Several synthetic progestins disrupt the glial cell specific-brain aromatase expression in developing zebra fish

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Cano-Nicolau, Joel [Team NEED, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Garoche, Clémentine; Hinfray, Nathalie [Unité d' Ecotoxicologie in vitro et in vivo , Institut National de l' Environnement Industriel et des Risques (INERIS), BP 2, 60550 Verneuil-en-Halatte (France); Pellegrini, Elisabeth [Team NEED, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Boujrad, Noureddine; Pakdel, Farzad [TREK, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Kah, Olivier, E-mail: oliver.kah@univ-rennes1.fr [Team NEED, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Brion, François, E-mail: francois.brion@ineris.fr [Unité d' Ecotoxicologie in vitro et in vivo , Institut National de l' Environnement Industriel et des Risques (INERIS), BP 2, 60550 Verneuil-en-Halatte (France)

2016-08-15

The effects of some progestins on fish reproduction have been recently reported revealing the hazard of this class of steroidal pharmaceuticals. However, their effects at the central nervous system level have been poorly studied until now. Notwithstanding, progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. Herein, we investigated the effects of a large set of synthetic ligands of the nuclear progesterone receptor on the glial-specific expression of the zebrafish brain aromatase (cyp19a1b) using zebrafish mechanism-based assays. Progesterone and 24 progestins were first screened on transgenic cyp19a1b-GFP zebrafish embryos. We showed that progesterone, dydrogesterone, drospirenone and all the progesterone-derived progestins had no effect on GFP expression. Conversely, all progestins derived from 19-nortesterone induced GFP in a concentration-dependent manner with EC{sub 50} ranging from the low nM range to hundreds nM. The 19-nortestosterone derived progestins levonorgestrel (LNG) and norethindrone (NET) were further tested in a radial glial cell context using U251-MG cells co-transfected with zebrafish ER subtypes (zfERα, zfERβ1 or zfERβ2) and cyp19a1b promoter linked to luciferase. Progesterone had no effect on luciferase activity while NET and LNG induced luciferase activity that was blocked by ICI 182,780. Zebrafish-ERs competition assays showed that NET and LNG were unable to bind to ERs, suggesting that the effects of these compounds on cyp19a1b require metabolic activation prior to elicit estrogenic activity. Overall, we demonstrate that 19-nortestosterone derived progestins elicit estrogenic activity by inducing cyp19a1b expression in radial glial cells. Given the crucial role of radial glial cells and neuro-estrogens in early development of brain, the consequences of exposure of fish to these compounds require further investigation. - Highlights: • P4 + 24

Characterization of a cis-acting element involved in cell-specific expression of the zebrafish brain aromatase gene.

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Le Page, Yann; Menuet, Arnaud; Kah, Olivier; Pakdel, Farzad

2008-10-01

The cytochrome P450 Aromatase is the key enzyme catalyzing the conversion of androgens into estrogens. In zebrafish, the brain aromatase is encoded by cyp19b. Expression of cyp19b is restricted to radial glial cells bordering forebrain ventricles and is strongly stimulated by estrogens during development. At the promoter level, we have previously shown that an estrogen responsive element (ERE) is required for induction by estrogens. Here, we investigated the role of ERE flanking regions in the control of cell-specific expression. First, we show that a 20 bp length motif, named G x RE (glial x responsive element), acts in synergy with the ERE to mediate the estrogenic induction specifically in glial cells. Second, we demonstrate that, in vitro, this sequence binds factors exclusively present in glial or neuro-glial cells and is able to confer a glial specificity to an artificial estrogen-dependent gene. Taken together, these results contribute to the understanding of the molecular mechanisms allowing cyp19b regulation by estrogens and allowed to identify a promoter sequence involved in the strong estrogen inducibility of cyp19b which is specific for glial cells. The exceptional aromatase activity measured in the brain of teleost fish could rely on such mechanisms.

In vivo imaging of brain aromatase in female baboons: [11C]vorozole kinetics and effect of the menstrual cycle.

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Pareto, Deborah; Biegon, Anat; Alexoff, David; Carter, Pauline; Shea, Coreen; Muench, Lisa; Xu, Youwen; Fowler, Joanna S; Kim, Sunny W; Logan, Jean

2013-01-01

The aim of this work was to quantify the brain distribution of the enzyme aromatase in the female baboon with positron emission tomography and the tracer [11C]vorozole using three different quantification methods for estimating the total distribution volume (V(T)): a graphical method, compartment modeling, and a tissue to plasma ratio. The graphical model and the compartment modeling gave similar estimates to the data and similar values (correlation R  =  .988; p  =  .0001). [11C]Vorozole shows a rapid uptake by the brain followed by a relatively constant accumulation, suggesting the possibility of using the tissue to plasma ratio as an estimate of V(T). The highest uptake of [11C]vorozole in the baboon brain was measured in the amygdala, followed by the preoptic area and hypothalamus, basal ganglia, and cortical areas. Pretreatment studies with vorozole or letrozole showed a generalized decrease in brain accumulation and V(T). The results suggested that the physiologic changes in gonadal hormone levels accompanying the menstrual cycle had a significant effect on brain aromatase V(T).

Effects of testosterone and its metabolites on aromatase-immunoreactive cells in the quail brain: relationship with the activation of male reproductive behavior.

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Balthazart, J; Foidart, A; Absil, P; Harada, N

1996-01-01

The enzyme aromatase converts testosterone (T) into 17 beta-estradiol and plays a pivotal role in the control of reproduction. In particular, the aromatase activity (AA) located in the preoptic area (POA) of male Japanese quail is a limiting step in the activation by T of copulatory behavior. Aromatase-immunoreactive (ARO-ir) cells of the POA are specifically localized within the cytoarchitectonic boundaries of the medial preoptic nucleus(POM), a sexually dimorphic and steroid-sensitive structure that is a necessary and sufficient site of steroid action in the activation of behavior. Stereotaxic implantation of aromatase inhibitors in but not around the POM strongly decreases the behavioral effects of a systemic treatment with T of castrated males. AA is decreased by castration and increased by aromatizable androgens and by estrogens. These changes have been independently documented at three levels of analysis: the enzymatic activity measured by radioenzymatic assays in vitro, the enzyme concentration evaluated semi-quantitatively by immunocytochemistry and the concentration of its messenger RNA quantified by reverse transcription-polymerase chain reaction (RT-PCR). These studies demonstrate that T acting mostly through its estrogenic metabolites regulates brain aromatase by acting essentially at the transcriptional level. Estrogens produced by central aromatization of T therefore have two independent roles: they activate male copulatory behavior and they regulate the synthesis of aromatase. Double label immunocytochemical studies demonstrate that estrogen receptors(ER) are found in all brain areas containing ARO-ir cells but the extent to which these markers are colocalized varies from one brain region to the other. More than 70% of ARO-ir cells contain detectable ER in the tuberal hypothalamus but less than 20% of the cells display this colocalization in the POA. This absence of ER in ARO-ir cells is also observed in the POA of the rat brain. This suggests that

Paternal retrieval behavior regulated by brain estrogen synthetase (aromatase in mouse sires that engage in communicative interactions with pairmates

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Shirin eAkther

2015-12-01

Full Text Available Parental behaviors involve complex social recognition and memory processes and interactive behavior with children that can greatly facilitate healthy human family life. Fathers play a substantial role in child care in a small but significant number of mammals, including humans. However, the brain mechanism that controls male parental behavior is much less understood than that controlling female parental behavior. Fathers of non-monogamous laboratory ICR mice are an interesting model for examining the factors that influence paternal responsiveness because sires can exhibit maternal-like parental care (retrieval of pups when separated from their pups along with their pairmates because of olfactory and auditory signals from the dams. Here we tested whether paternal behavior is related to femininity by the aromatization of testosterone. For this purpose, we measured the immunoreactivity of aromatase (cytochrome P450 family 19 (CYP19, which synthesizes estrogen from androgen, in nine brain regions of the sire. We observed higher levels of aromatase expression in these areas of the sire brain when they engaged in communicative interactions with dams in separate cages. The capacity of sires to retrieve pups was increased following a period of five days spent with the pups as a whole family after parturition, whereas the acquisition of this ability was suppressed in sires treated daily with an aromatase inhibitor. These results suggest that brain aromatization regulates the initiation, development, and maintenance of paternal behavior in the ICR mice.

Brain Aromatase Modulates Serotonergic Neuron by Regulating Serotonin Levels in Zebrafish Embryos and Larvae

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Zulvikar Syambani Ulhaq

2018-05-01

Full Text Available Teleost fish are known to express two isoforms of P450 aromatase, a key enzyme for estrogen synthesis. One of the isoforms, brain aromatase (AroB, cyp19a1b, is highly expressed during early development of zebrafish, thereby suggesting its role in brain development. On the other hand, early development of serotonergic neuron, one of the major monoamine neurons, is considered to play an important role in neurogenesis. Therefore, in this study, we investigated the role of AroB in development of serotonergic neuron by testing the effects of (1 estradiol (E2 exposure and (2 morpholino (MO-mediated AroB knockdown. When embryos were exposed to E2, the effects were biphasic. The low dose of E2 (0.005 µM significantly increased serotonin (5-HT positive area at 48 hour post-fertilization (hpf detected by immunohistochemistry and relative mRNA levels of tryptophan hydroxylase isoforms (tph1a, tph1b, and tph2 at 96 hpf measured by semi-quantitative PCR. To test the effects on serotonin transmission, heart rate and thigmotaxis, an indicator of anxiety, were analyzed. The low dose also significantly increased heart rate at 48 hpf and decreased thigmotaxis. The high dose of E2 (1 µM exhibited opposite effects in all parameters. The effects of both low and high doses were reversed by addition of estrogen receptor (ER blocker, ICI 182,780, thereby suggesting that the effects were mediated through ER. When AroB MO was injected to fertilized eggs, 5-HT-positive area was significantly decreased, while the significant decrease in relative tph mRNA levels was found only with tph2 but not with two other isoforms. AroB MO also decreased heart rate and increased thigmotaxis. All the effects were rescued by co-injection with AroB mRNA and by exposure to E2. Taken together, this study demonstrates the role of brain aromatase in development of serotonergic neuron in zebrafish embryos and larvae, implying that brain-formed estrogen is an important factor to

Neural stem cell sex dimorphism in aromatase (CYP19 expression: a basis for differential neural fate

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Jay Waldron

2010-11-01

Full Text Available Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Quebec, CanadaPurpose: Neural stem cell (NSC transplantation and pharmacologic activation of endogenous neurogenesis are two approaches that trigger a great deal of interest as brain repair strategies. However, the success rate of clinical attempts using stem cells to restore neurologic functions altered either after traumatic brain injury or as a consequence of neurodegenerative disease remains rather disappointing. This suggests that factors affecting the fate of grafted NSCs are largely understudied and remain to be characterized. We recently reported that aging differentially affects the neurogenic properties of male and female NSCs. Although the sex steroids androgens and estrogens participate in the regulation of neurogenesis, to our knowledge, research on how gender-based differences affect the capacity of NSCs to differentiate and condition their neural fate is lacking. In the present study, we explored further the role of cell sex as a determining factor of the neural fate followed by differentiating NSCs and its relationship with a potential differential expression of aromatase (CYP19, the testosterone-metabolizing enzyme.Results: Using NSCs isolated from the subventricular zone of three-month-old male and female Long-Evans rats and maintained as neurospheres, we showed that differentiation triggered by retinoic acid resulted in a neural phenotype that depends on cell sex. Differentiated male NSCs mainly expressed markers of neuronal fate, including ßIII-tubulin, microtubule associated protein 2, growth-associated protein 43, and doublecortin. In contrast, female NSCs essentially expressed the astrocyte marker glial fibrillary acidic protein. Quantification of the expression of aromatase showed a very low level of expression in undifferentiated female NSCs

Synthesis and PET studies of [(11)C-cyano]letrozole (Femara), an aromatase inhibitor drug.

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Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J; Fowler, Joanna S

2009-02-01

Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K(i)=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [(11)C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [(11)C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [(11)C-cyano]letrozole fraction in arterial plasma were also measured. [(11)C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16+/-2.21 Ci/mumol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. [(11)C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [(11)C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity and saturability in brain regions such as amygdala, which are known to

From molecule to behavior: Brain aromatase (cyp19a1b) characterization, expression analysis and its relation with social status and male agonistic behavior in a Neotropical cichlid fish.

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Ramallo, Martín R; Morandini, Leonel; Birba, Agustina; Somoza, Gustavo M; Pandolfi, Matías

2017-03-01

The enzyme aromatase, responsible for the conversion of C19 androgens to C18 estrogens, exists as two paralogue copies in teleost fish: Cyp19a1a mostly expressed in the gonads, referred as gonadal aromatase, and Cyp19a1b, mostly expressed in the brain, accordingly known as brain aromatase. The neural localization of Cyp19a1b is greatly contained within the social behavior network and mesolimbic reward system in fish, suggesting a strong role of estrogen synthesis in the regulation of social behavior. In this work we aimed to analyze the variation in cyp19a1b expression in brain and pituitary of males of a highly social cichlid, Cichlasoma dimerus (locally known as chanchita), and its relation with inter-individual variability in agonistic behavior in a communal social environment. We first characterized chanchita's cyp19a1b mRNA and deduced amino acid sequence, which showed a high degree of conservation when compared to other teleost brain aromatase sequences, and its tissue expression patterns. Within the brain, Cyp19a1b was solely detected at putative radial glial cells of the forebrain, close to the brain ventricles. We then studied the relative expression levels of cyp19a1b by Real Time PCR in the brain and pituitary of males of different social status, territorial vs. non-territorial, and its relationship with an index of agonistic behavior. We found that even though, brain aromatase expression did not differ between types of males, pituitary cyp19a1b expression levels positively correlated with the index of agonistic behavior. This suggests a novel role of the pituitary in the regulation of social behavior by local estrogen synthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

The sex-specific associations of the aromatase gene with Alzheimer's disease and its interaction with IL10 in the Epistasis Project.

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Medway, Christopher; Combarros, Onofre; Cortina-Borja, Mario; Butler, Helen T; Ibrahim-Verbaas, Carla A; de Bruijn, Renée F A G; Koudstaal, Peter J; van Duijn, Cornelia M; Ikram, M Arfan; Mateo, Ignacio; Sánchez-Juan, Pascual; Lehmann, Michael G; Heun, Reinhard; Kölsch, Heike; Deloukas, Panos; Hammond, Naomi; Coto, Eliecer; Alvarez, Victoria; Kehoe, Patrick G; Barber, Rachel; Wilcock, Gordon K; Brown, Kristelle; Belbin, Olivia; Warden, Donald R; Smith, A David; Morgan, Kevin; Lehmann, Donald J

2014-02-01

Epistasis between interleukin-10 (IL10) and aromatase gene polymorphisms has previously been reported to modify the risk of Alzheimer's disease (AD). However, although the main effects of aromatase variants suggest a sex-specific effect in AD, there has been insufficient power to detect sex-specific epistasis between these genes to date. Here we used the cohort of 1757 AD patients and 6294 controls in the Epistasis Project. We replicated the previously reported main effects of aromatase polymorphisms in AD risk in women, for example, adjusted odds ratio of disease for rs1065778 GG=1.22 (95% confidence interval: 1.01-1.48, P=0.03). We also confirmed a reported epistatic interaction between IL10 rs1800896 and aromatase (CYP19A1) rs1062033, again only in women: adjusted synergy factor=1.94 (1.16-3.25, 0.01). Aromatase, a rate-limiting enzyme in the synthesis of estrogens, is expressed in AD-relevant brain regions ,and is downregulated during the disease. IL-10 is an anti-inflammatory cytokine. Given that estrogens have neuroprotective and anti-inflammatory activities and regulate microglial cytokine production, epistasis is biologically plausible. Diminishing serum estrogen in postmenopausal women, coupled with suboptimal brain estrogen synthesis, may contribute to the inflammatory state, that is a pathological hallmark of AD.

Synthesis and PET studies of [{sup 11}C-cyano]letrozole (Femara), an aromatase inhibitor drug

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Kil, Kun-Eek [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, Stony Brook University, Stony Brook, NY 11794 (United States); Biegon, Anat [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Ding, Yu-Shin [Department of Radiology, Yale University School of Medicine, New Haven, CT 06520-8048 (United States); Fischer, Andre [Johannes-Gutenberg Universitaet Mainz, Institut fuer Organische Chemie, 55128 Mainz (Germany); Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, Stony Brook University, Stony Brook, NY 11794 (United States)], E-mail: fowler@bnl.gov

2009-02-15

Introduction: Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K{sub i}=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods: Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [{sup 11}C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [{sup 11}C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [{sup 11}C-cyano]letrozole fraction in arterial plasma were also measured. Results: [{sup 11}C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16{+-}2.21 Ci/{mu}mol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. Conclusion: [{sup 11}C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [{sup 11}C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity

Synthesis and PET studies of [11C-cyano]letrozole (Femara®), an aromatase inhibitor drug

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Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J.; Fowler, Joanna S.

2011-01-01

Introduction Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara®) is a high affinity aromatase inhibitor (Ki=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [11C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [11C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [11C-cyano]letrozole fraction in the arterial plasma were also measured. Results [11C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79–80%, with a radiochemical purity greater than 98% and a specific activity of 4.16±2.21 Ci/μmol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. Conclusion [11C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [11C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain

Reinvestigation of the synthesis and evaluation of [N-methyl-11C]vorozole, a radiotracer targeting cytochrome P450 aromatase

International Nuclear Information System (INIS)

Kim, Sung Won; Biegon, Anat; Katsamanis, Zachary E.; Ehrlich, Carolin W.; Hooker, Jacob M.; Shea, Colleen; Muench, Lisa; Xu Youwen; King, Payton; Carter, Pauline; Alexoff, David L.; Fowler, Joanna S.

2009-01-01

Introduction: We reinvestigated the synthesis of [N-methyl- 11 C]vorozole, a radiotracer for aromatase, and discovered the presence of an N-methyl isomer which was not removed in the original purification method. Herein we report the preparation and positron emission tomography (PET) studies of pure [N-methyl- 11 C]vorozole. Methods: Norvorozole was alkylated with [ 11 C]methyl iodide as previously described and also with unlabeled methyl iodide. A high-performance liquid chromatography (HPLC) method was developed to separate the regioisomers. Nuclear magnetic resonance (NMR) spectroscopy ( 13 C and 2D-nuclear Overhauser effect spectroscopy NMR) was used to identify and assign structures to the N-methylated products. Pure [N-methyl- 11 C]vorozole and the contaminating isomer were compared by PET imaging in the baboon. Results: Methylation of norvorozole resulted in a mixture of isomers (1:1:1 ratio) based on new HPLC analysis using a pentafluorophenylpropyl bonded silica column, in which vorozole coeluted one of its isomers under the original HPLC conditions. Baseline separation of the three labeled isomers was achieved. The N-3 isomer was the contaminant of vorozole, thus correcting the original assignment of isomers. PET studies of pure [N-methyl- 11 C]vorozole with and without the contaminating N-3 isomer revealed that only [N-methyl- 11 C]vorozole binds to aromatase. [N-methyl- 11 C]Vorozole accumulated in all brain regions with highest accumulation in the aromatase-rich amygdala and preoptic area. Accumulation was blocked with vorozole and letrozole consistent with reports of some level of aromatase in many brain regions. Conclusions: The discovery of a contaminating labeled isomer and the development of a method for isolating pure [N-methyl- 11 C]vorozole combine to provide a new scientific tool for PET studies of the biology of aromatase and for drug research and development.

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

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

2014-01-01

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

Post-proliferative immature radial glial cells female-specifically express aromatase in the medaka optic tectum.

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Akio Takeuchi

Full Text Available Aromatase, the key enzyme responsible for estrogen biosynthesis, is present in the brain of all vertebrates. Much evidence has accumulated that aromatase is highly and exclusively expressed in proliferating mature radial glial cells in the brain of teleost fish even in adulthood, unlike in other vertebrates. However, the physiological significance of this expression remains unknown. We recently found that aromatase is female-specifically expressed in the optic tectum of adult medaka fish. In the present study, we demonstrated that, contrary to the accepted view of the teleost brain, female-specific aromatase-expressing cells in the medaka optic tectum represent a transient subset of post-proliferative immature radial glial cells in the neural stem cell lineage. This finding led us to hypothesize that female-specific aromatase expression and consequent estrogen production causes some sex difference in the life cycle of tectal cells. As expected, the female tectum exhibited higher expression of genes indicative of cell proliferation and radial glial maturation and lower expression of an anti-apoptotic gene than did the male tectum, suggesting a female-biased acceleration of the cell life cycle. Complicating the interpretation of this result, however, is the additional observation that estrogen administration masculinized the expression of these genes in the optic tectum, while simultaneously stimulating aromatase expression. Taken together, these results provide evidence that a unique subpopulation of neural stem cells female-specifically express aromatase in the optic tectum and suggest that this aromatase expression and resultant estrogen synthesis have an impact on the life cycle of tectal cells, whether stimulatory or inhibitory.

Reinvestigation of the synthesis and evaluation of [N-methyl-{sup 11}C]vorozole, a radiotracer targeting cytochrome P450 aromatase

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Kim, Sung Won [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)], E-mail: swkim@bnl.gov; Biegon, Anat; Katsamanis, Zachary E. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Ehrlich, Carolin W. [Johannes-Gutenberg Universitaet Mainz, Institut fuer Organische Chemie, Duesbergweg 10-14, Mainz (Germany); Hooker, Jacob M.; Shea, Colleen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Muench, Lisa [National Institute on Alcoholism and Alcohol Abuse, Bethesda, MD (United States); Xu Youwen; King, Payton; Carter, Pauline; Alexoff, David L. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Psychiatry, Mount Sinai School of Medicine, New York, NY (United States); Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY (United States)

2009-04-15

Introduction: We reinvestigated the synthesis of [N-methyl-{sup 11}C]vorozole, a radiotracer for aromatase, and discovered the presence of an N-methyl isomer which was not removed in the original purification method. Herein we report the preparation and positron emission tomography (PET) studies of pure [N-methyl-{sup 11}C]vorozole. Methods: Norvorozole was alkylated with [{sup 11}C]methyl iodide as previously described and also with unlabeled methyl iodide. A high-performance liquid chromatography (HPLC) method was developed to separate the regioisomers. Nuclear magnetic resonance (NMR) spectroscopy ({sup 13}C and 2D-nuclear Overhauser effect spectroscopy NMR) was used to identify and assign structures to the N-methylated products. Pure [N-methyl-{sup 11}C]vorozole and the contaminating isomer were compared by PET imaging in the baboon. Results: Methylation of norvorozole resulted in a mixture of isomers (1:1:1 ratio) based on new HPLC analysis using a pentafluorophenylpropyl bonded silica column, in which vorozole coeluted one of its isomers under the original HPLC conditions. Baseline separation of the three labeled isomers was achieved. The N-3 isomer was the contaminant of vorozole, thus correcting the original assignment of isomers. PET studies of pure [N-methyl-{sup 11}C]vorozole with and without the contaminating N-3 isomer revealed that only [N-methyl-{sup 11}C]vorozole binds to aromatase. [N-methyl-{sup 11}C]Vorozole accumulated in all brain regions with highest accumulation in the aromatase-rich amygdala and preoptic area. Accumulation was blocked with vorozole and letrozole consistent with reports of some level of aromatase in many brain regions. Conclusions: The discovery of a contaminating labeled isomer and the development of a method for isolating pure [N-methyl-{sup 11}C]vorozole combine to provide a new scientific tool for PET studies of the biology of aromatase and for drug research and development.

