Scriptorium Estoniae

    Kuzmarskis, Aloizas


    Leedu stividorettevõtte "Bega" juht Aloizas Kuzmarskis ettevõtte asutamisest, terminali ehitamisest koostöös Klaipeda meresadamaga, kaupade lastimise mahtudest, kvaliteedisertifikaatide omandamisest ja Euroopa Liiduga liitumise mõjudest sadamateenustele

  7. Novõi sobstvennik planirujet rasshirjat sillamjaeskii neftjanoi terminal / Heiti Hääl ; interv. Aleksei Starkov

    Index Scriptorium Estoniae

    Hääl, Heiti, 1963-


    Ettevõtte Alexela Logistics ja Sillamäe ja Paldiski tütarfirmade juhatuse esimees räägib naftaterminali Sillamäe Oil Terminali omandamisest, naftavedudest ja Venemaa-Eesti naftatransiidi tulevikust

  8. LNG terminal location still a tossup

    Index Scriptorium Estoniae


    Lätti rajatava LNG terminali asukoht pole veel teada. 16. märtsil kohtus Poola president Bronislaw Komorowki Läti riigipea Valdis Zatlersiga ja kiitis selle projekti heaks. Venemaast energiasõltumatuse olulisusest

  9. Tonnõ uglja - a põli net / Andrei Babin

    Index Scriptorium Estoniae

    Babin, Andrei


    Muuga sadamas opereeriv AS Coal Terminal Operator planeerib investeerida 15,5 miljonit krooni keskkonnameetmetesse, et lõpetada ümbruskonna saastamine söetolmuga. Terminali tegevusest. Lisa: Muuga sadama söeterminal

  10. Grain operator miffed at port administration

    Index Scriptorium Estoniae


    Ventspils Grain Terminal saatis president Vaira Vike-Freibergale ja mitmetele ministritele kirja sõnumiga, et Ventspilsi Vabasadama (Ventspils Free Port) administratsiooni tegevus takistab terminali äritegevust

  11. Signal k objedineniju / Aleksei Zhigulin

    Index Scriptorium Estoniae

    Zhigulin, Aleksei


    Muuga sadamas asuvate naftatransiidi firmade baasil luuakse spetsialiseeritud terminalikompleks. Selle rahvusvahelise projekti, milles osaleb vene kontsern Severstaltrans, strateegiliseks eesmärgiks on arendada terminaliäri Baltimaades. Diagrammid

  12. Eesti Loto uuendab kesksüsteemi / Merike Ojasson

    Index Scriptorium Estoniae

    Ojasson, Merike


    Riigiettevõte Eesti Loto investeerib kümneid miljoneid kroone uude terminalisüsteemi lootuses, et kaasaegne tehnoloogia kasutuselevõtuga kasvab firma kasum lähema nelja aasta jooksul ligi viis korda

  13. Putin võttis esimesena ette nafta / Sirje Rank

    Index Scriptorium Estoniae

    Rank, Sirje, 1966-


    Venemaa peaminister Vladimir Putin külastas Primorski ja Ust-Luuga sadamaid, kus avas uue naftasaaduste terminali ning teatas Balti torujuhtmesüsteemi laiendamisest. Vt. samas: Soodne otsus Putini sõbrale

  14. Introduction: Addiction and Brain Reward and Anti-Reward Pathways (United States)

    Gardner, Eliot L.


    bio-psycho-social” model of etiology holds very well for addiction. Addiction appears to correlate with a hypo-dopaminergic dysfunctional state within the reward circuitry of the brain. Neuroimaging studies in humans add credence to this hypothesis. Credible evidence also implicates serotonergic, opioid, endocannabinoid, GABAergic, and glutamatergic mechanisms in addiction. Critically, drug addiction progresses from occasional recreational use to impulsive use to habitual compulsive use. This correlates with a progression from reward-driven to habit-driven drug-seeking behavior. This behavioral progression correlates with a neuroanatomical progression from ventral striatal (nucleus accumbens) to dorsal striatal control over drug-seeking behavior. The three classical sets of craving and relapse triggers are a) re-exposure to addictive drugs, b) stress, and c) re-exposure to environmental cues (“people, places, things”) previously associated with drug-taking behavior. Drug-triggered relapse involves the nucleus accumbens and the neurotransmitter dopamine. Stress-triggered relapse involves a) the central nucleus of the amygdala, the bed nucleus of the stria terminalis, and the neurotransmitter CRF; and b) the lateral tegmental noradrenergic nuclei of the brain stem and the neurotransmitter norepinephrine. Cue-triggered relapse involves the basolateral nucleus of the amygdala, the hippocampus, and the neurotransmitter glutamate. Knowledge of the neuroanatomy, neurophysiology, neurochemistry, and neuropharmacology of addictive drug action in the brain is currently producing a variety of strategies for pharmacotherapeutic treatment of drug addiction, some of which appear promising. PMID:21508625


    Directory of Open Access Journals (Sweden)

    Anderson Soncini Pelissari


    Full Text Available As organizações cujas estruturas, processos e tecnologias não estão alinhados com os negócios terão dificuldades em sobreviver. A fim de se manterem, estrategistas de gestão têm se apoiado em práticas como a Inteligência Competitiva (IC – que tem como base a informação e a velocidade de seu uso para melhor alinhar o negócio às estratégias, facilitando o processo de tomada de decisão. Posto isso, objetivou-se, com esta pesquisa, analisar a prática da inteligência competitiva de pequenas empresas do Município de Vila Velha/ES e a importância da aplicabilidade da Inteligência Competitiva Empreendedora – assumindo-se que a IC contribui para o alinhamento das informações ambientais às estratégias das organizações. Para a coleta de dados, utilizou-se o levantamento (survey, em que foi aplicado um questionário com perguntas fechadas a uma amostra não probabilística intencional, aplicado diretamente pelo próprio pesquisador, por e-mail e fax. Os resultados apontaram que, apesar de os administradores pesquisadosdemonstrarem interesse em estruturar suas informações com o objetivo de tomar decisões mais rápidas e assertivas, eles não desenvolvem um processo global de Inteligência Competitiva Empreendedora, vistonão gerenciarem de modo sistemático as informações do mercado.The organizations, whose structures, processes and technologies are not aligned with the businesses, they will have difficulties in surviving. In order to maintain, management strategists have reliedon practices such as Competitive Intelligence (CI - which is based on the information and the speed of its use to better align business strategies, facilitating the process of decision making. That said, the aim with this research, analyzing the practice of competitive intelligence for small businesses in the City of Vila Velha/ES, and the importance of applicability of Competitive Intelligence Entrepreneurship - assuming that, the IC contributes to the alignment of environmental information the strategies of organizations. For data collection, we used the survey (survey, which was applied a questionnaire with closed questions to a non-probabilistic intentional sample applied directly by the researcher by e-mail and fax. The surveyresults indicated that, although the administrators surveyed show interest in structuring your informationwith the objective to make quick decisions and assertive, they do not develop a global process ofCompetitive Intelligence Entrepreneurship, since no systematic way to manage market information.

  16. AvaliaÃÃo do uso de polÃmero EVA, resÃduo da indÃstria de calÃados (EVAR) e aditivos no desempenho reolÃgico de ligante asfÃltico de petrÃleo


    Ana Ellen Valentim de Alencar


    O desenvolvimento de novas metodologias no campo da engenharia rodoviÃria tem sido uma preocupaÃÃo, visando à melhoria da qualidade das vias pavimentadas, tornando-as mais seguras e resistentes. Algumas inovaÃÃes introduzidas nesta Ãrea tem sido praticadas com a aplicaÃÃo de ligantes asfÃlticos (LAs) modificados, que tem demonstrado melhorar o desempenho destes, contribuindo para a reduÃÃo da formaÃÃo das trilhas de roda e das trincas tÃrmicas. Neste estudo, o ligante asfÃltico (LA) brasileir...


    Directory of Open Access Journals (Sweden)

    Warley Efrem Campos


    Full Text Available

    Nutritive value of silages of Elephant grass (Pen-nisetum   purpureum, Schum. mixed with 0; 3.5%; 7.0%; 10.5% and 14.0 %  of dehydrated by product from juice industry of cashew fruit (Anacardium occidentale, L (DBC was determined. A randomized design was used with four replicates. Silages were opened after 65 days and samples taken for analysis of dry matter (DM, crude protein (CP, neutral detergent fiber (NDF, acid detergent fiber (ADF, hemicellulose HCEL, cellulose (CEL, lig-nin (LIG, crude energy (CE, ash, neutral detergent inso-luble nitrogen (NDIN and acid detergent insoluble nitro-gen (ADIN. Were also analyzed, pH, ammonia nitrogen and organic acids (lactic, acetic, butyric and propionic. Regarding fermentative parameters, there was an expected decrease in pH and the increasing levels of DBC did not affect the concentrations of N-NH3/NT and organic acids. It is concluded that dehydrated cashew by product can be ensiled along with Elephant grass without altering its fer-mentative characteristics. On the other side, the increased cell walls and ADIN contents of the silage may affect its nutritional value.

    Key-words: Cashew byproducts, nutritive value, tropical grass.

    O trabalho foi desenvolvido com o objetivo de se avaliar o valor nutritivo das silagens de capim-elefante (Pennisetum purpureum, Schum. com adição de 0%; 3,5%; 7%; 10,% e 14% do subproduto do pseudofruto do caju (Anacardium occidentale, L. desidratado (subproduto da agroindústria do suco de caju. Utilizou-se o delineamento inteiramente casualizado, com quatro repetições. Após 65 dias, os silos foram abertos e coletadas amostras para determinação dos teores de matéria seca (MS, proteína bruta (PB, fibra em detergente neutro (FDN, fibra em detergente ácido (FDA, hemicelulose (HCEL, celulose (CEL, lignina (LIG, energia bruta (EB, cinzas, nitrogênio insolúvel em detergente neutro (NIDN e nitrogênio insolúvel em detergente ácido (NIDA. Para avaliar as características fermentativas das silagens, determinaram-se os valores de pH e os teores de nitrogênio amoniacal (% do nitrogênio total e dos ácidos lático, acético, butírico e propiônico. A adição do subproduto do pseudofruto do caju desidratado (SPCD acarretou o aumento dos teores de MS, PB, FDA, LIG, NIDN e NIDA. Para os parâmetros fermentativos, observou-se redução dos valores de pH, porém não se registrou influência dos níveis de adição do SPCD sobre os teores de N-NH3/NT e ácidos orgânicos. Conclui-se que o subproduto do pseudofruto do caju desidratado pode ser ensilado com o capim-elefante, sem comprometer as características fermentativas das silagens de capim-elefante. Porém, o aumento nos componentes da parede celular e do NIDA pode comprometer o valor nutri-cional do ensilado final.

    Palavras-chaves: Gramínea tropical, subprodutos do caju, valor nutritivo.

  18. GESTÃO SUSTENTÁVEL NA CADEIA DE SUPRIMENTOS E DESEMPENHO INOVADOR EM PROCESSOS: UM ESTUDO NA INDÚSTRIA DO ALUMÍNIO / Sustainable management in supply chain and innovative in performance processes: a study in the aluminum industry


    Rocha, Adilson Carlos; Gomes, Clandia Maffini; Kneipp, Jordana Marques


    O presente estudo teve como objetivo associar a gestão sustentável da cadeia de suprimentos com o desempenho inovador do processo produtivo na indústria do alumínio. Para atingir esse objetivo, utilizaram-se como base os pressupostos teóricos de Pagell e Wu (2009), Makkonen e Van Der Have (2012) e Gunday et al. (2011). O estudo possui uma abordagem qualitativa e é de natureza exploratória e descritiva. Como estratégia de pesquisa, utilizou-se o estudo de caso, desenvolvido a partir de entrevi...


    Directory of Open Access Journals (Sweden)



    Full Text Available Diferentes materiales adsorbentes fueron preparados a partir de la cascarilla de arroz (un residuo lignocelulósico agroindustrial, para la remoción de cromo presente en las aguas resultantes de la curtición, debido a su alta toxicidad para la salud humana y a nivel ambiental. La cascarilla de arroz se evaluó como ceniza y carbón activado con acido fosfórico e hidróxido de sodio como agentes activantes. La parte experimental consistió en la calcinación de la cascarilla de arroz, activación química, caracterización, pruebas de adsorción y absorción atómica; obteniendo mejores resultados el adsorbente activado con hidróxido de sodio. Para la activación de la cascarilla de arroz con NaOH se requirió una serie de experimentos para determinar las mejores condiciones de operación en el proceso de obtenci��n del carbón activado. Se obtuvo una mayor remoción en el carbón que se activo a una temperatura de 600°C, un tiempo de activación de 30 minutos y una concentración de la solución de 1% p/p; la remoción de cromo fue del 72,8% comparado con la cascarilla de arroz activada con H3PO4 que fue del 54,5% y la ceniza de cascarilla de arroz 49,2%.Diferentes materiais adsorventes fórum preparados a partir da casca de arroz, um resíduo lignocelulósico agroindustrial, para a remoção de cromo das águas resultantes da curtição, devido a sua alta toxicidade na saúde e ao nível ambiental. A casca de arroz, a qual se avalia como cinza e carvão ativado com acido fosfórico e hidróxido de sódio como agentes ativadores. A parte experimental consta de calcinação da casca de arroz, ativação química, caracterização, testes de adsorção e absorção atômica; obtendo os melhores resultados o adsorvente ativado com hidróxido de sódio. A ativação da casca de arroz com NaOH se precisaram uma série de experimentos para determinar as melhores condições de operação no processo de obtenção do carvão ativado. Obteve-se uma maior remoção no carvão que se ativo a uma temperatura de 600°C, um tempo de ativação de 30 minutos e uma concentração da solução de 1% p/p; a remoção foi do 72,8% comparado com a casca de arroz ativada com H3PO4 que foi do 54,5% e a cinza de casca de arroz 49,2%.Several adsorbent materials were prepared from rice husk, a lignocellulosic waste from agro-industry, for the removal of chromium present in the effluents of the tanning, due to its high toxicity in the health and to environmental level. The rice husk was evaluated as ash and activated coal with phosphoric acid or hydroxide of sodium as activating agents. The experimental part consisted of calcination of the rice husk, chemical activation, characterization, tests of adsorption and tests of atomic absorption; obtaining better results the adsorbent activated with hydroxide of sodium. The activation of the rice husk with NaOH required a series of experiments to determine the best conditions of operation in the process of obtaining of the activated coal. A major removal was obtained in the coal that was activated at 600°C 30 minutes of activation time and 1% p/p of solution concentration; the removal was of the 72,8 % compared with the rice husk ash activated with H3PO4 that was of the 54,5% and the rice husk ash 49,2%.


    Directory of Open Access Journals (Sweden)

    Patricia Torres


    Full Text Available La agroindustria de extracción de almidón de yuca hace parte importante de la economía de Colombia, concentrándose su producción en el departamento del Cauca; el proceso emplea raíces frescas de yuca, agua y energía eléctrica como principales recursos, generando residuos sólidos y líquidos cuyo inadecuado aprovechamiento o vertimiento trae impactos ambientales y económicos. En este estudio se formularon medidas para la optimización de los procesos apoyándose en herramientas como el balance de masa y el estudio de métodos, tiempos y movimientos, considerando el contexto tecnológico y socioeconómico del sector. Los resultados mostraron una eficiencia del proceso entre 51 % y 59 %; se identificó que la etapa de colado presenta el mayor consumo de agua y generación de residuos sólidos (afrecho, la etapa de sedimentación genera la mayor cantidad de residuos líquidos con elevada carga contaminante. Se evidenció la necesidad de estandarizar y optimizar las etapas de lavado-pelado y colado por requerir los mayores tiempos, incrementar la capacidad del rallado (etapa crítica que influye en la eficiencia del proceso y calidad del almidón y registrar la información del proceso como estrategia de control.A agroindústria de extração de amido de mandioca faz parte importante da economia da Colômbia, concentrando-se sua produção no departamento do Cauca; o processo emprega raízes frescas de mandioca, água e energia elétrica como principais recursos, gerando resíduos sólidos e líquidos cujo inadequado aproveitamento ou eliminação traz impactos ambientais e econômicos. Neste estudo formularam-se medidas para a otimização dos processos apoiando-se em ferramentas como o balanço de massa e o estudo de métodos, tempos e movimentos, considerando o contexto tecnológico e socioeconômico do setor. Os resultados mostraram uma eficiência do processo entre 51 % e 59 %; identificou-se que a etapa de coado apresenta o maior consumo de água e geração de resíduos sólidos (farelo; a etapa de sedimentação gera a maior quantidade de resíduos líquidos com elevada carga contaminante. Evidenciou-se a necessidade de padronizar e otimizar os períodos de lavado-descascado e coado por requerer os maiores tempos, aumentar a capacidade do ralado (etapa crítica que influi na eficiência do processo e qualidade do amido e registrar a informação do processo como estratégia de controle.In Colombia, the agroindustry of cassava-starch extraction is an important sector of the country's economy; production is focused in Cauca Department; this process uses fresh cassava-roots, water, and electricity as main resources, generating solid and liquid wastes whose inadequate use or disposal brings environmental and economic impacts. In this study were made measures for process optimization supported by tools such as mass balance and study methods, time and motion, considering the technological and socio-economic context of the sector. The results showed process-efficiency between 51 and 59 %; it was identified that the straining stage has the highest water consumption and solid waste generation (fiber cassava pulp; the starch slurry’s sedimentation stage generates the most amount of liquid wastes with high-pollution load. It evidenced the need to standardize and optimize the washing-peeling and strain stages because they require the largest process times; to increase the grating-rasping machine capacity (this critical stage influences the process efficiency and the final starch quality besides recording the process information as control strategy.

  1. Trypanocidal properties of Terminalia ivorensis A. Chev ...

    African Journals Online (AJOL)

    The column fractions of the ethyl acetate fraction gave E.D50 value between 1.98 and 5.46 μg/mL for the very active fractions indicating prospect for the development of potential trypanocidal agent from the plant. Keywords: Terminalis ivorensis, Trypanosoma brucei rhodesiensis, trypanocidal. African Journal of Traditional, ...

  2. Alexela Terminal pääseb mõjude hindamisest / Lemmi Kann

    Index Scriptorium Estoniae

    Kann, Lemmi


    Heiti Hääle suuromanduses Alexela Terminal laiendab Paldiskis oma terminali täpselt nii palju, kui ilma keskkonnamõju hindamise kohustuseta lubatud on. Diagramm: Majandusnäitajad. Vt. samas: Paldiskis levib hais; Trahvid. Küsimustele vastab AS-i Alexela Terminal tegevjuht Aarto Eipre

  3. New records of brown algae (Phaeophyta) from the Azores.


    Parente, Manuela I.; Fletcher, Robert L.; Neto, Ana I.


    Copyright © 2000 Kluwer Academic Publishers. Printed in the Netherlands. The following five species of microscopic tuft-forming/encrusting brown algae (Phaeophyta) are newly recorded for the Island of São Miguel (Azores): Nemoderma tingitana Schousboe ex Bornet. Pseudolithoderma roscoffense Loiseaux (Lithodermataceae), Hecatonema terminalis (Kutzing) Kylin (Punctariaceae), Compsonema saxicolum (Kuckuck) Kuckuck, and Microspongium gelatinosum Reinke (Scytosiphonaceae). The species are descr...

  4. Merelt võetud terminal / Kadri Paas

    Index Scriptorium Estoniae

    Paas, Kadri, 1982-


    Ilmunud ka: Delovõje Vedomosti 18. juuni lk. 16. Perekond Vähi plaanib merelt võetud maale ehitada terminali, mis võimaldaks käsitleda 800 000 konteinerit aastas. Vt. samas: Vähide pereäri. Küsimusele vastavad Juhan Kolk ja majandusminister Juhan Parts

  5. Sillamäele võib tekkida väike tsemenditehas / Erik Müürsepp

    Index Scriptorium Estoniae

    Müürsepp, Erik


    Hispaania grupi Essentium ettevõte Essentium Cement Eesti OÜ tahab rajada Sillamäe sadama territooriumile terminali ja tehase. AS-i Kunda Nordic Tsement tegevdirektor arvab, et Eesti turul ei ole ruumi uutele tsemenditootjatele. Vt. samas: Investeering võib ulatuda kolme miljardini

  6. Russian-Belarusian propaganda war and Vilnius / Rokas M. Tracevskis

    Index Scriptorium Estoniae

    Tracevskis, Rokas M.


    Venemaa-Valgevene konfliktist, mille käigus tsenseeritakse meediat ning kritiseeritakse president Aleksandr Lukašenkot ja peaminister Vladimir Putinit, põhjuseks on maagaasi hind. 27. juulil toimunud Leedu peaministri Andrius Kubiliuse ja Valgevene peaministri Sergei Sidorski kohtumisel räägiti vedeldatud gaasi terminali projektist. 26. juunil toimunud Andrius Kubiliuse ja Aleksandr Lukašenko kohtumisest

  7. Energeetikast ja maagaasist / Einari Kisel

    Index Scriptorium Estoniae

    Kisel, Einari, 1972-


    Maagaasi osa Eesti energiabilansis on kasvanud 10,8%-lt 1995.a. 15,5%-ni 2005. a. Regionaalse gaasituru arengu mõju Eestile: Läänemerre kavandatav Venemaa ja Saksamaa gaasitoru, Eesti ja Soome vahelise gaasitoru Balticconnector uuringud, kaugemates plaanides Balti regiooni vedelgaasi terminali rajamine, uute maagaasi hoidlate rajamine Lätisse ja Leetu

  8. Kundas hoitakse Eesti vedelkütuse varusid / Raivo Raigna

    Index Scriptorium Estoniae

    Raigna, Raivo


    Eesti vedelkütusevarude hoiustamise hanke üks võitjaid on Soome firma Baltic Tank OY, mis on Baltic Tank AS-i emafirma. Kunda sadamas asuvas Baltic Tanki AS-i terminalis hoitakse Eesti riigi diislikütuse tagavara

  9. Pärnu raudteejaama futuristlik tulevik / Silvia Pärmann

    Index Scriptorium Estoniae

    Pärmann, Silvia


    Rail Baltic Pärnu reisijate terminali arhitektuurikonkursi võitis ideekavand "Water Strider", autorid Indrek Allmann, Jaan Jagomägi, Gunnar Kurusk, Tanno Tammesson, Holden Vides (arhitektuuribüroo Pluss). Teine koht projekt "Komeet", kolmas koht projekt "Hirv"

  10. Effect of stirring on striae in glass melts

    DEFF Research Database (Denmark)

    Jensen, Martin; Yue, Yuanzheng


    Chemical striae have often negative effect on the glass properties, and hence, elimination of striae has been a key issue in glass science and technology. To produce highly homogeneous glasses, it is necessary to stir melts during the melting process. To explore the physical origin of the stria...


    NARCIS (Netherlands)



    In experimental endolymphatic hydrops (EEH) a decrease in the endocochlear potential (EP) has been reported and is thought to be due to decreased activity of the enzyme Na+/K+-ATPase in the stria vascularis. By stimulating Na+/K+-ATPase, the EP, and thereby cochlear function as a whole, might be

  12. Effect of melting conditions on striae in iron-bearing silicate melts

    DEFF Research Database (Denmark)

    Jensen, Martin; Yue, Yuanzheng


    of melt temperature and/or a decrease of viscosity play a more important role in decreasing the stria content. We also demonstrate that the extent of striation is influenced by the crucible materials that causes a change of redox state of the melt, and hence its viscosity. We discuss the effect of other...

  13. Mapping of kisspeptin fibres in the brain of the pro-oestrus rat

    DEFF Research Database (Denmark)

    Desroziers, E; Mikkelsen, J; Simonneaux, V


    throughout the external layer including around the deeper part of the infundibular recess. Most regions of immunoreactive cells and fibres matched perfectly for the two antibodies. However, fibres in the dorso-lateral septum, anterior fornix, accumbens nucleus and the lateral bed nucleus of the stria...

  14. Neural and Behavioral Correlates of PTSD and Alcohol Use (United States)


    Table 4). Table 4: Participant Demographics. Age 31.5 ± 0.8 years Gender 89% Male, 11% Female Race/ Ethnicity 89% White, 5% Native American, 4...releasing factor (CRF) infused into the BNST [56]. This effect is presumed to result through facilitation of glutamate release from BLA afferents by...of Glutamate . Neurosci Lett. 379, 37-41. S0304-3940(04)01584-8 [pii] 10.1016/j.neulet.2004.12.047. [108] Mo B, Feng N, Renner K, Forster G (2008

  15. ENTENDENDO A DINÂMICA CULTURAL EM XINGÓ NA PERSPECTIVA INTER SÍTIOS: INDÚSTRIAS LÍTICAS E OS LUGARES PERSISTENTES NO BAIXO VALE DO RIO SÃO FRANCISCO, NORDESTE DO BRASIL (Entendiendo la dinámica cultural en Xingó en la perspectiva inter-sitios: industrias líticas y los lugares persistentes en el bajo valle del río São Francisco, Nordeste del Brasil; Understanding cultural dynamics in Xingó from an intersite perspective: lithic industries and persistent places in the São Francisco river low valley, Northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Marcelo Fagundes


    Full Text Available O presente artigo tem como objetivo apresentar parte dos resultados da tese de doutoramento acerca da dinâmica cultural evidenciada em dezesseis sítios arqueológicos localizados na Área 03 de Xingó, baixo vale do rio São Francisco, Brasil. Assim, apresentaremos os dados obtidos da pesquisa empírica da organização tecnológica de conjuntos líticos e como foi possível, por meio desses resultados, inferir sobre questões acerca da distribuição espacial dos sítios arqueológicos e suas possíveis inter-relações de forma a indicar um modelo de uso da paisagem à compreensão do sistema regional de assentamento em terraços do baixo vale do rio São Francisco. ESPAÑOL: Este artículo tiene como objetivo presentar parte de los resultados de mi tesis de doctorado sobre la dinámica cultural evidenciada en dieciséis sitios arqueológicos ubicados en el Área 03 de Xingó, bajo valle del río São Francisco, Brasil. Por lo tanto, se presentarán los datos obtenidos de la investigación empírica de la organización tecnológica de conjuntos líticos para inferir, por medio de esos resultados, aspectos sobre la distribución espacial de los sitios arqueológicos y sus posibles interrelaciones, buscando generar un modelo de uso del paisaje para la comprensión del sistema regional de asentamiento en bancales del bajo valle del río São Francisco. ENGLISH: This paper presents part of the results of my doctoral thesis on the cultural dynamics of sixteen archaeological sites situated in Area 03 in Xingó, São Francisco river valley, Brazil. Empirical data are presented that demonstrate the technological organization of the lithic industries at the sites. Then, through these data, it is shown what we can infer about the archaeological sites’ spatial distribution and interrelationship. These inferences are used to indicate a model of landscape use that can be used to understand the regional system of distribution and placement of archaeological sites.

  16. A Cultural Resources Reconnaissance for the Wailua River Hydropower Study, (United States)


    Prominent vegetation on the slopes above include occasional ki (Cordyline terminalis), patches of lau’ae (Polypodium phymatodes), guava (Psidium guajava...trees were noted growing from the swampy ground within the stands of hau. These plants are probably growing from seed washed down by the ri.,er or thrown...makai a section of the wall has been washed out by stream flow. This terrace ranges from about 12 feet to 24 feet wide and is bordered on the south by

  17. Milleks Eestile gaasitorud? / Mirko Ojakivi

    Index Scriptorium Estoniae

    Ojakivi, Mirko


    Poliitikud soovivad eraldada Eesti gaasi ülekandevõrgu ehk suurema torustiku gaasi müüvast ettevõttest Eesti Gaas. USA-st toodav veeldatud gaas on 30% odavam kui Gazpromi gaas, Eestis on ettevalmistamisel kaks veeldatud gaasi terminali. Ekspertide hinnangul ei ole seda gaasi müüa soovivatel ettevõtetel Eesti turule asja, kui Eesti Gaasile kuulub võrk ja ta tegeleb ka gaasi müügiga

  18. Manga tüdruku kampaania

    Index Scriptorium Estoniae


    8. märtsil avati Tallinna D-terminalis ülemaailmse seljaajusonga ja vesipeahaigete katusorganisatsiooni IF SpBH kampaania-aasta, millega juhitakse tähelepanu kaasasündinud kesknärvisüsteemihaigustele ning nende ennetamisele foolhappe ehk B9-vitamiiniga ning foolhappega. Manga tüdrukuga märgistatud kampaaniatoodetega teadvustatakse foolhappega rikastatud toidutooteid ning kogutakse Mati Karmini meremiinist valmistatud korjanduskastidega raha Tallinna reisisadama d-terminaalis

  19. Neural correlates of expression-independent memories in the crab Neohelice. (United States)

    Maza, F J; Locatelli, F F; Delorenzi, A


    The neural correlates of memory have been usually examined considering that memory retrieval and memory expression are interchangeable concepts. However, our studies in the crab Neohelice (Chasmagnathus) granulata and in other memory models have shown that memory expression is not necessary for memory to be re-activated and become labile. In order to examine putative neural correlates of memory in the crab Neohelice, we contrast changes induced by training in both animal's behavior and neuronal responses in the medulla terminalis using in vivo Ca(2+) imaging. Disruption of long-term memory by the amnesic agents MK-801 or scopolamine (5μg/g) blocks the learning-induced changes in the Ca(2+) responses in the medulla terminalis. Conversely, treatments that lead to an unexpressed but persistent memory (weak training protocol or scopolamine 0.1μg/g) do not block these learning-induced neural changes. The present results reveal a set of changes in the neural activity induced by training that correlates with memory persistence but not with the probability of this memory to be expressed in the long-term. In addition, the study constitutes the first in vivo evidence in favor of a role of the medulla terminalis in learning and memory in crustaceans, and provides a physiological evidence indicating that memory persistence and the probability of memory to be expressed might involve separate components of memory traces. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Немоторные проявления болезни Паркинсона


    Пиллипович, Анна; Гойтемирова, П.; Ноздрюхина, Наталия; Струценко, Алла; Гарабова, Наида; Чебоксаров, Дмитрий; Бунтина, Мария


    Parkinson's disease a chronic degenerative disease of the central nervous system, clinically manifested by a combination of hypokinesia and postural disorders with rigidity and resting tremor, and autonomic disorders and mental functions. The pathogenesis of Parkinson's disease is inhibition of the functions of dopaminergic systems of the central nervous system (stria negroid, tuberoinfundibular, olfactory, retinal, and so on). With a comprehensive defeat of dopaminergetic systems associated ...

  1. Nonischemic Left Ventricular Scar as a Substrate of Life-Threatening Ventricular Arrhythmias and Sudden Cardiac Death in Competitive Athletes. (United States)

    Zorzi, Alessandro; Perazzolo Marra, Martina; Rigato, Ilaria; De Lazzari, Manuel; Susana, Angela; Niero, Alice; Pilichou, Kalliopi; Migliore, Federico; Rizzo, Stefania; Giorgi, Benedetta; De Conti, Giorgio; Sarto, Patrizio; Serratosa, Luis; Patrizi, Giampiero; De Maria, Elia; Pelliccia, Antonio; Basso, Cristina; Schiavon, Maurizio; Bauce, Barbara; Iliceto, Sabino; Thiene, Gaetano; Corrado, Domenico


    The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain to be elucidated. We compared 35 athletes (80% men, age: 14-48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls. Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography. © 2016 The Authors.

  2. Estudo qu?mico de res?duos madeireiros de Bagassa guianensis (Aubl.) Eschweilera coriaceae (Mori, Scott A.) e Ocotea cymbarum (Kunth)


    Hayasida, Willian


    A madeira ? um material de origem natural amplamente utilizado em diversos setores industriais, formado por componentes qu?micos que usualmente n?o s?o considerados durante o seu processamento, principalmente os metab?litos secund?rios que por consequ?ncia acabam rejeitados. Neste trabalho avaliaram-se os res?duos madeireiros de louro-preto (Ocotea cymbarum, Lauraceae), tatajuba (Bagassa guianensis, Moraceae) e pe?ozinho (Eschweleira coriaceae, Lecythidaceae), proveniente da ind?stria de conf...

  3. Dopamine release from serotonergic nerve fibers is reduced in L-DOPA-induced dyskinesia


    Nevalainen, Nina; af Bjerkén, Sara; Lundblad, Martin; Gerhardt, Greg A.; Strömberg, Ingrid


    L-DOPA (3,4-dihydroxyphenyl-L-alanine) is the most commonly used treatment for symptomatic control in patients with Parkinson’s disease. Unfortunately, most patients develop severe side effects, such as dyskinesia, upon chronic L-DOPA treatment. The patophysiology of dyskinesia is unclear, however, involvement of serotonergic nerve fibers in converting L-DOPA to dopamine has been suggested. Therefore, potassium-evoked dopamine release was studied after local application of L-DOPA in the stria...

  4. Characterizing the contrast of white matter and grey matter in high-resolution phase difference enhanced imaging of human brain at 3.0 T

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Li [Fudan University, Department of Radiology, Shanghai Institute of Medical Imaging, Zhongshan Hospital, Shanghai (China); Shandong University, Shandong Medical Imaging Research Institute, Shandong Provincial Key Laboratory of Diagnosis and Treatment of Cardio-cerebral Vascular Diseases, Jinan, Shandong (China); Wang, Shanshan; Yao, Bin; Li, Lili; Guo, Lingfei; Zhang, Xinjuan; Wang, Guangbin [Shandong University, Shandong Medical Imaging Research Institute, Shandong Provincial Key Laboratory of Diagnosis and Treatment of Cardio-cerebral Vascular Diseases, Jinan, Shandong (China); Xu, Xiaofei [Erasmus University Rotterdam, Laboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Rotterdam (Netherlands); Zhao, Lianxin [Shandong University, Department of Radiology, Qilu Hospital, Jinan, Shandong (China); Chen, Weibo; Chan, Queenie [Philips Healthcare, Shanghai (China)


    The purpose of this study was to address the feasibility of characterizing the contrast both between and within grey matter and white matter using the phase difference enhanced (PADRE) technique. PADRE imaging was performed in 33 healthy volunteers. Vessel enhancement (VE), tissue enhancement (TE), and PADRE images were reconstructed from source images and were evaluated with regard to differentiation of grey-to-white matter interface, the stria of Gennari, and the two layers, internal sagittal stratum (ISS) and external sagittal stratum (ESS), of optic radiation. White matter regions showed decreased signal intensity compared to grey matter regions. Discrimination was sharper between white matter and cortical grey matter in TE images than in PADRE images, but was poorly displayed in VE images. The stria of Gennari was observed on all three image sets. Low-signal-intensity bands displayed in VE images representing the optic radiation were delineated as two layers of different signal intensities in TE and PADRE images. Statistically significant differences in phase shifts were found between frontal grey and white matter, as well as between ISS and ESS (p < 0.01). The PADRE technique is capable of identifying grey-to-white matter interface, the stria of Gennari, and ISS and ESS, with improved contrast in PADRE and TE images compared to VE images. (orig.)

  5. Cochlear changes in presbycusis with tinnitus. (United States)

    Terao, Kyoichi; Cureoglu, Sebahattin; Schachern, Patricia A; Morita, Norimasa; Nomiya, Shigenobu; Deroee, Armin F; Doi, Katsumi; Mori, Kazunori; Murata, Kiyotaka; Paparella, Michael M


    The pathophysiology of tinnitus is obscure and its treatment is therefore elusive. Significant progress in this field can only be achieved by determining the mechanisms of tinnitus generation, and thus, histopathologic findings of the cochlea in presbycusis with tinnitus become crucial. We revealed the histopathologic findings of the cochlea in subjects with presbycusis and tinnitus. The subjects were divided into 2 groups, presbycusis with tinnitus (tinnitus) group and presbycusis without tinnitus (control) group, with each group comprising 8 temporal bones from 8 subjects. We quantitatively analyzed the number of spiral ganglion cells, loss of cochlear inner and outer hair cells, and areas of the stria vascularis and spiral ligament. There was a significantly greater loss of outer hair cells in the tinnitus group compared with the control group in the basal and upper middle turns. The stria vascularis was more atrophic in the tinnitus group compared with the control group in the basal turn. Tinnitus is more common in patients with presbycusis who have more severe degeneration of outer hair cells and stria vascularis. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Progression of changes in the sensorial elements of the cochlear and peripheral vestibular systems: The otitis media continuum. (United States)

    Monsanto, Rafael da Costa; Schachern, Patricia; Paparella, Michael M; Cureoglu, Sebahattin; Penido, Norma de Oliveira


    Our study aimed to evaluate pathologic changes in the cochlear (inner and outer hair cells and stria vascularis) and vestibular (vestibular hair cells, dark, and transitional cells) sensorial elements in temporal bones from donors who had otitis media. We studied 40 temporal bones from such donors, which were categorized in serous otitis media (SOM), serous-purulent otitis media (SPOM), mucoid/mucoid-purulent otitis media (MOM/MPOM), and chronic otitis media (COM); control group comprised 10 nondiseased temporal bones. We found significant loss of inner and outer cochlear hair cells in the basal turn of the SPOM, MOM/MPOM and COM groups; significant loss of vestibular hair cells was observed in the MOM/MPOM and COM groups. All otitis media groups had smaller mean area of the stria vascularis in the basal turn of the cochlea when compared to controls. In conclusion, our study demonstrated more severe pathologic changes in the later stages of the continuum of otitis media (MOM/MPOM and COM). Those changes seem to progress from the basal turn of the cochlea (stria vascularis, then inner and outer hair cells) to the middle turn of the cochlea and to the saccule and utricle in the MOM/MPOM and COM stages. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. A transgenic rat for investigating the anatomy and function of corticotrophin releasing factor circuits

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    Matthew B Pomrenze


    Full Text Available Corticotrophin-releasing factor (CRF is a 41 amino acid neuropeptide that coordinates adaptive responses to stress. CRF projections from neurons in the central nucleus of the amygdala (CeA to the brainstem are of particular interest for their role in motivated behavior. To directly examine the anatomy and function of CRF neurons, we generated a BAC transgenic Crh-Cre rat in which bacterial Cre recombinase is expressed from the Crh promoter. Using Cre-dependent reporters, we found that Cre expressing neurons in these rats are immunoreactive for CRF and are clustered in the lateral CeA (CeL and the oval nucleus of the BNST. We detected major projections from CeA CRF neurons to parabrachial nuclei and the locus coeruleus, dorsal and ventral BNST, and more minor projections to lateral portions of the substantia nigra, ventral tegmental area, and lateral hypothalamus. Optogenetic stimulation of CeA CRF neurons evoked GABA-ergic responses in 11% of non-CRF neurons in the medial CeA (CeM and 44% of non-CRF neurons in the CeL. Chemogenetic stimulation of CeA CRF neurons induced Fos in a similar proportion of non-CRF CeM neurons but a smaller proportion of non-CRF CeL neurons. The CRF1 receptor antagonist R121919 reduced this Fos induction by two-thirds in these regions. These results indicate that CeL CRF neurons provide both local inhibitory GABA and excitatory CRF signals to other CeA neurons, and demonstrate the value of the Crh-Cre rat as a tool for studying circuit function and physiology of CRF neurons.

  8. Phrenic nerve protection via packing of gauze into the pericardial space during ablation of cristal atrial tachycardia in a child. (United States)

    Takahashi, Kazuhiro; Fuchigami, Tai; Nabeshima, Taisuke; Sashinami, Arata; Nakayashiro, Mami


    The success of catheter ablation of focal atrial tachycardia is limited by possible collateral damage to the phrenic nerve. Protection of the phrenic nerve is required. Here we present a case of a 9-year-old girl having a history of an unsuccessful catheter ablation of a focal atrial tachycardia near the crista terminalis (because of proximity of the phrenic nerve) who underwent a successful ablation by means of a novel technique for phrenic nerve protection: packing of gauze into the pericardial space. This method is a viable approach for patients with a failed endocardial ablation due to the proximity of the phrenic nerve.

  9. Data on knowledge of psocoptera and neuropterida in Sălaj county

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    Sziráki G.


    Full Text Available In the framework of the project „Invertebrate faunistical investigation of Sălaj county” 23 Psocoptera, 1 Megaloptera, 1 Raphidioptera and 30 Neuroptera specimens were collected, belonging to 5 Psocoptera, 1 Megaloptera, 1 Raphidioptera and 7 Neuroptera species. In spite of these low numbers, three of the found insects are worth to mention. Regarding the fauna of Romania, Kolbia quisquiliarum Bertkau, 1882 (Psocoptera hitherto was mentioned only from Bucovina, Sialis fuliginosa Pictet, 1836 (Megaloptera was known only from Sinaia and Sibiu, while Sisyra terminalis Curtis, 1854 (Neuroptera was reported only one occasion and more than hundred years ago.

  10. Isolated Crohn's disease of the stomach

    International Nuclear Information System (INIS)

    Traxler, M.; Weiss, W.; Rohrmoser, G.