Are separable aromatase systems involved in hormonal regulation of the male brain

International Nuclear Information System (INIS)

Hutchison, J.B.; Schumacher, M.; Steimer, T.; Gahr, M.

1990-01-01

In vitro study of testosterone (T) metabolism shows that formation of estradiol-17 beta (E2) is regionally specific within the preoptic area (POA) of the male ring dove. The POA is known to be involved in the formation of E2 required for specific components of male sexual behavior. Two sub-areas of high aromatase activity, anterior (aPOA) and posterior preoptic (pPOA) areas, have been identified. Aromatase activity is higher in aPOA than in pPOA. The aromatase activity within the aPOA is also more sensitive to the inductive effects of low circulating T, derived from subcutaneous silastic implants, than the enzyme activity in pPOA. Kinetic analysis of preoptic fractions indicates that a similar high-affinity enzyme occurs in both areas (apparent Km less than 14 nM), but the Vmax of aPOA enzyme activity is higher than pPOA. Cells containing estrogen receptors (ER) are localized in areas of high aromatase activity. There is overlap between immunostained cells in the aPOA and in samples containing inducible aromatase activity measured in vitro. Within the aPOA there is a higher density of ER cells in the nucleus preopticus medialis. The pPOA area also contains ER, notably in the nucleus interstitialis, but at a lower density. We conclude that the hormonal regulation of the male preoptic-anterior hypothalamic region, which is a target for the behavioral action of T, involves at least two inducible aromatase systems with associated estrogen receptor cells

Disruptions in aromatase expression in the brain, reproductive behavior, and secondary sexual characteristics in male guppies (Poecilia reticulata) induced by tributyltin.

Science.gov (United States)

Tian, Hua; Wu, Peng; Wang, Wei; Ru, Shaoguo

2015-05-01

Although bioaccumulation of tributyltin (TBT) in fish has been confirmed, information on possible effects of TBT on reproductive system of fish is still relatively scarce, particularly at environmentally relevant levels. To evaluate the adverse effects and intrinsic toxicological properties of TBT in male fish, we studied aromatase gene expression in the brain, sex steroid contents, primary and secondary sexual characteristics, and reproductive behavior in male guppies (Poecilia reticulata) exposed to tributyltin chloride at the nominal concentrations of 5, 50, and 500 ng/L for 28 days in a semi-static exposure system. Radioimmunoassay demonstrated that treatment with 50 ng/L TBT caused an increase in systemic levels of testosterone of male guppies. Gonopodial index, which showed a positive correlation with testosterone levels, was elevated in the 5 ng/L and 50 ng/L TBT treated groups. Real-time PCR revealed that TBT exposure had inhibiting effects on expression of two isoforms of guppy aromatase in the brain, and these changes at the molecular levels were associated with a disturbance of reproductive behavior of the individuals, as measured by decreases in frequencies of posturing, sigmoid display, and chase activities when males were paired with females. This study provides the first evidence that TBT can cause abnormalities of secondary sexual characteristics in teleosts and that suppression of reproductive behavior in teleosts by TBT is due to its endocrine-disrupting action as an aromatase inhibitor targeting the nervous system. Copyright © 2015 Elsevier B.V. All rights reserved.

Potential effects of environmental contaminants on P450 aromatase activity and DNA damage in swallows from the Rio Grande and Somerville, Texas

Science.gov (United States)

Sitzlar, M.A.; Mora, M.A.; Fleming, J.G.W.; Bazer, F.W.; Bickham, J.W.; Matson, C.W.

2009-01-01

Cliff swallows (Petrochelidon pyrrhonota) and cave swallows (P. fulva) were sampled during the breeding season at several locations in the Rio Grande, Texas, to evaluate the potential effects of environmental contaminants on P450 aromatase activity in brain and gonads and DNA damage in blood cells. The tritiated water-release aromatase assay was used to measure aromatase activity and flow cytometry was used to measure DNA damage in nucleated blood cells. There were no significant differences in brain and gonadal aromatase activities or in estimates of DNA damage (HPCV values) among cave swallow colonies from the Lower Rio Grande Valley (LRGV) and Somerville. However, both brain and gonadal aromatase activities were significantly higher (P male cliff swallows from Laredo than in those from Somerville. Also, DNA damage estimates were significantly higher (P males and females combined) from Laredo than in those from Somerville. Contaminants of current high use in the LRGV, such as atrazine, and some of the highly persistent organochlorines, such as toxaphene and DDE, could be potentially associated with modulation of aromatase activity in avian tissues. Previous studies have indicated possible DNA damage in cliff swallows. We did not observe any differences in aromatase activity or DNA damage in cave swallows that could be associated with contaminant exposure. Also, the differences in aromatase activity and DNA damage between male cliff swallows from Laredo and Somerville could not be explained by contaminants measured at each site in previous studies. Our study provides baseline information on brain and gonadal aromatase activity in swallows that could be useful in future studies. ?? 2008 Springer Science+Business Media, LLC.

Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women

International Nuclear Information System (INIS)

Biegon, Anat; Fowler, Joanna S.; Alexoff, David L.; Kim, Sung Won; Logan, Jean; Pareto, Deborah; Schlyer, David; Wang, Gene-Jack

2015-01-01

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with (11)C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aims to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathological situations can be studied. Methods: (11)C-vorozole (111-296 MBq/subject) was injected I.V in 13 men and 20 women (age range 23 to 67). PET data were acquired over a 90 minute period. Each subject had 4 scans, 2/day separated by 2-6 weeks, including brain and torso or pelvis scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned following pretreatment with a clinical dose of the aromatase inhibitor letrozole.Time activity curves were obtained and standard uptake values (SUV) calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole body radiation exposures were calculated using Olinda software. Results: Liver uptake was higher than all other organs, but was not blocked by pretreatment with letrozole. Mean SUVs in men were higher than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than all other organs (ranging from 0.48±0.05 in lungs to 1.5±0.13 in kidneys). Mean ovarian SUVs (3.08±0.7) were comparable to brain levels and higher than all other organs. Furthermore, ovarian SUVs In young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, while aging and cigarette smoking reduced (11)C-vorozole uptake. Conclusions: PET with (11)C-vorozole is useful for assessing physiological changes in estrogen synthesis capacity in the human body. Baseline levels in

New Insights Into the Role of Estrogens in Male Fertility Based on Findings in Aromatase-Deficient Zebrafish.

Science.gov (United States)

Tang, Haipei; Chen, Yu; Liu, Yun; Yin, Yike; Li, Gaofei; Guo, Yin; Liu, Xiaochun; Lin, Haoran

2017-09-01

It has been demonstrated that estrogens are indispensable for male fertility in mammals. Aromatase (encoded by CYP19) catalyzes the final step of estradiol biosynthesis. However, less is known about the role of aromatase in male fertility in nonmammalian species. Fish aromatase is encoded by two separate genes: the gonad-specific cyp19a1a and the brain-specific cyp19a1b. In a recent study, we used transcription activatorlike effector nucleases to systematically generate cyp19a1a and cyp19a1b mutant lines and a cyp19a1a;cyp19a1b double-mutant line in zebrafish and demonstrated that cyp19a1a was indispensable for sex differentiation. In this study, we focused on male fertility in these aromatase-deficient zebrafish. Our results showed that all aromatase-deficient male fish had normal fertility even at 1 year after fertilization. Interestingly, we observed more spermatozoa in the cyp19a1a and double-mutant males than in the wild-type and cyp19a1b mutant males. The whole-body androgen levels, follicle-stimulating hormone β and luteinizing hormone β protein levels in the pituitary, and transcript levels of genes known to be involved in spermatogenesis and steroidogenesis in the testes were significantly higher in the cyp19a1a mutant and aromatase double-mutant males than in the wild-type and cyp19a1b mutant males. These results might explain why more spermatozoa were observed in these fish. Collectively, our findings indicate that estrogens are not needed to achieve and maintain normal fertility in male zebrafish. This finding challenges the traditional view that estrogens are indispensable for male fertility. Copyright © 2017 Endocrine Society.

Aromatase inhibitors in pediatrics.

Science.gov (United States)

Wit, Jan M; Hero, Matti; Nunez, Susan B

2011-10-25

Aromatase, an enzyme located in the endoplasmic reticulum of estrogen-producing cells, catalyzes the rate-limiting step in the conversion of androgens to estrogens in many tissues. The clinical features of patients with defects in CYP19A1, the gene encoding aromatase, have revealed a major role for this enzyme in epiphyseal plate closure, which has promoted interest in the use of inhibitors of aromatase to improve adult height. The availability of the selective aromatase inhibitors letrozole and anastrozole--currently approved as adjuvant therapy for breast cancer--have stimulated off-label use of aromatase inhibitors in pediatrics for the following conditions: hyperestrogenism, such as aromatase excess syndrome, Peutz-Jeghers syndrome, McCune-Albright syndrome and functional follicular ovarian cysts; hyperandrogenism, for example, testotoxicosis (also known as familial male-limited precocious puberty) and congenital adrenal hyperplasia; pubertal gynecomastia; and short stature and/or pubertal delay in boys. Current data suggest that aromatase inhibitors are probably effective in the treatment of patients with aromatase excess syndrome or testotoxicosis, partially effective in Peutz-Jeghers and McCune-Albright syndrome, but probably ineffective in gynecomastia. Insufficient data are available in patients with congenital adrenal hyperplasia or functional ovarian cysts. Although aromatase inhibitors appear effective in increasing adult height of boys with short stature and/or pubertal delay, safety concerns, including vertebral deformities, a decrease in serum HDL cholesterol levels and increase of erythrocytosis, are reasons for caution.

A game of two? Gene expression analysis of brain (cyp19a1b) and gonadal (cyp19a1a) aromatase in females of a Neotropical cichlid fish through the parental care period and removal of the offspring.

Science.gov (United States)

Ramallo, Martín R; Honji, Renato M; Birba, Agustina; Morandini, Leonel; Varela, María L; Genovese, Griselda; Moreira, Renata G; Somoza, Gustavo M; Pandolfi, Matías

2017-10-01

For many species parental behavior is essential for the survival of the offspring. While the ultimate causes of teleost parental behavior have been widely studied, comparatively little is known about its proximate causes. The aim of this study was to analyze the yet unexplored, potential dual role of brain and gonadal aromatases, the enzymes responsible for the conversion of androgens to estrogens in the brains and gonads of teleosts, respectively, on the different stages of the maternal care period of the biparental cichlid Cichlasoma dimerus, locally known as chanchita. By immunohistochemistry we analyzed the neural distribution of brain aromatase and observed it exclusively within the forebrain, including areas involved in the regulation of parental behavior. We next analyzed the gene expression of brain aromatase in the brain, and gonadal aromatase in the ovary, of female chanchitas through the parental care period. To further characterize the physiological environment associated to maternal care, we also evaluated sex steroid levels (17β-estradiol, testosterone and 11-ketotestoterone) and ovarian follicle percentage. The onset of parental behavior specifically downregulated sex steroids synthesis and the rate of ovarian maturation, as denoted by a more than 10-fold decrease in steroid levels and delayed detection of mature follicles in females with offspring, compared to females which eggs were removed. Gene expression levels of both aromatases were independent of maternal care at the evaluated time points, even though they varied during the parental care period. Copyright © 2017 Elsevier Inc. All rights reserved.

Aromatase imaging with [N-methyl-11C]vorozole PET in healthy men and women.

Science.gov (United States)

Biegon, Anat; Alexoff, David L; Kim, Sung Won; Logan, Jean; Pareto, Deborah; Schlyer, David; Wang, Gene-Jack; Fowler, Joanna S

2015-04-01

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with (11)C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aimed to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathologic situations can be studied. (11)C-vorozole (111-296 MBq/subject) was injected intravenously in 13 men and 20 women (age range, 23-67 y). PET data were acquired over a 90-min period. Each subject had 4 scans, 2 per day separated by 2-6 wk, including brain and torso or pelvis scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned after pretreatment with a clinical dose of the aromatase inhibitor letrozole. Time-activity curves were obtained, and standardized uptake values (SUV) were calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone, and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole-body radiation exposures were calculated using OLINDA software. Liver uptake was higher than uptake in any other organ but was not blocked by pretreatment with letrozole. Mean SUVs were higher in men than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than SUVs in any other organ (ranging from 0.48 ± 0.05 in lungs to 1.5 ± 0.13 in kidneys). Mean ovarian SUVs (3.08 ± 0.7) were comparable to brain levels and higher than in any other organ. Furthermore, ovarian SUVs in young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, whereas aging and cigarette smoking reduced (11)C-vorozole uptake. PET with (11)C-vorozole is useful for assessing physiologic changes in estrogen synthesis capacity in the human body. Baseline levels

Additive effects of levonorgestrel and ethinylestradiol on brain aromatase (cyp19a1b) in zebrafish specific in vitro and in vivo bioassays

Energy Technology Data Exchange (ETDEWEB)

Hinfray, N., E-mail: nathalie.hinfray@ineris.fr [INERIS, Unité d' écotoxicologie in vitro et in vivo , Verneuil-en-Halatte (France); Tebby, C. [INERIS, Unité Modèles pour l' Ecotoxicologie et la Toxicologie, Verneuil-en-Halatte (France); Garoche, C.; Piccini, B. [INERIS, Unité d' écotoxicologie in vitro et in vivo , Verneuil-en-Halatte (France); Bourgine, G. [IRSET, équipe NEED, Université de Rennes 1, Rennes (France); Aït-Aïssa, S. [INERIS, Unité d' écotoxicologie in vitro et in vivo , Verneuil-en-Halatte (France); Kah, O. [IRSET, équipe NEED, Université de Rennes 1, Rennes (France); Pakdel, F. [IRSET, Inserm U1085, équipe TREC, Université de Rennes 1, Rennes (France); Brion, F. [INERIS, Unité d' écotoxicologie in vitro et in vivo , Verneuil-en-Halatte (France)

2016-09-15

Estrogens and progestins are widely used in combination in human medicine and both are present in aquatic environment. Despite the joint exposure of aquatic wildlife to estrogens and progestins, very little information is available on their combined effects. In the present study we investigated the effect of ethinylestradiol (EE2) and Levonorgestrel (LNG), alone and in mixtures, on the expression of the brain specific ER-regulated cyp19a1b gene. For that purpose, recently established zebrafish-derived tools were used: (i) an in vitro transient reporter gene assay in a human glial cell line (U251-MG) co-transfected with zebrafish estrogen receptors (zfERs) and the luciferase gene under the control of the zebrafish cyp19a1b gene promoter and (ii) an in vivo bioassay using a transgenic zebrafish expressing GFP under the control of the zebrafish cyp19a1b gene promoter (cyp19a1b-GFP). Concentration-response relationships for single chemicals were modeled and used to design the mixture experiments following a ray design. The results from mixture experiments were analyzed to predict joint effects according to concentration addition and statistical approaches were used to characterize the potential interactions between the components of the mixtures (synergism/antagonism). We confirmed that some progestins could elicit estrogenic effects in fish brain. In mixtures, EE2 and LNG exerted additive estrogenic effects both in vitro and in vivo, suggesting that some environmental progestin could exert effects that will add to those of environmental (xeno-)estrogens. Moreover, our zebrafish specific assays are valuable tools that could be used in risk assessment for both single chemicals and their mixtures. - Highlights: • Combined effects of EE2 and LNG were assessed on ER-dependent cyp19a1b expression. • EE2 and LNG alone induced brain aromatase in zebrafish specific bioassays. • Experimental ray design allowed complete concentration-response surfaces modeling. • EE2 and

Effect of dioxin exposure on aromatase expression in ovariectomized rats

International Nuclear Information System (INIS)

Ye Lan; Leung, Lai K.

2008-01-01

Because of their persistence in the environment dioxins are one of the most concerned classes of carcinogens. Displaying both pro- and anti-agonistic properties to some hormone receptors, the pollutants are also known to be endocrine disruptors. Humans can be exposed to this pollutant through contaminated food, air, drinking water, etc. The female hormone estrogen may initiate various physiological functions, and excessive exposure to this hormone is a documented risk factor for carcinogenesis. Cyp19 (aromatase) catalyses the last step of estrogen biosynthesis, while cyp1a1 can hydroxylate and deactivate the hormone. In the present study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) on aromatase expression in the brain and adipose tissue in ovariectomized Sprague Dawley rats. Female rats were given 2.5 μg/kg TCDD p.o. before and after ovariectomy. Real-time PCR and western blot analysis indicated that pre-ovariectomy administration of TCDD could significantly reduce aromatase expression in the brain but increase the expression in the adipose tissue. In addition, increased plasma estrogen level and uterine weight were observed in these rats. These parameters did not change in rats with post-ovariectomy TCDD treatment. Our results suggested that the timing of exposure to the toxicant could determine the estrogenicity of TCDD. No correlation between cyp1a1 and cyp19 expression was observed

Mechanism-based Categorization of Aromatase Inhibitors: A Potential Discovery and Screening Tool

Science.gov (United States)

Cytochrome P450 aromatase is a key steroidogenic enzyme that converts androgens to estrogens in vertebrates. There is much interest in aromatase inhibitors (AIs) because a number of environmental contaminants can act as AIs, thereby disrupting endocrine function in humans and wil...

Direct Regulation of Aromatase B Expression by 17β-Estradiol and Dopamine D1 Receptor Agonist in Adult Radial Glial Cells

OpenAIRE

Xing, Lei; Esau, Crystal; Trudeau, Vance L.

2016-01-01

Aromatase cytochrome P450arom (cyp19) is the only enzyme that has the ability to convert androgens into estrogens. Estrogens, which are produced locally in the vertebrate brain play many fundamental roles in neuroendocrine functions, reproductive functions, socio-sexual behaviors, and neurogenesis. Radial glial cells (RGCs) are neuronal progenitor cells that are abundant in fish brains and are the exclusive site of aromatase B expression and neuroestrogen synthesis. Using a novel in vitro RGC...

Aromatase and estrogen receptors in male reproduction.

Science.gov (United States)

Carreau, Serge; Delalande, Christelle; Silandre, Dorothée; Bourguiba, Sonia; Lambard, Sophie

2006-02-26

Aromatase is a terminal enzyme which transforms irreversibly androgens into estrogens and it is present in the endoplasmic reticulum of numerous tissues. We have demonstrated that mature rat germ cells express a functional aromatase with a production of estrogens equivalent to that of Leydig cells. In humans in addition to Leydig cells, we have shown the presence of aromatase in ejaculated spermatozoa and in immature germ cells. In most tissues, high affinity estrogen receptors, ERalpha and/or ERbeta, mediate the role of estrogens. Indeed, in human spermatozoa, we have successfully amplified ERbeta mRNA but the protein was not detectable. Using ERalpha antibody we have detected two proteins in human immature germ cells: one at the expected size 66 kDa and another at 46 kDa likely corresponding to the ERalpha isoform lacking exon 1. In spermatozoa only the 46 kDa isoform was present, and we suggest that it may be located on the membrane. In addition, in men genetically deficient in aromatase, it is reported that alterations of spermatogenesis occur both in terms of the number and motility of spermatozoa. All together, these observations suggest that endogenous estrogens are important in male reproduction.

Brain and gonadal aromatase activity and steroid hormone levels in female and polymorphic males of the peacock blenny Salaria pavo.

Science.gov (United States)

Gonçalves, David; Teles, Magda; Alpedrinha, João; Oliveira, Rui F

2008-11-01

In the peacock blenny Salaria pavo large males with well-developed secondary sexual characters establish nests and attract females while small "sneaker" males mimic female sexual displays in order to approach the nests of larger males and parasitically fertilize eggs. These alternative reproductive tactics are sequential, as sneakers irreversibly switch into nesting males. This transition involves major morphologic and behavioral changes and is likely to be mediated by hormones. This study focuses on the role of aromatase, an enzyme that catalyses the conversion of androgens into estrogens, in the regulation of male sexual polymorphism in S. pavo. For this, sex steroid plasma levels and aromatase activity (AA) in gonads, whole brain and brain macroareas were determined in sneakers, transitional males (i.e. sneakers undergoing the transition into nesting males), nesting males and females collected in the field. AA was much higher in ovarian tissue than in testicular tissue and accordingly circulating estradiol levels were highest in females. This supports the view that elevated AA and estradiol levels are associated with the development of a functional ovary. Transitional males are in a non-reproductive phase and had underdeveloped testes when compared with sneakers and nesting males. Testicular AA was approximately 10 times higher in transitional males when compared with sneakers and nesting males, suggesting high AA has a suppressive effect on testicular development. Nesting males had significantly higher plasma levels of both testosterone (T) and 11-ketotestosterone when compared with the other male morphs and previous studies demonstrated that these androgens suppress female-like displays in sneakers. In the brain, AA was highest in macroareas presumably containing hypothalamic nuclei traditionally associated with the regulation of reproductive behaviors. Overall, females presented the highest levels of brain AA. In male morphs AA increased from sneakers, to

Fish with thermolabile sex determination (TSD) as models to study brain sex differentiation.