    The spectrum of this disease has undergone major changes since 1932 when Crohn, Ginzberg and Oppenheimer differentiated Ileitis terminalis from nonspecific inflammations of the bowels. Initially, Crohn assumed an inflammation restricted to the terminal ileum. Today, Crohn's disease has been verified to affect the total gastro-intestinal tract from the cavity of the mouth to the anus. In 1949 Ross et al. were the first to report Crohn's disease in the region of the stomach and duodenum. Its localization in the upper intestinal tract, however, is a rare occurrence on the whole. (orig.) [de

  11. Loss of KCNJ10 protein expression abolishes endocochlear potential and causes deafness in Pendred syndrome mouse model

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    Wall Susan M


    Full Text Available Abstract Background Pendred syndrome, a common autosomal-recessive disorder characterized by congenital deafness and goiter, is caused by mutations of SLC26A4, which codes for pendrin. We investigated the relationship between pendrin and deafness using mice that have (Slc26a4+/+ or lack a complete Slc26a4 gene (Slc26a4-/-. Methods Expression of pendrin and other proteins was determined by confocal immunocytochemistry. Expression of mRNA was determined by quantitative RT-PCR. The endocochlear potential and the endolymphatic K+ concentration were measured with double-barreled microelectrodes. Currents generated by the stria marginal cells were recorded with a vibrating probe. Tissue masses were evaluated by morphometric distance measurements and pigmentation was quantified by densitometry. Results Pendrin was found in the cochlea in apical membranes of spiral prominence cells and spindle-shaped cells of stria vascularis, in outer sulcus and root cells. Endolymph volume in Slc26a4-/- mice was increased and tissue masses in areas normally occupied by type I and II fibrocytes were reduced. Slc26a4-/- mice lacked the endocochlear potential, which is generated across the basal cell barrier by the K+ channel KCNJ10 localized in intermediate cells. Stria vascularis was hyperpigmented, suggesting unalleviated free radical damage. The basal cell barrier appeared intact; intermediate cells and KCNJ10 mRNA were present but KCNJ10 protein was absent. Endolymphatic K+ concentrations were normal and membrane proteins necessary for K+ secretion were present, including the K+ channel KCNQ1 and KCNE1, Na+/2Cl-/K+ cotransporter SLC12A2 and the gap junction GJB2. Conclusions These observations demonstrate that pendrin dysfunction leads to a loss of KCNJ10 protein expression and a loss of the endocochlear potential, which may be the direct cause of deafness in Pendred syndrome.

  12. Loss of KCNJ10 protein expression abolishes endocochlear potential and causes deafness in Pendred syndrome mouse model (United States)

    Wangemann, Philine; Itza, Erin M; Albrecht, Beatrice; Wu, Tao; Jabba, Sairam V; Maganti, Rajanikanth J; Ho Lee, Jun; Everett, Lorraine A; Wall, Susan M; Royaux, Ines E; Green, Eric D; Marcus, Daniel C


    Background Pendred syndrome, a common autosomal-recessive disorder characterized by congenital deafness and goiter, is caused by mutations of SLC26A4, which codes for pendrin. We investigated the relationship between pendrin and deafness using mice that have (Slc26a4+/+) or lack a complete Slc26a4 gene (Slc26a4-/-). Methods Expression of pendrin and other proteins was determined by confocal immunocytochemistry. Expression of mRNA was determined by quantitative RT-PCR. The endocochlear potential and the endolymphatic K+ concentration were measured with double-barreled microelectrodes. Currents generated by the stria marginal cells were recorded with a vibrating probe. Tissue masses were evaluated by morphometric distance measurements and pigmentation was quantified by densitometry. Results Pendrin was found in the cochlea in apical membranes of spiral prominence cells and spindle-shaped cells of stria vascularis, in outer sulcus and root cells. Endolymph volume in Slc26a4-/- mice was increased and tissue masses in areas normally occupied by type I and II fibrocytes were reduced. Slc26a4-/- mice lacked the endocochlear potential, which is generated across the basal cell barrier by the K+ channel KCNJ10 localized in intermediate cells. Stria vascularis was hyperpigmented, suggesting unalleviated free radical damage. The basal cell barrier appeared intact; intermediate cells and KCNJ10 mRNA were present but KCNJ10 protein was absent. Endolymphatic K+ concentrations were normal and membrane proteins necessary for K+ secretion were present, including the K+ channel KCNQ1 and KCNE1, Na+/2Cl-/K+ cotransporter SLC12A2 and the gap junction GJB2. Conclusions These observations demonstrate that pendrin dysfunction leads to a loss of KCNJ10 protein expression and a loss of the endocochlear potential, which may be the direct cause of deafness in Pendred syndrome. PMID:15320950

  13. Cell-specific accumulation patterns of gentamicin in the guinea pig cochlea. (United States)

    Heinrich, Ulf-Rüdiger; Schmidtmann, Irene; Strieth, Sebastian; Helling, Kai


    Intratympanic gentamicin therapy has become a popular treatment modality for Ménière's disease (MD) through controlled elimination of vertigo spells caused by the balance organ. However, the known ototoxic properties of aminoglycosides lead to cochlear damage. In order to gain more information about cellular preferences for aminoglycoside accumulation within the cochlea, gentamicin was immuno histochemically localized by light microscopy in male guinea pigs 1 and 7 days after intratympanic application (n = 8 ears/incubation time). Differences in the gentamicin-specific cellular storage capacities were quantified by determination of the local immuno staining intensities. Gentamicin was detected in every cochlear cell type, but with spatiotemporal variability. One day after application, an intense staining reaction was found in all cell types except the spiral ganglion cells and the stria vascularis. Six days later, gentamicin staining intensities were additionally reduced in the nerve fibers and the spiral ligament. Statistic analysis revealed strong cellular associations in respect to aminoglycoside accumulation. Furthermore, associations with recorded hearing losses were identified comparing the cellular gentamicin content in the organ of Corti, in the stria vascularis, in the spiral ganglion cells and in fibrocytes of the Limbus. In the lateral wall, clear differences in cellular gentamicin accumulation were found between type I fibrocytes of the spiral ligament compared with basal and intermediate cells of the stria vascularis. This finding was unexpected as these three cell types belong to a well-developed gap-junction system which normally enables unhampered cell communication. Cellular differences in local gentamicin storage capacities, transport processes and inherent diffusion barriers are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Presbycusis: a human temporal bone study of individuals with downward sloping audiometric patterns of hearing loss and review of the literature. (United States)

    Nelson, Erik G; Hinojosa, Raul


    The purpose of this retrospective case review was to identify patterns of cochlear element degeneration in individuals with presbycusis exhibiting downward sloping audiometric patterns of hearing loss and to correlate these findings with those reported in the literature to clarify conflicting concepts regarding the association between hearing loss and morphologic abnormalities. Archival human temporal bones from individuals with presbycusis were selected on the basis of strict audiometric criteria for downward-sloping audiometric thresholds. Twenty-one temporal bones that met these criteria were identified and compared with 10 temporal bones from individuals with normal hearing. The stria vascularis volumes, spiral ganglion cell populations, inner hair cells, and outer hair cells were quantitatively evaluated. The relationship between the severity of hearing loss and the degeneration of cochlear elements was analyzed using univariate linear regression models. Outer hair cell loss and ganglion cell loss was observed in all individuals with presbycusis. Inner hair cell loss was observed in 18 of the 21 individuals with presbycusis and stria vascularis loss was observed in 10 of the 21 individuals with presbycusis. The extent of degeneration of all four of the cochlear elements evaluated was highly associated with the severity of hearing loss based on audiometric thresholds at 8,000 Hz and the pure-tone average at 500, 1,000, and 2,000 Hz. The extent of ganglion cell degeneration was associated with the slope of the audiogram. Individuals with downward-sloping audiometric patterns of presbycusis exhibit degeneration of the stria vascularis, spiral ganglion cells, inner hair cells, and outer hair cells that is associated with the severity of hearing loss. This association has not been previously reported in studies that did not use quantitative methodologies for evaluating the cochlear elements and strict audiometric criteria for selecting cases.

  15. CaracterizaÃÃo do modelo de agroindustrializaÃÃo de pequeno porte voltado à propriedade rural familiar do MunicÃpio de Guarapuava - Pr


    Luci Nychai


    Caracterizou-se o modelo de agroindustrializaÃÃo de pequeno porte do municÃpio de Guarapuava-PR, ao ser evidenciada a inserÃÃo da propriedade rural familiar e ressaltados os aspectos de sobrevivÃncia no mercado como fator de sustentabilidade. Considerou-se o levantamento das agroindÃstrias dos sistemas alimentar e nÃo alimentar que compÃem o setor econÃmico secundÃrio, bem como o perfil da pequena propriedade rural familiar, de 1 a 50 hectares, integrada ao cooperativismo. P...

  16. CompulsÃo por compras: uma anÃlise psicossocial crÃtica acerca das subjetividades contemporÃneas


    Rebeca Carvalho de Morais


    A construÃÃo subjetiva contemporÃnea apresenta-se marcadamente permeada pela lÃgica do mercado responsÃvel por fabricar â via IndÃstria cultural â os mais diversos estilos de vida a serem consumidos pelo homem. A partir deste contexto, reflete-se acerca dos novos transtornos hipermodernos, tendo por figura exemplar o comportamento compulsivo por compras, analisado a partir do referencial teÃrico da Escola de Frankfurt. O objetivo à compreender os sentidos da compulsÃo por compras, considerand...

  17. An?lise econ?mico-financeira das empresas AMBEV, Coca-Cola e Pepsi com base nos crit?rios de investimento de Warren Buffett


    Ueda, Diego Santelli


    Atualmente, o consumo de bebidas n?o alco?licas est? encolhendo, o que antes era de 88,9 litros por pessoa em 2010 passou para 80,6 litros em 2014 (ABIR, 2015). Esse ambiente desafiador em que se encontram as ind?strias de bebidas requer cada vez mais aten??o dos administradores e investidores na tomada de decis?o. Assim, ? por meio da avalia??o econ?mico-financeira dos investimentos que se pode projetar o sucesso ou insucesso econ?mico deste, tendo como base as vari?veis que comp?e os demons...

  18. Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity. (United States)

    Topdag, M; Iseri, M; Gelenli, E; Yardimoglu, M; Yazir, Y; Ulubil, S A; Topdag, D O; Ustundag, E


    This study aimed to contribute to the literature on the prevention and treatment of ototoxicity due to various drugs and chemicals. This study compared the histological effects of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity, in 36 rats. Dexamethasone and memantine had significant effects on the stria vascularis, organ of Corti and spiral ganglion (p piracetam decreased the apoptosis rate, this effect was not statistically significant (p > 0.05). Dexamethasone and memantine were found superior to piracetam in reducing apoptosis due to cisplatin ototoxicity. Further studies of this subject are needed, incorporating electron microscopy and auditory brainstem response testing.

  19. Feasibility of the combination of 3D CTA and 2D CT imaging guidance for clipping microsurgery of anterior communicating artery aneurysm. (United States)

    Wada, Kojiro; Nawashiro, Hiroshi; Ohkawa, Hidenori; Arimoto, Hirohiko; Takeuchi, Satoru; Mori, Kentaro


    We report the technique of three-dimensional computed tomography angiography (3D CTA)+two-dimensional computed tomographic (2D CT) imaging as an adjunct in early surgery for a ruptured anterior communicating artery (ACoA) aneurysm by adopting an anterior interhemispheric approach. These combined imaging modalities provide accurate intraoperative anatomical information. To produce images for an anterior interhemispheric approach, 3D CTA+2D coronal CT images, which are perpendicular to the direction of the surgical approach at three levels (brain surface, genu of the corpus callosum and aneurysm neck), were constructed. We also produced two 3D CTA+2D CT images of the lamina terminalis, with a horizontal 10-degree difference, to clarify the vascular architecture around the aneurysm stereotactically, as well as the dissection point and direction to open the lamina terminalis. Furthermore, we produced a 3D CTA+2D sagittal CT image at the midline, which allowed us to understand the anatomical architecture of the aneurysm, planum sphenoidale and tuberculum sellae. In addition, four different 3D CTA aneurysm images were produced for deciding the clip size preoperatively. The imaging findings in 28 patients with 28 ACoA aneurysms facilitated early clipping. Based on these 3D CTA+2D CT images, we conducted aneurysm surgery, and successfully performed neck clipping via an anterior interhemispheric approach. The combination of 3D CTA and 2D CT images is a feasible and useful method of image guidance for ACoA aneurysm microsurgery.

  20. Brain ventricular wall movement assessed by a gated cine MR trueFISP sequence in patients treated with endoscopic third ventriculostomy

    Energy Technology Data Exchange (ETDEWEB)

    Hodel, Jerome [Unite Analyse et Restauration du mouvement, UMR-CNRS, Paris (France); Faculte de Medecine Paris XII, Paris (France); Assistance Publique-Hopitaux de Paris, Paris (France); Hopital Henri MONDOR, Department of Neuroradiology, Creteil (France); Hopital Henri Mondor, Creteil (France); Decq, Philippe [Unite Analyse et Restauration du mouvement, UMR-CNRS, Paris (France); Faculte de Medecine Paris XII, Paris (France); Assistance Publique-Hopitaux de Paris, Paris (France); Hopital Henri MONDOR, Department of Neurosurgery, Creteil (France); Rahmouni, Alain [Faculte de Medecine Paris XII, Paris (France); Assistance Publique-Hopitaux de Paris, Paris (France); Hopital Henri MONDOR, Department of Radiology, Creteil (France); Bastuji-Garin, Sylvie [Faculte de Medecine Paris XII, Paris (France); Assistance Publique-Hopitaux de Paris, Paris (France); Hopital Henri MONDOR, Department of Public Health, Creteil (France); Maraval, Anne; Combes, Catherine; Gaston, Andre [Faculte de Medecine Paris XII, Paris (France); Assistance Publique-Hopitaux de Paris, Paris (France); Hopital Henri MONDOR, Department of Neuroradiology, Creteil (France); Jarraya, Bechir [Faculte de Medecine Paris XII, Paris (France); Assistance Publique-Hopitaux de Paris, Paris (France); Hopital Henri MONDOR, Department of Neurosurgery, Creteil (France); Le Guerinel, Caroline [Assistance Publique-Hopitaux de Paris, Paris (France); Hopital Henri MONDOR, Department of Neurosurgery, Creteil (France)


    The purpose of this study was to investigate the value of brain ventricular wall movement assessment with a gated cine trueFISP MR sequence for the diagnosis of endoscopic third ventriculostomy (ETV) patency. Sixteen healthy volunteers and ten consecutive patients with noncommunicating hydrocephalus were explored with a MR scanner (Siemens, Avanto 1.5 T) before, 1 week and 3 months after ETV. TrueFISP was evaluated qualitatively (ventricular wall movement and CSF flow through ETV) and quantitatively [distance moved (DMLT) during a cardiac cycle by the lamina terminalis]. The third ventricle volume (TVV) was assessed. Statistical analysis was performed using nonparametric tests. There was no motion of the lamina terminalis (LT) detected on preoperative data. A pulsatile motion of the LT was found for patients with a patent ETV and for controls. DMLT and TVV were correlated (r = 0.79, P = 0.006). A transient dysfunction of ETV was successfully diagnosed on the trueFISP sequence with no motion of the LT or CSF flow observed. The trueFISP sequence appears reliable for the diagnosis of ETV patency and provides non-invasive assessment of the movement of the ventricular wall related to CSF pressure changes. (orig.)

  1. Catheter Ablation of a Complex Atrial Tachycardia after Surgical Repair of Tetralogy of Fallot Guided by Combined Noncontact and Contact Mapping

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    Eitaro Fujii, MD


    Full Text Available A 34-year-old man with a surgically repaired Tetralogy of Fallot complained of palpitation, fatigue, and presyncope. A 12-lead ECG showed atrial tachycardia with a cycle length of 250 ms and a P wave morphology positive in leads II, III and aVF, and negative in lead V1. Although the EnSite system (version 6.OJ made use of noncontact mapping to delineate the counterclockwise reentry around the crista tenninalis, it was difficult to rule out the incisional atrial reentry because the location of the surgical incision was far from the multi-electrode array. Since the bipolar contact mapping of the EnSite system revealed the location of the atriotomy incision, entrainment mapping during the tachycardia demonstrated the critical reentry circuit around the crista terminalis. Radiofrequency ablation targeting the critical isthmus from the lower position of the crista terminalis to the posterior dense scar which was continuous with the inferior vena cava, and to the atriotomy scar, eliminated the tachycardia.

  2. Novadessus viracocha, a new genus and species of Bidessini Sharp from Peru (Coleoptera, Adephaga, Dytiscidae, Hydroporinae

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    Kelly Miller


    Full Text Available Novadessus viracocha gen. n. and sp. n. is described from Peru. The genus distinctly is characterized by having the following combination: (1 a transverse occipital line absent on the head; (2 the anterior clypeal margin not modified; (3 a pair of basal pronotal striae present; (4 the basal elytral stria absent; (5 the elytral sutural stria absent; (6 the elytron without longitudinal carinae; (7 the epipleuron without a transverse carina at the humeral angle; (8 the lateral lobes of the male aedeagus two-segmented; (9 the overall habitus elongate and oval, with lateral pronotal and elytral margins discontinuous; (10 without distinct denticles along the posterior margins of the abdominal sternites; (11 the male genitalia (both median lobe and lateral lobes bilaterally symmetrical; and (12 the metatrochanter small relative to the metafemur, approximately 0.6 × the length of the metafemur. The genus is diagnostically similar to Fontidessus Miller and Spangler and Neobidessodes Hendrich and Balke, but is superficially more similar to Liodessus Guignot. The habitus and male genitalia are illustrated, and a distribution map is provided.

  3. Striated dust tail of Comet West 1976 VI as a particle fragmentation phenomenon

    International Nuclear Information System (INIS)

    Sekanina, Z.; Farrell, J.A.