Science.gov (United States)

Blázquez, Mercedes; Somoza, Gustavo M

2010-05-01

As fish are ectothermic animals, water temperature can affect their basic biological processes such as larval development, growth and reproduction. Similar to reptiles, the incubation temperature during early phases of development is capable to modify sex ratios in a large number of fish species. This phenomenon, known as thermolabile sex determination (TSD) was first reported in Menidia menidia, a species belonging to the family Atherinopsidae. Since then, an increasing number of fish have also been found to exhibit TSD. Traditionally, likewise in reptiles, several TSD patterns have been described in fish, however it has been recently postulated that only one, females at low temperatures and males at high temperatures, may represent the "real" or "true" TSD. Many studies regarding the influence of temperature on the final sex ratios have been focused on the expression and activity of gonadal aromatase, the enzyme involved in the conversion of androgens into estrogens and encoded by the cyp19a1a gene. In this regard, teleost fish, may be due to a whole genome duplication event, produce another aromatase enzyme, commonly named brain aromatase, encoded by the cyp19a1b gene. Contrary to what has been described in other vertebrates, fish exhibit very high levels of aromatase activity in the brain and therefore they synthesize high amounts of neuroestrogens. However, its biological significance is still not understood. In addition, the mechanism whereby temperature can induce the development of a testis or an ovary still remains elusive. In this context the present review is aimed to discuss several theories about the possible role of brain aromatase using fish as models. The relevance of brain aromatase and therefore of neuroestrogens as the possible cue for gonadal differentiation is raised. In addition, the possible role of brain aromatase as the way to keep the high levels of neurogenesis in fish is also considered. Several key examples of how teleosts and aromatase

Aromatase inhibitors and breast cancer prevention.

Science.gov (United States)

Litton, Jennifer Keating; Arun, Banu K; Brown, Powel H; Hortobagyi, Gabriel N

2012-02-01

Endocrine therapy with selective estrogen receptor modulators (SERMs) has been the mainstay of breast cancer prevention trials to date. The aromatase inhibitors, which inhibit the final chemical conversion of androgens to estrogens, have shown increased disease-free survival benefit over tamoxifen in patients with primary hormone receptor-positive breast cancer, as well as reducing the risk of developing contralateral breast cancers. The aromatase inhibitors are being actively evaluated as prevention agents for women with a history of ductal carcinoma in situ as well as for women who are considered to be at high risk for developing primary invasive breast cancer. This review evaluates the available prevention data, as evidenced by the decrease in contralateral breast cancers, when aromatase inhibitors are used in the adjuvant setting, as well as the emerging data of the aromatase inhibitors specifically tested in the prevention setting for women at high risk. Exemestane is a viable option for breast cancer prevention. We continue to await further follow-up on exemestane as well as other aromatase inhibitors in the prevention setting for women at high risk of developing breast cancer or with a history of ductal carcinoma in situ.

Social factors and aromatase gene expression during adult male-to-female sex change in captive leopard grouper Mycteroperca rosacea.

Science.gov (United States)

Romo-Mendoza, Daniel; Campos-Ramos, Rafael; Vázquez-Islas, Grecia; Burgos-Aceves, Mario A; Esquivel-Gutiérrez, Edgar R; Guerrero-Tortolero, Danitzia A

2018-01-25

Social factors and aromatase gene expression in the leopard grouper Mycteroperca rosacea was studied when captive fish were separated by sex during the reproductive (April-June) and post-reproductive (July-September) seasons. Monosex females, monosex males, and mixed-sex, held in social sextet units were analyzed for sex steroids throughout confinement. At the end of the experiment, the gonad-sex was defined by histology, and gonad and brain aromatase gene expressions were quantified. Only males held in the monosex social units changed sex. Histology showed one male remained unchanged, six were found in a transitional sexual stage, in which two had intersex-predominantly-testes, and four had a more defined intersex ovo-testes pattern, and 11 were immature de novo females (neofemales). Neofemales and most intersex fish did not survive. In spring, 11-ketosterone showed a specific male profile, which suggests that male-to-female sex change was not triggered during the reproductive season. The low steroid levels in summer made it impossible to associate the sex change to a gonad hormonal shift; in September, gonad aromatase gene expression was not significantly different among groups. However, brain aromatase expression in intersex fish was significantly higher than monosex females, mixed-sex females, and neofemale groups. These results suggest that in the absence of female hormonal compounds, and at a time when male gonad steroidogenesis was diminished, the brain mediated male-to-male social-behavioral interactions, including stress, by increasing aromatization, resulting in derived intersex-male, which triggered more aromatization, followed by a sex change. Copyright © 2018 Elsevier Inc. All rights reserved.

Aromatase Inhibitor-Induced Erythrocytosis in a Patient Undergoing Hormonal Treatment for Breast Cancer

Directory of Open Access Journals (Sweden)

Sri Lakshmi Hyndavi Yeruva

2015-01-01

Full Text Available Aromatase inhibitors (AIs are most commonly used for breast cancer patients with hormone receptor positive disease. Although the side effect profile of aromatase inhibitors is well known, including common side effects like arthralgia, bone pain, arthritis, hot flashes, and more serious problems like osteoporosis, we present a case of an uncommon side effect of these medications. We report the case of a postmenopausal woman on adjuvant hormonal therapy with anastrozole after completing definitive therapy for stage IIIB estrogen receptor-positive breast cancer, who was referred to hematology service for evaluation of persistent erythrocytosis. Primary and known secondary causes of polycythemia were ruled out. On further evaluation, we found that her erythrocytosis began after initiation of anastrozole and resolved after it was discontinued. We discuss the pathophysiology of aromatase inhibitor-induced erythrocytosis and reference of similar cases reported in the literature.

Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome

Directory of Open Access Journals (Sweden)

Maki Fukami

2012-01-01

Full Text Available Aromatase excess syndrome (AEXS is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon. These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens.

Big enough for an aromatase inhibitor? How adiposity affects male fertility.

Science.gov (United States)

Stephens, Sahar M; Polotsky, Alex J

2013-07-01

Obesity is a pandemic and is associated with multiple medical problems including subfertility. Male obesity has been associated with altered semen parameters and reproductive hormonal levels, including a reduced testosterone:estradiol (T:E₂) ratio. Treatment methods employed for obesity-related male subfertility include gonadotropin administration, weight loss, and aromatase inhibitors. Letrozole is a highly effective nonsteroidal aromatase inhibitor that has been used to treat male subfertility in several case series with promising results. Adequately designed randomized controlled studies are needed to produce evidence-based data on the role of aromatase inhibitors in male subfertility management and evaluate the side-effect profile. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Aromatase inhibitors in men: effects and therapeutic options

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de Jong Frank H

2011-06-01

Full Text Available Abstract Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic short stature and constitutional delay of puberty. Long-term efficacy and safety of the use of aromatase inhibitors has not yet been established in males, however, and their routine use is therefore not yet recommended.

Aromatase expression is increased in BRCA1 mutation carriers

International Nuclear Information System (INIS)

Chand, Ashwini L; KConFab; Simpson, Evan R; Clyne, Colin D

2009-01-01

Until recently, the molecular mechanisms explaining increased incidence of ovarian and breast cancers in carriers of BRCA1 gene mutations had not been clearly understood. Of significance is the finding that BRCA1 negatively regulates aromatase expression in vitro. Our objective was to characterise aromatase gene (CYP19A1) and its promoter expression in breast adipose and ovarian tissue in BRCA1 mutation carriers and unaffected controls. We measured aromatase transcripts, total and promoter-specific (PII, PI.3, PI.4) in prophylactic oophorectomy or mastectomy, therapeutic mastectomy, ovarian and breast tissue from unaffected women. We demonstrate that the lack of functional BRCA1 protein correlates to higher aromatase levels in 85% of BRCA1 mutation carriers. This increase is mediated by aberrant transcriptional regulation of aromatase; in breast adipose by increases in promoter II/I.3 and I.4-specific transcripts; and in the ovary with elevation in promoter I.3 and II-specific transcripts. Understanding the link between BRCA1 and aromatase is significant in terms of understanding why carcinogenesis is restricted to estrogen-producing tissues in BRCA1 mutation carriers

Aromatase inhibitor (anastrozole) affects growth of endometrioma cells in culture.

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Badawy, Shawky Z A; Brown, Shereene; Kaufman, Lydia; Wojtowycz, Martha A

2015-05-01

To study the effects of aromatase inhibitor (anastrozole) on the growth and estradiol secretion of endometrioma cells in culture. Endometrioma cells are grown in vitro until maximum growth before used in this study. This was done in the research laboratory for tissue culture, in an academic hospital. Testosterone at a concentration of 10 μg/mL was added as a substrate for the intracellular aromatase. In addition, aromatase inhibitor was added at a concentration of 200 and 300 μg/mL. The effect on cell growth and estradiol secretion is evaluated using Student's t-test. The use of testosterone increased estradiol secretion by endometrioma cells in culture. The use of aromatase inhibitor significantly inhibited the growth of endometrioma cells, and estradiol secretion. Aromatase inhibitor (anastrozole) may be an effective treatment for endometriosis due to inhibition of cellular aromatase. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comprehensive and Automated Linear Interaction Energy Based Binding-Affinity Prediction for Multifarious Cytochrome P450 Aromatase Inhibitors

NARCIS (Netherlands)

van Dijk, Marc; Ter Laak, Antonius M; Wichard, Jörg D; Capoferri, Luigi; Vermeulen, Nico P E; Geerke, Daan P

2017-01-01

Cytochrome P450 aromatase (CYP19A1) plays a key role in the development of estrogen dependent breast cancer, and aromatase inhibitors have been at the front line of treatment for the past three decades. The development of potent, selective and safer inhibitors is ongoing with in silico screening

Computational drug designing of fungal pigments as potential aromatase inhibitors

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Nighat Fatima

2014-12-01

Full Text Available The existing aromatase inhibitors produced unwelcome effects impose the discovery of novel drugs with privileged selectivity, a reduced amount of toxicity and humanizing potency. In this study, we illuminate the binding mode of polyketide azaphilanoid pigments monascin, ankaflavin, monascorubrin and monascorubramine isolated from Monascus fungus to the aromatase by molecular docking. The 3-dimensional structure of aromatase enzyme (PDB: 4KQ8 was obtained from the Protein Data Bank. PatchDock docking software was used to analyze structural complexes of the aromatase with monascus pigments. Comparatively, the AutoGrid model presented the most briskly constructive binding mode of monascin to aromatase. Docked energies in kcal/mol are: monascin;-13.2; monascorubramine:-12.8, monascorubrin:-12.3; ankaflavin: -10.5. These outcomes exposed these ligands could be potential drugs to treat hormone dependent breast cancer.

Effects of transferrin on aromatase activity in porcine granulosa cells in vitro.

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Małgorzata Duda

2009-01-01

Full Text Available Proliferating cells have an absolute requirement for iron, which is delivered by transferrin with subsequent intracellular transport via the transferrin receptor. Recent studies have reported that transferrin plays a crucial role in the local regulation of ovarian function, apart from its iron-binding characteristic. Therefore, the present study was undertaken to explore the possible role of transferrin in porcine granulosa cells function by examining its influence on aromatase activity, the most important indicator of follicular cell differentiation. In the first series of studies, pig granulosa cells isolated from small, immature follicles were cultured in the presence of transferrin alone (10 microg/ml or 100 microg/ml or with the addition of FSH (100ng/ml. The second series of studies was undertaken to determine transferrin-stimulated granulosa cells ability to aromatize exogenous testosterone (1x10(-7M. One hour after the establishment of cultures an aromatase inhibitor CGS16949A was added to test its influence on estradiol production. After 48 hours, cultures were terminated and cells were processed for immunocytochemical staining of aromatase. Media were frozen for further estradiol level analysis. Positive immunostaining for aromatase was found in all granulosa cell cultures. The intensity of immunostaining was always stronger in cultures supplemented with FSH whereas the addition of transferrin had no effect. Granulosa cells in vitro synthesized the highest amount of estradiol after the addition of FSH and exogenous testosterone as measured radioimmunologically. Concomitant treatment with FSH and transferrin caused an inhibition of FSH-stimulated aromatase activity. The production of estradiol also declined in the presence of FSH, testosterone and transferrin. This study demonstrates that transferrin had a dose-dependent inhibitory effect on FSH-stimulated aromatase activity, which was confirmed by radioimmunoassay. Our results indicate

Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia.

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Alejandra Perez-Sepulveda

Full Text Available Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE.Serum samples were collected at 32-36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16 and pregnant controls (n = 32. The effect of oxygen tension on placental cells was assessed by incubation JEG-3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6 were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels. Aromatase content and estrogens and androgens concentrations were measured.The protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG-3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be associated with chronic

Endocrine disrupting chemicals (bisphenol A, 4-nonylphenol, 4-tert-octylphenol) modulate expression of two distinct cytochrome P450 aromatase genes differently in gender types of the hermaphroditic fish Rivulus marmoratus.

Science.gov (United States)

Lee, Young-Mi; Seo, Jung Soo; Kim, Il-Chan; Yoon, Yong-Dal; Lee, Jae-Seong

2006-06-30

To understand the effect of endocrine-disrupting chemicals (EDCs) on cytochrome P450 aromatase (rm-cyp19) gene expression between gender types in the hermaphroditic fish Rivulus marmoratus, we cloned two distinct rm-cyp19 genes using RT-PCR with degenerative primers, obtained full-length cDNAs using 5'- and 3'-RACE-PCR methods, and completely sequenced them. The brain aromatase (rm-cyp19b) cDNA consisted of 2,124 bp including the open reading frame (ORF), which encoded a putative protein of 505 amino acids. The ovarian aromatase (rm-cyp19a) cDNA consisted of 2,075 bp, including the ORF encoding a putative protein of 516 amino acids. Expression patterns of rm-cyp19b and rm-cyp19a mRNAs were investigated in embryos of different developmental stages and in seven different tissues of adult fish. The rm-cyp19b gene in hermaphrodite and secondary male R. marmoratus was predominantly expressed in the brain, while the rm-cyp19a gene was expressed gender-specifically in the gonad. The expression of rm-cyp19b mRNA increased from stage 1 (2 d post fertilization) to stage 4 (12 d post fertilization) in a developmental stage-dependent manner but steeply decreased in the hatching stage. Compared to the rm-cyp19b gene, the abundance of ovarian aromatase rm-cyp19a transcripts was very low, and its expression was first detected at stage 3 and then decreased gradually to the hatching stage. Alteration of rm-cyp19b and rm-cyp19a gene expression was further analyzed in the brain and gonad by real-time RT-PCR 96 h after EDC exposure in hermaphrodites and secondary males. The brain aromatase rm-cyp19b gene was up-regulated in the brain after 4-nonylphenol (4-NP)-exposure, while the ovarian aromatase rm-cyp19a gene was significantly down-regulated in the gonad. In 300 microg/L 4-tert octylphenol (4-tert-OP), or 600 microg/L bisphenol A-exposed brain and gonad, both rm-cyp19b and rm-cyp19a genes were up-regulated. In the case of secondary males, the rm-cyp19b gene was highly expressed in

Which patients benefit most from adjuvant aromatase inhibitors?

DEFF Research Database (Denmark)

Viale, G; Regan, M M; Dell'Orto, P

2011-01-01

On average, aromatase inhibitors are better than tamoxifen when used as initial or sequential therapy for postmenopausal women with endocrine-responsive early breast cancer. Because there may be contraindications to their use based on side-effects or cost, we investigated subgroups in which aroma...

Aromatase Expression in the Hippocampus of AD Patients and 5xFAD Mice

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Janine Prange-Kiel

2016-01-01

Full Text Available Numerous studies show that 17β-estradiol (E2 protects against Alzheimer’s disease (AD induced neurodegeneration. The E2-synthesizing enzyme aromatase is expressed in healthy hippocampi, but although the hippocampus is severely affected in AD, little is known about the expression of hippocampal aromatase in AD. To better understand the role of hippocampal aromatase in AD, we studied its expression in postmortem material from patients with AD and in a mouse model for AD (5xFAD mice. In human hippocampi, aromatase-immunoreactivity was observed in the vast majority of principal neurons and signal quantification revealed higher expression of aromatase protein in AD patients compared to age- and sex-matched controls. The tissue-specific first exons of aromatase I.f, PII, I.3, and I.6 were detected in hippocampi of controls and AD patients by RT-PCR. In contrast, 3-month-old, female 5xFAD mice showed lower expression of aromatase mRNA and protein (measured by qRT-PCR and semiquantitative immunohistochemistry than WT controls; no such differences were observed in male mice. Our findings stress the importance of hippocampal aromatase expression in neurodegenerative diseases.

Dry eye syndrome in aromatase inhibitor users.

Science.gov (United States)

Turaka, Kiran; Nottage, Jennifer M; Hammersmith, Kristin M; Nagra, Parveen K; Rapuano, Christopher J

2013-04-01

Aromatase inhibitors are frequently used as an adjuvant therapy in the treatment of breast cancer. We observed that several patients taking aromatase inhibitors presented with severe dry eye symptoms, and we investigated whether there is a relationship between aromatase inhibitors and dry eyes in these patients. Retrospective chart review. Forty-one women. A computerized search of health records was performed to identify patients using anastrazole, letrozole and exemestane seen by the Cornea Service from August 2008 to March 2011. The results were compared with age-matched controls. Ocular surface changes among aromatase inhibitors users. Of the 41 women, 39 were Caucasians. Thirty-nine patients had breast cancer (95%), one patient had ovarian cancer (2.5%) and one had an unknown primary cancer. Mean age was 68 ± 11.3 years (range 47-95). Most common presenting symptoms were blurred vision in 28 (68%) patients, irritation/foreign body sensation in 12 (29%) patients, redness in 9 (22%) patients, tearing in 6 (22%) patients and photosensitivity in 2 (5%) patients. Mean Schirmer's test measurement was 11 ± 5.8 mm (range 0.5-20 mm). Blepharitis was noted in 68 of 82 eyes (73%), decreased or poor tear function in 24 eyes (29%), conjunctival injection in 18 eyes (22%) and superficial punctate keratitis in 12 eyes (29%). Among an age-matched population (45-95 years), dry eye syndrome was found in only 9.5% of patients. Because the prevalence of ocular surface disease signs and symptoms appears to be higher in study group than control patients, aromatase inhibitors might be a contributing factor to the dry eye symptoms. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

Molecular cloning of P450 aromatase from the leopard gecko and its expression in the ovary.

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Endo, Daisuke; Park, Min Kyun

2005-07-01

In this study, we identified the cDNA of P450 aromatase in the leopard gecko, a lizard with temperature-dependent sex determination. The cDNA encodes a putative protein of 505 amino acids. The deduced amino acid sequence of leopard gecko aromatase cDNA showed 80% identity with that of turtles, 70% with humans and 77% with chickens. This is the first report of the identification of P450 aromatase cDNA in squamata species. It has been reported that this gene is expressed in different layers of cells in the ovary of mammalian species and avian species. Thus, we also investigated cells expressing the mRNA of this gene in the ovary of the leopard gecko by RT-PCR and in situ hybridization. The mRNA expression of leopard gecko P450 aromatase was localized in both the thecal and granulosa cell layers in the ovary. The expression in thecal and granulosa cell layers was examined in the largest follicle, second largest follicle and third largest follicle by RT-PCR. A higher level of mRNA expression was observed in the granulosa cell layer of the second largest follicle than in other cell layers. This result may reflect the characteristics of follicles in species with automonochronic ovulation.

Aromatase inhibitors - a viable option for recurrent granulosa cell tumour of ovary: overview and case report

International Nuclear Information System (INIS)

Munem, A.A.; Bahrani, B.A.; Mehdi, I.

2012-01-01

Granulosa cell tumour of the ovary in adults is a rare tumour of low malignant potential affecting middle aged peri or post menopausal patients. These tumours are often diagnosed at an early stage, due to their hormonally active nature. They, however, have unique distinguishing histologic features and behaviour of frequent and late local or systemic relapses. The diagnosis can be challenging with unusual presentations. There is high association of endometrial carcinoma. Surgery is the mainstay of management in early low risk disease, while radiotherapy and systemic platinum based chemotherapy are employed in higher stage with poor prognostic indices. Survival is good in early stage disease. Recurrent, progressive, and treatment refractory disease is not infrequent and poses management challenge. Endocrine manipulation and hormone treatment are employed in few cases with equivocal results, as reported in literature. We present a case of recurrent and treatment refractory GCT in a postmenopausal patient, managed by aromatase inhibitor Anastrozole with reasonable efficacy. (author)

The ovine sexually dimorphic nucleus, aromatase, and sexual partner preferences in sheep.

Science.gov (United States)

Roselli, C E; Stormshak, F

2010-02-28

We are using the domestic ram as an experimental model to examine the role of aromatase in the development of sexual partner preferences. This interest has arisen because of the observation that as many as 8% of domestic rams are sexually attracted to other rams (male-oriented) in contrast to the majority of rams that are attracted to estrous ewes (female-oriented). Our findings demonstrate that aromatase expression is enriched in a cluster of neurons in the medial preoptic nucleus called the ovine sexually dimorphic nucleus (oSDN). The size of the oSDN is associated with a ram's sexual partner preference, such that the nucleus is 2-3 times larger in rams that are attracted to females (female-oriented) than in rams that are attracted to other rams (male-oriented). Moreover, the volume of the oSDN in male-oriented rams is similar to the volume in ewes. These volume differences are not influenced by adult concentrations of serum testosterone. Instead, we found that the oSDN is already present in late gestation lamb fetuses (approximately day 135 of gestation) when it is approximately 2-fold greater in males than in females. Exposure of genetic female fetuses to exogenous testosterone during the critical period for sexual differentiation masculinizes oSDN volume and aromatase expression when examined subsequently on day 135. The demonstration that the oSDN is organized prenatally by testosterone exposure suggests that the brain of the male-oriented ram may be under-androgenized during development. Copyright 2009 Elsevier Ltd. All rights reserved.

Genetics Home Reference: aromatase deficiency

Science.gov (United States)

... to impaired female sexual development, unusual bone growth, insulin resistance, and other signs and symptoms of aromatase deficiency . In women who are pregnant with an affected fetus, excess androgens in the ...

Vaginal Gene Expression During Treatment With Aromatase Inhibitors.

Science.gov (United States)

Kallak, Theodora Kunovac; Baumgart, Juliane; Nilsson, Kerstin; Åkerud, Helena; Poromaa, Inger Sundström; Stavreus-Evers, Anneli

2015-12-01

Aromatase inhibitor (AI) treatment suppresses estrogen biosynthesis and causes genitourinary symptoms of menopause such as vaginal symptoms, ultimately affecting the quality of life for many postmenopausal women with breast cancer. Thus, the aim of this study was to examine vaginal gene expression in women during treatment with AIs compared with estrogen-treated women. The secondary aim was to study the presence and localization of vaginal aromatase. Vaginal biopsies were collected from postmenopausal women treated with AIs and from age-matched control women treated with vaginal estrogen therapy. Differential gene expression was studied with the Affymetrix Gene Chip Gene 1.0 ST Array (Affymetrix Inc, Santa Clara, CA) system, Ingenuity pathway analysis, quantitative real-time polymerase chain reaction, and immunohistochemistry. The expression of 279 genes differed between the 2 groups; AI-treated women had low expression of genes involved in cell differentiation, proliferation, and cell adhesion. Some differentially expressed genes were found to interact indirectly with the estrogen receptor alpha. In addition, aromatase protein staining was evident in the basal and the intermediate vaginal epithelium layers, and also in stromal cells with a slightly stronger staining intensity found in AI-treated women. In this study, we demonstrated that genes involved in cell differentiation, proliferation, and cell adhesion are differentially expressed in AI-treated women. The expression of vaginal aromatase suggests that this could be the result of local and systemic inhibition of aromatase. Our results emphasize the role of estrogen for vaginal cell differentiation and proliferation and future drug candidates should be aimed at improving cell differentiation and proliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

Aromatase inhibitor treatment limits progression of peritoneal endometriosis in baboons.

Science.gov (United States)

Langoi, David; Pavone, Mary Ellen; Gurates, Bilgin; Chai, Daniel; Fazleabas, Asgerally; Bulun, Serdar E

2013-03-01

To determine the effect of inhibiting aromatase activity on endometrial lesion growth and aromatase expression in a baboon model of induced endometriosis. Prospective study. Primate research institute. Sixteen olive baboons. Sixteen olive baboons with induced endometriosis were examined with laparoscopy 10 months after disease inoculation. Animals in group 1 (n = 10) were treated with 1.25 mg/d of the aromatase inhibitor (AI) letrozole, and animals in group 2 (n = 6) were given a placebo for a total of 6 months. Total number of endometriotic lesions, morphology, and volume of lesions, as well as semiquantitative reverse transcription-polymerase chain reaction and quantitative polymerase chain reaction for levels of aromatase cytochrome messenger RNA were measured. Ovarian volumes were evaluated before treatment initiation and every 2 months during the study. Treatment of group 1 animals with an AI significantly decreased lesion volume from baseline measurements, whereas the placebo-treated animals showed an increase in lesion volume. Aromatase messenger RNA levels in lesions in the AI-treated animals were significantly lower compared with the placebo-treated animals. Ovarian volumes were significantly increased at 6 months of AI treatment compared with pretreatment volumes. These findings suggest that suppression of aromatase cytochrome P450 may inhibit the in vivo growth of endometriotic lesions in baboons. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cell-Based High-Throughput Screening for Aromatase Inhibitors in the Tox21 10K Library.

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Chen, Shiuan; Hsieh, Jui-Hua; Huang, Ruili; Sakamuru, Srilatha; Hsin, Li-Yu; Xia, Menghang; Shockley, Keith R; Auerbach, Scott; Kanaya, Noriko; Lu, Hannah; Svoboda, Daniel; Witt, Kristine L; Merrick, B Alex; Teng, Christina T; Tice, Raymond R

2015-10-01

Multiple mechanisms exist for endocrine disruption; one nonreceptor-mediated mechanism is via effects on aromatase, an enzyme critical for maintaining the normal in vivo balance of androgens and estrogens. We adapted the AroER tri-screen 96-well assay to 1536-well format to identify potential aromatase inhibitors (AIs) in the U.S. Tox21 10K compound library. In this assay, screening with compound alone identifies estrogen receptor alpha (ERα) agonists, screening in the presence of testosterone (T) identifies AIs and/or ERα antagonists, and screening in the presence of 17β-estradiol (E2) identifies ERα antagonists. Screening the Tox-21 library in the presence of T resulted in finding 302 potential AIs. These compounds, along with 31 known AI actives and inactives, were rescreened using all 3 assay formats. Of the 333 compounds tested, 113 (34%; 63 actives, 50 marginal actives) were considered to be potential AIs independent of cytotoxicity and ER antagonism activity. Structure-activity analysis suggested the presence of both conventional (eg, 1, 2, 4, - triazole class) and novel AI structures. Due to their novel structures, 14 of the 63 potential AI actives, including both drugs and fungicides, were selected for confirmation in the biochemical tritiated water-release aromatase assay. Ten compounds were active in the assay; the remaining 4 were only active in high-throughput screen assay, but with low efficacy. To further characterize these 10 novel AIs, we investigated their binding characteristics. The AroER tri-screen, in high-throughput format, accurately and efficiently identified chemicals in a large and diverse chemical library that selectively interact with aromatase. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dopamine D1 receptor activation regulates the expression of the estrogen synthesis gene aromatase B in radial glial cell

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Lei eXing

2015-09-01

Full Text Available Radial glial cells (RGCs are abundant stem-like non-neuronal progenitors that are important for adult neurogenesis and brain repair, yet little is known about their regulation by neurotransmitters. Here we provide evidence for neuronal-glial interactions via a novel role for dopamine to stimulate RGC function. Goldfish were chosen as the model organism due to the abundance of RGCs and regenerative abilities of the adult central nervous system. A close anatomical relationship was observed between tyrosine hydroxylase-positive catecholaminergic cell bodies and axons and dopamine-D1 receptor expressing RGCs along the ventricular surface of telencephalon, a site of active neurogenesis. A primary cell culture model was established and immunofluorescence analysis indicates that in vitro RGCs from female goldfish retain their major characteristics in vivo, including expression of glial fibrillary acidic protein and brain lipid binding protein. The estrogen synthesis enzyme aromatase B is exclusively found in RGCs, but this is lost as cells differentiate to neurons and other glial types in adult teleost brain. Pharmacological experiments using the cultured RGCs established that specific activation of dopamine D1 receptors up-regulates aromatase B mRNA through a cyclic adenosine monophosphate-dependent molecular mechanism. These data indicate that dopamine enhances the steroidogenic function of this neuronal progenitor cell.

In Silico Prediction of Chemicals Binding to Aromatase with Machine Learning Methods.

Science.gov (United States)

Du, Hanwen; Cai, Yingchun; Yang, Hongbin; Zhang, Hongxiao; Xue, Yuhan; Liu, Guixia; Tang, Yun; Li, Weihua

2017-05-15

Environmental chemicals may affect endocrine systems through multiple mechanisms, one of which is via effects on aromatase (also known as CYP19A1), an enzyme critical for maintaining the normal balance of estrogens and androgens in the body. Therefore, rapid and efficient identification of aromatase-related endocrine disrupting chemicals (EDCs) is important for toxicology and environment risk assessment. In this study, on the basis of the Tox21 10K compound library, in silico classification models for predicting aromatase binders/nonbinders were constructed by machine learning methods. To improve the prediction ability of the models, a combined classifier (CC) strategy that combines different independent machine learning methods was adopted. Performances of the models were measured by test and external validation sets containing 1336 and 216 chemicals, respectively. The best model was obtained with the MACCS (Molecular Access System) fingerprint and CC method, which exhibited an accuracy of 0.84 for the test set and 0.91 for the external validation set. Additionally, several representative substructures for characterizing aromatase binders, such as ketone, lactone, and nitrogen-containing derivatives, were identified using information gain and substructure frequency analysis. Our study provided a systematic assessment of chemicals binding to aromatase. The built models can be helpful to rapidly identify potential EDCs targeting aromatase.

Inhibitory effect of Sphagnum palustre extract and its bioactive compounds on aromatase activity

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Hee Jeong Eom

2016-09-01

Full Text Available Sphagnum palustre (a moss has been traditionally used in Korea for the cure of several diseases such as cardiac pain and stroke. In this research, the inhibitory effect of S. palustre on aromatase (cytochrome P450 19, CYP19 activity was studied. [1β-3H] androstenedione was used as a substrate and incubated with S. palustre extract and recombinant human CYP19 in the presence of NADPH. S. palustre extract inhibited aromatase in a concentration-dependent manner (IC50 value: 36.4 ± 8.1 µg/mL. To elucidate the major compounds responsible for the aromatase inhibitory effects of S. palustre extract, nine compounds were isolated from the extract and tested for their inhibition of aromatase activity. Compounds 1, 6, and 7 displayed aromatase inhibition, while the inhibition by the other compounds was negligible.

Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels

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Nicolas Defarge

2016-02-01

Full Text Available Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH, the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18–2000 times for co-formulants, 8–141 times for formulations, and not the declared active ingredient glyphosate (G alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine—POEA and alkyl polyglucoside—APG and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.

Ekspresi Gen CYP19 Aromatase, Estrogen, Androgen pada penderita Periodontitis Agresif

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Dahlia Herawati

2016-11-01

Full Text Available Kepadatan tulang tubuh ditentukan oleh gen CYP19 aromatase, hormon estrogen dan androgen. Pada periodontitis agresif terjadi perkembangan cepat kerusakan tulang alveolar, dan kerusakan tulang alveoler tersebut tidak diimbangioleh regenerasi tulang. Tujuan penelitian ini adalah menunjukkan ekspresi gen CYP19 aromatase, estrogen, androgen pada penderita periodontitis agresif agar dapat untuk menjadi pertimbangan pada saat melakukan perawatan periodontal. Metode penelitian, pemeriksaan ekspresi gen aromatse CYP19 berasal dari spesimen tulang alveolar menggunakan imunohistokimia, pengukuran hormon estrogen dan androgen dari serum menggunakan Vidas: Elfa. Hasil penelitian ekspresi gene CYP19 aromatase pada periodontitis agresif menunjukkan gambaran lebih rendah densitasnya dibandingkan pada nonperiodontitis. Estrogen dan androgen pad aperiodontitis agresif ada kecenderungan lebih rendah dibandingkan pada nonperiodontitis. Kesimpulan regenerasi tulang alveoler pad a periodontitis agresif terhambat karena sedikitnya gen CYP19 aromatase dan hormon estrogen dan androgen yang berperan pada pembentukan tulang alveoler kurang memadai.

Testosterone-induced adult neurosphere growth is mediated by sexually-dimorphic aromatase expression

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Mark Ian Ransome

2015-07-01

Full Text Available We derived adult neural stem/progenitor cells (NSPCs from the sub-ventricular zone of male and female mice to examine direct responses to principal sex hormones. In the presence of epidermal growth factor (EGF and fibroblast growth factor-2 (FGF2 NSPCs of both sexes expressed nestin and sox2 and could be maintained as neurospheres without addition of any sex hormones. The reverse was not observed; neither testosterone (T, 17β-oestradiol (E2 nor progesterone (P4 was able to support neurosphere growth in the absence of EGF and FGF2. 10nM T, E2 or P4 induced nestin(+ cell proliferation within 20 minutes and enhanced neurosphere growth over 7 days irrespective of sex, which was abolished by Erk inhibition with 20M U0126. Maintaining neurospheres with each sex hormone did not affect subsequent neuronal differentiation. However, 10nM T, E2 or P4 added during differentiation increased III tubulin(+ neuron production with E2 being more potent compared to T and P4 in both sexes. Androgen receptor (AR inhibition with 20M flutamide but not aromatase inhibition with 10M letrozole reduced basal and T-induced neurosphere growth in females, while only concurrent inhibition of AR and aromatase produced the same effect in males. This sex-specific effect was supported by higher aromatase expression in male neurospheres compared to females measured by Western blot and green fluorescent protein reporter. 10M menadione induced oxidative stress, impaired neurosphere growth and up-regulated aromatase expression in both sexes. However, under oxidative stress letrozole significantly exacerbated impaired neurosphere growth in males only. While both E2 and T could prevent oxidative stress-induced growth reduction in both sexes, the effects of T were dependent on innate aromatase activity. We show for the first time that intrinsic androgen and estrogen signalling may impact the capacity of NSPCs to produce neural progenitors under pathological conditions of

Pyridine-substituted thiazolylphenol derivatives: Synthesis, modeling studies, aromatase inhibition, and antiproliferative activity evaluation.

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Ertas, Merve; Sahin, Zafer; Berk, Barkin; Yurttas, Leyla; Biltekin, Sevde N; Demirayak, Seref

2018-04-01

Drugs used in breast cancer treatments target the suppression of estrogen biosynthesis. During this suppression, the main goal is to inhibit the aromatase enzyme that is responsible for the cyclization and structuring of estrogens either with steroid or non-steroidal-type inhibitors. Non-steroidal derivatives generally have a planar aromatic structure attached to the triazole ring system in their structures, which inhibits hydroxylation reactions during aromatization by coordinating the heme group. Bioisosteric replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase the selectivity for aromatase enzyme inhibition. In this study, pyridine-substituted thiazolylphenol derivatives, which are non-steroidal triazole bioisosteres, were synthesized using the Hantzsch method, and physical analysis and structural determination studies were performed. The IC 50 values of the compounds were determined by a fluorescence-based aromatase inhibition assay. Then, their antiproliferative activities on the MCF7 and HEK 293 cell lines were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, the crystal structure of human placental aromatase was subjected to a series of docking experiments to identify the possible interactions between the most active structure and the active site. Lastly, an in silico technique was performed to analyze and predict the drug-likeness, molecular and ADME properties of the synthesized molecules. © 2018 Deutsche Pharmazeutische Gesellschaft.

A qualitative systematic review of the evidence base for non-cross-resistance between steroidal and non-steroidal aromatase inhibitors in metastatic breast cancer.

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Beresford, M; Tumur, I; Chakrabarti, J; Barden, J; Rao, N; Makris, A

2011-04-01

The most effective sequence of tamoxifen and both steroidal (SAIs) and non-steroidal aromatase inhibitors (NSAIs) has been extensively studied in the adjuvant setting. However, treatments for women who have failed initial aromatase inhibitor therapy in the metastatic setting have received relatively little attention. A systematic review was undertaken to assess the use of SAIs and NSAIs in metastatic breast cancer. Medline, Embase and the Cochrane library were searched using free text and MeSH terms. Studies assessing the cross-resistance, efficacy and safety of SAIs and NSAIs for postmenopausal women with advanced metastatic breast cancer confirmed by histology/cytology were included. Patients had progressed/relapsed from previous adjuvant, first- or second-line aromatase inhibitor treatment and had undergone treatment with at least two regimens consisting of aminoglutethimide, anastrozole, letrozole and/or exemestane. Nine studies reported results for patients treated with an SAI after treatment failure with an NSAI. For SAI after NSAI, clinical benefit was the most frequently reported outcome. The clinical benefit for exemestane (SAI) after any NSAI failure or before treatment ranged from 12% (complete response not recorded, partial response 2%, stable disease 10%) to 55% (complete response 6%, partial response 13%, stable disease 35%) Survival outcomes were infrequently reported; four studies reported disease progression. The time to progression ranged from 3.7 to 5.2 months. Only one study reported a median overall survival with exemestane at 15.2 months. Only one study reported information for an NSAI after SAI and an NSAI followed by another NSAI. This review suggests that switching from an NSAI to an SAI is a reasonable option. This would be particularly important for patients who would probably respond to further endocrine manoeuvres; strongly oestrogen receptor-positive disease, non-visceral disease, a good prior response or a long duration of response

Sex change strategy and the aromatase genes.

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Gardner, L; Anderson, T; Place, A R; Dixon, B; Elizur, A

2005-04-01

Sequential hermaphroditism is a common reproductive strategy in many teleosts. Steroid production is known to mediate both the natural and induced sex change, yet beyond this the physiology directing this process has received little attention. Cytochrome P450 aromatase is a key enzyme in the hormonal pathway catalysing the conversion of sex steroids, androgens to oestrogens, and thus is highly relevant to the process of sex change. This study reports the isolation of cDNA sequences for aromatase isoforms CYP19A1 and CYP19A2 from teleost species representing three forms of sexual hermaphroditism: Lates calcarifer (protandry), Cromileptes altivelis (protogyny), and Gobiodon histrio (bi-directional). Deduced amino acid analysis of these isoforms with other reported isoforms from gonochoristic (single sex) teleosts revealed 56-95% identity within the same isoform while only 48-65% identity between isoforms irrespective of species and sexual strategy. Phylogenetic analysis supported this result separating sequences into isoform exclusive clades in spite of species apparent evolutionary distance. Furthermore, this study isolates 5' flanking regions of all above genes and describes putative cis-acting elements therein. Elements identified include steroidogenic factor 1 binding site (SF-1), oestrogen response element (ERE), progesterone response element (PRE), androgen response element (ARE), glucocorticoid response elements (GRE), peroxisome proliferator-activated receptor alpha/retinoid X receptor alpha heterodimer responsive element (PPARalpha/RXRalpha), nuclear factor kappabeta (NF-kappabeta), SOX 5, SOX 9, and Wilms tumor suppressor (WTI). A hypothetical in vivo model was constructed for both isoforms highlighting potential roles of these putative cis-acting elements with reference to normal function and sexual hermaphroditism.

Investigation of aromatase inhibitory activity of metal complexes of 8-hydroxyquinoline and uracil derivatives

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Prachayasittikul V

2014-08-01

and other estrogen-related diseases. Keywords: aromatase inhibitor, anticancer, metal-based compound

Formestane, a steroidal aromatase inhibitor after failure of non-steroidal aromatase inhibitors (anastrozole and letrozole): is a clinical benefit still achievable?

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Carlini, P; Frassoldati, A; De Marco, S; Casali, A; Ruggeri, E M; Nardi, M; Papaldo, P; Fabi, A; Paoloni, F; Cognetti, F

2001-11-01

There are few clinical data on the sequential use of aromatase inhibitors (AI). This paper focuses on the relevance of clinical benefit CB (CR + PR + SD > or = 6 months) in postmenopausal metastatic breast cancer (MBC) patients treated with the steroidal aromatase inhibitor (SAI) formestane (FOR). who had already received non-steroidal aromatase inhibitor (nSAI): letrozole (LTZ) or anastrozole (ANZ). Twenty postmenopausal women with MBC were analysed in this retrospective two-centre study with the sequence nSAI-FOR. When receiving ANZ, 1 of 11 achieved a complete response and 9 of 11 a stable disease > or = 6 months, and receiving LTZ 1 of 9 achieved a partial response and 4 of 9 a stable disease > or = 6 months. The analysis of the entire population treated with FOR showed an overall CB of 55% (11 of 20) with a median duration of 15 months and median time to progression (TTP) of 6 months. Formestane 250 mg once bi-weekly seems to be an attractive alternative third-line hormonal therapy for the treatment of patients with MBC, previously treated with nSAI.

Inhibitory effect of luteolin on estrogen biosynthesis in human ovarian granulosa cells by suppression of aromatase (CYP19).

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Lu, Dan-feng; Yang, Li-juan; Wang, Fei; Zhang, Guo-lin

2012-08-29

Inhibition of aromatase, the key enzyme in estrogen biosynthesis, is an important strategy in the treatment of breast cancer. Several dietary flavonoids show aromatase inhibitory activity, but their tissue specificity and mechanism remain unclear. This study found that the dietary flavonoid luteolin potently inhibited estrogen biosynthesis in a dose- and time-dependent manner in KGN cells derived from human ovarian granulosa cells, the major source of estrogens in premenopausal women. Luteolin decreased aromatase mRNA and protein expression in KGN cells. Luteolin also promoted aromatase protein degradation and inhibited estrogen biosynthesis in aromatase-expressing HEK293A cells, but had no effect on recombinant expressed aromatase. Estrogen biosynthesis in KGN cells was inhibited with differing potencies by extracts of onion and bird chili and by four other dietary flavonoids: kaempferol, quercetin, myricetin, and isorhamnetin. The present study suggests that luteolin inhibits estrogen biosynthesis by decreasing aromatase expression and destabilizing aromatase protein, and it warrants further investigation as a potential treatment for estrogen-dependent cancers.

Currently used pesticides and their mixtures affect the function of sex hormone receptors and aromatase enzyme activity

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Kjeldsen, Lisbeth Stigaard; Ghisari, Mandana; Bonefeld-Jørgensen, Eva Cecilie, E-mail: ebj@mil.au.dk

2013-10-15

The endocrine-disrupting potential of pesticides is of health concern, since they are found ubiquitously in the environment and in food items. We investigated in vitro effects on estrogen receptor (ER) and androgen receptor (AR) transactivity, and aromatase enzyme activity, of the following pesticides: 2-methyl-4-chlorophenoxyacetic acid (MCPA), terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb, cypermethrin, tau fluvalinate, malathion and the metabolite ethylene thiourea (ETU). The pesticides were analyzed alone and in selected mixtures. Effects of the pesticides on ER and AR function were assessed in human breast carcinoma MVLN cells and hamster ovary CHO-K1 cells, respectively, using luciferase reporter gene assays. Effects on aromatase enzyme activity were analyzed in human choriocarcinoma JEG-3 cells, employing the classical [{sup 3}H]{sub 2}O method. Five pesticides (terbuthylazine, propiconazole, prothioconazole, cypermethrin and malathion) weakly induced the ER transactivity, and three pesticides (bitertanol, propiconazole and mancozeb) antagonized the AR activity in a concentration-dependent manner. Three pesticides (terbuthylazine, propiconazole and prothioconazole) weakly induced the aromatase activity. In addition, two mixtures, consisting of three pesticides (bitertanol, propiconazole, cypermethrin) and five pesticides (terbuthylazine, bitertanol, propiconazole, cypermethrin, malathion), respectively, induced the ER transactivity and aromatase activity, and additively antagonized the AR transactivity. In conclusion, our data suggest that currently used pesticides possess endocrine-disrupting potential in vitro which can be mediated via ER, AR and aromatase activities. The observed mixture effects emphasize the importance of considering the combined action of pesticides in order to assure proper estimations of related health effect risks

Localization of the aromatase enzyme expression in the human pituitary gland and its effect on growth hormone, prolactin, and thyroid stimulating hormone axis.

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Caglar, Asli Sezgin; Kapucu, Aysegul; Dar, Kadriye Akgun; Ozkaya, Hande Mefkure; Caglar, Erkan; Ince, Haluk; Kadioglu, Pinar

2015-08-01

The aim of this study is to evaluate aromatase expression in prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) secreting cells. Nontumoral human pituitary specimens were obtained from autopsy samples. Aromatase co-expression was determined by double immunohistochemical staining and assessed using H scores. H scores for GH-aromatase co-expression (GH-aromatase), TSH-aromatase co-expression (TSH-aromatase), and PRL-aromatase co-expression (PRL-aromatase) were 83.1 ± 13.1, 95.6 ± 16.1, and 83.7 ± 14.5, respectively. TSH producing cells exhibited the highest H score for co-expression of aromatase (p 0.05 for all). There was a negative correlation between the H scores for aromatase and PRL-aromatase, GH-aromatase and TSH-aromatase, respectively (r = -0.592, p 0.05 for all). Age was negatively correlated with PRL-aromatase H score (r = -0.373, p = 0.008). Our study demonstrated significant aromatase co-expression in PRL, GH, and TSH secreting cells of the human anterior pituitary gland. The mutual paracrinal regulation between aromatase and three adenohypophyseal hormones indicates that aromatase may have a regulatory role on the synthesis and secretion of these hormones.