    The motions of 16 striae in the dust tail of Comet West between 4 and 7 March 1976 have been successfully fitted on four small-scale photographs. Our model assumes that the striae are the result of the ejection of dust particles that subsequently fragment in the tail. The particles responsible for the formation of a discrete stria must be emitted simultaneously, be subjected to the same repulsive acceleration in the tail, and break up simultaneously. The results of the analysis indicate a strong correlation between the ejection times and the times of known explosive events. The repulsive accelerations of the fragments are found to be between 0.6 and 2.7 times the solar attraction, indicating submicron-sized absorbing particles. We also find that the repulsive accelerations of parent particles are only slightly smaller than those of their fragments, suggesting comparable area-to-mass ratios between parents and fragments, and therefore highly nonspherical shapes of parents. Complex, tenuously bonded, chain-like aggregates of submicron-sized grains would satisfy these conditions. The mass of dust in an average stria is estimated to be about 10 9 g. There was no measurable effect from the Lorentz force, indicating an upper limit of a few volts for the electric charge of the fragments. We consider rotational bursting caused by a ''windmill'' effect of radiation pressure to be a possible fragmentation mechanism. Application of a simple chain-particle model suggests the existence of discrete particle types

  4. Factors associated with hearing loss in a normal-hearing guinea pig model of Hybrid cochlear implants. (United States)

    Tanaka, Chiemi; Nguyen-Huynh, Anh; Loera, Katherine; Stark, Gemaine; Reiss, Lina


    The Hybrid cochlear implant (CI), also known as Electro-Acoustic Stimulation (EAS), is a new type of CI that preserves residual acoustic hearing and enables combined cochlear implant and hearing aid use in the same ear. However, 30-55% of patients experience acoustic hearing loss within days to months after activation, suggesting that both surgical trauma and electrical stimulation may cause hearing loss. The goals of this study were to: 1) determine the contributions of both implantation surgery and EAS to hearing loss in a normal-hearing guinea pig model; 2) determine which cochlear structural changes are associated with hearing loss after surgery and EAS. Two groups of animals were implanted (n = 6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no direct acoustic or electric stimulation during this time frame. A third group (n = 6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem response thresholds were followed over time at 1, 2, 6, and 16 kHz. At the end of the study, the following cochlear measures were quantified: hair cells, spiral ganglion neuron density, fibrous tissue density, and stria vascularis blood vessel density; the presence or absence of ossification around the electrode entry was also noted. After surgery, implanted animals experienced a range of 0-55 dB of threshold shifts in the vicinity of the electrode at 6 and 16 kHz. The degree of hearing loss was significantly correlated with reduced stria vascularis vessel density and with the presence of ossification, but not with hair cell counts, spiral ganglion neuron density, or fibrosis area. After 10 weeks of stimulation, 67% of implanted, stimulated animals had more than 10 dB of additional threshold shift at 1 kHz, compared to 17% of implanted, non-stimulated animals and 0% of non-implanted animals. This 1-kHz hearing loss was not associated with changes in any of the cochlear measures

  5. Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling. (United States)

    Resch, Jon M; Fenselau, Henning; Madara, Joseph C; Wu, Chen; Campbell, John N; Lyubetskaya, Anna; Dawes, Brian A; Tsai, Linus T; Li, Monica M; Livneh, Yoav; Ke, Qingen; Kang, Peter M; Fejes-Tóth, Géza; Náray-Fejes-Tóth, Anikó; Geerling, Joel C; Lowell, Bradford B


    Sodium deficiency increases angiotensin II (ATII) and aldosterone, which synergistically stimulate sodium retention and consumption. Recently, ATII-responsive neurons in the subfornical organ (SFO) and aldosterone-sensitive neurons in the nucleus of the solitary tract (NTS HSD2 neurons) were shown to drive sodium appetite. Here we investigate the basis for NTS HSD2 neuron activation, identify the circuit by which NTS HSD2 neurons drive appetite, and uncover an interaction between the NTS HSD2 circuit and ATII signaling. NTS HSD2 neurons respond to sodium deficiency with spontaneous pacemaker-like activity-the consequence of "cardiac" HCN and Na v 1.5 channels. Remarkably, NTS HSD2 neurons are necessary for sodium appetite, and with concurrent ATII signaling their activity is sufficient to produce rapid consumption. Importantly, NTS HSD2 neurons stimulate appetite via projections to the vlBNST, which is also the effector site for ATII-responsive SFO neurons. The interaction between angiotensin signaling and NTS HSD2 neurons provides a neuronal context for the long-standing "synergy hypothesis" of sodium appetite regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Serotonin modulation of CHH secretion by isolated cells of the crayfish retina and optic lobe. (United States)

    Escamilla-Chimal, Elsa G; Hiriart, Marcia; Sánchez-Soto, Ma Carmen; Fanjul-Moles, Maria Luisa


    The authors used the reverse hemolytic plaque assay to investigate whether single retinal and optic lobe cells of juvenile and adult crayfish secrete crustacean hyperglycemic hormone (CHH) and whether the secretion rate depends on extracellular serotonin (5-HT) concentration. Nearly 25% of individual retinal and optic lobe cells of juvenile and adult organisms secrete CHH in response to KCl depolarization. In this condition, CHH secretion increased as a function of 5-HT concentration. In both cases, the dose-response curve indicates two different populations of CHH-secreting cells. Juveniles showed a higher CHH secretion index than did adult organisms, demonstrating a developmental interstage variation of CHH secretion. The authors conclude that (1) retinal CHH-secreting cells correspond to a population of retinal tapetal cells and (2) optic lobe CHH-secreting cells correspond to two subpopulations of CHH of medulla terminalis-X organ.

  7. [Study on Camellia Sect. Chrysantha Chang species identification by FTIR technology]. (United States)

    Qin, Xiao-Ling; Shi, Yan-Cai; Li, Cheng-Zhuo; Wei, Xiao; Huang, Rong-Shao; Kong, De-Xin; Huang, Shu-Shi


    FTIR spectra from 16 kinds of Camellia Sect. Chrysantha by Fourier transform infrared spectroscopy (FTIR) method combined with the system clustering and correlation coefficient method were used to analyze and compare these spectral data. The results, show that: Camellia Sect. Chrysantha of 16 kinds were divided into three groups, the first kind was: C. longzhouensis etc, in all eleven kinds; The second kind was: C. achrysantha, C. limonia, C. pingguoensis and C. chuongtsoensis; The third kind was C. microcarpa, which for a class alone. According to the difference in related anatomy and morphology, this study supported that C. longgangensis and C. ptilosperma should be incorporated into one kind; C. multipetala, C. longgangensis, C. parvipetala, C. tunghinensis and C. limonia, C. achrysantha, C. microcarpa, C. nitidissima, C. terminali and C. pingguoensis should be divided into separate species. FTIR-cluster analysis can be used as a possible means for the identification of Camellia Sect. Chrysantha.

  8. Comparative investigations on xeroradiography and conventional X-radiation with chronical polyarthritis

    International Nuclear Information System (INIS)

    Meisl, T.A.


    We compared the roentgenologic and xeroradiographic findings of the hands of 50 patients suffering from polyarthritis. Both techniques were compared with respect to their imaging quality of roentgenologically significant alterations occurring with chronical polyarthritis. The superiority of xeroradiography bases on the better contour delineation facilities. Disadvantages are the loss of detailed information due to neutralisation effects and also to the impaired representation of areal density differences and of the absolute density of an object. The conventional roentgenologic method is superior with respect to the more informative imaging of areal density modifications, also to the partly better representation of cystic transluences and to a minor degree with respect to a more distinct reproduction of an atrophy of the subchondral lamina terminalis. However, in general it can be said that the results of the two compared techniques do not differ significantly. Consequently the traditional roentgenologic method appears to be the more suitable technique for the diagnosis of chronical polyarthritis. (orig./MG) [de

  9. Dicty_cDB: Contig-U15045-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available e) Bacillus anthracis str. CDC 684... 286 2e-75 EU302126_1( EU302126 |pid:none) Luciola terminali... AE006470_46( AE006470 |pid:none) Chlorobium tepidum TLS, complete ... 207 2e-51 AM494956_128( AM494956 |pid...centrotus purpuratus clone R3-42P23, WOR... 36 0.051 11 ( EK354403 ) 1095468426890 Global-Ocean-Sampling_GS-...** SEQUENCI... 38 0.25 13 ( EJ594751 ) 1092961073324 Global-Ocean-Sampling_GS-29-01-01-1... 40 0.26 2 ( BA00...170 ) 1093018401251 Global-Ocean-Sampling_GS-36-01-01-2... 50 0.35 1 ( ER486373 ) 1093015301415 Global-Ocean-Sampli

  10. Dicty_cDB: Contig-U06400-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available . pom... 36 0.72 AF489463_2( AF489463 |pid:none) Orussus terminalis NADH dehydrogen... 36 0.94 CP001229_564(...K566108 ) 1095521042507 Global-Ocean-Sampling_GS-32-01-01-1... 34 1.0 2 ( CU469464 ) Candidatus Phytopl...tus clone R3-3117D16, W... 46 1.4 1 ( EJ362356 ) 1092963691825 Global-Ocean-Sampling_GS-28-01-01-1... 46 1.4...SE... 44 5.7 1 ( EK340302 ) 1095467059309 Global-Ocean-Sampling_GS-31-01-01-1... 44 5.7 1 ( EK314173 ) 10954...62407059 Global-Ocean-Sampling_GS-31-01-01-1... 44 5.7 1 ( EK262899 ) 1095462187822 Global-Ocean-Sampling_GS

  11. Dicty_cDB: Contig-U06881-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available T, clone G000... 44 4.9 1 ( CB077241 ) hj51d10.g1 Hedyotis terminalis flower - Stage 2 (... 44 4.9 1 ( BI739...) 1092959732476 Global-Ocean-Sampling_GS-31-01-01-1... 36 0.16 3 ( EJ122584 ) 1092343379871 mth2-12f13... 38 0.28 7 ( EJ342623 ) 1092963526465 Global-Ocean-Sampling_GS-28-01-01-1... 48 0.32 1 ( CE...2 ) 1095469414961 Global-Ocean-Sampling_GS-31-01-01-1... 40 0.59 2 ( AJ871361 ) Nyctotherus ovalis partial g...180574 ) Strongylocentrotus purpuratus clone R3-3095P18, W... 46 1.2 1 ( EJ372544 ) 1092963729038 Global-Ocean-Sampli

  12. Dicty_cDB: Contig-U05044-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available pSkeMus1 Xenopus (Sil... 40 0.47 3 ( CB078367 ) hj66g06.g1 Hedyotis terminalis flower - Stage 2 (... 36 0.48...) 1092343402430 Global-Ocean-Sampling_GS-27-01-01-1... 44 0.013 2 ( CR389591 ) Gallus gallus finished cDNA, ...cigd039p01, 3' en... 48 9e-04 2 ( EJ556699 ) 1092959507186 Global-Ocean-Sampling_GS-29-01-01-1... 42 0.001 2... ( EJ554022 ) 1092959481122 Global-Ocean-Sampling_GS-29-01-01-1... 42 0.001 2 ( FM928382 ) Brachionus pli...s ML CMVsport jasme... 50 0.18 1 ( EK107136 ) 1092963062468 Global-Ocean-Sampli

  13. The morphological variation of Myzus persicae (Hemiptera: Aphididae from peach and tobacco in Serbia and Montenegro

    Directory of Open Access Journals (Sweden)

    Vučetić Anđa


    Full Text Available Multivariate morphometric analysis was used to compare nine characteristics of 47 populations of Myzus persicae (Sulzer originating from two host-plants, peach and tobacco, from 13 localities in 2004 and 34 localities in 2005, in Serbia and Montenegro. Multivariant discriminant analysis showed there to be a distinct discrimination between the populations from the peach and tobacco host-plants. The most important discrimination characteristics are the ultimate rostral segment length and processes terminalis length, which are greater in the aphids from tobacco than in those from peach. This is the first indication that in this part of Europe there are two subspecies: M. persicae (Sulzer and M. persicae nicotianae Blackman. .

  14. Mapping of kisspeptin fibres in the brain of the pro-oestrus rat

    DEFF Research Database (Denmark)

    Desroziers, E; Mikkelsen, J; Simonneaux, V


    Abstract Kisspeptins are a family of small peptides that play a key role in the neuroendocrine regulation of the reproductive function through neural pathways which have not yet been completely identified. This study aimed to investigate the distribution of kisspeptin neurone fibres in the female...... rat brain by comparing precisely the immunoreactive pattern obtained with two antibodies: one specifically directed against kisspeptin-52 (Kp-52), the longest isoform, and the other directed against kisspeptin-10 (Kp-10) whose sequence is common to all putative mature isoforms. With both antibodies...... terminalis were only recognised by antibody anti-Kp-10, suggesting that anti-Kp-10 may recognise a wider range of kisspeptin isoforms than anti-Kp-52 or cross-react with molecules other than kisspeptin in rat tissue. Overall, these results illustrate the variety of projection sites of kisspeptin neurones...

  15. Hydrocephalus after Subarachnoid Hemorrhage: Pathophysiology, Diagnosis, and Treatment

    Directory of Open Access Journals (Sweden)

    Sheng Chen


    Full Text Available Hydrocephalus (HCP is a common complication in patients with subarachnoid hemorrhage. In this review, we summarize the advanced research on HCP and discuss the understanding of the molecular originators of HCP and the development of diagnoses and remedies of HCP after SAH. It has been reported that inflammation, apoptosis, autophagy, and oxidative stress are the important causes of HCP, and well-known molecules including transforming growth factor, matrix metalloproteinases, and iron terminally lead to fibrosis and blockage of HCP. Potential medicines for HCP are still in preclinical status, and surgery is the most prevalent and efficient therapy, despite respective risks of different surgical methods, including lamina terminalis fenestration, ventricle-peritoneal shunting, and lumbar-peritoneal shunting. HCP remains an ailment that cannot be ignored and even with various solutions the medical community is still trying to understand and settle why and how it develops and accordingly improve the prognosis of these patients with HCP.

  16. The Neuroendocrinology of Thirst and Salt Appetite: Visceral Sensory Signals and Mechanisms of Central Integration (United States)

    Johnson, Alan Kim; Thunhorst, Robert L.


    This review examines recent advances in the study of the behavioral responses to deficits of body water and body sodium that in humans are accompanied by the sensations of thirst and salt appetite. Thirst and salt appetite are satisfied by ingesting water and salty substances. These behavioral responses to losses of body fluids, together with reflex endocrine and neural responses, are critical for reestablishing homeostasis. Like their endocrine and neural counterparts, these behaviors are under the control of both excitatory and inhibitory influences arising from changes in osmolality, endocrine factors such as angiotensin and aldosterone, and neural signals from low and high pressure baroreceptors. The excitatory and inhibitory influences reaching the brain require the integrative capacity of a neural network which includes the structures of the lamina terminalis, the amygdala, the perifornical area, and the paraventricular nucleus in the forebrain, and the lateral parabrachial nucleus (LPBN), the nucleus tractus solitarius (NTS), and the area postrema in the hindbrain. These regions are discussed in terms of their roles in receiving afferent sensory input and in processing information related to hydromineral balance. Osmoreceptors controlling thirst are located in systemic Viscera and in central structures that lack the blood-brain barrier. Angiotensin and aldosterone act on and through structures of the lamina terminalis and the amygdala to stimulate thirst and sodium appetite under conditions of hypovolemia. The NTS and LPBN receive neural signals from baroreceptors and are responsible for inhibiting the ingestion of fluids under conditions of increased volume and pressure and for stimulating thirst under conditions of bypovolemia and hypotension. The interplay of multiple facilitory influences within the brain may take the form of interactions between descending angiotensinergic systems originating in the forebrain and ascending adrenergic systems emanating

  17. Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring. (United States)

    Xue, Baojian; Yin, Haifeng; Guo, Fang; Beltz, Terry G; Thunhorst, Robert L; Johnson, Alan Kim


    Numerous findings demonstrate that there is a strong association between maternal health during pregnancy and cardiovascular disease in adult offspring. The purpose of the present study was to test whether maternal gestational hypertension modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory cytokines that sensitizes angiotensin II-elicited hypertensive response in adult offspring. In addition, the role of renal nerves and the RAAS in the sensitization process was investigated. Reverse transcription polymerase chain reaction analyses of structures of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAAS components and proinflammatory cytokines in 10-week-old male offspring of hypertensive dams. Most of these increases were significantly inhibited by either renal denervation performed at 8 weeks of age or treatment with an angiotensin-converting enzyme inhibitor, captopril, in drinking water starting at weaning. When tested beginning at 10 weeks of age, a pressor dose of angiotensin II resulted in enhanced upregulation of mRNA expression of RAAS components and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented pressor response in male offspring of hypertensive dams. The augmented blood pressure change and most of the increases in gene expression in the offspring were abolished by either renal denervation or captopril. The results suggest that maternal hypertension during pregnancy enhances pressor responses to angiotensin II through overactivity of renal nerves and the RAAS in male offspring and that upregulation of the brain RAAS and proinflammatory cytokines in these offspring may contribute to maternal gestational hypertension-induced sensitization of the hypertensive response to angiotensin II. © 2017 American Heart Association, Inc.

  18. Microneurosurgical Management of Posterior Communicating Artery Aneurysm: A Contemporary Series from Helsinki. (United States)

    Thiarawat, Peeraphong; Jahromi, Behnam Rezai; Kozyrev, Danil A; Intarakhao, Patcharin; Teo, Mario K; Choque-Velasquez, Joham; Hernesniemi, Juha


    The objectives of this study were to analyze microsurgical techniques and to determine correlations between microsurgical techniques and the radiographic findings in the microneurosurgical treatment of posterior communicating artery aneurysms (PCoAAs). We retrospectively analyzed radiographic findings and videos of surgeries in 64 patients with PCoAAs who underwent microsurgical clipping by the senior author from August 2010 to 2014. From 64 aneurysms, 30 (47%) had acute subarachnoid hemorrhage (SAH) that necessitated lamina terminalis fenestration (odds ratio [OR], 67.67; P < 0.001) and Liliequist membrane fenestration (OR, 19.62; P < 0.001). The low-lying aneurysms significantly necessitated the coagulation of the dura covering the anterior clinoid process (ACP) (OR, 7.43; P = 0.003) or anterior clinoidectomy (OR, 91.0; P < 0.001). We preferred straight clips in 45 (83%) of 54 posterolateral projecting aneurysms (OR, 45.0; P < 0.001), but preferred curved clips for posteromedial projecting aneurysms (OR, 6.39; P = 0.008). The mean operative time from the brain retraction to the final clipping was 17 minutes and 43 seconds. Postoperative computed tomography angiography revealed complete occlusion of 60 (94%) aneurysms. Three (4.6%) patients with acute SAH suffered postoperative lacunar infarction. For ruptured aneurysms, lamina terminalis and Liliequist membrane fenestration are useful for additional cerebrospinal fluid drainage. For low-lying aneurysms, coagulation of the dura covering the ACP or tailored anterior clinoidectomy might be necessary for exposing the proximal aneurysm neck. Type of clips depends on the direction of projection. The microsurgical clipping of the PCoAAs can achieve good immediate complete occlusion rate with low postoperative stroke rate. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Francesco Bruni (a cura di, L'italiano nelle regioni. Lingua nazionale e identità regionali; La Nostra Lingua, Biblioteca storica di linguistica italiana, UTET, Torino 1992; XXXIII + 1038 pp.

    Directory of Open Access Journals (Sweden)

    Pavao Tekavčić


    Full Text Available Gli italianisti di tutto il mondo sanno quanto ricca sia in Italia la tradizione della filologia, della critica e della perenne Questione della lingua. Recentemente questi domini scientifici si sono arricchiti di un' opera davvero monumentale come materia, impostazione, trattazione e mole: il volume di formato enciclopedico che qui recensiamo. È un'ennesima storia della lingua italiana, impostata tuttavia da un angolo visuale diverso, quello cioè della diffusione progressiva dell'italiano dalle origini ai giorni nostri nelle regioni dello stato italiano e in certe altre aree (Dalmazia e stria, Canton Ticino, Valle d'Aosta, Malta, Corsica. Si esaminano le caratteristiche dell'italianizzazione delle singole aree: da qui il sottotitolo.

  20. Estudo das propriedades do cimento asfÃltico de petrÃleo modificado por copolÃmero de etileno e acetato de vinila(eva)


    Ana Ellen Valentim de Alencar


    Cimento AsfÃltico de PetrÃleo (CAP), caracterizado como CAP 50/60, oriundo do Campo Fazenda Alegre, no estado do EspÃrito Santo, foi modificado por adiÃÃo de CopolÃmero de Etileno e Acetato de Vinila (EVA). Na modificaÃÃo foram incorporadas amostras do copolÃmero EVA puro e proveniente do resÃduo da indÃstria de calÃados (EVAR). Os CAPS, polÃmeros e CAPS modificados, foram inicialmente caracterizados por espectroscopia no infravermelho (FTIR) e ressonÃncia magnÃtica nuclear (RMN). AnÃlise tÃr...

  1. Ototoxicity of loop diuretics. (United States)

    Rybak, L P


    The loop diuretics are drugs that increase the excretion of water and electrolytes in the urine by their action on the cells in the loop of Henle. Clinical reports of ototoxicity of these agents are reviewed, and the results of a number of studies in experimental animals are discussed. These drugs can cause either a temporary, or in some cases, a permanent loss of hearing in patients. Animal experiments show that these drugs act on the stria vascularis, producing edema of these tissues and a temporary loss of function, resulting in a decrease of the endocochlear potential. This can result in secondary effects on sound-evoked measures of hearing. As new information unfolds about protective agents, it may be possible to preserve hearing and maintain the desired therapeutic effect.

  2. Intracochlear microprobe analysis

    International Nuclear Information System (INIS)

    Bone, R.C.; Ryan, A.F.


    Energy dispersive x-ray analysis (EDXA) or microprobe analysis provides cochlear physiologists with a means of accurately assessing relative ionic concentrations in selected portions of the auditory mechanism. Rapid freezing followed by lyophilization allows the recovery of fluid samples in crystalline form not only from perilymphatic and endolymphatic spaces, but also from much smaller subregions of the cochlea. Because samples are examined in a solid state, there is no risk of diffusion into surrounding or juxtaposed fluids. Samples of cochlear tissues may also be evaluated without the danger of intercellular ionic diffusion. During direct visualization by scanning electron microscopy, determination of the biochemical makeup of the material being examined can be simultaneously, assuring the source of the data collected. Other potential advantages and disadvantages of EDXA are reviewed. Initial findings as they relate to endolymph, perilymph, stria vascularis, and the undersurface of the tectorial membrane are presented

  3. High-resolution X-ray tomography of the human inner ear: synchrotron radiation-based study of nerve fibre bundles, membranes and ganglion cells. (United States)

    Lareida, A; Beckmann, F; Schrott-Fischer, A; Glueckert, R; Freysinger, W; Müller, B


    The combination of osmium tetroxide staining and high-resolution tomographic imaging using monochromatic X rays allows visualizing cellular structures of the human inner ear, that is, the organ of Corti, the stria vascularis and further soft tissues of the membranous labyrinth, in three-dimensional space with isotropic micrometre resolution. This approach permits to follow the course of nerve fibre bundles in a major part of the specimen and reveals the detailed three-dimensional arrangement of individual ganglion cells with distinct nuclei by means of X-ray tomography for the first time. The non-destructive neuron cell counting in a selected volume of 125 microm x 800 microm x 600 microm = 0.06 mm(3) gives rise to the estimate that 2000 ganglion cells are present along 1 mm organ of Corti.