Aromatase inhibitors in the treatment of deep endometriosis

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Simone Ferrero

2009-09-01

Full Text Available Recent case reports and pilot studies suggested that aromatase inhibitors might be effective in treating pain symptoms related to the presence of endometriosis. We present the case of a 32-year-old woman who suffered dysmenorrhea, dyspareunia, chronic pelvic pain, and dyschezia caused by rectovaginal endometriosis. Pain symptoms recurred after treatment with the oral contraceptive pill; the patient refused surgery. Therefore a double-drug regimen including letrozole (2.5 mg/day and norethisterone acetate (2.5 mg/day was offered to the patient. The scheduled length of treatment was six months. This double-drug regimen determined a quick and significant improvement in all pain symptoms. During treatment, the patient complained mild arthralgia. After the interruption of treatment, pain symptoms quickly recurred and at 6-month follow-up their intensity was similar to baseline values. Operative laparoscopy was performed, the presence of rectovaginal endometriosis was confirmed and all visible endometriotic lesions were excised. Aromatase inhibitors might be offered when pain symptoms caused by endometriosis persist during the administration of other hormonal therapies and the patient refuses surgery. However, women must be informed that these drugs determine only a temporary relief of pain symptoms and might cause adverse effects (such as arthralgia.

Managing arthralgia in a postmenopausal woman taking an aromatase inhibitor for hormonesensitive early breast cancer: a case study

International Nuclear Information System (INIS)

Bryce, Jane; Bauer, Martina; Hadji, Peyman

2012-01-01

In order to reduce the risk of recurrence, adjuvant treatment with an aromatase inhibitor (AI) is recommended for postmenopausal women following surgery for hormone receptor-positive breast cancer. AIs are associated with improved disease-free survival compared with tamoxifen. The adverse events associated with AIs resemble those of menopause, such as bone density loss and musculoskeletal symptoms. We examine the case of a postmenopausal woman who was prescribed anastrozole, a nonsteroidal AI, as adjuvant therapy following surgery for estrogen and progesterone receptor-positive (ER and PgR+) breast cancer. A 58-year-old postmenopausal woman diagnosed with ER and PgR+ breast cancer was prescribed anastrozole as adjuvant therapy following a right-inferior quadrantectomy. After experiencing joint pain and stiffness, she was prescribed paracetamol and a topical nonsteroidal anti-inflammatory drug. She was also counseled on nonpharmacological interventions. However, she continued to experience symptoms, and reported that she was not taking anastrozole regularly. The case study patient ultimately found relief by switching to letrozole, another aromatase inhibitor. This approach is supported by recent studies examining the benefits of switching strategies between aromatase inhibitors in order to relieve symptoms of arthralgia/myalgia. Both adherence and strategies for managing aromatase inhibitor-associated arthralgia are key to deriving maximal clinical benefit from AI therapy. Switching from one aromatase inhibitor to another may provide a viable option in managing adverse events and enhancing adherence to medication

Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitro

DEFF Research Database (Denmark)

Vinggaard, A.M.; Hnida, C.; Breinholt, V.

2000-01-01

than 50 mu M. The positive control 4-hydroxyandrostendione (1 mu M) caused an inhibition of aromatase activity by 74%. The compounds, which did not affect the aromatase activity, were bromopropylate, chlorfenvinphos. chlorobenzilate, chlorpyrifos, diuron, heptachlor, iprodion, linuron, pentachlorphenol...

Overexpression of aromatase alone is sufficient for ovarian development in genetically male chicken embryos.

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Luke S Lambeth

Full Text Available Estrogens play a key role in sexual differentiation of both the gonads and external traits in birds. The production of estrogen occurs via a well-characterised steroidogenic pathway, which is a multi-step process involving several enzymes, including cytochrome P450 aromatase. In chicken embryos, the aromatase gene (CYP19A1 is expressed female-specifically from the time of gonadal sex differentiation. To further explore the role of aromatase in sex determination, we ectopically delivered this enzyme using the retroviral vector RCASBP in ovo. Aromatase overexpression in male chicken embryos induced gonadal sex-reversal characterised by an enlargement of the left gonad and development of ovarian structures such as a thickened outer cortex and medulla with lacunae. In addition, the expression of key male gonad developmental genes (DMRT1, SOX9 and Anti-Müllerian hormone (AMH was suppressed, and the distribution of germ cells in sex-reversed males followed the female pattern. The detection of SCP3 protein in late stage sex-reversed male embryonic gonads indicated that these genetically male germ cells had entered meiosis, a process that normally only occurs in female embryonic germ cells. This work shows for the first time that the addition of aromatase into a developing male embryo is sufficient to direct ovarian development, suggesting that male gonads have the complete capacity to develop as ovaries if provided with aromatase.

Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives.

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Sahin, Zafer; Ertas, Merve; Berk, Barkın; Biltekin, Sevde Nur; Yurttas, Leyla; Demirayak, Seref

2018-05-01

Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects. Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition. In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC 50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC 50 :0.42 nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site. Copyright © 2018 Elsevier Ltd. All rights reserved.

Merlin, the product of NF2 gene, is associated with aromatase expression and estrogen formation in human liver tissues and liver cancer cells.

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Cocciadiferro, Letizia; Miceli, Vitale; Granata, Orazia M; Carruba, Giuseppe

2017-09-01

The product of neurofibromatosis type 2 (NF2) gene, also known as Merlin/neurofibromin 2, homeostatically regulates liver stem cells by controlling abundance and signaling of epidermal growth factor receptor (EGFR), with a mechanism independent of the Hippo pathway. We have reported that locally elevated estrogen formation, driven by abnormally high expression and function of aromatase, may be implicated in development and progression of human hepatocellular carcinoma (HCC) through activation of a rapid signaling pathway mediated by amphiregulin (AREG) and EGFR. We have recently presented a model by which the aromatase-estrogen-amphiregulin-EGFR axis is activated in response to tissue injury and/or inflammatory disease, with its alteration eventually leading to development of major human tumors (liver, breast, prostate) and other chronic diseases (diabetes, obesity, Alzheimer's and heart disease). In this study, we investigated NF2 expression in liver cancer cells and tissues in relation to aromatase expression/function, estrogen receptor (ER) status and amphiregulin. Our data indicate that NF2 expression is associated with aromatase and AREG expression, being elevated in HCC tissues and HepG2 cells, intermediate in cirrhotic tissues and Huh7 cells, and lower in nontumoral liver and HA22T cells. In addition, NF2 expression is inversely related to wild type hERα66 and proportional to the expression of the membrane-associated hERα36 splice variant, as measured by exon-specific RT-PCR analysis, both in vivo and in vitro. Furthermore, incubation with estradiol induced a significant decrease of NF2 expression in both HA22T and Huh7 cells (over 54% and 22%, respectively), while no change could be observed in HepG2 cells, this effect being inversely related to aromatase expression and activity in HCC cell lines. Based on the above combined evidence, we hypothesize that NF2 behaves as a protein sensing tissue damage and aromatase-driven local estrogen formation

Inhibition of human aromatase complex (CYP19) by antiepileptic drugs

DEFF Research Database (Denmark)

Jacobsen, Naja Wessel; Halling-Sørensen, Bent; Birkved, Franziska Maria A Kramer

2008-01-01

of 1.4-49.7 mM. Carbamazepine, gabapentin, primidone, topiramate and vigabatrin showed no inhibition. Additionally, binary drug combinations were tested to investigate if combination therapy could potentiate the aromatase inhibition. Additive inhibition was seen in combination experiments...... with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered....

Purification of human placental aromatase cytochrome P-450 with monoclonal antibody and its characterization

International Nuclear Information System (INIS)

Yoshida, Nobutaka; Osawa, Yoshio

1991-01-01

A simple and efficient method is described for the purification of microsomal aromatase cytochrome P-450 from human placenta. The enzyme was solubilized with Emulgen 913 and sodium cholate and subjected to chromatography on a column of Sepharose 4B couples with a specific monoclonal antibody, followed by hydroxyapatite column chromatography. The specific cytochrome P-450 content of purified aromatase was 13.1 (12-14.8) nmol/mg of protein. Aromatase assays were carried out with reconstituted systems of bovine liver P-450 reductase and dilauroyl-L-α-phosphatidylcholine with [1β- 3 H,4- 14 C]androstenedione as substrate. The total recovery of purified aromatase activity was 32.2%, and P-450 recovery was 17.6%. The very high K m value for 16α-hydroxytestosterone aromatization gives a reasonable indication that estriol is not the directly aromatized product in the fetoplacental unit of human pregnancy. The aromatase P-450 was subjected to SDS-polyacrylamide gel electrophoresis in increasing quantities. Silver stain detection techniques indicated a single band having a molecular mass of 55 kDa with greater than 97% purity. The stability analysis showed a half-life of over 4 years on storage at -80C

DIFERENSIASI KELAMIN TIGA GENOTIPE IKAN NILA YANG DIBERI BAHAN AROMATASE INHIBITOR

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Didik Ariyanto

2016-11-01

Full Text Available Penggunaan hormon sintetik 17 a-metiltestosterone untuk sex reversal ikan konsumsi sudah dilarang. Salah satu bahan yang terbukti efektif dalam sex reversal adalah bahan aromatase inhibitor. Bahan ini dapat digunakan dalam proses pembalikan kelamin karena menghambat sekresi enzim aromatase yang bertanggung jawab dalam konversi hormon androgen menjadi estrogen. Tingginya kadar androgen dalam tubuh akan mengarahkan proses diferensiasi kelamin ke arah kelamin jantan. Penelitian ini bertujuan mengetahui pengaruh pemberian bahan aromatase inhibitor terhadap diferensiasi kelamin tiga genotipe ikan nila. Bahan utama yang digunakan adalah larva ikan nila genotipe XX, XY, dan YY yang diberi bahan aromatase inhibitor, khususnya imidazole. Penambahan hormon sintetik 17a-metiltestosterone digunakan sebagai kontrol (+. Pemberian imidazole dilakukan melalui pakan pada larva ikan nila yang berumur 7 hari setelah menetas, selama 28 hari. Selanjutnya benih dipelihara dalam hapa pendederan selama 60 hari di kolam tanah. Pada akhir pendederan dilakukan identifikasi jenis kelamin, bobot individu rata-rata, dan sintasan. Hasil penelitian menunjukkan bahwa imidazole efektif meningkatkan rasio kelamin jantan pada ikan nila genotipe XX dan YY, tetapi tidak pada genotipe XY. Sampai akhir tahap pendederan, semua genotipe dan perlakuan yang berbeda tidak memberikan efek yang berbeda nyata terhadap laju pertumbuhan maupun nilai sintasan, kecuali pada genotipe YY

Correlation between aromatase expression in the eutopic endometrium of symptomatic patients and the presence of endometriosis

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Maia Jr H

2012-02-01

Full Text Available Hugo Maia Jr1,2, Clarice Haddad1,2, Julio Casoy11CEPARH, 2Itaigara Memorial Day Hospital, Salvador, Bahia, BrazilObjective: To investigate whether aromatase expression in the eutopic endometrium correlates with the presence and severity of endometriosis in patients with infertility and/or dysmenorrhea undergoing laparoscopy and hysteroscopy.Patients: The study involved 106 patients of reproductive age with symptoms of dysmenorrhea and infertility. Sixteen endometriosis-free asymptomatic patients were used as a control group.Methods: Concomitant laparoscopy and hysteroscopy was carried out in all cases. An endometrial biopsy was taken to determine aromatase p450 expression by immunohistochemistry. Endometriosis was staged according to the American Society of Reproductive Medicine classification.Results: Endometriosis was diagnosed by laparoscopy in 92/106 symptomatic patients. In this group, aromatase expression was detected in the eutopic endometrium of 66/92 patients with endometriosis (72% and in 13/14 (95% patients in the symptomatic, endometriosis-free group (P = 0.09. Aromatase expression was not detected in any patients from the control group. In the endometriosis group, aromatase expression was detected in the eutopic endometrium of 28/45 patients (62% with American Society of Reproductive Medicine classification stage 1 of the disease, in 11/14 patients (78% with stage II, 14/20 patients (70% with stage III, and in 12/13 patients (92% with stage IV; however, the difference was only statistically significant between stages I and IV (P = 0.04.Conclusion: Aromatase expression in the endometrium was associated with the presence of dysmenorrhea and infertility irrespective of the presence of endometriosis. When endometriosis was present, however, there was a tendency for aromatase expression to be positively correlated with dysmenorrhea severity.Keywords: aromatase, endometrium, endometriosis, Cox-2, dysmenorrhea

Gonadal expression of Sf1 and aromatase during sex determination in the red-eared slider turtle (Trachemys scripta), a reptile with temperature-dependent sex determination.

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Ramsey, Mary; Shoemaker, Christina; Crews, David

2007-12-01

Many egg-laying reptiles have temperature-dependent sex determination (TSD), where the offspring sex is determined by incubation temperature during a temperature-sensitive period (TSP) in the middle third of development. The underlying mechanism transducing a temperature cue into an ovary or testis is unknown, but it is known that steroid hormones play an important role. During the TSP, exogenous application of estrogen can override a temperature cue and produce females, while blocking the activity of aromatase (Cyp19a1), the enzyme that converts testosterone to estradiol, produces males from a female-biased temperature. The production of estrogen is a key step in ovarian differentiation for many vertebrates, including TSD reptiles, and temperature-based differences in aromatase expression during the TSP may be a critical step in ovarian determination. Steroidogenic factor-1 (Sf1) is a key gene in vertebrate sex determination and regulates many steroidogenic enzymes, including aromatase. We find that Sf1 and aromatase are differentially expressed during sex determination in the red-eared slider turtle, Trachemys scripta elegans. Sf1 is expressed at higher levels during testis development while aromatase expression increases during ovary determination. We also assayed Sf1 and aromatase response to sex-reversing treatments via temperature or the modulation of estrogen availability. Sf1 expression was redirected to low-level female-specific patterns with feminizing temperature shift or exogenous estradiol application and redirected to more intense male-specific patterns with male-producing temperature shift or inhibition of aromatase activity. Conversely, aromatase expression was redirected to more intense female-specific patterns with female-producing treatment and redirected toward diffuse low-level male-specific patterns with masculinizing sex reversal. Our data do not lend support to a role for Sf1 in the regulation of aromatase expression during slider turtle sex

Molecular cloning and expression analysis of fushi tarazu factor 1 in the brain of air-breathing catfish, Clarias gariepinus.

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Parikipandla Sridevi

Full Text Available BACKGROUND: Fushi tarazu factor 1 (FTZ-F1 encodes an orphan nuclear receptor belonging to the nuclear receptor family 5A (NR5A which includes adrenal 4-binding protein or steroidogenic factor-1 (Ad4BP/SF-1 and liver receptor homologue 1 (LRH-1 and plays a pivotal role in the regulation of aromatases. METHODOLOGY/PRINCIPAL FINDINGS: Present study was aimed to understand the importance of FTZ-F1 in relation to brain aromatase (cyp19a1b during development, recrudescence and after human chorionic gonadotropin (hCG induction. Initially, we cloned FTZ-F1 from the brain of air-breathing catfish, Clarias gariepinus through degenerate primer RT-PCR and RACE. Its sequence analysis revealed high homology with other NR5A1 group members Ad4BP/SF-1 and LRH-1, and also analogous to the spatial expression pattern of the latter. In order to draw functional correlation of cyp19a1b and FTZ-F1, we analyzed the expression pattern of the latter in brain during gonadal ontogeny, which revealed early expression during gonadal differentiation. The tissue distribution both at transcript and protein levels revealed its prominent expression in brain along with liver, kidney and testis. The expression pattern of brain FTZ-F1 during reproductive cycle and after hCG induction, in vivo was analogous to that of cyp19a1b shown in our earlier study indicating its involvement in recrudescence. CONCLUSIONS/SIGNIFICANCE: Based on our previous results on cyp19a1b and the present data, it is plausible to implicate potential roles for brain FTZ-F1 in ovarian differentiation and recrudescence process probably through regulation of cyp19a1b in teleosts. Nevertheless, these interactions would require primary coordinated response from ovarian aromatase and its related transcription factors.

Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole: endocrine and clinical effects.

Science.gov (United States)

Berstein, Lev; Maximov, Sergei; Gershfeld, Eduard; Meshkova, Irina; Gamajunova, Vera; Tsyrlina, Evgenia; Larionov, Alexei; Kovalevskij, Anatolii; Vasilyev, Dmitry

2002-11-15

To investigate the short-term hormonal and clinical effects of the aromatase inhibitor letrozole (Femara) in patients with endometrial cancer. Ten previously untreated, post-menopausal patients (mean age 59 years) with endometrial cancer, predominantly stage I disease, received letrozole 2.5mg per day for 14 days before surgery. Clinical, sonographic, morphologic, cytologic, and hormonal-metabolic parameters (blood estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), glucose, and cholesterol by radioimmunoassay, enzyme immune assay, or enzyme-colorimetric methods; tumor progesterone receptors by ligand-binding assay; and aromatase activity by 3H-water release assay) were evaluated before and after treatment. Treatment was well-tolerated in all patients. In two patients, pain relief in the lower part of the belly and/or decrease in intensity of uterine discharge was reported. In the three cases, substantial decreases in endometrial M-echo (ultrasound) signal were noted; the mean value of this parameter after treatment was 31.1% lower than before treatment. Blood estradiol concentration decreased by an average of 37.8% after letrozole therapy, and tumor progesterone receptor levels and aromatase activity decreased by 34.4 and 17.5%, respectively. Treatment with letrozole did not influence surgery. These data show that short-term treatment with letrozole in the neoadjuvant setting resulted in some positive clinical changes. Longer-term and larger-scale trials of neoadjuvant letrozole in endometrial cancer are warranted.

IGF-I stimulates ERβ and aromatase expression via IGF1R/PI3K/AKT-mediated transcriptional activation in endometriosis.

Science.gov (United States)

Zhou, Yan; Zeng, Cheng; Li, Xin; Wu, Pei-Li; Yin, Ling; Yu, Xiao-Lan; Zhou, Ying-Fang; Xue, Qing

2016-08-01

Estrogen receptor beta (ERβ, encoded by ESR2 gene) and cytochrome P450 aromatase (encoded by CYP19A1 gene) play critical roles in endometriosis, and the levels of insulin-like growth factor-I (IGF-I) in the peritoneal fluid are significantly higher in patients with endometriosis compared with those in normal women. However, the effects and mechanisms of IGF-I on ERβ and aromatase expression remain to be fully elucidated. In this study, human endometriotic stromal cells (ESCs) and endometrial cells (EMs) derived from ovarian endometriomas and eutopic endometrial tissues. ESCs were cultured with IGF-I, signal pathway inhibitors, and siRNAs. ERβ and aromatase expression were measured by real-time PCR and Western, respectively. The binding of c-Jun and CREB to the ESR2 and CYP19A1 promoters was assessed by chromatin immunoprecipitation assay. Animal experiments were performed in a xenograft mouse model. Levels of IGF-I mRNA in ESCs were markedly higher than those in EMs. IGF-I upregulated ERβ and aromatase expression in ESCs after stimulation of the IGF1R/PI3K/AKT pathway. Following IGF-I treatment, a marked increase in c-Jun and CREB phosphorylation occurred, enhancing binding to the ESR2 and CYP19A1 promoters. An IGF1R inhibitor in vivo reduced IGF-I-induced endometriosis graft growth and ERβ and aromatase expression. In conclusion, this is the first report to describe a mechanistic analysis of ERβ and aromatase expression regulated by IGF-I in ESCs. Moreover, an IGF1R inhibitor impeded ectopic lesion growth in nude mice. These findings suggest that an inhibitor of IGF1R might have therapeutic potential as an antiendometriotic drug. Level of IGF-I mRNA in ESCs is markedly higher than that in EMs. IGF-I up-regulates ERβ and aromatase expression via IGF1R/PI3K/AKT pathway. C-Jun and CREB are recruited to ESR2 or CYP19A1 promoter by IGF-I stimulation. IGF-1R inhibitors in vivo impede the growth of ectopic lesions in nude mice.

Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination

International Nuclear Information System (INIS)

Benachour, Nora; Moslemi, Safa; Sipahutar, Herbert; Seralini, Gilles-Eric

2007-01-01

Xenobiotics may cause long-term adverse effects in humans, especially at the embryonic level, raising questions about their levels of exposure, combined effects, and crucial endpoints. We are interested in the possible interactions between xenobiotic endocrine disrupters, cellular viability and androgen metabolism. Accordingly, we tested aroclor 1254 (A1254), atrazine (AZ), o,p'-DDT, vinclozolin (VZ), p,p'-DDE, bisphenol A (BPA), chlordecone (CD), nonylphenol (NP), tributylin oxide (TBTO), and diethylstilbestrol (DES) for cellular toxicity against human embryonic 293 cells, and activity against cellular aromatase, but also on placental microsomes and on the purified equine enzyme. Cellular viability was affected in 24 h by all the xenobiotics with a threshold at 50 μM (except for TBTO and DES, 10 μM threshold), and aromatase was inhibited at non-toxic doses. In combination synergism was observed reducing the threshold values of toxicity to 4-10 μM, and aromatase activity by 50% in some cases. In placental microsomes the most active xenobiotics rapidly inhibited microsomal aromatase in a manner independent of NADPH metabolism. Prolonged exposures to low doses in cells generally amplified by 50 times aromatase inhibition. These xenobiotics may act by inhibition of the active site or by allosteric effects on the enzyme. Bioaccumulation is a feature of some xenobiotics, especially chlordecone, DDT and DDE, and low level chronic exposures can also affect cell signaling mechanisms. This new information about the mechanism of action of these xenobiotics will assist in improved molecular design with a view to providing safer compounds for use in the (human) environment

Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN.