  4. UtilizaÃÃo de mÃtodos multivariados na avaliaÃÃo sensorial de bebidas de goiaba, caju e cajà adoÃadas com diferentes edulcorantes


    Aline Gurgel Fernandes


    Alguns indivÃduos precisam substituir a sacarose por adoÃantes nÃo calÃricos, deste modo procuram por produtos que sejam dotados de gosto e caracterÃsticas prÃximas Ãs da sacarose. Esta à uma tendÃncia que vem sendo observada a nÃvel mundial no setor de bebidas nÃo alcoÃlicas. Com isso, a proposta das indÃstrias de sucos prontos de baixa caloria (light) à desenvolver produtos mais saudÃveis, sem comprometer o sabor. As frutas consistem em fonte nutricional de vitaminas, minerais e carboidrato...



    Ivone Garros Rosa; UFMA; Andressa Almeida Santana; N�uton Silva Souza; Herm�nio de Sousa Lima


    A Leucaena leucocephala (Lam.) de Wit � uma Mimosasea, cujas sementes s�o ricas em polissacar�deos que sugerem a predomin�ncia de galactose e manose. Esses polissacar�deos possuem caracter�sticas espec�ficas, tais como: teor de umidade 8,8%, teor de cinzas 7,51%, �ndice de refra��o variando de 1.335� a 1.338,75� e a capacidade de formar g�is e solu��es coloidais �s quais poder�o ser utilizados nos mais variados ramos da ind�stria de alimento, farmac�utica, t�xtil, m�dica, cosm�tico, papel e m...

  6. Studies on the use of aluminum processing residues as raw material ceramic


    Gilberto Rocha Santiago Junior


    Os resÃduos da produÃÃo de aluminio a partir da bauxita, chamados de borra, contÃm uma quantidade razoÃvel daquele metal, justificando seu reaproveitamento. ApÃs a retirada do aluminio em fornos rotatÃrios com sal fundido, resta uma âborra pretaâ, rica em sais solÃveis (50 a 70%), e contendo uma boa quantidade de aluminio (cerca de 5%). Esse material à danoso ao ambiente, exigindo tratamentos e aterros especÃficos. à possÃvel utilizÃ-lo como matÃria-prima para as indÃstrias de cimento e...

  7. Waardenburg syndrome type 2: an orthodontic perspective. (United States)

    Şuhani, Raluca Diana; Şuhani, Mihai Flaviu; Muntean, Alexandrina; Mesaroş, Michaela Florica; Badea, Mîndra Eugenia


    Waardenburg syndrome is a rare form of neurocristopathy. It is a disorder in the development of neural crest cells, caused by an altered cellular migration during the embryonic phase. That alteration causes an association of different abnormalities such as pigmentary disturbances of the hair, iris, skin, stria vascularis of the cochlea, dystopia canthorum and sensorineural hearing loss. We report a case of a 14-year-old Romanian male, with a family history of Waardenburg syndrome (mother) and Usher syndrome (father - congenitally sensorineural hearing loss and retinal degeneration). The case particularities are: the correlation between malocclusion and Waardenburg syndrome due to hypoplastic alae nasi and also factors that produced hearing loss, which could be Waardenburg syndrome, Usher syndrome or the presence of the connexin 26 (W24X) gene mutation.

  8. Partial corrosion casting to assess cochlear vasculature in mouse models of presbycusis and CMV infection. (United States)

    Carraro, Mattia; Park, Albert H; Harrison, Robert V


    Some forms of sensorineural hearing loss involve damage or degenerative changes to the stria vascularis and/or other vascular structures in the cochlea. In animal models, many methods for anatomical assessment of cochlear vasculature exist, each with advantages and limitations. One methodology, corrosion casting, has proved useful in some species, however in the mouse model this technique is difficult to achieve because digestion of non vascular tissue results in collapse of the delicate cast specimen. We have developed a partial corrosion cast method that allows visualization of vasculature along much of the cochlear length but maintains some structural integrity of the specimen. We provide a detailed step-by-step description of this novel technique. We give some illustrative examples of the use of the method in mouse models of presbycusis and cytomegalovirus (CMV) infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Pathogenesis of presbycusis in animal models: a review. (United States)

    Fetoni, Anna R; Picciotti, Pasqualina M; Paludetti, Gaetano; Troiani, Diana


    Presbycusis is the most common cause of hearing loss in aged subjects, reducing individual's communicative skills. Age related hearing loss can be defined as a progressive, bilateral, symmetrical hearing loss due to age related degeneration and it can be considered a multifactorial complex disorder, with both environmental and genetic factors contributing to the aetiology of the disease. The decline in hearing sensitivity caused by ageing is related to the damage at different levels of the auditory system (central and peripheral). Histologically, the aged cochlea shows degeneration of the stria vascularis, the sensorineural epithelium, and neurons of the central auditory pathways. The mechanisms responsible for age-associated hearing loss are still incompletely characterized. This work aims to give a broad overview of the scientific findings related to presbycusis, focusing mainly on experimental studies in animal models. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss. (United States)

    Yoo, T J; Du, Xiaoping; Zhou, Bin


    The aim of this study was to examine the activities of hASCs (Human Adipose tissue Derived Stem Cells) on experimental autoimmune hearing loss (EAHL) and how human stem cells regenerated mouse cochlea cells. We have restored hearing in 19 years old white female with autoimmune hearing loss with autologous adipose tissue derived stem cells and we wish to understand the mechanism of restoration of hearing in animal model. BALB/c mice underwent to develop EAHL; mice with EAHL were given hASCs intraperitoneally once a week for 6 consecutive weeks. ABR were examined over time. The helper type 1 autoreactive responses and T-reg cells were examined. H&E staining or immunostaining with APC conjugated anti-HLA-ABC antibody were conducted. The organ of Corti, stria vascularis, spira ligament and spiral ganglion in stem cell group are normal. In control group, without receiving stem cells, the organ of Corti is replaced by a single layer of cells, atrophy of stria vascularis. Systemic infusion of hASCs significantly improved hearing function and protected hair cells in established EAHL. The hASCs decreased the proliferation of antigen specific Th1/Th17 cells and induced the production of anti-inflammatory cytokine interleukin10 in splenocytes. They also induced the generation of antigen specific CD4(+)CD25(+)Foxp3(+)T-reg cells. The experiment showed the restoration is due to the paracrine activities of human stem cells, since there are newly regenerated mice spiral ganglion cells, not human mesenchymal stem cells derived tissue given by intraperitoneally. Copyright © 2015. Published by Elsevier B.V.

  11. Headbobber: a combined morphogenetic and cochleosaccular mouse model to study 10qter deletions in human deafness.

    Directory of Open Access Journals (Sweden)

    Annalisa Buniello

    Full Text Available The recessive mouse mutant headbobber (hb displays the characteristic behavioural traits associated with vestibular defects including headbobbing, circling and deafness. This mutation was caused by the insertion of a transgene into distal chromosome 7 affecting expression of native genes. We show that the inner ear of hb/hb mutants lacks semicircular canals and cristae, and the saccule and utricle are fused together in a single utriculosaccular sac. Moreover, we detect severe abnormalities of the cochlear sensory hair cells, the stria vascularis looks severely disorganised, Reissner's membrane is collapsed and no endocochlear potential is detected. Myo7a and Kcnj10 expression analysis show a lack of the melanocyte-like intermediate cells in hb/hb stria vascularis, which can explain the absence of endocochlear potential. We use Trp2 as a marker of melanoblasts migrating from the neural crest at E12.5 and show that they do not interdigitate into the developing strial epithelium, associated with abnormal persistence of the basal lamina in the hb/hb cochlea. We perform array CGH, deep sequencing as well as an extensive expression analysis of candidate genes in the headbobber region of hb/hb and littermate controls, and conclude that the headbobber phenotype is caused by: 1 effect of a 648 kb deletion on distal Chr7, resulting in the loss of three protein coding genes (Gpr26, Cpmx2 and Chst15 with expression in the inner ear but unknown function; and 2 indirect, long range effect of the deletion on the expression of neighboring genes on Chr7, associated with downregulation of Hmx3, Hmx2 and Nkx1.2 homeobox transcription factors. Interestingly, deletions of the orthologous region in humans, affecting the same genes, have been reported in nineteen patients with common features including sensorineural hearing loss and vestibular problems. Therefore, we propose that headbobber is a useful model to gain insight into the mechanisms underlying deafness in

  12. Protective role of misoprostol in prevention of gentamicin ototoxicity. (United States)

    Dogan, Murat; Polat, Halil; Yasar, Mehmet; Bayram, Ali; Karatas, Duran; Hira, İbrahim; Kale, Ahmet; Senel, Fatma; Özcan, İbrahim


    To demonstrate potential protective effect of misoprostol on cochlear toxicity caused by gentamicin with electrophysiological tests and histopathological studies. The study included 80 ears of 40 rats with normal hearing threshold and DPOAE value in both ears. Animals were assigned into 4 groups. The rats were randomized into 4 groups. Group I (n = 10): Gentamicin, Group II (n = 10): Gentamicin plus misoprostol, Group III (n = 10): Saline; Group IV (n = 10): Misoprostol. All drugs used in the study were given once daily for 15 days. DPOAE and ABR measurements were repeated after drug administration. Subsequently, the rats' cochleae were examined histopathologically. Baseline DPOAE and ABR values were compared to those obtained after drug exposure and cochlear toxicity was evaluated in electrophysiological manner. When At baseline, there were no significant differences in DPOAE responses at frequencies of 1001, 1501, 2002, 3003, 4004, 6006 and 7996 Hz among groups. However In DPOAE test, statistically significant difference was observed between the pre-study basal values and post-study results in groups other than gentamicin + misoprostol group. Additionally, It was found that there was a significant difference in DPOAE response at frequency of 4004 Hz obtained at baseline and after drug exposure according to measurements of epithelial vacuolization in stria vascularis. While ABR threshold values were compared at baseline, there were no significant difference in ABR threshold values of left and right ear between groups. Histopathologically it was also found that there were significant differences measurements of epithelial vacuolization in stria vascularis and inflammation among groups (p misoprostol, a potent antioxidant, has protective effect against cochlear damage, and that may be a safe alternative. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Reduced Membrane Insertion of CLC-K by V33L Barttin Results in Loss of Hearing, but Leaves Kidney Function Intact

    Directory of Open Access Journals (Sweden)

    Hua Tan


    Full Text Available In the mammalian ear, transduction of sound stimuli is initiated by K+ entry through mechano-sensitive channels into inner hair cells. K+ entry is driven by a positive endocochlear potential that is maintained by the marginal cell layer of the stria vascularis. This process requires basolateral K+ import by NKCC1 Na+−2Cl−−K+ co-transporters as well as Cl− efflux through ClC-Ka/barttin or ClC-Kb/barttin channels. Multiple mutations in the gene encoding the obligatory CLC-K subunit barttin, BSND, have been identified in patients with Bartter syndrome type IV. These mutations reduce the endocochlear potential and cause deafness. As CLC-K/barttin channels are also expressed in the kidney, patients with Bartter syndrome IV typically also suffer from salt-wasting hyperuria and electrolyte imbalances. However, there was a single report on a BSND mutation that resulted only in deafness, but not kidney disease. We herein studied the functional consequences of another recently discovered BSND mutation that predicts exchange of valine at position 33 by leucine. We combined whole-cell patch clamp, confocal microscopy and protein biochemistry to analyze how V33L affects distinct functions of barttin. We found that V33L reduced membrane insertion of CLC-K/barttin complexes without altering unitary CLC-K channel function. Our findings support the hypothesis of a common pathophysiology for the selective loss of hearing due to an attenuation of the total chloride conductance in the stria vascularis while providing enough residual function to maintain normal kidney function.

  14. RNA analysis of inner ear cells from formalin fixed paraffin embedded (FFPE) archival human temporal bone section using laser microdissection--a technical report. (United States)

    Kimura, Yurika; Kubo, Sachiho; Koda, Hiroko; Shigemoto, Kazuhiro; Sawabe, Motoji; Kitamura, Ken


    Molecular analysis using archival human inner ear specimens is challenging because of the anatomical complexity, long-term fixation, and decalcification. However, this method may provide great benefit for elucidation of otological diseases. Here, we extracted mRNA for RT-PCR from tissues dissected from archival FFPE human inner ears by laser microdissection. Three human temporal bones obtained at autopsy were fixed in formalin, decalcified by EDTA, and embedded in paraffin. The samples were isolated into spiral ligaments, outer hair cells, spiral ganglion cells, and stria vascularis by laser microdissection. RNA was extracted and heat-treated in 10 mM citrate buffer to remove the formalin-derived modification. To identify the sites where COCH and SLC26A5 mRNA were expressed, semi-nested RT-PCR was performed. We also examined how long COCH mRNA could be amplified by semi-nested RT-PCR in archival temporal bone. COCH was expressed in the spiral ligament and stria vascularis. However, SLC26A5 was expressed only in outer hair cells. The maximum base length of COCH mRNA amplified by RT-PCR was 98 bp in 1 case and 123 bp in 2 cases. We detected COCH and SLC26A5 mRNA in specific structures and cells of the inner ear from archival human temporal bone. Our innovative method using laser microdissection and semi-nested RT-PCR should advance future RNA study of human inner ear diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Pax3 function is required specifically for inner ear structures with melanogenic fates. (United States)

    Kim, Hongkyung; Ankamreddy, Harinarayana; Lee, Dong Jin; Kong, Kyoung-Ah; Ko, Hyuk Wan; Kim, Myoung Hee; Bok, Jinwoong


    Pax3 mutations result in malformed inner ears in Splotch mutant mice and hearing loss in humans with Waardenburg's syndrome type I. In the inner ear, Pax3 is thought to be involved mainly in the development of neural crest. However, recent studies have shown that Pax3-expressing cells contribute extensively to multiple inner ear structures, some of which were considered to be derived from the otic epithelium. To examine the specific functions of Pax3 during inner ear development, fate mapping of Pax3 lineage was performed in the presence or absence of functional Pax3 proteins using Pax3(Cre) knock-in mice bred to Rosa26 reporter (R26R) line. β-gal-positive cells were widely distributed in Pax3(Cre/+); R26R inner ears at embryonic day (E) 15.5, including the endolymphatic duct, common crus, cristae, maculae, cochleovestibular ganglion, and stria vascularis. In the absence of Pax3 in Pax3(Cre/Cre); R26R inner ears, β-gal-positive cells disappeared from regions with melanocytes such as the stria vascularis of the cochlea and dark cells in the vestibule. Consistently, the expression of Dct, a melanoblast marker, was also absent in the mutant inner ears. However, when examined at E11.5, β-gal positive cells were present in Pax3(Cre/Cre) mutant otocysts, whereas Dct expression was absent, suggesting that Pax3 lineage with a melanogenic fate migrated to the inner ear, yet failed to differentiate and survive without Pax3 function. Gross inner ear morphology was generally normal in Pax3(Cre/Cre) mutants, unless neural tube defects extended to the cranial region. Taken together, these results suggest that despite the extensive contribution of Pax3-expressing cells to multiple inner ear tissues, Pax3 function is required specifically for inner ear components with melanogenic fates. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model.

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    Alissa R Carver

    Full Text Available Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention.For the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra "experimental group" or water (sFlt-1 "positive control" until weaning. The mFc group ("negative control" received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI. MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis.Compared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes.Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model.

  17. Modification of oil and glucosinolate content in canola seeds with altered expression of Brassica napus LEAFY COTYLEDON1. (United States)

    Elahi, Nosheen; Duncan, Robert W; Stasolla, Claudio


    Over the last few decades, research focusing on canola (Brassica napus L.) seed oil content and composition has expanded. Oil production and accumulation are influenced by genes participating in embryo and seed development. The Arabidopsis LEAFY COTYLEDON1 (LEC1) is a well characterized regulator of embryo development that also enhances the expression of genes involved in fatty acid (FA) synthesis. B. napus lines over-expressing or down-regulating BnLEC1 were successfully generated by Agrobacterium-mediated transformation. The constitutive expression of BnLEC1 in B. napus var. Polo, increased seed oil content by 7-16%, while the down-regulation of BnLEC1 in B. napus var. Topas reduced oil content by 9-12%. Experimental manipulation of BnLEC1 caused transcriptional changes in enzymes participating in sucrose metabolism, glycolysis, and FA biosynthesis, suggesting an enhanced carbon flux towards FA biosynthesis in tissues over-expressing BnLEC1. The increase in oil content induced by BnLEC1 was not accompanied by alterations in FA composition, oil nutritional value or glucosinolate (GLS) levels. Suppression of BnLEC1 reduced seed oil accumulation and elevated the level of GLS possibly through the transcriptional regulation of BnST5a (Sulphotransferase5a), the last GLS biosynthetic enzyme. Collectively, these findings demonstrate that experimental alterations of BnLEC1 expression can be used to influence oil production and quality in B. napus. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Imaging the neural circuitry and chemical control of aggressive motivation

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    Blanchard D Caroline


    Full Text Available Abstract Background With the advent of functional magnetic resonance imaging (fMRI in awake animals it is possible to resolve patterns of neuronal activity across the entire brain with high spatial and temporal resolution. Synchronized changes in neuronal activity across multiple brain areas can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviors. To this end, fMRI in conscious rats combined with 3D computational analysis was used to identifying the putative distributed neural circuit involved in aggressive motivation and how this circuit is affected by drugs that block aggressive behavior. Results To trigger aggressive motivation, male rats were presented with their female cage mate plus a novel male intruder in the bore of the magnet during image acquisition. As expected, brain areas previously identified as critical in the organization and expression of aggressive behavior were activated, e.g., lateral hypothalamus, medial basal amygdala. Unexpected was the intense activation of the forebrain cortex and anterior thalamic nuclei. Oral administration of a selective vasopressin V1a receptor antagonist SRX251 or the selective serotonin reuptake inhibitor fluoxetine, drugs that block aggressive behavior, both caused a general suppression of the distributed neural circuit involved in aggressive motivation. However, the effect of SRX251, but not fluoxetine, was specific to aggression as brain activation in response to a novel sexually receptive female was unaffected. Conclusion The putative neural circuit of aggressive motivation identified with fMRI includes neural substrates contributing to emotional expression (i.e. cortical and medial amygdala, BNST, lateral hypothalamus, emotional experience (i.e. hippocampus, forebrain cortex, anterior cingulate, retrosplenial cortex and the anterior thalamic nuclei that bridge the motor and cognitive components of aggressive responding

  19. Common brain activations for painful and non-painful aversive stimuli

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    Hayes Dave J


    Full Text Available Abstract Background Identification of potentially harmful stimuli is necessary for the well-being and self-preservation of all organisms. However, the neural substrates involved in the processing of aversive stimuli are not well understood. For instance, painful and non-painful aversive stimuli are largely thought to activate different neural networks. However, it is presently unclear whether there is a common aversion-related network of brain regions responsible for the basic processing of aversive stimuli. To help clarify this issue, this report used a cross-species translational approach in humans (i.e. meta-analysis and rodents (i.e. systematic review of functional neuroanatomy. Results Animal and human data combined to show a core aversion-related network, consisting of similar cortical (i.e. MCC, PCC, AI, DMPFC, RTG, SMA, VLOFC; see results section or abbreviation section for full names and subcortical (i.e. Amyg, BNST, DS, Hab, Hipp/Parahipp, Hyp, NAc, NTS, PAG, PBN, raphe, septal nuclei, Thal, LC, midbrain regions. In addition, a number of regions appeared to be more involved in pain-related (e.g. sensory cortex or non-pain-related (e.g. amygdala aversive processing. Conclusions This investigation suggests that aversive processing, at the most basic level, relies on similar neural substrates, and that differential responses may be due, in part, to the recruitment of additional structures as well as the spatio-temporal dynamic activity of the network. This network perspective may provide a clearer understanding of why components of this circuit appear dysfunctional in some psychiatric and pain-related disorders.