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Saitoh, M; Yanase, T; Morinaga, H; Tanabe, M; Mu, Y M; Nishi, Y; Nomura, M; Okabe, T; Goto, K; Takayanagi, R; Nawata, H

2001-11-23

The superimposition of male sex organs (penis and vas deferens) in a female gastropod, called imposex, is widely attributed to the exposure to tributyltin (TBT) compounds, used world-wide in antifouling paints for ships. It has been hypothesized that the TBT-induced imposex is mediated by an increasing androgen level relative to the estrogen level, namely a decreased conversion of androgens to estrogens (i.e., aromatization). In the present study, we tested this hypothesis by examining the effects of TBT or triphenyltin (TPT) on the aromatase activity in a cultured human granulosa-like tumor cell line, KGN, which was recently established by our group. Treatment with more than 1000 ng/ml TBT compounds was very toxic to the cells and caused immediate cell death within 24 h, while 200 ng/ml was found to cause apoptosis of the cells. Treatment of the KGN cells for more than 48 h with 20 ng/ml TBT or TPT, which is a concentration level reported to cause imposex in marine species, did not affect cell proliferation but significantly suppressed the aromatase activity determined by a [(3)H]H(2)O release assay. Treatment with 20 ng/ml TBT compounds for 7 days also resulted in a reduction of the E2 production from Delta 4-androstenedione stimulated by db-cAMP. The changes in the aromatase activity by TBT compounds were associated with comparable changes in P450arom mRNA assessed by RT-PCR. The luciferase activity of the P450arom promoter II (1 kb) decreased after the addition of 20 ng/ml TBT compounds in transfected KGN cells either in a basic state or in states stimulated by db-cAMP. The Ad4BP-dependent increase in the luciferase activity of P450arom promoter II was also downregulated by such treatments. These results indicate that TBT compounds inhibited the aromatase activity and also decreased the P450arom mRNA level at the transcriptional level in KGN cells. The direct inhibitory effect of TBT compounds on the aromatase activity may therefore partly explain the induction

Oestrogen-deficient female aromatase knockout (ArKO) mice exhibit depressive-like symptomatology.

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Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

2004-07-01

We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety or 'depressive-like' symptomatology due to chronic oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild-type (WT) females, as oestrogens have been shown to modulate dopaminergic, serotonergic and noradrenergic brain activities. ArKO females did not differ from WT in spontaneous motor activity, exploration or anxiety. These findings are in line with the absence of major neurochemical alterations in hypothalamus, prefrontal cortex or striatum, which are involved in the expression of these behaviours. By contrast, ArKO females displayed decreased active behaviours, such as struggling and swimming, and increased passive behaviours, such as floating, in repeated sessions of the forced swim test, indicating that these females exhibit 'depressive-like' symptoms. Adult treatment with oestradiol did not reverse the behavioural deficits observed in the forced swim test, suggesting that they may be due to the absence of oestradiol during development. Accordingly, an increased serotonergic activity was observed in the hippocampus of ArKO females compared with WT, which was also not reversed by adult oestradiol treatment. The possible organizational role of oestradiol on the hippocampal serotonergic system and the 'depressive-like' profile of ArKO females provide new insights into the pathophysiology of depression and the increased vulnerability of women to depression.

Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant

DEFF Research Database (Denmark)

Kümler, Iben; Knoop, Ann S; Jessing, Christina A R

2016-01-01

. However, overall survival was not significantly increased. CONCLUSION: Conventional treatment with an aromatase inhibitor or fulvestrant may be an adequate treatment option for most patients with hormone receptor-positive advanced breast cancer. Mammalian target of rapamycin (mTOR) inhibition and cyclin...

Potential role of aromatase inhibitors in the treatment of endometriosis

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Abu Hashim H

2014-07-01

Full Text Available Hatem Abu HashimDepartment of Obstetrics and Gynecology, Faculty of Medicine, Mansoura University, Mansoura, EgyptAbstract: Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5%–10% of reproductive-age women, with a prevalence of 5%–50% in infertile women and >33% of women with chronic pelvic pain. Third-generation aromatase inhibitors (AIs are approved adjuvants for the treatment of estrogen receptor-positive breast cancer. Molecular studies have revealed the presence of aromatase P450, the key enzyme in the biosynthesis of ovarian estradiol, inside the endometriotic tissue, indicating local synthesis of estradiol. Thereby, AIs represent an appealing medical option for the management of different aspects of this enigmatic disease, especially pelvic pain and infertility. Accordingly, this review aims to evaluate the potential role of AIs in the treatment of endometriosis-associated symptoms, mainly pain and infertility. Notably, several studies have demonstrated that the combination of AIs with conventional therapy as oral contraceptive pills, progestins, or gonadotropin-releasing hormone analogs can be used to control endometriosis-associated pain and pain recurrence in premenopausal women, particularly those with pain due to rectovaginal endometriosis refractory to other medical or surgical treatment. Some case reports have shown promising results in the treatment of postmenopausal endometriosis as first-line treatment, when surgery is contraindicated, or as second-line treatment in the case of postoperative recurrence. Third-generation AIs, especially letrozole, have challenged clomiphene citrate as an ovulation-induction agent in patients with polycystic ovary syndrome and in cases of unexplained infertility. However, few studies are available regarding the use of AIs to treat endometriosis-associated infertility. Therefore, larger multicenter randomized trials using AIs for the treatment of endometriosis

Metabolism of 19-methyl-substituted steroids by human placental aromatase

International Nuclear Information System (INIS)

Beusen, D.D.; Carrell, H.L.; Covey, D.F.

1987-01-01

The 19-methyl analogues of androstenedione and its aromatization intermediates (19-hydroxyandrostenedione and 19-oxoandrostenedione) were evaluated as substrates of microsomal aromatase in order to determine the effect of a 19-alkyl substituent on the enzyme's regiospecificity. Neither the androstenedione analog [10-ethylestr-4-ene-3,17-dione (1c) nor the 19-oxoandrostenedione analog [10-acetylestr-4-ene-3,17-dione (3c)] was converted to estrogens or oxygenated metabolites by placental microsomes. In contrast, both analogues of 19-hydroxyandrostenedione [10-[(1S)-1-hydroxyethyl] extr-4-ene-3,17-dione (2c) and 10-[(1R)-1-hydroxyethyl]estr-4-ene-3,17-dione (2e)] were converted to the intermediate analog 3c in a process requiring O 2 and either NADH or NADPH. No change in enzyme regiospecificity was detected. The absolute configuration of 2e was determined by X-ray crystallography. Experiments with 18 O 2 established that 3c generated from 2c retained little 18 O ( 18 O (≅ 70%). All four 19-methyl steroids elicited type I difference spectra from placental microsomes in addition to acting as competitive inhibitors of aromatase. Pretreatment of microsomes with 4-hydroxyandrostenedione (a suicide inactivator of aromatase) abolished the metabolism of 2c and 2e to 3c, as well as the type I difference spectrum elicited by 2c and 2e. The failure of 2c, 2e, and 3c to undergo aromatization was rationalized in the context of a mechanistic proposal for the third oxygenation of aromatase requiring hydrogen abstraction at C 1 of 19,19-dihydroxyandrostenedione, homolytic cleavage of the C 10 -C 19 bond, and oxygen rebound at C 19

The interaction between aromatase, metalloproteinase 2,9 and cd44 in breast cancer A interação entre aromatase, metalloproteinase 2, 9 e cd44 no câncer de mama

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Fábio Bagnoli

2010-01-01

Full Text Available OBJECTIVE: This study intends to verify the expression levels and correlation of aromatase, matrix metalloproteinase 2 (MMP-2, matrix metalloproteinase 9 (MMP-9 and CD44 in ductal carcinoma in situ (DCIS and infiltrating ductal carcinoma (IDC when both are found in the same breast. METHODS: One hundred and ten cases were evaluated by tissue microarray (TMA and immunohistochemically screened with anti-aromatase polyclonal antibodies, anti-MMP-2 monoclonal antibodies, anti-MMP-9 policlonal antibodies and anti-CD44 monoclonal antibodies. RESULTS: Aromatase was expressed in IDC and DCIS in 63 (57.3% and 60 (67% of the cases respectively; MMP-2 was similarly expressed in IDC and DCIS in 15 (13.60% cases; MMP-9 was positively expressed in IDC and DCIS in 83 (75.50% and 82 (74.50% cases, respectively; CD44 was positively expressed in IDC and DCIS in 49 (44.50% and 48 (42.60% of the cases, respectively; all of them were highly correlated (pOBJETIVO: O objetivo desse estudo é verificar as expressões e correlações da aromatase, metalloproteinase 2 da matriz (MMP2, metalloproteinase 9 da matriz (MMP-9 e CD44 no carcinoma ductal in situ (CDIS e carcinoma ductal infiltrativo (CDI quando ambos estão presentes simultaneamente na mesma mama. MÉTODOS: Foram avaliados 110 casos pelo método de tissue microarray (TMA e através da utilização de anticorpos policlonais antiaromatase, anticorpos monoclonais anti-MMP-2, anticorpos policlonais anti-MMP-9 e anticorpos monoclonais anti-CD44. RESULTADOS: A aromatase estava expressa de forma positiva no CDI e CDIS em 63 (57,3% e 60 (67% casos, respectivamente. A expressão de MMP-2 estava expressa de forma positiva em 15 (13,6% casos tanto no CDI, quanto no CDIS. A expressão da MMP-9 estava expressa de forma positiva em 83 (75,5% e 82 (74,5% casos de CDI e CDIS, respectivamente. A expressão de CD44 estava expressa de forma positiva em 49 (44,5% e 48 (42,6% casos de CDI e CDIS, respectivamente. Todos eles

Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer

International Nuclear Information System (INIS)

Sun, Bin; Hoshino, Juma; Jermihov, Katie; Marler, Laura; Pezzuto, John M.; Mesecar, Andrew D.; Cushman, Mark

2010-01-01

A series of new resveratrol analogues were designed and synthesized and their inhibitory activities against aromatase were evaluated. The crystal structure of human aromatase (PDB 3eqm) was used to rationalize the mechanism of action of the aromatase inhibitor 32 (IC 50 0.59 μM) through docking, molecular mechanics energy minimization, and computer graphics molecular modeling, and the information was utilized to design several very potent inhibitors, including compounds 82 (IC 50 70 nM) and 84 (IC 50 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC 50 of 80 μM. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC 50 1.7 μM and 0.27 μM, respectively) and the high-resolution X-ray structures of QR2 in complex with these two compounds provide insight into their mechanism of QR2 inhibition. The aromatase and quinone reductase inhibitors resulting from these studies have potential value in the treatment and prevention of cancer.

Modulation of Aromatase Activity as a Mode of Action for Endocrine Disrupting Chemicals in a Marine Fish

Science.gov (United States)

The steroidogenic enzyme aromatase catalyzes the conversion of androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) and therefore plays a central role in reproduction. In contrast to most vertebrates, teleost fish have two distinct forms of aromatase....

Modulation of Δ9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase

International Nuclear Information System (INIS)

Takeda, Shuso; Yamamoto, Ikuo; Watanabe, Kazuhito

2009-01-01

Δ 9 -Tetrahydrocannabinol (Δ 9 -THC), a major constituent of marijuana, has been shown to stimulate the growth of MCF-7 breast cancer cells through cannabinoid receptor-independent signaling [Takeda, S., Yamaori, S., Motoya, E., Matsunaga, T., Kimura, T., Yamamoto, I., Watanabe, K., 2008. Δ 9 -Tetrahydrocannabinol enhances MCF-7 cell proliferation via cannabinoid receptor-independent signaling. Toxicology 245, 141-146]. Although the growth of MCF-7 cells is known to be stimulated by 17β-estradiol (E 2 ), the interaction of Δ 9 -THC and E 2 in MCF-7 cell growth is not fully clarified so far. In the present study, by using E 2 -sensitive MCF-7 cells that have expressed cyclooxygenase-2 (COX-2) and cytochrome P450 19 (aromatase), we studied whether or not COX-2 and aromatase are involved in Δ 9 -THC-mediated MCF-7 cell proliferation. It was shown that Δ 9 -THC-induced MCF-7 cell growth was inhibited by COX-2 inhibitors and was stimulated by arachidonic acid (a COX substrate). However, the growth of MCF-7 cells induced by Δ 9 -THC was not stimulated by PGE 2 , and the expression of aromatase was not affected by COX-2 inhibitors, arachidonic acid, and PGE 2 , suggesting that there is a disconnection between COX-2 (PGE 2 ) and aromatase in Δ 9 -THC-mediated MCF-7 cell proliferation. On the other hand, Δ 9 -THC-induced MCF-7 cell growth was elevated by two kinds of aromatase inhibitors. Taken together with the evidence that Δ 9 -THC-induced MCF-7 cell proliferation was interfered with testosterone (an aromatase substrate) and exogenously provided E 2 , it is suggested that (1) the growth stimulatory effects of Δ 9 -THC are mediated by the product(s) of COX-2 except for PGE 2 , (2) the action of Δ 9 -THC is modulated by E 2 , and (3) COX-2 and aromatase are individually engaged in the proliferation of MCF-7 cells induced by Δ 9 -THC.

Interaction of Zinc Chloride with an Aromatase Inhibitor (Letrozole on Anxiety in Adult Male Rats

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Sahar Charghan

2016-12-01

Full Text Available Abstract Background: Aromatase is an enzyme converts androstenedione and testosterone to estrone and estradiol, respectively. According to the role of testosterone and zinc in reducing anxiety and the relation between androgenic system function and zinc supplementations, in this research, the effect of zinc chloride injection was analysed in rats which aromatase enzyme was inhibited by aromatase inhibitor (letrozole. Materials and Methods: Adult male Wistar rats (weighing 225±25 g were used. Animals were divided into 12 groups and based on their weight, aromatase inhibitor (letrozole was injected (subcutaneously, and 30 minutes later, ZnCl2 or its solvent (saline was injected intra-peritoneal. Control group was received both solvents (DMSO and saline respectively. Anxiety levels were tested in the elevated plus maze 30 minutes after the last injection, and thereafter, open field was used for measurement of the locomotors activity of animals. Results: The results showed a significant decrease in the percentage of time spent in open arms in letrozole (1.25 mg/kg treated group as compared to that of solvent group. The locomotors activity significantly decreased between letrozole (1.25 mg/kg with the control group. The combined groups received letrozole (2.5 mg/kg and different amounts of zinc chloride (2.5, 5, 10 mg/kg, significantly reduced (p<0.05 the percentage of time spent in the open arm, comparing to the control group. Groups that received the combination of zinc chloride (2.5 mg/kg and different amounts of letrozole (1.25, 5, 10 mg/kg, showed no significant difference in the percentage of entry and time spent in the open arms. Conclusion: Totally, the present study suggests that letrozole alone increased anxiety and decreased locomotors activity and could interfere with anxiolytic effect of ZnCl2 as well.

In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats disrupts brain sexual differentiation

International Nuclear Information System (INIS)

Ikeda, Masahiko; Mitsui, Tetsuo; Setani, Kaoru; Tamura, Masashi; Kakeyama, Masaki; Sone, Hideko; Tohyama, Chiharu; Tomita, Takako

2005-01-01

The effects of in utero and lactational exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on brain sexual differentiation were investigated. TCDD was orally administered to pregnant Holtzman rats on gestation day (GD) 15, and the activity of brain aromatase, a key enzyme for sexual differentiation, was measured in offspring on postnatal day (PND) 2. Changes in sexual dimorphisms of saccharin preference and the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) were examined in adult offspring. In controls, litter means of brain aromatase activity were higher in males than in females. In utero exposure to 200 ng/kg TCDD significantly decreased the sex ratio of aromatase activity (male/female) on PND 2. Offspring were weaned on PND28 and the saccharin test was started on PND84. In controls, saccharin (0.25%) intake (g/kg body weight) was significantly higher in female offspring than in males. In utero exposure to 200 ng/kg TCDD significantly increased saccharin intake in male offspring compared with control males, whereas 800 ng/kg TCDD had no effect. Neither dose of TCDD influenced saccharin intake of female offspring. In controls, SDN-POA volume was significantly greater in males than in females at 14 weeks of age. Exposure to 200 ng/kg TCDD significantly decreased SDN-POA volume in males, whereas 800 ng/kg TCDD had no effect. Neither doses of TCDD influenced the SDN-POA volume in female offspring. These results suggest that in utero and lactational TCDD exposure dose-dependently induces demasculinization in male offspring by inhibiting brain aromatase activity in the hypothalamus-preoptic area during central nervous system development

Inhibition of aromatase activity by methyl sulfonyl PCB metabolites in primary culture of human mammary fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Berg, M. van den; Heneweer, M.; Geest, M. de; Sanderson, T. [Inst. for Risk Assessment Sciences and Utrecht Univ. (Netherlands); Jong, P. de [St. Antonius Hospital, Nieuwegein (Netherlands); Bergman, A. [Stockholm Univ., Stockholm (Sweden)

2004-09-15

Methyl sulfonyl PCB metabolites (MeSO2-PCBs) are persistent contaminants and are ubiquitously present in humans and the environment. Lipophilicity of MeSO2- PCB metabolites is similar to the parent compounds and they have been detected in human milk, adipose, liver and lung tissue. 4- MeSO2-PCB-149 is the most abundant PCB metabolite in human adipose tissue and milk at a level of 1.5 ng/g lipids. Human blood concentration of 4-MeSO2-PCB-149 is approximately 0.03 nM. 3- MeSO2-PCB-101 is the predominant PCB metabolite in muscle and blubber in wildlife, such as otter, mink and grey seal. In the environment, they have been linked to chronic and reproductive toxicity in exposed mink. Additionaly, some MeSO{sub 2}-PCBs have been shown to be glucocorticoid receptor (GR) antagonists. Since approximately 60% of all breast tumors are estrogen responsive, exposure to compounds that are able to alter estrogen synthesis through interference with the aromatase enzyme, can lead to changes in estrogen levels and possibly to accelerated or inhibit breast tumor growth. Therefore, it is important to identify exogenous compounds that can alter aromatase activity in addition to those compounds which have direct interaction with the estrogen receptor (ER). Aromatase (CYP19) comprises the ubiquitous flavoprotein, NADPH-cytochrome P450 reductase, and a unique cytochrome P450 that is exclusively expressed in estrogen producing cells. Previous studies have revealed that expression of the aromatase gene is regulated in a species- and tissue specific manner. In healthy breast tissue, the predominantly active aromatase promoter region I.4 is regulated by glucocorticoids and class I cytokines. Therefore, it is important to investigate possible aromatase inhibiting properties of MeSO{sub 2}-PCBs (as anti glucocorticoids?) in relevant human tissues. We used primary human mammary fibroblasts because of their role in breast cancer development. We compared the results in primary fibroblasts with

In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer

International Nuclear Information System (INIS)

Lykkesfeldt, Anne E; Henriksen, Katrine L; Rasmussen, Birgitte B; Sasano, Hironobu; Evans, Dean B; Møller, Susanne; Ejlertsen, Bent; Mouridsen, Henning T

2009-01-01

New, third-generation aromatase inhibitors (AIs) have proven comparable or superior to the anti-estrogen tamoxifen for treatment of estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer. AIs suppress total body and intratumoral estrogen levels. It is unclear whether in situ carcinoma cell aromatization is the primary source of estrogen production for tumor growth and whether the aromatase expression is predictive of response to endocrine therapy. Due to methodological difficulties in the determination of the aromatase protein, COX-2, an enzyme involved in the synthesis of aromatase, has been suggested as a surrogate marker for aromatase expression. Primary tumor material was retrospectively collected from 88 patients who participated in a randomized clinical trial comparing the AI letrozole to the anti-estrogen tamoxifen for first-line treatment of advanced breast cancer. Semi-quantitative immunohistochemical (IHC) analysis was performed for ER, PR, COX-2 and aromatase using Tissue Microarrays (TMAs). Aromatase was also analyzed using whole sections (WS). Kappa analysis was applied to compare association of protein expression levels. Univariate Wilcoxon analysis and the Cox-analysis were performed to evaluate time to progression (TTP) in relation to marker expression. Aromatase expression was associated with ER, but not with PR or COX-2 expression in carcinoma cells. Measurements of aromatase in WS were not comparable to results from TMAs. Expression of COX-2 and aromatase did not predict response to endocrine therapy. Aromatase in combination with high PR expression may select letrozole treated patients with a longer TTP. TMAs are not suitable for IHC analysis of in situ aromatase expression and we did not find COX-2 expression in carcinoma cells to be a surrogate marker for aromatase. In situ aromatase expression in tumor cells is associated with ER expression and may thus point towards good prognosis. Aromatase expression in cancer

3D-QSAR Study of Steroidal and Azaheterocyclic Human Aromatase Inhibitors using Quantitative Profile of Protein-Ligand Interactions

Science.gov (United States)

Aromatase is a member of the cytochrome P450 superfamily responsible for a key step in the biosynthesis of estrogens. As estrogens are involved in the control of important reproduction-related processes, including sexual differentiation and maturation, aromatase is a potential ta...

Synthesis of Triphenylethylene Bisphenols as Aromatase Inhibitors That Also Modulate Estrogen Receptors.

Science.gov (United States)

Lv, Wei; Liu, Jinzhong; Skaar, Todd C; O'Neill, Elizaveta; Yu, Ge; Flockhart, David A; Cushman, Mark

2016-01-14

A series of triphenylethylene bisphenol analogues of the selective estrogen receptor modulator (SERM) tamoxifen were synthesized and evaluated for their abilities to inhibit aromatase, bind to estrogen receptor α (ER-α) and estrogen receptor β (ER-β), and antagonize the activity of β-estradiol in MCF-7 human breast cancer cells. The long-range goal has been to create dual aromatase inhibitor (AI)/selective estrogen receptor modulators (SERMs). The hypothesis is that in normal tissue the estrogenic SERM activity of a dual AI/SERM could attenuate the undesired effects stemming from global estrogen depletion caused by the AI activity of a dual AI/SERM, while in breast cancer tissue the antiestrogenic SERM activity of a dual AI/SERM could act synergistically with AI activity to enhance the antiproliferative effect. The potent aromatase inhibitory activities and high ER-α and ER-β binding affinities of several of the resulting analogues, together with the facts that they antagonize β-estradiol in a functional assay in MCF-7 human breast cancer cells and they have no E/Z isomers, support their further development in order to obtain dual AI/SERM agents for breast cancer treatment.

Comparing exercise responses to aerobic plus resistance training between postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy and healthy women.

Science.gov (United States)

Paulo, Thais R S de; Winters-Stone, Kerri M; Viezel, Juliana; Rossi, Fabricio E; Aro, Bruna L; Trindade, Ana Carolina A C; Codogno, Jamile S; Freitas Junior, Ismael F

2018-04-12

The aim of this study was to explore whether postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy differ from healthy postmenopausal women in their response to the same aerobic + resistance training. The participants were separated into two groups: postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy for an average of 20 months (18 women) and healthy postmenopausal women (24 women). We assessed aerobic capacity (predicted maximum oxygen uptake (VO 2 max) and maximum running velocity test (Vmax)) through a walking test, upper and lower body muscle strength using an estimated one-repetition maximum test, and body composition by dual-energy X-ray absorptiometry at baseline and at three, six, and nine months, respectively. The exercise program was performed three times/week over nine months and consisted of 40 min of machine-based strength training (seated cable row, bench press, leg extension, leg press, and leg curl, as well as bridge, abdominal, and standard plank exercises) followed by 30 min of treadmill walking. Analysis of variance (ANOVA) with repeated measures was used to compare the groups over time. Postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy and healthy postmenopausal women presented similar improvements in estimated lower body strength, predicted VO 2max and V max , and body fat mass. For maximal upper body strength, there was a significant group x time interaction after six months of training (p = 0.01). The healthy postmenopausal women presented a significant increase in upper body strength after six months, while postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy demonstrated an improvement only at nine months of training. The breast cancer survivors undergoing aromatase inhibitor therapy presented increased lean mass while healthy postmenopausal women maintained values over time (Breast cancer: 33.7 ± 3.9(Pre) vs. 34.1�

Breast Cancer, Aromatase Inhibitor Therapy, and Sexual Functioning: A Pilot Study of the Effects of Vaginal Testosterone Therapy

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Melissa Dahir, DNP, IF

2014-04-01

Conclusions: The use of a compounded testosterone vaginal cream applied daily for 4 weeks improves reported sexual health quality of life in women with breast cancer taking AIs. Dahir M and Travers‐Gustafson D. Breast cancer, aromatase inhibitor therapy, and sexual functioning: A pilot study of the effects of vaginal testosterone therapy. Sex Med 2014;2:8–15.

A pilot randomized trial to prevent sexual dysfunction in postmenopausal breast cancer survivors starting adjuvant aromatase inhibitor therapy.

Science.gov (United States)

Advani, Pragati; Brewster, Abenaa M; Baum, George P; Schover, Leslie R

2017-08-01

A randomized pilot trial evaluated the hypothesis that early intervention lessens sexual dysfunction in the first year on aromatase inhibitors. A secondary aim was comparing the efficacy of two vaginal moisturizers. Fifty-seven postmenopausal women with early stage breast cancer starting aromatase inhibitors were randomized to three treatment groups. All received a handout on managing sexual and other side effects. The Usual Care group received no additional therapy. The Active Treatment groups received a 6-month supply of a vaginal moisturizer (hyaluronic acid-based in Active Group-H and prebiotic in Active Group-P) and a vaginal lubricant and dilator, plus access to an educational website and phone coaching. Questionnaires completed at baseline, 6, and 12 months included the Female Sexual Function Index (FSFI), Menopausal Sexual Interest Questionnaire (MSIQ), Female Sexual Distress Scale-Revised (FSDS-R), and a menopausal symptom scale. Forty-nine women (86%) provided follow-up data. Mean age was 59 and 77% were non-Hispanic Caucasian. Sexual function was impaired at baseline, but remained stable over 12 months for all groups. The combined active treatment group had less dyspareunia (P = 0.07) and sexual distress (P = 0.02) at 6 months than the Usual Care group. At 6 months, the Active-H group improved significantly more than the Active-P group on FSFI total score (P = 0.04). Sexual counseling helped women maintain stable sexual function on aromatase inhibitors. Active intervention resulted in better outcomes at 6 months. This promising pilot trial suggests a need for more research on preventive counseling to maintain sexual function during aromatase inhibitor treatment.

Brain Gene Expression is Influenced by Incubation Temperature During Leopard Gecko (Eublepharis macularius) Development.

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Pallotta, Maria Michela; Turano, Mimmo; Ronca, Raffaele; Mezzasalma, Marcello; Petraccioli, Agnese; Odierna, Gaetano; Capriglione, Teresa

2017-06-01

Sexual differentiation (SD) during development results in anatomical, metabolic, and physiological differences that involve not only the gonads, but also a variety of other biological structures, such as the brain, determining differences in morphology, behavior, and response in the breeding season. In many reptiles, whose sex is determined by egg incubation temperature, such as the leopard gecko, Eublepharis macularius, embryos incubated at different temperatures clearly differ in the volume of brain nuclei that modulate behavior. Based on the premise that "the developmental decision of gender does not flow through a single gene", we performed an analysis on E. macularius using three approaches to gain insights into the genes that may be involved in brain SD during the thermosensitive period. Using quantitative RT-PCR, we studied the expression of genes known to be involved in gonadal SD such as WNT4, SOX9, DMRT1, Erα, Erβ, GnRH, P450 aromatase, PRL, and PRL-R. Then, further genes putatively involved in sex dimorphic brain differentiation were sought by differential display (DDRT-PCR) and PCR array. Our findings indicate that embryo exposure to different sex determining temperatures induces differential expression of several genes that are involved not only in gonadal differentiation (PRL-R, Wnt4, Erα, Erβ, p450 aromatase, and DMRT1), but also in neural differentiation (TN-R, Adora2A, and ASCL1) and metabolic pathways (GP1, RPS15, and NADH12). These data suggest that the brains of SDT reptiles might be dimorphic at birth, thus behavioral experiences in postnatal development would act on a structure already committed to male or female. © 2017 Wiley Periodicals, Inc.

Inhibition of human placental aromatase activity by hydroxylated polybrominated diphenyl ethers (OH-PBDEs).

Science.gov (United States)

Cantón, Rocío F; Scholten, Deborah E A; Marsh, Göran; de Jong, Paul C; van den Berg, Martin

2008-02-15

Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants in many different polymers, resins and substrates. Due to their widespread production and use, their high binding affinity to particles, and their lipophilic properties, several PBDE congeners can bioaccumulate in the environment. As a result, PBDEs and their hydroxylated metabolites (OH-PBDEs) have been detected in humans and various wildlife samples, such as birds, seals, and whales. Furthermore, certain OH-PBDEs and their methoxylated derivatives (MeO-PBDEs) are natural products in the marine environment. Recently, our laboratory focused on the possible effects on steroidogenesis of PBDEs and OH-PBDEs, e.g. in the human adrenocortical carcinoma (H295R) cell line indicating that some OH-PBDEs can significantly influence steroidogenic enzymes like CYP19 (aromatase) and CYP17. In the present study, human placental microsomes have been used to study the possible interaction of twenty two OH-PBDEs and MeO-PBDEs with aromatase, the enzyme that mediates the conversion of androgens into estrogens. All OH-PBDE derivates showed significant inhibition of placental aromatase activity with IC(50) values in the low micromolar range, while the MeO-PBDEs did not have any effect on this enzyme activity. Enzyme kinetics studies indicated that two OH-PBDEs, 5-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (5-OH-BDE47) and 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE47), had a mixed-type inhibition of aromatase activity with apparent K(i)/K(i)' of 7.68/0,02 microM and 5.01/0.04 microM respectively. For comparison, some structurally related compounds, a dihydroxylated polybrominated biphenyl, which is a natural product (2,2'-dihyroxy-3,3',5,5'-tetrabromobiphenyl (2,2'-diOH-BB80)) and its non-bromo derivative were also included in the study. Again inhibition of aromatase activity could be measured, but their potency was significantly less than those observed for the OH-PBDEs. These results show that a

Inhibition of human placental aromatase activity by hydroxylated polybrominated diphenyl ethers (OH-PBDEs)

International Nuclear Information System (INIS)

Canton, Rocio F.; Scholten, Deborah E.A.; Marsh, Goeran; Jong, Paul C. de; Berg, Martin van den

2008-01-01

Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants in many different polymers, resins and substrates. Due to their widespread production and use, their high binding affinity to particles, and their lipophilic properties, several PBDE congeners can bioaccumulate in the environment. As a result, PBDEs and their hydroxylated metabolites (OH-PBDEs) have been detected in humans and various wildlife samples, such as birds, seals, and whales. Furthermore, certain OH-PBDEs and their methoxylated derivatives (MeO-PBDEs) are natural products in the marine environment. Recently, our laboratory focused on the possible effects on steroidogenesis of PBDEs and OH-PBDEs, e.g. in the human adrenocortical carcinoma (H295R) cell line indicating that some OH-PBDEs can significantly influence steroidogenic enzymes like CYP19 (aromatase) and CYP17. In the present study, human placental microsomes have been used to study the possible interaction of twenty two OH-PBDEs and MeO-PBDEs with aromatase, the enzyme that mediates the conversion of androgens into estrogens. All OH-PBDE derivates showed significant inhibition of placental aromatase activity with IC 50 values in the low micromolar range, while the MeO-PBDEs did not have any effect on this enzyme activity. Enzyme kinetics studies indicated that two OH-PBDEs, 5-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (5-OH-BDE47) and 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE47), had a mixed-type inhibition of aromatase activity with apparent K i /K i ' of 7.68/0,02 μM and 5.01/0.04 μM respectively. For comparison, some structurally related compounds, a dihydroxylated polybrominated biphenyl, which is a natural product (2,2'-dihyroxy-3,3',5,5'-tetrabromobiphenyl (2,2'-diOH-BB80)) and its non-bromo derivative were also included in the study. Again inhibition of aromatase activity could be measured, but their potency was significantly less than those observed for the OH-PBDEs. These results show that a wide

[Sex differentiation of central nervous system--brain of man and woman].

Science.gov (United States)

Arai, Yasumasa

2004-02-01

Sex differentiation of human brain is mostly dependent on the prenatal exposure to androgen(testosterone). Congenital aromatase deficiency does not disturb male brain development in men. This is quite different from experimental evidence from rodents whose brains need intraneuronal aromatization from androgen to estrogen to induce sex differentiation. There is evidence for male-female differences in brain structures. Some of them(INHA-3) appear to be related with sexual orientation. The other(BNST) might participate in forming gender-identity. In addition, sexually dimorphic features are recognized in some cognitive activities. The possible involvement of genetic factors in human brain sex differentiation is also discussed.

Promoter characteristics of two cyp19 genes differentially expressed in the brain and ovary of teleost fish.

Science.gov (United States)

Tchoudakova, A; Kishida, M; Wood, E; Callard, G V

2001-11-01

Teleost fish are characterized by exceptionally high levels of neural estrogen biosynthesis when compared with the brains of other vertebrates or to the ovaries of the same fish. Two P450arom mRNAs which derive from separate gene loci (cyp19a and cyp19b) are differentially expressed in brain (b>a) and ovary (a>b) and have a different developmental program (b>a) and estrogen upregulation (b only). A polymerase chain reaction (PCR)-based genomic walking strategy was used to isolate the 5'-flanking regions of the goldfish (Carassius auratus) cyp19 genes. Sequence analysis of the cyp19b gene approximately 1.8 kb upstream of the transcription start site revealed a TATA box at nucleotide (nt) -30, two estrogen responsive elements (EREs; nt -351 and -211) and a consensus binding site (NBRE) for nerve growth factor inducible-B protein (NGFI-B/Nur77) at -286, which includes another ERE half-site. Also present were a sequence at nt -399 (CCCTCCT) required for neural specificity of the zebrafish GATA-2 gene, and 16 copies of an SRY/SOX binding motif. The 5'-flanking region ( approximately 1.0 kb) of the cyp19a gene had TATA (nt -48) and CAAT (nt -71) boxes, a steroidogenic factor-1 (SF-1) binding site (nt -265), eight copies of the SRY/SOX motif, and two copies of a recognition site for binding the arylhydrocarbon receptor (AhR)/AhR nuclear translocator factor (ARNT) heterodimer. Both genes had elements previously identified in the brain specific exon I promoter of the mouse aromatase gene. Cyp19a- and -b/luciferase constructs showed basal promoter activity in aromatase-expressing rodent pituitary (GH3) cells, but differences (a>b) did not reflect expression in fish pituitary in vivo (b>a), implying a lack of appropriate cell factors. Consistent with the onset of cyp19b expression in zebrafish embryos, microinjection of a green fluorescent protein (GFP) reporter plasmid into fertilized eggs revealed labeling in neural tissues at 30-48 h post-fertilization (hpf), most

Pharmacogenetics and aromatase inhibitor induced side effects in breast cancer patients.

Science.gov (United States)

Sini, Valentina; Botticelli, Andrea; Lunardi, Gianluigi; Gori, Stefania; Marchetti, Paolo

2017-06-01

This paper reviews genetic variations mainly related to the onset of adverse events during aromatase inhibitors in early breast cancer. Genetic variability could occur at different steps. The analysis included studies that involved breast cancer patients, treated with an aromatase inhibitor, genotyped for CYP19A1 and/or CYP17A1 and/or CYP27B1 and/or TCLA1, and/or RANK/RANKL/OPG and/or ESR1/ESR2, and assessed for toxicity profile. Twenty-two articles were included for the analysis. Three studies evaluated outcomes and adverse events; 19 studies assessed only side effects. Functional variations may be useful in predicting the onset of toxicities. The identification of polymorphisms at increased risk of toxicity may enable patient management. However, more data are needed to be applied in the individualization of treatment in daily practice.

Dietary administration of the licorice flavonoid isoliquiritigenin deters the growth of MCF-7 cells overexpressing aromatase.

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Ye, Lan; Gho, Wai M; Chan, Franky L; Chen, Shiuan; Leung, Lai K

2009-03-01

Licorice is the sweet-tasting rhizomes of a bean plant and is quite commonly used in Western countries for culinary purposes, while it is a medicinal herb in China. Many flavonoids have been isolated from licorice, and their pharmacological properties may be applicable in preventive medicine. Overexposure to estrogen has been implicated in the etiology of breast cancer, and cytochrome P450 (CYP) 19 enzyme, or aromatase, catalyzes the rate-limiting reaction. Phytocompounds that are able to inhibit this enzyme may potentially suppress breast cancer development. In the present study the licorice flavonoid isoliquiritigenin (ILN) was shown to be an aromatase inhibitor in recombinant protein and MCF-7 cells stably transfected with CYP19 (MCF-7aro). ILN displayed a K(i) value of around 3 muM, and it also blocked the MCF-7aro cell growth pertaining to the enzyme activity in vitro. Subsequently, the compound administered in diet was given to ovariectomized athymic mice transplanted with MCF-7aro cells. This mouse model is widely accepted for studying postmenopausal breast cancer. The phytochemical significantly deterred the xenograft growth without affecting the body weight. Subsequently, the flavonoid's effect on CYP19 transcriptional control in vitro was also investigated. At the mRNA level, ILN could also suppress the expression in wild-type MCF-7 cells. Reporter gene assay and real-time PCR verified that the transactivity of CYP19 driven by promoters I.3 and II was suppressed in these cells. Deactivation of C/EBP could be the underlying molecular mechanism. Our study demonstrated that ILN was an inhibitor of aromatase and a potential chemopreventive agent against breast cancer.

Brain aromatase and circulating corticosterone are rapidly regulated by combined acute stress and sexual interaction in a sex-specific manner.

Science.gov (United States)

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

2012-10-01

Neural production of 17β-oestradiol via aromatisation of testosterone may play a critical role in rapid, nongenomic regulation of physiological and behavioural processes. In brain nuclei implicated in the control of sexual behaviour, sexual or stressfull stimuli induce, respectively, a rapid inhibition or increase in preoptic aromatase activity (AA). In the present study, we tested quail that were either nonstressed or acutely stressed (15 min of restraint) immediately before sexual interaction (5 min) with stressed or nonstressed partners. We measured nuclei-specific AA changes, corresponding behavioural output, fertilisation rates and corticosterone (CORT) concentrations. In males, sexual interaction rapidly reversed stress-induced increases of AA in the medial preoptic nucleus (POM). This time scale (sexual stimuli on POM AA may actively preserve sexual behaviour despite stress exposure. We also found distinct sex differences in contextual physiological responses: males did not show any effect of partner status, whereas females responded to both their stress exposure and the male partner's stress exposure at the level of circulating CORT and AA. In addition, fertilisation rates and female CORT correlated with the male partner's exhibition of sexually aggressive behaviour, suggesting that female perception of the male can affect their physiology as much as direct stress. Overall, male reproduction appears relatively simple: sexual stimuli, irrespective of stress, drives major neural changes including rapid reversal of stress-induced changes of AA. By contrast, female reproduction appears more nuanced and context specific, with subjects responding physiologically and behaviourally to stress, the male partner's stress exposure, and female-directed male behaviour. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

Brain aromatase and circulating corticosterone are rapidly regulated by combined acute stress and sexual interaction in a sex specific manner

Science.gov (United States)

Dickens, M.J.; Balthazart, J.; Cornil, C. A.

2012-01-01

Neural production of 17β-oestradiol via aromatisation of testosterone may play a critical role in rapid, non-genomic regulation of physiological and behavioural processes. In brain nuclei implicated in the control of sexual behaviour, sexual or stressfull stimuli induce respectively a rapid inhibition or increase in preoptic aromatase activity (AA). Here, we tested quail that were either non-stressed or acutely stressed (15 min restraint) immediately prior to sexual interaction (5 min) with stressed or non-stressed partners. We measured nuclei-specific AA changes, corresponding behavioural output, fertilisation rates and corticosterone (CORT) concentrations. In males, sexual interaction rapidly reversed stress-induced increases of AA in the medial preoptic nucleus (POM). This time scale (behaviour suggesting that the input from the sexual stimuli on POM AA may actively preserve sexual behaviour despite stress exposure. We also found distinct sex differences in contextual physiological responses: while males did not show any effect of partner status, females responded to both their stress exposure and the male partner’s stress exposure at the level of circulating CORT and AA. In addition, fertilisation rates and female CORT correlated with the male partner’s exhibition of sexually aggressive behaviour suggesting that female perception of the male can affect their physiology as much as direct stress. Overall, male reproduction appears relatively simple – sexual stimuli, irrespective of stress, drives major neural changes including rapid reversal of stress-induced changes of AA. In contrast, female reproduction appears more nuanced and context specific, with subjects responding physiologically and behaviourally to stress, the male partner’s stress exposure, and female-directed male behaviour. PMID:22612582

Evidence for an Elevated Aspartate pKa in the Active Site of Human Aromatase*

Science.gov (United States)

Di Nardo, Giovanna; Breitner, Maximilian; Bandino, Andrea; Ghosh, Debashis; Jennings, Gareth K.; Hackett, John C.; Gilardi, Gianfranco

2015-01-01

Aromatase (CYP19A1), the enzyme that converts androgens to estrogens, is of significant mechanistic and therapeutic interest. Crystal structures and computational studies of this enzyme shed light on the critical role of Asp309 in substrate binding and catalysis. These studies predicted an elevated pKa for Asp309 and proposed that protonation of this residue was required for function. In this study, UV-visible absorption, circular dichroism, resonance Raman spectroscopy, and enzyme kinetics were used to study the impact of pH on aromatase structure and androstenedione binding. Spectroscopic studies demonstrate that androstenedione binding is pH-dependent, whereas, in contrast, the D309N mutant retains its ability to bind to androstenedione across the entire pH range studied. Neither pH nor mutation perturbed the secondary structure or heme environment. The origin of the observed pH dependence was further narrowed to the protonation equilibria of Asp309 with a parallel set of spectroscopic studies using exemestane and anastrozole. Because exemestane interacts with Asp309 based on its co-crystal structure with the enzyme, its binding is pH-dependent. Aromatase binding to anastrozole is pH-independent, consistent with the hypothesis that this ligand exploits a distinct set of interactions in the active site. In summary, we assign the apparent pKa of 8.2 observed for androstenedione binding to the side chain of Asp309. To our knowledge, this work represents the first experimental assignment of a pKa value to a residue in a cytochrome P450. This value is in agreement with theoretical calculations (7.7–8.1) despite the reliance of the computational methods on the conformational snapshots provided by crystal structures. PMID:25425647

Effect of β-agonist on the dexamethasone-induced expression of aromatase by the human monocyte cells

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Masatada Watanabe

2017-02-01

Full Text Available Emerging evidence suggests that sex steroids are important for human skin health. In particular, estrogen improves skin thickness, elasticity and moisture of older women. The major source of circulating estrogen is the ovary; however, local estrogen synthesis and secretion have important roles in, for example, bone metabolism and breast cancer development. We hypothesized that infiltrated peripheral monocytes are one of the sources of estrogen in skin tissues. We also hypothesized that, during atopic dermatitis under stress, a decline in the hypothalamus–pituitary–adrenal axis (HPA and facilitation of the (hypothalamus–sympathetic–adrenomedullary system (SAM attenuates estrogen secretion from monocytes. Based on this hypothesis, we tested aromatase expression in the human peripheral monocyte-derived cell line THP-1 in response to the synthetic glucocorticoid dexamethasone (Dex, the synthetic β-agonist isoproterenol (Iso and the β-antagonist propranolol (Pro. Dex mimics glucocorticoid secreted during excitation of the HPA, and Iso mimics catecholamine secreted during excitation of the SAM. We found that aromatase activity and the CYP19A1 gene transcript were both upregulated in THP-1 cells in the presence of Dex. Addition of Iso induced their downregulation and further addition of Pro rescued aromatase expression. These results may suggest that attenuation of estrogen secretion from peripheral monocytes could be a part of the pathology of stress-caused deterioration of atopic dermatitis. Further examination using an in vitro human skin model including THP-1 cells might be a valuable tool for investigating the therapeutic efficacy and mechanism of estrogen treatment for skin health.

Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

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Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

2005-09-08

It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer

DEFF Research Database (Denmark)

Lykkesfeldt, Anne E; Henriksen, Katrine L; Rasmussen, Birgitte B

2009-01-01

BACKGROUND: New, third-generation aromatase inhibitors (AIs) have proven comparable or superior to the anti-estrogen tamoxifen for treatment of estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer. AIs suppress total body and intratumoral estrogen levels. It is unclear...... whether in situ carcinoma cell aromatization is the primary source of estrogen production for tumor growth and whether the aromatase expression is predictive of response to endocrine therapy. Due to methodological difficulties in the determination of the aromatase protein, COX-2, an enzyme involved...... of advanced breast cancer. Semi-quantitative immunohistochemical (IHC) analysis was performed for ER, PR, COX-2 and aromatase using Tissue Microarrays (TMAs). Aromatase was also analyzed using whole sections (WS). Kappa analysis was applied to compare association of protein expression levels. Univariate...