  20. Staying put or leaving home: endocrine, neuroendocrine and behavioral consequences in male African striped mice. (United States)

    Schradin, Carsten; Kenkel, Wiliam; Krackow, Sven; Carter, C Sue


    Social flexibility occurs when individuals of both sexes can change their social and reproductive tactics, which in turn can influence the social system of an entire population. However, little is known regarding the extent to which individuals of socially flexible species vary in their social behavior and in the underlying physiological mechanisms that support different social tactics. The present study in African striped mice modeled in captivity three male tactics described from the field: (a) philopatric males remaining in the family; (b) solitary roamers; or (c) group-living breeding males. Sixteen pairs and their offspring were kept in captivity, while one male offspring from the family remained as singly housed after he reached 21 days of age. Differences in behavior, morphology, hormone and neuropeptide levels were tested, and physiological measurements were correlated with behavioral measurements. In standardized arena experiments group-living males (philopatrics and breeders) were significantly more aggressive than singly housed males, in agreement with previous data suggesting that group-living, but not roaming males, are territorial. Philopatric males showed signs of reproductive suppression, small testes, lower testosterone and higher corticosterone levels than their singly housed brothers. Higher levels of arginine vasopressin (AVP) were measured in the PVN and BNST of singly housed males compared to group-living males. Based on these findings we hypothesize that roamers are physiologically primed, and capable, if the opportunity to mate arises, to release AVP, form social bonds and become territorial, thus quickly adopting the tactic as breeding male which would yield a higher reproductive success. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Variations of the internal pudendal artery as a congenital contributing factor to age at onset of erectile dysfunction in Japanese. (United States)

    Kawanishi, Yasuo; Muguruma, Hiroshi; Sugiyama, Hiroaki; Kagawa, Junichirou; Tanimoto, Syuji; Yamanaka, Masahito; Kojima, Keiji; Numata, Akira; Kishimoto, Tomoteru; Nakanishi, Ryoichi; Kanayama, Hiro-omi


    To investigate the relationship between variations of the pelvic artery arrangement and the age at erectile dysfunction (ED) onset, as some men develop ED while relatively young, while others maintain erectile function into old age despite having cardiovascular diseases, thus congenital factors might be involved. We examined 290 units of internal iliac arteries (IIA) in 145 patients showing repeated incomplete erectile response to intracavernosal injections with prostaglandin E(1). Patients with cardiovascular risk factors, neurological disease or pelvic injury were excluded. The pelvic artery arrangement, evaluated by three-dimensional computed tomographic angiography, was classified anatomically into five types: Type 1 (normal or basic type), in which the internal pudendal artery (IPA) originates from the anterior trunk at the level between the linea terminalis and the major ischial notch; Type 2, the IPA originates from the anterior trunk of the IIA at the level of the major ischial notch or more distally; Type 3, the IPA originates directly from the IIA at a level proximal to the linea terminalis; Type 4, the IPA originates together with the superior and inferior gluteal artery within 1 cm of each other; and Type 5, the penile blood supply is dependent on arteries other than the IPA, such as the obturator artery. Among the 290 units, eight could not be classified due to poor image quality. There were no statistically significant differences in blood flow parameters among the types of IIAs, but there was a statistically significant difference in the IPA type at the age of onset of ED. Type 1 (153 units or 53%) anatomy, was more common in patients who developed ED at an advanced age. Types 2, 3 and 4 were more common in patients with onset of ED at an early age (log-rank test P < 0.001, P = 0.044, P < 0.001, respectively). Compared with patients with the common type of IIAs bilaterally, patients with any of the variations bilaterally are at risk of early onset of

  2. Temporal Patterns of Larval Fish Occurrence in a Large Subtropical River.

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    Fangmin Shuai

    Full Text Available Knowledge of temporal patterns of larval fish occurrence is limited in south China, despite its ecological importance. This research examines the annual and seasonal patterns of fish larval presence in the large subtropical Pearl River. Data is based on samples collected every two days, from 2006 to 2013. In total, 45 taxa representing 13 families and eight orders were sampled. The dominant larval family was Cyprinidae, accounting for 27 taxa. Squaliobarbus curriculus was the most abundant species, followed by Megalobrama terminalis, Xenocypris davidi, Cirrhinus molitorella, Hemiculter leuscisculus and Squalidus argentatus. Fish larvae abundances varied significantly throughout the seasons (multivariate analyses: Cluster, SIMPROF and ANOSIM. The greatest numbers occurred between May and September, peaking from June through August, which corresponds to the reproductive season. In this study, redundancy analysis was used to describe the relationship between fish larval abundance and associated environmental factors. Mean water temperature, river discharge, atmospheric pressure, maximum temperature and precipitation play important roles in larval occurrence patterns. According to seasonal variations, fish larvae occurrence is mainly affected by water temperature. It was also noted that the occurrence of Salanx reevesii and Cyprinus carpio larvae is associated with higher dissolved oxygen (DO concentrations, higher atmospheric pressure and lower water temperatures which occur in the spring. On the other hand, M. terminalis, X. davidi, and C. molitorella are associated with high precipitation, high river discharge, low atmospheric pressure and low DO concentrations which featured during the summer months. S. curriculus also peaks in the summer and is associated with peak water temperatures and minimum NH3-N concentrations. Rhinogobius giurinus occur when higher atmospheric pressure, lower precipitation and lower river discharges occur in the autumn

  3. Potential functional foods in the traditional Maori diet. (United States)

    Cambie, Richard C; Ferguson, Lynnette R


    The Maori people were early New Zealand settlers of Polynesian descent. The incidence of non-infectious diseases appears to have been low in these people, perhaps in part due to the presence of protective chemical constituents within their food plant supply. Three of the tropical crops they introduced are still eaten here today: the sweet potato or kumara (Ipomoea batatas), the taro (Colocasia esculenta) and the cabbage tree or ti (Cordyline terminalis). Sporamins A and B, the major storage proteins of kumara tubers, act as proteinase inhibitors, and may have other anti-cancer properties. The tubers also contain the anti-coagulant coumarins, scopoletin, aesculetin, and umbelliferone. The corms of taro contain the anthocyanins, cyanidin 3-glucoside, pelargonidin 3-glucoside and cyanidin 3-rhamnoside, reported to have antioxidant and anti-inflammatory properties. Anthocyanins are also major components of a so-called "Maori potato", a variety officially known as Ureniki, which has a purple skin and flesh and was widely eaten in the early 1900s. Anthocyanins are also present in ripe berries of the ramarama (Lophomyrtus bullata) and rohutu (Neomyrtus pedunculata). Both the leaves and seeds of the introduced cabbage tree (Cordyline terminalis) and the native Cordyline spp., C. australis, C. indivisa, and C. pumilo, were eaten. The seeds of C. australis, of some Astelia spp., and of hinau (Elaeocarpus dentatus) are good sources of various essential fatty acids, generally regarded as protective against cardiovascular disease. Shoots and leaves from a wide range of native species were traditionally eaten as greens, especially "sow thistle" or puha (Sonchus spp.), reportedly high in Vitamin C and various phenolics. "New Zealand spinach" (Tetragonia tetragonioides or T. expansa) has anti-ulcerogenic activity that has been traced to two cerebrosides and anti-inflammatory activity that has been traced to novel water-soluble polysaccharides, as well as antioxidant

  4. Interleukin-10 Attenuates Hypochlorous Acid-Mediated Cytotoxicity to HEI-OC1 Cochlear Cells

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    Martin Mwangi


    Full Text Available Inflammatory reaction plays a crucial role in the pathophysiology of acquired hearing loss such as ototoxicity and labyrinthitis. In our earlier work, we showed the pivotal role of otic fibrocytes in cochlear inflammation and the critical involvement of proinflammatory cytokines in cisplatin ototoxicity. We also demonstrated that otic fibrocytes inhibit monocyte chemoattractant protein 1 (CCL2 upregulation in response to interleukin-10 (IL-10 via heme oxygenase 1 (HMOX1 signaling, resulting in suppression of cochlear inflammation. However, it is still unclear how IL-10 affects inflammation-mediated cochlear injury. Here we aim to determine how hypochlorous acid, a model inflammation mediator affects cochlear cell viability and how IL-10 affects hypochlorous acid-mediated cochlear cell injury. NaOCl, a sodium salt of hypochlorous acid (HOCl was found to induce cytotoxicity of HEI-OC1 cells in a dose-dependent manner. Combination of hydrogen peroxide and myeloperoxidase augmented cisplatin cytotoxicity, and this synergism was inhibited by N-Acetyl-L-cysteine and ML-171. The rat spiral ligament cell line (RSL appeared to upregulate the antioxidant response element (ARE activities upon exposure to IL-10. RSL cells upregulated the expression of NRF2 (an ARE ligand and NR0B2 in response to CoPP (a HMOX1 inducer, but not to ZnPP (a HMOX1 inhibitor. Adenovirus-mediated overexpression of NR0B2 was found to suppress CCL2 upregulation. IL-10-positive cells appeared in the mouse stria vascularis 1 day after intraperitoneal injection of lipopolysaccharide (LPS. Five days after injection, IL-10-positive cells were observed in the spiral ligament, spiral limbus, spiral ganglia, and suprastrial area, but not in the stria vascularis. IL-10R1 appeared to be expressed in the mouse organ of Corti as well as HEI-OC1 cells. HEI-OC1 cells upregulated Bcl-xL expression in response to IL-10, and IL-10 was shown to attenuate NaOCl-induced cytotoxicity. In addition, HEI

  5. Hydrogen Inhalation Protects against Ototoxicity Induced by Intravenous Cisplatin in the Guinea Pig

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    Anette E. Fransson


    Full Text Available Introduction: Permanent hearing loss and tinnitus as side-effects from treatment with the anticancer drug cisplatin is a clinical problem. Ototoxicity may be reduced by co-administration of an otoprotective agent, but the results in humans have so far been modest.Aim: The present preclinical in vivo study aimed to explore the protective efficacy of hydrogen (H2 inhalation on ototoxicity induced by intravenous cisplatin.Materials and Methods: Albino guinea pigs were divided into four groups. The Cispt (n = 11 and Cispt+H2 (n = 11 groups were given intravenous cisplatin (8 mg/kg b.w., injection rate 0.2 ml/min. Immediately after, the Cispt+H2 group also received gaseous H2 (2% in air, 60 min. The H2 group (n = 5 received only H2 and the Control group (n = 7 received neither cisplatin nor H2. Ototoxicity was assessed by measuring frequency specific ABR thresholds before and 96 h after treatment, loss of inner (IHCs and outer (OHCs hair cells, and by performing densitometry-based immunohistochemistry analysis of cochlear synaptophysin, organic transporter 2 (OCT2, and copper transporter 1 (CTR1 at 12 and 7 mm from the round window. By utilizing metabolomics analysis of perilymph the change of metabolites in the perilymph was assessed.Results: Cisplatin induced electrophysiological threshold shifts, hair cell loss, and reduced synaptophysin immunoreactivity in the synapse area around the IHCs and OHCs. H2 inhalation mitigated all these effects. Cisplatin also reduced the OCT2 intensity in the inner and outer pillar cells and in the stria vascularis as well as the CTR1 intensity in the synapse area around the IHCs, the Deiters' cells, and the stria vascularis. H2 prevented the majority of these effects.Conclusion: H2 inhalation can reduce cisplatin-induced ototoxicity on functional, cellular, and subcellular levels. It is proposed that synaptopathy may serve as a marker for cisplatin ototoxicity. The effect of H2 on the antineoplastic activity of

  6. Codeficiency of Lysosomal Mucolipins 3 and 1 in Cochlear Hair Cells Diminishes Outer Hair Cell Longevity and Accelerates Age-Related Hearing Loss. (United States)

    Wiwatpanit, Teerawat; Remis, Natalie N; Ahmad, Aisha; Zhou, Yingjie; Clancy, John C; Cheatham, Mary Ann; García-Añoveros, Jaime


    Acquired hearing loss is the predominant neurodegenerative condition associated with aging in humans. Although mutations on several genes are known to cause congenital deafness in newborns, few genes have been implicated in age-related hearing loss (ARHL), perhaps because its cause is likely polygenic. Here, we generated mice lacking lysosomal calcium channel mucolipins 3 and 1 and discovered that both male and female mice suffered a polygenic form of hearing loss. Whereas mucolipin 1 is ubiquitously expressed in all cells, mucolipin 3 is expressed in a small subset of cochlear cells, hair cells (HCs) and marginal cells of the stria vascularis, and very few other cell types. Mice lacking both mucolipins 3 and 1, but not either one alone, experienced hearing loss as early as at 1 month of age. The severity of hearing impairment progressed from high to low frequencies and increased with age. Early onset of ARHL in these mice was accompanied by outer HC (OHC) loss. Adult mice conditionally lacking mucolipins in HCs exhibited comparable auditory phenotypes, thereby revealing that the reason for OHC loss is mucolipin codeficiency in the HCs and not in the stria vascularis. Furthermore, we observed that OHCs lacking mucolipins contained abnormally enlarged lysosomes aggregated at the apical region of the cell, whereas other organelles appeared normal. We also demonstrated that these aberrant lysosomes in OHCs lost their membrane integrity through lysosomal membrane permeabilization, a known cause of cellular toxicity that explains why and how OHCs die, leading to premature ARHL. SIGNIFICANCE STATEMENT Presbycusis, or age-related hearing loss (ARHL), is a common characteristic of aging in mammals. Although many genes have been identified to cause deafness from birth in both humans and mice, only a few are known to associate with progressive ARHL, the most prevalent form of deafness. We have found that mice lacking two lysosomal channels, mucolipins 3 and 1, suffer

  7. Na+/K+-ATPase α1 identified as an abundant protein in the blood-labyrinth barrier that plays an essential role in the barrier integrity.

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    Yue Yang


    Full Text Available The endothelial-blood/tissue barrier is critical for maintaining tissue homeostasis. The ear harbors a unique endothelial-blood/tissue barrier which we term "blood-labyrinth-barrier". This barrier is critical for maintaining inner ear homeostasis. Disruption of the blood-labyrinth-barrier is closely associated with a number of hearing disorders. Many proteins of the blood-brain-barrier and blood-retinal-barrier have been identified, leading to significant advances in understanding their tissue specific functions. In contrast, capillaries in the ear are small in volume and anatomically complex. This presents a challenge for protein analysis studies, which has resulted in limited knowledge of the molecular and functional components of the blood-labyrinth-barrier. In this study, we developed a novel method for isolation of the stria vascularis capillary from CBA/CaJ mouse cochlea and provided the first database of protein components in the blood-labyrinth barrier as well as evidence that the interaction of Na(+/K(+-ATPase α1 (ATP1A1 with protein kinase C eta (PKCη and occludin is one of the mechanisms of loud sound-induced vascular permeability increase.Using a mass-spectrometry, shotgun-proteomics approach combined with a novel "sandwich-dissociation" method, more than 600 proteins from isolated stria vascularis capillaries were identified from adult CBA/CaJ mouse cochlea. The ion transporter ATP1A1 was the most abundant protein in the blood-labyrinth barrier. Pharmacological inhibition of ATP1A1 activity resulted in hyperphosphorylation of tight junction proteins such as occludin which increased the blood-labyrinth-barrier permeability. PKCη directly interacted with ATP1A1 and was an essential mediator of ATP1A1-initiated occludin phosphorylation. Moreover, this identified signaling pathway was involved in the breakdown of the blood-labyrinth-barrier resulting from loud sound trauma.The results presented here provide a novel method for

  8. Presbycusis in Nigerians at the University College Hospital, Ibadan. (United States)

    Ogunleye, A O A; Labaran, A O


    Presbycusis refers to sensori-neural hearing impairment in elderly individuals resulting from the degenerative changes of aging. Characteristically, it involves bilateral sensorineural hearing loss, worse at high frequencies, which is associated with difficulty in speech discrimination and central auditory processing of information. The aim of this study is to present our observations on presbycusis as seen in Nigerians. A 41/2-year prospective study of 67 patients that presented with features of presbycusis in the Ear, Nose and Throat Department of the University College Hospital, Ibadan, Nigeria between January 2000 and June 2004 was done. The diagnosis of presbycusis in each subject was based on history, clinical findings, and pure tone audiometry. 67 patients with features of presbycusis were seen and treated over the studied period with 37 males (55.2%), 30 females (44.8%) (M:F 1.2:1) and with an average age of 69.3 years (age range 46-90 years). Presbycusis constituted 2.4% of the 2817 otological cases seen during the studied period. Majority (64.1%) of the cases were of 6th to 8th decades of life. The symptoms were mainly of hearing loss 34 (50.7%), tinnitus 19 (28.4%), hearing loss and tinnitus together in 14 (20.9%) cases. Stria (metabolic) presbycusis 20 (29.9%) constituted the most common type of presbycusis seen in this study followed by mechanical presbycusis 15 (22.4%), neural presbycusis 14 (20.9%) and sensory presbycusis 7 (10.4%) respectively. Presbycusis has been found in this study to affect both males and females subjects almost equally, has an insidious onset as from fourth decades of life in our environment, of stria (metabolic) type mostly, presents with moderate to severe sensori-neural hearing loss (SNHL), and constitute an important problem in the society as it occurs in an elderly population that relies on their special senses (especially auditory) to compensate for other age-associated disabilities.

  9. In Silico Screening Hepatitis B Virus DNA Polymerase Inhibitors from Medicinal Plants

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    Mokhtar Nosrati


    Full Text Available Abstract Background: Hepatitis B virus infection (HBV is a significant global health problem and is a major cause of morbidity and mortality worldwide. Therefore, currently, introducing novel anti Hepatitis B drugs is taken into consideration. This study was planned to in silico screening novel Hepatitis B virus DNA polymerase inhibitors from two medicinal plants Terminalis chebula and Caesalpinia sappan. Materials and Methods: This is a descriptive-analytic study. In the study, three-dimensional structure of the Hepatitis B virus DNA polymerase was predicted using homology modeling method. A set of phytochemicals from mentioned plants were retrieved from Pubchem database in SDF format. In silico screening was carried out using molecular docking between mentioned phytochemicals and modeled polymerase by iGemdock 2.1 software. Results: Results of the study confirmed that all evaluated ligands have appropriate interactions to the polymerase with least toxicity and without genotoxicity potential. Results also showed that most interactions occur in reverse transcriptase domain which located in 354-694 area in the amino acid sequence of tested polymerase. Analysis of energy and amino acids involved in ligand-polymerase interaction revealed that Terchebin, Chebulinic Acid and Terflavin A have more effective interaction with the polymerase in compared to other ligands. Conclusion: Based on the results it can be concluded that evaluated compounds could be good candidates for in vitro and in vivo research in order to develop novel anti- Hepatitis B drugs.

  10. Scanning electron microscopy of corrosion casting in medicine. (United States)

    Konerding, M A


    The aims of this review are: 1. to provide a bibliography of the publications that have used the corrosion casting technique; 2. to describe the advantages and limitations of the methodology; 3. to illustrate possible applications in the field of medicine, and 4. to highlight the significance of this method in the teaching of medical students. Thus, this paper is primarily focused on the scanning electron microscopical examination of vascular corrosion casts. The unsurpassed three-dimensionality of the corrosion casting technique compared to any other means stands out in particular. This can be especially useful when complex vascular-anatomical relationships are present. This applies not only to the portrayal of the modes of branching and varying vascular densities but also to regulatory arrangements, such as sphincters and arteriovenous anastomoses. Between 1966 and 1990, a total of 549 publications were found in the Medline literature data bank, containing the key words "corrosion casting", "microvascular cast", or "vascular cast" (as of August, 1990). Of those publications, most dealt with applications to experimental animals. By contrast, only 142 reports were mainly or partially concerned with human investigational material. The normal vascular system of nearly all organs, insofar as this is of direct medical relevance, has been largely resolved. In our opinion, one of the most important potential applications of the corrosion casting technique lies in the investigation of gastrointestinal, renal or hepatic ailments, which coincide with the reconstruction or rarefication of the vascular bed, e.g., in ulcers, ileitis terminalis, colitis ulcerosa, cirrhosis or glomerulonephritis.

  11. Sequential palynostratigraphy of the Queen City and Weches formations (Middle Eocene Claiborne Group), southeast central Texas

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    Elsik, W.C. (MycoStrat Connection, Houston, TX (United States))


    Palynomorph sequences of several orders of magnitude were found in the Queen City and Weches formations respectively at Six Mile and Burleson bluffs on the Brazos River, Milam and Burleson counties, Texas. The long term development of the subtropical to tropical Claibornian palynoflora included Engelhardtia spp., Friedrichipollis claibornensis, Nudopollis terminalis, Pollenites laesius and Symplocoipollenites spp. Shorter term fluctuations in sea level were reflected by common herbaceous pollen in the Queen City, and common mangrove pollen in the Weches. Paleoenvironments were marginally to fully marine; dinocysts occurred throughout. The Wetzeliella group of dinocysts were present only in the Queen City at Six Mile Bluff. Late Paleocene to Early Eocene pollen, and Early Middle Eocene pollen with last effective occurrences near the Queen City and Weches boundary included Aesculiidites circumstriatus, Annona foveoreticulata and a new species of Platycarya. Five short term warmer-cooler couplet events were represented by successive abundance peaks of Juglandaceae followed by Ulmus; Alnus supports the three upper Ulmus peaks. One deep water event was recorded by an abundance of fresh water Pediastrum at the Queen City and Weches boundary. That boundary event was bracketed by two of the Alnus and Ulmus peaks.

  12. Neurophysiology of magnocellular neuroendocrine cells: recent advances. (United States)

    Hatton, G I; Li, Z H


    Magnocellular neuroendocrine cells of the hypothalamic paraventricular and supraoptic nuclei are responsible for most of the vasopressin and oxytocin in the peripheral blood as well as for central release of these peptides in selected brain areas. As the principal component of the hypothalamo-neurohypophysial system, these neurons have been a subject of continual study for half a century. The wealth of solid information from decades of in vivo studies has provided a firm basis for in vitro, brain slice and explant investigations of neural mechanisms involved in the control and regulation of vasopressin and oxytocin neurons. In vitro methods have revealed the presence and permitted the study of monosynaptic projections to supraoptic neurons from the olfactory bulbs, the tuberomammillary nuclei of the posterior hypothalamus and from the organum vasculosum of the lamina terminalis. Such methods have also facilitated the elucidation of the various ionic currents controlling neurosecretory cell activity as well as the roles of calcium binding proteins and release of calcium from internal stores. This review summarizes recent advances in our understanding of the afferent inputs that impinge upon these two cell types, and the cellular and molecular mechanisms intrinsic to these neurons that determine their activity patterns and, in part, their responses to incoming stimuli.

  13. Distribution of serotonin and dopamine in the central nervous system of the female mud crab, Scylla olivacea (Herbst). (United States)

    Khornchatri, Kanjana; Kornthong, Napamanee; Saetan, Jirawat; Tinikul, Yotsawan; Chotwiwatthanakun, Charoonroj; Cummins, Scott F; Hanna, Peter J; Sobhon, Prasert


    In crustaceans serotonin (5-HT) and dopamine (DA) are neurotransmitters that play roles in the modulation of numerous physiological functions, including reproduction. However, in the mud crab, Scylla olivacea, the distributions of 5-HT and DA in the CNS have not yet been investigated. The aim of our study was to map the distributions of these two neurotransmitters in the central nervous system (CNS) of the female of this crab during the late stage of ovarian development. We found 5-HT immunoreactivity (-ir) and DA-ir in many parts of the CNS, including the eyestalk, brain, and thoracic ganglia. In the eyestalk, 5-HT-ir was localized in the medulla terminalis (MT), hemi-ellipsoid body (HB), and protocerebral tract (PT), whereas DA-ir was present in neuronal cluster 1, the LG neuropils, and PT. In the brain, 5-HT-ir and DA-ir were detected in cells and fibers of neuronal clusters 6, 7, 8, 9, 10, 11, 14, and 15. In the ventral nerve cord, 5-HT-ir was present in neurons of the abdominal ganglia, whereas DA was only present in fibers. These spatial distributions of 5-HT and DA suggest that they may be involved in the neuromodulation of important physiological functions, including ovarian maturation, as shown in other non-crab decapods. Copyright © 2014 Elsevier GmbH. All rights reserved.

  14. Autoradiographic localization of angiotensin II receptors in rat brain

    International Nuclear Information System (INIS)

    Mendelsohn, F.A.O.; Quirion, R.; Saavedra, J.M.; Aguilera, G.; Catt, K.J.


    The 125 I-labeled agonist analog [1-sarcosine]-angiotensin II ([Sar 1 ]AII) bound with high specificity and affinity (K/sub a/ = 2 x 10 9 M -1 ) to a single class of receptor sites in rat brain. This ligand was used to analyze the distribution of AII receptors in rat brain by in vitro autoradiography followed by computerized densitometry and color coding. A very high density of AII receptors was found in the subfornical organ, paraventricular and periventricular nuclei of the hypothalamus, nucleus of the tractus solitarius, and area postrema. A high concentration of receptors was found in the suprachiasmatic nucleus of the hypothalamus, lateral olfactory tracts, nuclei of the accessory and lateral olfactory tracts, triangular septal nucleus, subthalamic nucleus, locus coeruleus, and inferior olivary nuclei. Moderate receptor concentrations were found in the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial habenular nucleus, lateral septum, ventroposterior thalamic nucleus, median eminence, medial geniculate nucleus, superior colliculus, subiculum, pre- and parasubiculum, and spinal trigeminal tract. Low concentrations of sites were seen in caudate-putamen, nucleus accumbens, amygdala, and gray matter of the spinal cord. These studies have demonstrated that AII receptors are distributed in a highly characteristic anatomical pattern in the brain. The high concentrations of AII receptors at numerous physiologically relevant sites are consistent with the emerging evidence for multiple roles of AII as a neuropeptide in the central nervous system. 75 references, 2 figures

  15. Brain architecture of the Pacific White Shrimp Penaeus vannamei Boone, 1931 (Malacostraca, Dendrobranchiata): correspondence of brain structure and sensory input? (United States)

    Meth, Rebecca; Wittfoth, Christin; Harzsch, Steffen


    Penaeus vannamei (Dendrobranchiata, Decapoda) is best known as the "Pacific White Shrimp" and is currently the most important crustacean in commercial aquaculture worldwide. Although the neuroanatomy of crustaceans has been well examined in representatives of reptant decapods ("ground-dwelling decapods"), there are only a few studies focusing on shrimps and prawns. In order to obtain insights into the architecture of the brain of P. vannamei, we use neuroanatomical methods including X-ray micro-computed tomography, 3D reconstruction and immunohistochemical staining combined with confocal laser-scanning microscopy and serial sectioning. The brain of P. vannamei exhibits all the prominent neuropils and tracts that characterize the ground pattern of decapod crustaceans. However, the size proportion of some neuropils is salient. The large lateral protocerebrum that comprises the visual neuropils as well as the hemiellipsoid body and medulla terminalis is remarkable. This observation corresponds with the large size of the compound eyes of these animals. In contrast, the remaining median part of the brain is relatively small. It is dominated by the paired antenna 2 neuropils, while the deutocerebral chemosensory lobes play a minor role. Our findings suggest that visual input from the compound eyes and mechanosensory input from the second pair of antennae are major sensory modalities, which this brain processes.

  16. Electrophysiologic and anatomical characteristics of the right atrial posterior wall in patients with and without atrial flutter. Analysis by intracardiac echocardiography

    International Nuclear Information System (INIS)

    Okumura, Yasuo; Watanabe, Ichiro; Ashino, Sonoko


    The posterior right atrial transverse conduction capability during typical atrial flutter (AFL) is well known, but its relationship to the anatomical characteristics remains controversial. Thirty-four AFL and 16 controls underwent intracardiac echocardiography after placement of a 20-polar catheter at the posterior block site during AFL or pacing. In 31 patients, the effective refractory period (ERP) at the block site was determined as the longest coupling interval that resulted in double potentials during extrastimuli from the mid-septal (SW) and free (FW) walls. The block site was located 3.0-29.0 mm posterior to the crista terminalis (CT) in each AFL and control patient. The CT area indexed to the body surface area was larger in AFL patients than in control patients (16.4±6.5 mm 2 /m 2 vs 11.3±6.4 mm 2 /m 2 , p=0.01), and was positively correlated to age (r=0.34, p=0.02). The ERP was longer in the AFL patients than in controls (SW: median value 600 [270-725] ms vs 220 [200-253] ms; FW: 280 [230-675] ms vs 215 [188-260] ms, p<0.05 for each). A functional block line was located on the septal side of the CT in all patients. A limited conduction capability and age-related CT enlargement might have important implications for the pathogenesis in AFL. (author)

  17. [Penis-preserving surgery in patients with primary penile urethral cancer]. (United States)

    Maek, M; Musch, M; Arnold, G; Kröpfl, D


    Primary urethral cancer in males is a rare entity with only approximately 800 cases described, which is why it is difficult to formulate evidence-based guidelines for treatment. For tumors in the pT2 stage with a localization distal to the membranous urethra, a penis-preserving operation can be carried out. In the period from November 2006 to February 2014 a total of 4 patients with primary urethral cancer underwent a penis-preserving urethral resection. The tumor characteristics and treatment results were collated retrospectively. Of the four patients one had a transitional cell carcinoma of the mid-penile urethra in stage pT2 G2. In two out of the four patients a squamous cell carcinoma (PEC) was present in the mid-penile urethra in stages pT2 G2 and pT2 G3, respectively, with concomitant carcinoma in situ (CIS). The fourth patient had a PEC of the fossa terminalis in stage pT2 G2. Initially all patients underwent a penis-preserving resection. In one case, despite an initial R0 resection a local recurrence occurred and a complete penectomy was performed. Irradiation and lymphadenectomy were not carried out. At a mean follow-up of 37 months all patients are currently in complete remission. Primary penile urethral cancer can be treated by a penis-preserving operation. Close follow-up is essential because recurrence can arise despite an initial R0 resection.

  18. Centrally administered relaxin-3 induces Fos expression in the osmosensitive areas in rat brain and facilitates water intake. (United States)

    Otsubo, Hiroki; Onaka, Tatsushi; Suzuki, Hitoshi; Katoh, Akiko; Ohbuchi, Toyoaki; Todoroki, Miwako; Kobayashi, Mizuki; Fujihara, Hiroaki; Yokoyama, Toru; Matsumoto, Tetsuro; Ueta, Yoichi


    The expression of the relaxin-3 gene, detected as a new member of the insulin superfamily using human genomic databases, is abundantly present in the brain and testis. Intracerebroventricularly (icv) administered relaxin-3 stimulates food intake. Icv administered relaxin (identical to relaxin-2 in humans) affects the secretion of vasopressin and drinking behavior. Relaxin-3 partly binds relaxin family peptide receptor 1, which is a specific receptor to relaxin. Thus, we hypothesized that relaxin-3 would have physiological effects in the body fluid balance. However, the effects of relaxin-3 in the body fluid balance remain unknown. In the present study, we revealed that icv administered relaxin-3 induced dense Fos-like immunoreactivity (Fos-LI) in the rat hypothalamus and circumventricular organs including the organum vasculosum of the lamina terminalis, the median preoptic nucleus, supraoptic nucleus (SON), the subfornical organ (SFO) and the paraventricular nucleus (PVN), that are related to the central regulation of body fluid balance. Icv administered relaxin-3 (54, 180 and 540 pmol/rat) also induced a significant increase in c-fos gene expression in a dose-dependent manner in the SON, SFO and PVN. Further, icv administered relaxin-3 (180 pmol/rat) significantly increased water intake, and the effect was as strong as that of relaxin-2 (180 pmol/rat). These results suggest that icv administered relaxin-3 activates osmosensitive areas in the brain and plays an important role in the regulation of body fluid balance. Copyright 2010 Elsevier Inc. All rights reserved.

  19. Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states

    Directory of Open Access Journals (Sweden)

    Allison eGraebner


    Full Text Available A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools have greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

  20. Reasons of leaves withering in tropical plants cultivated under greenhouse conditions

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    Z. Czerwiński


    Full Text Available In order to determine the reasons of necrosis of exotic plants leaves cultivated in greenhouses plants belonging to ten following species were examined: Ceratozamia mexicana Brongn., Stangeria eriopus (Kunze Nash (Cycadaceae, Eriobotrya japonica Lindl. (Rosaceae, Camellia japonica L. (Theaceae, Phoenix roebeleni O'Brien (Palmae, Sequoia sempervirens Endl. (Taxodiaceae, Calathea bachemiana Morr. (Marantaceae, Cordyline terminalis Kunth (Agavaceae, Spathiphyllum wallisii Reg. and Anthurium magnificum Lind. (Araceae. Chemical analysis were performed in soil samples in which these plants grow, in samples of tap-water applied for watering and in samples of decaying and healthy leaves. In order to examine the process of withdrawal of mineral components from necrotic leaves, both: necrotic and green parts of decaying leaves were subjected to examination. On the basis of the research it was concluded, that - in spite of generally low level of salinity of the water used for watering - some ions content, particularity that of CI-, was unfavourable to plants. Unfavourable ionic composition was discovered in water extracts derived from some of the breeding-ground soils. A comparison of healthy and decaying, necrotic leaves chemism proves that CI- assimilated by the plants from the breeding-grounds and accumulated in leaves, affects them toxically.

  1. Virtual endoscopy combined with intraoperative neuronavigation for planning of endoscopic surgery in patients with occlusive hydrocephalus and intracranial cysts

    Energy Technology Data Exchange (ETDEWEB)

    Krombach, G.A.; Haage, P.; Kilbinger, M. [Department of Diagnostic Radiology, University of Technology, Aachen (Germany); Rohde, V. [Department of Neurosurgery, University of Technology, Aachen (Germany); Struffert, T. [Department of Neuroradiology, University of Technology, Aachen (Germany); Department of Neuroradiology, University of Saarland, Homburg (Germany); Thron, A. [Department of Neuroradiology, University of Technology, Aachen (Germany)


    We assessed the clinical value of MR ventriculoscopy (virtual endoscopy, VE) combined with image-guided frameless stereotaxy for endoscopic surgery of occlusive hydrocephalus and intracranial cysts. VE was obtained in 20 patients with hydrocephalus and three with intracranial cysts. All surgical operations were endoscopic. The path of the rigid endoscope to the target point was planned using neuronavigation. VE was carried out along the same trajectory retrospectively in 20 cases and prospectively in three. The results were analysed for demonstration of anatomical landmarks and structures at risk. VE was successful in all patients. Possible obstacles to endoscopic access to the lamina terminalis and the basal cisterns and structures at risk, such as the basilar artery, were clearly shown in relation to the direction of the endoscope. However, the floor of the third ventricle and septum pellucidum were not clearly seen and possible abnormalities could therefore not be appreciated. VE can provide realistic simulation of endoscopic third ventriculostomy and cystostomy. The appropriate trepanation point and trajectory of the endoscope can be assessed with regard to the size of the foramen of Monro and the position of vulnerable structures. This simulated trajectory can be adapted to the field of operation by image-guided neuronavigation. This regime may potentially reduce the risk of damage to intracranial structures. (orig.)

  2. Inhibition of tissue angiotensin converting enzyme. Quantitation by autoradiography

    International Nuclear Information System (INIS)

    Sakaguchi, K.; Chai, S.Y.; Jackson, B.; Johnston, C.I.; Mendelsohn, F.A.


    Inhibition of angiotensin converting enzyme (ACE) in serum and tissues of rats was studied after administration of lisinopril, an ACE inhibitor. Tissue ACE was assessed by quantitative in vitro autoradiography using the ACE inhibitor [ 125 I]351A, as a ligand, and serum ACE was measured by a fluorimetric method. Following oral administration of lisinopril (10 mg/kg), serum ACE activity was acutely reduced but recovered gradually over 24 hours. Four hours after lisinopril administration, ACE activity was markedly inhibited in kidney (11% of control level), adrenal (8%), duodenum (8%), and lung (33%; p less than 0.05). In contrast, ACE in testis was little altered by lisinopril (96%). In brain, ACE activity was markedly reduced 4 hours after lisinopril administration in the circumventricular organs, including the subfornical organ (16-22%) and organum vasculosum of the lamina terminalis (7%; p less than 0.05). In other areas of the brain, including the choroid plexus and caudate putamen, ACE activity was unchanged. Twenty-four hours after administration, ACE activity in peripheral tissues and the circumventricular organs of the brain had only partially recovered toward control levels, as it was still below 50% of control activity levels. These results establish that lisinopril has differential effects on inhibiting ACE in different tissues and suggest that the prolonged tissue ACE inhibition after a single oral dose of lisinopril may reflect targets involved in the hypotensive action of ACE inhibitors

  3. Daily cycle and body characteristics of mating Litopenaeus vannamei shrimps (Decapoda: Penaeidae) in the wild off southern Sinaloa, Mexico. (United States)

    Calderón-Pérez, J A; Rendón-Rodríguez, S; Solís-Ibarra, R


    Mating behavior has been described for very few species of penaeoid shrimps. We describe some of the environmental conditions under which mating of Litopenaeus vannamei took place in the ocean, as inferred by the presence of attached spermatophores on the thelycum of females, combined with the presence of mature males with empty ampulla terminalis, both evidence of recent copulation. Out of a total of twelve 24 hr samplings on board the research vessel B/O "EL PUMA", one was selected to examine mating. There were four periods of observation. The highest frequency of females with attached spermatophores were found during the daytime whilst the lowest was registered during the night. Females with attached spermatophore were mostly at stages IV and V of ovarian maturity and fell within the 30-50 mm of C.L. range. Copulating male size ranged between 30 and 40 mm of C.L. and there was a close relation between the percentage of mating females and males. Male to female ratio varied throughout the sampling period but it was never 1:1. The female mean size was, in all cases, bigger than the male mean size. Among the environmental factors, salinity and oxygen varied very slightly throughout the sampling period; temperature variation was more pronounced and those changes were attributed to the tidal oscillation.

  4. I sistemi biometrici lo sviluppo dei mercati negli Usa, UE e nel mondo. La normativa frena quello italiano

    Directory of Open Access Journals (Sweden)

    Franco Zucchetti


    Full Text Available Negli ultimi anni il settore biometrico sta compiendo, a livello mondiale, importanti passi in avanti soprattutto in termini di sviluppo e di diffusione. Questo trend positivo riguarda il mondo anglosassone e, in particolare, la realtà statunitense dove i sistemi biometrici vengono utilizzati, nelle più svariate situazioni, sia come controllo della sicurezza fisica delle persone, sia come terminali per l’autorizzazione all’accesso. La stessa diffusione non è riscontrabile nella maggior parte dei Paesi europei e in Italia dove raffrontiamo una realtà assai atipica nella quale la biometria fa un gran parlare di sé ma, in concreto, viene utilizzata con molta difficoltà. Tuttavia, un punto di contatto tra tutti gli attori europei ed extraeuropei può essere individuato nello sviluppo del settore relativo al riconoscimento biometrico applicato ai passaporti ed alle carte di identità. Il processo di globalizzazione ha generato, infatti, grandi masse di individui in continuo e costante movimento da un Paese all’altro e, contestualmente, ha prodotto una crescente domanda di sicurezza soprattutto nei confronti della minaccia terroristica. Appare chiaro, quindi, come l’identificazione certa delle persone diventi una necessità e debba presentare tecnologie simili per essere utilizzate ovunque.

  5. Chicken primordial germ cells use the anterior vitelline veins to enter the embryonic circulation

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    Ana De Melo Bernardo


    During gastrulation, chicken primordial germ cells (PGCs are present in an extraembryonic region of the embryo from where they migrate towards the genital ridges. This is also observed in mammals, but in chicken the vehicle used by the migratory PGCs is the vascular system. We have analysed the migratory pathway of chicken PGCs, focusing on the period of transition from the extraembryonic region to the intraembryonic vascular system. Our findings show that at Hamburger and Hamilton developmental stage HH12–HH14 the majority of PGCs concentrate axially in the sinus terminalis and favour transport axially via the anterior vitelline veins into the embryonic circulation. Moreover, directly blocking the blood flow through the anterior vitelline veins resulted in an accumulation of PGCs in the anterior region and a decreased number of PGCs in the genital ridges. We further confirmed the key role for the anterior vitelline veins in the correct migration of PGCs using an ex ovo culture method that resulted in defective morphogenetic development of the anterior vitelline veins. We propose a novel model for the migratory pathway of chicken PGCs whereby the anterior vitelline veins play a central role at the extraembryonic and embryonic interface. The chicken model of PGC migration through the vasculature may be a powerful tool to study the process of homing (inflammation and metastasis due to the striking similarities in regulatory signaling pathways (SDF1–CXCR4 and the transient role of the vasculature.

  6. Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat

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    Jian-Dong Li


    Full Text Available Heart failure (HF is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS activity and elevated levels of proinflammatory cytokines (PICs. Renal denervation (RD has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO- induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD.

  7. Gene transfection mediated by polyethyleneimine-polyethylene glycol nanocarrier prevents cisplatin-induced spiral ganglion cell damage

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    Guan-gui Chen


    Full Text Available Polyethyleneimine-polyethylene glycol (PEI-PEG, a novel nanocarrier, has been used for transfection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein (XIAP in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats, via scala tympani fenestration, before daily cisplatin injections. Auditory brainstem reflex tests demonstrated the protective effects of XIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels of XIAP mRNA expression in the cochlea. The present findings suggest that PEI-PEG nanocarrier-mediated XIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.

  8. Idiopathic sudden sensorineural hearing loss: vascular or viral? (United States)

    Linthicum, Fred H; Doherty, Joni; Berliner, Karen I


    To demonstrate that sudden sensorineural hearing loss is possibly of viral origin rather than vascular. The histopathologic morphology in 7 temporal bones with known vascular impairment due to surgical interventions was compared with that of 11 bones with a history of idiopathic sudden sensorineural hearing loss (ISSNHL). Attention was paid to the spiral ligament, stria vascularis, organ of Corti hair cells, tectorial membrane, ganglion cell population, and degree of perilymph fibrosis and the auditory nerve. A temporal bone laboratory that has been in operation for more than 50 years and includes a database consisting of clinical and histopathological information that facilitates quantitative and qualitative analysis. Eight hundred forty-nine individuals who pledged their temporal bones for scientific study, of which 18 were selected for this study by means of the database criteria of sudden sensorineural hearing loss and postmiddle fossa and retro sigmoid sinus tumor removal or vestibular nerve section. Sudden sensorineural hearing loss bones exhibited no perilymph fibrosis compared with 6 of 7 vascular cases with fibrosis (P ≤ .001), exhibited less loss of ganglion cells (P ≤ .026), exhibited greater survival of spiral ligament (P ≤ .029), and averaged twice the survival of hair cells and more widespread tectorial membrane abnormalities. Analysis of human temporal bones from patients with a sudden sensorineural hearing loss does not support a vascular insufficiency but is more suggestive of a viral etiology.

  9. Deafness and permanently reduced potassium channel gene expression and function in hypothyroid Pit1dw mutants (United States)

    Mustapha, Mirna; Fang, Qing; Gong, Tzy-Wen; Dolan, David F.; Raphael, Yehoash; Camper, Sally A.; Duncan, R. Keith


    The absence of thyroid hormone (TH) during late gestation and early infancy can cause irreparable deafness in both humans and rodents. A variety of rodent models have been utilized in an effort to identify the underlying molecular mechanism. Here, we characterize a mouse model of secondary hypothyroidism, pituitary transcription factor 1 (Pit1dw), which has profound, congenital deafness that is rescued by oral TH replacement. These mutants have tectorial membrane abnormalities, including a prominent Hensen's stripe, elevated β-tectorin composition, and disrupted striated-sheet matrix. They lack distortion product otoacoustic emissions and cochlear microphonic responses, and exhibit reduced endocochlear potentials, suggesting defects in outer hair cell function and potassium recycling. Auditory system and hair cell physiology, histology and anatomy studies reveal novel defects of hormone deficiency related to deafness: (1) permanently impaired expression of KCNJ10 in the stria vascularis of Pit1dw mice, which likely contributes to the reduced endocochlear potential, (2) significant outer hair cell loss in the mutants, which may result from cellular stress induced by the lower KCNQ4 expression and current levels in Pit1dw mutant outer hair cells and (3) sensory and strial cell deterioration, which may have implications for thyroid hormone dysregulation in age related hearing impairment. In summary, we suggest that these defects in outer hair cell and strial cell function are important contributors to the hearing impairment in Pit1dw mice. PMID:19176829

  10. The role of the habenula in drug addiction

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    Kenia Marisela Velasquez


    Full Text Available Interest in the habenula has greatly increased in recent years. The habenula is a small brain structure located posterior to the thalamus and adjacent to the third ventricle. Despite its small size, the habenula can be divided into medial (MHb and lateral (LHb nuclei that are anatomically and transcriptionally distinct. The habenula receives inputs from the limbic system and basal ganglia primarily via the stria medullaris. The fasciculus retroflexus is the primary habenular output from the habenula to the midbrain and governs release of glutamate onto gabaergic cells in the rostromedial tegmental nucleus (RMTg and onto the interpeduncular nucleus (IPN. The resulting GABA released from RMTg neurons inactivates dopaminergic cells in the ventral tegmental area (VTA/substantia nigra compacta (SNc. Through this process, the habenula controls dopamine levels in the striatum. Thus, the habenula plays a critical role in reward and reward-associated learning. The LHb also modulates serotonin levels and norepinephrine release, while the MHb modulates acetylcholine. The habenula is a critical crossroad that influences the brain’s response to pain, stress, anxiety, sleep, and reward. Dysfunction of the habenula has been linked to depression, schizophrenia, and the effects of drugs of abuse. This review focuses on the possible relationships between the habenula and drug abuse.

  11. Histopathology of the Human Inner Ear in a Patient With Sensorineural Hearing Loss Caused by a Variant in DFNA5. (United States)

    Nadol, Joseph B; Handzel, Ophir; Amr, Sami


    Describe the histopathology of the inner ear in a patient with hearing loss caused by a pathogenic variant of the DFNA5 gene. Variants in DFNA5 have been described as causing an autosomal dominant nonsyndromic sensorineural hearing loss. To date, there has been no description of the histopathology of the inner ear in humans with hearing loss because of pathogenic variants in DFNA5. Temporal bone histopathology by light microscopy, next-generation sequencing (NGS) of DNA obtained from blood, and Sanger sequencing of DNA obtained from formalin fixed temporal bone sections. Both the temporal bone donor and her daughter were shown to have the same pathogenic variant in the DFNA5 gene. The principal histopathologic correlates of the hearing loss were loss of the inner and outer hair cells and severe degeneration of the stria vascularis and spiral ligament throughout the cochlea. In addition, there was severe degeneration of spiral ganglion cells, particularly in the basal turn, and degeneration of vestibular neuroepithelium and neurons. The donor had undergone unilateral cochlear implantation during life. Histopathology demonstrated that the cochlear implant was inserted into the scala vestibuli with considerable new bone formation around the track of the implanted electrode. This is the first report of the histopathology of the inner ear in a patient with hearing loss caused by a pathogenic variant in the DFNA5 gene.

  12. Cochleovestibular Manifestations in Fabry Disease

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    Alberto Ciceran MD


    Full Text Available Fabry disease is a rare, X-linked lysosomal storage disorder resulting from deficient α-galactosidase A activity and globotriaosylceramide accumulation throughout the body. This accumulation leads to various clinical disorders, including inner ear lesions, with sensorineural hearing loss and dizziness. Although hearing loss is recognized in these patients, its incidence and natural history have not been characterized. Hearing disorders develop mainly in adulthood, and tinnitus may be an earlier symptom in Fabry disease. A significant incidence of mid- and high-frequency sensorineural hearing loss in affected males is commonly reported, whereas in female carriers, it is much less frequent. In addition, a high incidence of vestibular disorders with dizziness and chronic instability is also observed in these patients. The few studies about the effects of enzyme replacement therapy (ERT on cochleovestibular symptoms show controversial results. Based on the model of densely stained material accumulation in the inner ear, stria vascularis cell, and organ damage, an early indication of ERT may prevent hearing loss due to the reduction in substrate accumulation.

  13. Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

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    Tohru Tanigawa

    Full Text Available Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG, one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV, which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

  14. [Iatrogenic and non-iatrogenic factors as causes of progressive sensorineural hearing loss]. (United States)

    De Capua, B; Barbieri, M T; Tozzi, A; Passàli, D


    The aim of our study was to analyze factors such as noise, chemical drugs, industrial solvents and radiotherapy, which can cause cochlear lesions with progressive sensorineural hearing loss. Although an acute overstimulation by acoustic energy may induce an irreversible hearing loss, in most cases the noise-induced deafness is related to the duration of the exposure and to the level of the acoustic stimulation. A permanent hearing deficit occurs when the acoustic level exceeds 85 dBs. Also several classes of drugs are described as having ototoxic potential: aminoglycoside antibiotics, loop diuretics, antimalarial drugs such as quinine, salicylates, some chemotherapeutic antineoplastic agents. Their potential ototoxic effect seems to be related not only to the molecule, but also to individual predisposition, dose and route of administration. Regarding the benzene derivatives, there is a relationship between their ototoxicity and factors such as duration of exposure and concentration in the local environment. Finally, radiotherapy to areas near the temporal bone may produce a degenerative insult to the vascular stria and the hair cell causing a progressive sensorineural hearing loss.

  15. An experimental study of inner ear injury in an animal model of eosinophilic otitis media. (United States)

    Matsubara, Atsushi; Nishizawa, Hisanori; Kurose, Akira; Nakagawa, Takashi; Takahata, Junko; Sasaki, Akira


    As the periods of intratympanic injection of ovalbumin (OVA) to the middle ear became longer, marked eosinophil infiltration in the perilymphatic space was observed. Moreover severe morphological damage of the organ of Corti was observed in the 28-day antigen-stimulation side. These results indicate that eosinophilic inflammation occurred in the inner ear and caused profound hearing loss. The purpose of the present study was to elucidate the inner ear damage in a new animal model of eosinophilic otitis media (EOM) which we recently constructed. We constructed the animal model of EOM by intraperitoneal and intratympanic injection of OVA. Infiltrating cells and the inner ear damage were examined by histological study. In the inner ear, a few eosinophils were seen in the scala tympani of the organ of Corti and the dilation of capillaries of the stria vascularis was observed in the 7-day stimulation side. In the 14-day antigen stimulation side, some eosinophils and macrophages were seen in not only the scala tympani but also the scala vestibule. In the 28-day antigen-stimulation side, severe morphological damage of the organ of Corti and many eosinophils, red blood cells, and plasma cells infiltrating the perilymph were observed.

  16. Distribution of an 125I-labelled chloroquine analogue in a pregnant macaca monkey

    International Nuclear Information System (INIS)

    Dencker, L.; Lindquist, N.G.; Ullberg, S.


    Whole body autoradiography of a pregnant monkey (Macaca irus) of late gestation was performed 72 h after an intravenous injection of the 125 I-labelled chloroquine analogue 4-(3-dimethylaminopropylamino)-7-iodoquinoline (DAPQ). The overall distribution pattern in the monkey was similar to that which was earlier observed in rodents. A few species differences, however, were found in the monkey as compared to the rodents: a high accumulation in the inner part of the adrenal cortex, a high level in the central nervous system, and generally a higher retention in the tissues. The accumulation in the cortex may be of significance for the cortisone-like effects of the 4-aminoquinolines in rheumatoid arthritis and allied conditions. The fact that no accumulation was found in the adrenal cortex of mice and rats indicates that these species may not be appropriate in studies on the mechanisms involved in the anti-inflammatory action of the 4-aminoquinolines. As was earlier observed in small rodents the melanin containing structures accumulated the drug. In both the mother and the fetus a high concentration was thus seen in the uveal tract of the eye, in the inner ear (in the stria vascularis of the cochlea and the planum semilunatum of the ampullae) and in the hair follicles. This accumulation can be related to reported disturbances-also transplacentally induced-in vision and hearing

  17. Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome. (United States)

    Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi


    Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1(-/-) mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0-P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner's membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1(-/-) mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  18. Age-Related Hearing Loss in Mn-SOD Heterozygous Knockout Mice

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    Makoto Kinoshita


    Full Text Available Age-related hearing loss (AHL reduces the quality of life for many elderly individuals. Manganese superoxide dismutase (Mn-SOD, one of the antioxidant enzymes acting within the mitochondria, plays a crucial role in scavenging reactive oxygen species (ROS. To determine whether reduction in Mn-SOD accelerates AHL, we evaluated auditory function in Mn-SOD heterozygous knockout (HET mice and their littermate wild-type (WT C57BL/6 mice by means of auditory brainstem response (ABR. Mean ABR thresholds were significantly increased at 16 months when compared to those at 4 months in both WT and HET mice, but they did not significantly differ between them at either age. The extent of hair cell loss, spiral ganglion cell density, and thickness of the stria vascularis also did not differ between WT and HET mice at either age. At 16 months, immunoreactivity of 8-hydroxydeoxyguanosine was significantly greater in the SGC and SV in HET mice compared to WT mice, but that of 4-hydroxynonenal did not differ between them. These findings suggest that, although decrease of Mn-SOD by half may increase oxidative stress in the cochlea to some extent, it may not be sufficient to accelerate age-related cochlear damage under physiological aging process.

  19. Localization of the NO/cGMP-pathway in the cochlea of guinea pigs. (United States)

    Michel, O; Hess, A; Bloch, W; Stennert, E; Su, J; Addicks, K


    The presence of nitric oxide synthase (NOS) in substructures of the cochlea of guinea pigs is an issue of current focus. Moreover, information concerning the localization of cells effected by the NO/cGMP-pathway are rare. Paraffin sections of guinea pig cochlea were incubated with specific antibodies to the three known NOS isoforms, soluble guanylyl cyclase (sGC) and cyclic guanosine-monophosphate (cGMP), the second messenger system of NO. While detection of inducible iNOS failed in all cochlear structures, expression of endothelial eNOS was found in the spiral ligament, in the stria vascularis, in cells of the organ of Corti, in nerve fibers and in some perikaryia of the spiral ganglion. The cochlear nerve showed an accentuated affinity for immunostaining in distal, basal segments of the cochlea. Neuronal bNOS was found predominantly in the endosteum of the modiolus and cochlea and was less intensively present in all perikaryia of the spiral ganglion and in the spiral ligament. Supporting cells of the organ of Corti and cells in the limbus spiralis displayed only modest immunostaining, while bNOS was not found in outer and inner hair cells. NOS detection was accompanied by immunoreactivity to sGC and to cGMP. The presence of NOS and its second messenger system gives evidence for a possible involvement in neurotransmission, regulation of the cochlear amplifier and in homeostasis.

  20. Inflammatory and immune responses in the cochlea: potential therapeutic targets for sensorineural hearing loss

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    Masato eFujioka


    Full Text Available The inner ear was previously assumed to be an immune-privileged organ due to the existence of its tight junction-based blood-labyrinth barrier. However, studies performed during the past decade revealed that the mesenchymal region of the cochlea, including its lateral wall, is a common site of inflammation. Neutrophils do not enter this region, which is consistent with the old dogma; however, bone marrow-derived resident macrophages are always present in the spiral ligament of the lateral wall and are activated in response to various types of insults, including noise exposure, ischemia, mitochondrial damage and surgical stress. Recent studies have also revealed another type of immune cell, called perivascular melanocyte-like macrophages (PVM/Ms, in the stria vascularis. These dedicated antigen-presenting cells also control vascular contraction and permeability. This review discusses a series of reports regarding inflammatory/immune cells in the cochlear lateral wall, the pathways involved in cochlear damage and their potential as therapeutic targets.

  1. Light microscopy study of cisplatin-induced ototoxicity in rats. (United States)

    de Freitas, M R; de Castro Brito, G A; de Carvalho, J V; Gomes, R M; Barreto Martins, M J; de Albuquerque Ribeiro, R


    Although most studies on animal ototoxicity employ scanning electron microscopy, all cochlear structures may be identified with light microscopy. This paper describes a simple method of histological assessment of cisplatin-induced ototoxicity in rats, and relates morphological changes to functional changes in hearing detected by distortion product evoked otoacoustic emissions. Male Wistar rats were injected with 8 mg/kg/day cisplatin, or with an equivalent volume of saline solution, for three consecutive days. They underwent distortion product evoked otoacoustic emission testing at baseline and at 24 or 48 hours after the last administration. At the end of the experiment, the animals were sacrificed and their cochleae were retrieved and prepared for haematoxylin and eosin staining. A four-point scoring system was used to grade injury to the external ciliated cells, as indicated by the number of cells absent from the basal turn of the cochlear duct. A four-point scoring system was also used to grade stria vascularis injury, as indicated by the degree of shrinkage of the intermediate cells. Scores were significantly higher in groups treated with cisplatin compared with controls. Morphological changes were confirmed by decreased distortion product evoked otoacoustic emission amplitudes in animals treated with cisplatin. This method is simple to perform with routine histology equipment and is appropriate for the study of acute, cisplatin-induced ototoxicity in rats.

  2. Hearing dysfunction in heterozygous Mitf(Mi-wh) /+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome. (United States)

    Ni, Christina; Zhang, Deming; Beyer, Lisa A; Halsey, Karin E; Fukui, Hideto; Raphael, Yehoash; Dolan, David F; Hornyak, Thomas J


    The human deafness-pigmentation syndromes, Waardenburg syndrome (WS) type 2a, and Tietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF. To illuminate differences between cutaneous and otic melanocytes in these syndromes, their development and survival in heterozygous Microphthalmia-White (Mitf(Mi-wh) /+) mice were studied and hearing function of these mice characterized. Mitf(Mi-wh) /+ mice have a profound hearing deficit, characterized by elevated auditory brainstem response thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. Mitf(Mi-wh) /+ embryos have fewer melanoblasts during embryonic development than their wild-type littermates. Although cochlear melanocytes are present at birth, they disappear from the Mitf(Mi-wh) /+ cochlea between P1 and P7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness-pigmentation syndromes such as WS and Tietz syndrome and illustrate differences between otic and follicular melanocytes. © 2012 John Wiley & Sons A/S.

  3. Creation of miniature pig model of human Waardenburg syndrome type 2A by ENU mutagenesis. (United States)

    Hai, Tang; Guo, Weiwei; Yao, Jing; Cao, Chunwei; Luo, Ailing; Qi, Meng; Wang, Xianlong; Wang, Xiao; Huang, Jiaojiao; Zhang, Ying; Zhang, Hongyong; Wang, Dayu; Shang, Haitao; Hong, Qianlong; Zhang, Rui; Jia, Qitao; Zheng, Qiantao; Qin, Guosong; Li, Yongshun; Zhang, Tao; Jin, Weiwu; Chen, Zheng-Yi; Wang, Hongmei; Zhou, Qi; Meng, Anming; Wei, Hong; Yang, Shiming; Zhao, Jianguo


    Human Waardenburg syndrome 2A (WS2A) is a dominant hearing loss (HL) syndrome caused by mutations in the microphthalmia-associated transcription factor (MITF) gene. In mouse models with MITF mutations, WS2A is transmitted in a recessive pattern, which limits the study of hearing loss (HL) pathology. In the current study, we performed ENU (ethylnitrosourea) mutagenesis that resulted in substituting a conserved lysine with a serine (p. L247S) in the DNA-binding domain of the MITF gene to generate a novel miniature pig model of WS2A. The heterozygous mutant pig (MITF +/L247S ) exhibits a dominant form of profound HL and hypopigmentation in skin, hair, and iris, accompanied by degeneration of stria vascularis (SV), fused hair cells, and the absence of endocochlear potential, which indicate the pathology of human WS2A. Besides hypopigmentation and bilateral HL, the homozygous mutant pig (MITF L247S/L247S ) and CRISPR/Cas9-mediated MITF bi-allelic knockout pigs both exhibited anophthalmia. Three WS2 patients carrying MITF mutations adjacent to the corresponding region were also identified. The pig models resemble the clinical symptom and molecular pathology of human WS2A patients perfectly, which will provide new clues for better understanding the etiology and development of novel treatment strategies for human HL.

  4. Ion microprobe assessment of the heterogeneity of Mg/Ca, Sr/Ca and Mn/Ca ratios in Pecten maximus and Mytilus edulis (bivalvia shell calcite precipitated at constant temperature

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    P. S. Freitas


    Full Text Available Small-scale heterogeneity of biogenic carbonate elemental composition can be a significant source of error in the accurate use of element/Ca ratios as geochemical proxies. In this study ion microprobe (SIMS profiles showed significant small-scale variability of Mg/Ca, Sr/Ca and Mn/Ca ratios in new shell calcite of the marine bivalves Pecten maximus and Mytilus edulis that was precipitated during a constant-temperature culturing experiment. Elevated Mg/Ca, Sr/Ca and Mn/Ca ratios were found to be associated with the deposition of elaborate shell features, i.e. a shell surface stria in P. maximus and surface shell disturbance marks in both species, the latter a common occurrence in bivalve shells. In both species the observed small-scale elemental heterogeneity most likely was not controlled by variable transport of ions to the extra-pallial fluid, but by factors such as the influence of shell organic content and/or crystal size and orientation, the latter reflecting conditions at the shell crystal-solution interface. In the mid and innermost regions of the P. maximus shell the lack of significant small-scale variation of Mg/Ca ratios, which is consistent with growth at constant temperature, suggest a potential application as a palaeotemperature proxy. Cross-growth band element/Ca ratio profiles in the interior of bivalve shells may provide more promising palaeo-environmental tools than sampling from the outer region of bivalve shells.


    Directory of Open Access Journals (Sweden)

    Paolo Magrini