Efficacy and mechanism of action of Proellex, an antiprogestin in aromatase overexpressing and Letrozole resistant T47D breast cancer cells.

Science.gov (United States)

Gupta, Akash; Mehta, Rajeshwari; Alimirah, Fatouma; Peng, Xinjian; Murillo, Genoveva; Wiehle, Ronald; Mehta, Rajendra G

2013-01-01

Aromatase inhibitors (AI) are considered as a first line therapy for ER+PR+ breast cancers. However, many patients acquire resistance to AI. In this study, we determined the response of antiprogestin CDB-4124 (Proellex) on the aromatase overexpressing and Letrozole resistant cell lines and also studies its mechanism of action in inhibition of breast cancer cell proliferation. For these studies we generated aromatase overexpressing T47D (T47Darom) and respective control (T47Dcon) breast cancer cell lines by stable transfection with plasmid containing CYP19A1 gene, or empty vector respectively. Letrozole resistant cell line (T47DaromLR) was generated by incubating T47Darom for 75 weeks in the presence of 10 μM Letrozole. Cell proliferation was determined by MTT or crystal violet assays. Gene expressions were quantified by QRT-PCR whereas proteins were identified by western blot analyses, flow cytometry and immunofluorescence staining. Aromatase activity was determined by estradiol ELISA. The effects of Proellex on the anchorage independent growth were measured by soft agar colony formation. Statistical differences between the various groups were determined by Student's 't' test or ANOVA followed by Bonferroni's post hoc test. Results showed that T47Darom and T47DaromLR cell lines had significantly higher aromatase expression (mRNA; 80-90 fold and protein) and as a result exhibited increased aromatization of testosterone to estradiol as compared to T47Dcon. Both these cell lines showed enhanced growth in the presence of Testosterone (50-60%). In T47DaromLR cells increased PR-B and EGFR expression as compared to T47Dcon cells was observed. Proellex and other known aromatase inhibitors (Letrozole, Anastrozole, and Exemestane) inhibited testosterone induced cell proliferation and anchorage independent growth of T47Darom cells. Cell growth inhibition was significantly greater when cells were treated with Proellex alone or in combination with other AIs as compared to AIs

Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity

International Nuclear Information System (INIS)

Christman, G.M.; Randolph, J.F. Jr.; Peegel, H.; Menon, K.M.

1991-01-01

The objective of this study was to examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from [1B-3H]androstenedione. Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity in response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long-term cultures

DNA methylation of the gonadal aromatase (cyp19a promoter is involved in temperature-dependent sex ratio shifts in the European sea bass.

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Laia Navarro-Martín

2011-12-01

Full Text Available Sex ratio shifts in response to temperature are common in fish and reptiles. However, the mechanism linking temperature during early development and sex ratios has remained elusive. We show in the European sea bass (sb, a fish in which temperature effects on sex ratios are maximal before the gonads form, that juvenile males have double the DNA methylation levels of females in the promoter of gonadal aromatase (cyp19a, the enzyme that converts androgens into estrogens. Exposure to high temperature increased the cyp19a promoter methylation levels of females, indicating that induced-masculinization involves DNA methylation-mediated control of aromatase gene expression, with an observed inverse relationship between methylation levels and expression. Although different CpGs within the sb cyp19a promoter exhibited different sensitivity to temperature, we show that the increased methylation of the sb cyp19a promoter, which occurs in the gonads but not in the brain, is not a generalized effect of temperature. Importantly, these effects were also observed in sexually undifferentiated fish and were not altered by estrogen treatment. Thus, methylation of the sb cyp19a promoter is the cause of the lower expression of cyp19a in temperature-masculinized fish. In vitro, induced methylation of the sb cyp19a promoter suppressed the ability of SF-1 and Foxl2 to stimulate transcription. Finally, a CpG differentially methylated by temperature and adjacent to a Sox transcription factor binding site is conserved across species. Thus, DNA methylation of the aromatase promoter may be an essential component of the long-sought-after mechanism connecting environmental temperature and sex ratios in vertebrate species with temperature-dependent sex determination.

Hypothalamic-pituitary-ovarian axis during infancy, early and late prepuberty in an aromatase-deficient girl who is a compound heterocygote for two new point mutations of the CYP19 gene.

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Belgorosky, Alicia; Pepe, Carolina; Marino, Roxana; Guercio, Gabriela; Saraco, Nora; Vaiani, Elisa; Rivarola, Marco A

2003-11-01

A loss of function mutation of the CYP19 aromatase gene leads to excess circulating androgens in the fetus and in the mother, resulting in ambiguous genitalia in the female fetus. Later on, lack of aromatase is responsible for sexual infantilism, primary amenorrhea, tall stature, and multicystic ovaries, even in preadolescent girls. Up to now, 11 CYP19 aromatase point mutations and 10 well-documented cases have been reported. In the present case, we are reporting the clinical and hormonal follow-up, from birth to 7 yr of age, of an affected girl with ambiguous genitalia. Gene analysis showed that she was a compound heterozygote for two new CYP19 aromatase point mutations. In the father's allele, there was a consensus 5' splice donor sequence mutation, GAA-AAA at cDNA position bp 655 in exon 5, which probably results in a cryptic donor site. In the mother's allele, there was a base A deletion in exon 9 (Delta A GLU 412X), causing a frame shift mutation, and a stop codon after 98 bp (33 codons) downstream, altering the critical heme-binding region. Basal serum LH and FSH levels were high at 8 d of age (42.9 and 51.3 U/liter), 26 d of age (76.2 and 119 U/liter), and 60 d of age (58.7 and 150 U/liter, respectively). Both gonadotropins dropped dramatically between the second and fifth months of age (to 1.79 and 14.9 U/liter) but remained higher than in normal control girls (0.64 and 8.5 U/liter, respectively). Serum testosterone (T) and androstenedione (Delta(4)A) levels were high during the first month, but Delta(4)A was normal at 2 months of age. However, at 5 months of age, along with significant decrements of serum LH and FSH levels and increments in serum Delta(4)A and T levels, a large ovarian cyst was removed from each gonad. Relatively high levels of T [27.3 ng/ml (94.6 nmol/liter); control, 34.9 ng/ml (121 nmol/liter)], but not of estradiol [1.8 ng/ml (6.6 nmol/liter); control 62.9 ng/ml (231 nmol/liter)], and a high T/estradiol ratio [15.2; control < 1] were

Analysis of Obesity-Related Factors and their Association with Aromatase Expression in Canine Malignant Mammary Tumours.

Science.gov (United States)

Shin, J-I; Lim, H-Y; Kim, H-W; Seung, B-J; Ju, J-H; Sur, J-H

2016-07-01

This study was designed to investigate the role of obesity in canine malignant mammary tumours (CMMTs), by assessing aromatase expression and the regulatory roles of immune mediators such as cyclo-oxygenase-2 (COX2), prostaglandin E2 (PGE2), nuclear factor kappa beta (NF-κB), hypoxia inducible factor-1α (HIF-1α) and adipokines (i.e. leptin) in lean, optimal body weight, overweight and obese animals. Clinicopathological data, including the breed, body weight, body condition score and age and neutering status, were collected, together with histopathological characteristics (i.e. histological types, grading and lymphatic invasion). To determine the expression of each factor, immunohistochemistry was conducted with 60 samples of malignant CMMTs. CMMTs from overweight and obese animals had significantly elevated levels of PGE2, and aromatase expression correlated significantly with PGE2, NF-κB and leptin expression. However, no significant difference was observed in terms of histopathological characteristics. The results suggest that PGE2, a known obesity-related immune mediator, could be upregulated in CMMTs from overweight and obese animals. In addition, PGE2, NF-κB and leptin influenced the expression of aromatase, as observed in women. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interactions between aromatase (estrogen synthase) and dopamine in the control of male sexual behavior in quail.

Science.gov (United States)

Balthazart, Jacques; Baillien, Michelle; Ball, Gregory F

2002-05-01

In male quail, like in other vertebrates including rodents, testosterone acting especially through its estrogenic metabolites is necessary for the activation of male sexual behavior. Also, the administration of dopamine agonists and antagonists profoundly influences male sexual behavior. How the steroid-sensitive neural network and dopamine interact physiologically, remains largely unknown. It is often implicitly assumed that testosterone or its metabolite estradiol, stimulates male sexual behavior via the modification of dopaminergic transmission. We have now identified in quail two possible ways in which dopamine could potentially affect sexual behavior by modulating the aromatization of testosterone into an estrogen. One is a long-acting mechanism that presumably involves the modification of dopaminergic transmission followed by the alteration of the genomic expression of aromatase. The other is a more rapid mechanism that does not appear to be dopamine receptor-mediated and may involve a direct interaction of dopamine with aromatase (possibly via substrate competition). We review here the experimental data supporting the existence of these controls of aromatase activity by dopamine and discuss the possible contribution of these controls to the activation of male sexual behavior.

Leptin stimulates aromatase in the growth plate: limiting catch-up growth efficiency.

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Masarwi, Majdi; Shamir, Raanan; Phillip, Moshe; Gat-Yablonski, Galia

2018-06-01

Catch-up growth (CUG) in childhood is defined as periods of growth acceleration, after the resolution of growth attenuation causes, bringing the children back to their original growth trajectory. Sometimes, however, CUG is incomplete, leading to permanent growth deficit and short stature. The aim of this study was to investigate the mechanisms that limit nutritional-CUG. Specifically, we focused on the crosstalk between leptin, increased by re-feeding, and sex hormones, which increase with age. In vivo studies were performed in young male Sprague Dawley rats fed ad libitum or subjected to 10/36 days of 40% food restriction followed by 90-120 days of re-feeding. In vitro studies were performed on ATDC5 cells. Analyses of mRNA and protein levels were done using qPCR and Western blot, respectively. CUG was complete in body weight and humerus length in animals that were food-restricted for 10 days but not for those food-restricted for 36 days. In vitro studies showed that leptin significantly increased aromatase gene expression and protein level as well as the expression of estrogen and leptin receptors in a dose- and time-dependent manner. The effect of leptin on aromatase was direct and was mediated through the MAPK/Erk, STAT3 and PI3K pathways. The crosstalk between leptin and aromatase in the growth plate suggests that re-feeding during puberty may lead to increased estrogen level and activity, and consequently, irreversible premature epiphyseal growth plate closure. These results may have important implications for the development of novel treatment strategies for short stature in children. © 2018 Society for Endocrinology.

New insights about the evaluation of human sperm quality: the aromatase example.

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A Saad

2010-01-01

Full Text Available Male contribution to the couple's infertility is at first evaluated by the routine examination of semen parameters upon optical microscopy providing valuable information for a rational initial diagnosis and for a clinical management of infertility. But the different forms of infertility defined according to the WHO criteria especially teratozoospermia are not always related to the chromatin structure or to the fertilization capacity. New investigations at the molecular level (transcript and protein could be developed in order to understand the nature of sperm malformation responsible of human infertility and thus to evaluate the sperm quality. The profile analysis of spermatozoal transcripts could be considered as a fingerprint of the past spermatogenic events. The selection of representative transcripts of normal spermatozoa remains complex because a differential expression (increased, decreased or not modified levels of specific transcripts has been revealed between immotile and motile sperm fractions issued from normozoospermic donors. Microarrays tests or real-time quantitative PCR could be helpful for the identification of factors involved in the male infertility. Differences in the expression of specific transcripts have been reported between normal and abnormal semen samples. With the aromatase example, we have noted a negative strong correlation between the amount of transcript and the percentage of abnormal forms especially in presence of head defects. Immunocytochemical procedures using fluorescent probes associated with either confocal microscopy or flow cytometry can be also helpful to proceed with further investigations about the localization of proteins in the compartmentalized spermatozoa or the acrosome reaction. The dual location of aromatase both in the equatorial segment, the mid-piece and the tail could explain the double role of this enzyme in acrosome reaction and motility.

Successful treatment of low-grade endometrial cancer in premenopausal women with an aromatase inhibitor after failure with oral or intrauterine progesterone

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Alli Straubhar

2017-08-01

Full Text Available Introduction: Young women with endometrial intraepithelial hyperplasia or low-grade endometrial carcinoma are potential candidates for conservative fertility sparing therapy utilizing progesterone rather than hysterectomy. High-dose progesterone treatment is associated with 55–80% initial response but high relapse rates. Using aromatase inhibitors in conjunction with high-dose progesterone has largely been unstudied. Case descriptions: Three obese premenopausal women with endometrial cancer failed to respond to oral or intrauterine progesterone as first line therapy. Due to their desire to continue to pursue fertility sparing treatment options, an aromatase inhibitor was added to their treatment regimen. This resulted in resolution of their malignancy in each case. Discussion: In obese premenopausal women, the mechanism of malignant transformation in endometrial carcinoma is considered to be an association with relatively high levels of serum estrogen from peripheral conversion of androgens to estrone in adipose tissue with a deficiency in progesterone exposure due to chronic anovulation. Using aromatase inhibitors seems reasonable as an adjunct to progesterone given the high likelihood that this population has a significant proportion of their estrogen production coming from peripheral conversion in adipose tissue. This case series is unique in that each woman initially failed to respond to progesterone but had resolution when an aromatase inhibitor was added to their treatment regimen. This would suggest that obese women with low grade malignancy or hyperplasia who have no radiographic evidence of deep myometrial invasion, ovarian or retroperitoneal metastases and who wish to retain their fertility may be treated with intrauterine progesterone and an aromatase inhibitor.

Synthesis and evaluation of a dimer of 2-(4-pyridylmethyl)-1-indanone as a novel nonsteroidal aromatase inhibitor.

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Gupta, Ranju; Jindal, Dharam Paul; Jit, Birinder; Narang, Gaurav; Palusczak, Anja; Hartmann, Rolf W

2004-07-01

A novel dimer of 2-(4-pyridylmethyl)-1-indanone (2) was obtained while carrying out aldol condensation of 1-indanone with pyridine-4-carboxaldehyde in potassium hydroxide. The structure of dimer 3 has been established using various spectral techniques and was screened for its ability to inhibit the cytochrome P(450) enzyme aromatase. The dimer showed strong inhibition of human placental aromatase and was found 3 times more potent (RP = 3, IC(50) = 10.2 microM) as compared to aminoglutethimide (RP = 1, IC(50) = 18.5 microM.

Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19)

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Guo, Jiajia [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Yuan, Yun [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang (China); Lu, Danfeng; Du, Baowen [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Xiong, Liang; Shi, Jiangong [State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Yang, Lijuan [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Liu, Wanli [MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084 (China); Yuan, Xiaohong [School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang (China); Zhang, Guolin, E-mail: zhanggl@cib.ac.cn [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu (China); Wang, Fei, E-mail: wangfei@cib.ac.cn [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu (China)

2014-08-15

Aromatase is the only enzyme in vertebrates to catalyze the biosynthesis of estrogens. Although inhibitors of aromatase have been developed for the treatment of estrogen-dependent breast cancer, the whole-body inhibition of aromatase causes severe adverse effects. Thus, tissue-selective aromatase inhibitors are important for the treatment of estrogen-dependent cancers. In this study, 63 natural products with diverse structures were examined for their effects on estrogen biosynthesis in human ovarian granulosa-like KGN cells. Two compounds—trans-phytol (SA-20) and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol (SA-48)—were found to potently inhibit estrogen biosynthesis (IC{sub 50}: 1 μM and 0.5 μM, respectively). Both compounds decreased aromatase mRNA and protein expression levels in KGN cells, but had no effect on the aromatase catalytic activity in aromatase-overexpressing HEK293A cells and recombinant expressed aromatase. The two compounds decreased the expression of aromatase promoter I.3/II. Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). The effects of these two compounds on extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs), and AKT/phosphoinositide 3-kinase (PI3K) pathway were examined. Inhibition of p38 MAPK could be the mechanism underpinning the actions of these compounds. Our results suggests that natural products structurally similar to SA-20 and SA-48 may be a new source of tissue-selective aromatase modulators, and that p38 MAPK is important in the basal control of aromatase in ovarian granulosa cells. SA-20 and SA-48 warrant further investigation as new pharmaceutical tools for the prevention and treatment of estrogen-dependent cancers. - Highlights: • Two natural products inhibited estrogen biosynthesis in human ovarian granulosa cells. • They

Pemodelan Molekul Turunan p-Metoksi sinnamoil Hidrazida Sebagai Inhibitor Checkpoint Kinase 1 dan Inhibitor Aromatase secara In silico

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Galih Satrio Putra

2017-08-01

Full Text Available The development of anticancer drugs from ethyl p-methoxycinnamate (EPMC derivatives continues to obtain compounds that have high ability of cancer cells apoptosis and minimal side effects. p-Methoxycinnamoyl hydrazide derivate compounds from EPMC structure modification were docked into the ligand-binding pocket of Check point kinase 1 enzymes (2YWP and the aromatase enzyme (3S7S using software Molegro Virtual Docker (MVD Ver.5.5. We compared the Rerank score of native ligand with derivate compounds of p-Methoxycinnamoyl hydrazide. Rerank scores of compounds 4b and 4c (-99.98 Kcal/mol and -99.80 Kcal/mol were lower than the native ligand A42 in inhibiting the enzyme checkpoint kinase 1. Rerank values of p-Methoxycinnamoyl hydrazide derivate compounds were greater than the native ligand EXM in inhibiting the enzyme aromatase. p-Methoxycinnamoyl hydrazide derivate compounds, especially compounds 4b and 4c, had anticancer mechanism by inhibiting the enzyme pathway checkpoint kinase 1 and had not activity in inhibiting the aromatase enzyme.

High abundance androgen receptor in goldfish brain: characteristics and seasonal changes

International Nuclear Information System (INIS)

Pasmanik, M.; Callard, G.V.

1988-01-01

Testosterone (T) exerts its actions in brain directly via androgen receptors or, after aromatization to estradiol, via estrogen receptors. Brain aromatase activity in teleost fish is 100-1000 times greater than in mammals and would be expected to significantly reduce the quantity of androgen available for receptor binding. Experiments were carried out on the goldfish Carassius auratus to determine if androgen receptors are present in teleost brain and whether their physicochemical properties reflect elevated aromatase. Cytosolic and nuclear extracts were assayed with the use of [ 3 H]T and charcoal, Sephadex LH-20, or DNA-cellulose chromatography to separate bound and free steroids. Binding activity was saturable and had an equally high affinity for T and 5 alpha-dihydrotestosterone. Although mibolerone was a relatively weak competitor, the putative teleost androgen 11-ketotestosterone, methyltrienolone (R1881), estradiol, progesterone, and cortisol were poor ligands. Characteristics that distinguish this receptor from a steroid-binding protein in goldfish serum are the presence of binding activity in both nuclear and cytosolic extracts, a low rate of ligand-receptor dissociation, electrophoretic mobility, sedimentation properties in low vs. high salt, and tissue distribution. DNA cellulose-adhering and nonadhering forms were detected, but these did not differ in other variables measured. Although goldfish androgen receptors resembled those of mammals in all important physicochemical characteristics, they were unusually abundant compared to levels in rat brain, but comparable to levels in prostate and other male sex hormone target organs. Moreover, there were seasonal variations in total receptors, with a peak at spawning (April) 4- to 5-fold higher than values in reproductively inactive fish

Insight into the binding interactions of CYP450 aromatase inhibitors with their target enzyme: a combined molecular docking and molecular dynamics study.

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Galeazzi, Roberta; Massaccesi, Luca

2012-03-01

CYP450 aromatase catalyzes the terminal and rate-determining step in estrogen synthesis, the aromatization of androgens, and its inhibition is an efficient approach to treating estrogen-dependent breast cancer. Insight into the molecular basis of the interaction at the catalytic site between CYP450 aromatase inhibitors and the enzyme itself is required in order to design new and more active compounds. Hence, a combined molecular docking-molecular dynamics study was carried out to obtain the structure of the lowest energy association complexes of aromatase with some third-generation aromatase inhibitors (AIs) and with other novel synthesized letrozole-derived compounds which showed high in vitro activity. The results obtained clearly demonstrate the role of the pharmacophore groups present in the azaheterocyclic inhibitors (NSAIs)-namely the triazolic ring and highly functionalized aromatic moieties carrying H-bond donor or acceptor groups. In particular, it was pointed out that all of them can contribute to inhibition activity by interacting with residues of the catalytic cleft, but the amino acids involved are different for each compound, even if they belong to the same class. Furthermore, the azaheterocyclic group strongly coordinates with the Fe(II) of heme cysteinate in the most active NSAI complexes, while it prefers to adopt another orientation in less active ones.

Potential effect of Olea europea leaves, Sonchus oleraceus leaves and Mangifera indica peel extracts on aromatase activity in human placental microsomes and CYP19A1 expression in MCF-7 cell line: Comparative study.

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Shaban, N Z; Hegazy, W A; Abdel-Rahman, S M; Awed, O M; Khalil, S A

2016-08-29

Aromatase inhibitors (AIs) provide novel approaches to the adjuvant therapy for postmenopausal women with estrogen-receptor-positive (ER+) breast cancers. In this study, different plant extracts from Olea europaea leaves (OLE), Sonchus oleraceus L. (SOE) and Mangifera indica peels (MPE) were prepared to identify phytoconstituents and measure antioxidant capacities. The effects of these three extracts on aromatase activity in human placental microsomes were evaluated. Additionally, the effects of these extracts on tissue-specific promoter expression of CYP19A1 gene in cell culture model (MCF-7) were assessed using qRT-PCR. Results showed a concentration-dependent decrease in aromatase activity after treatment with OLE and MPE, whereas, SOE showed a biphasic effect. The differential effects of OLE, SOE and MPE on aromatase expression showed that OLE seems to be the most potent suppressor followed by SOE and then MPE. These findings indicate that OLE has effective inhibitory action on aromatase at both the enzymatic and expression levels, in addition to its cytotoxic effect against MCF-7 cells. Also, MPE may be has the potential to be used as a tissue-specific aromatase inhibitor (selective aromatase inhibitor) and it may be promising to develop a new therapeutic agent against ER+ breast cancer.

Hypothesis testing with computational modeling: linking aromatase inhibition with plasma vitellogenin dynamics in fathead minnows

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Fadrozole inhibits aromatase (CYP19A), a key enzyme that converts testosterone to estradiol (E2). In fish, E2 concentrations control hepatic synthesis ofthe glycolipoprotein vitellogenin (VTG), an egg yolk precursor protein essential to oocyte development and larval survival. Whe...

Immunoexpression of androgen receptors and aromatase in testes of patient with Klinefelter's syndrome.

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Stanisław Fracki

2005-02-01

Full Text Available Klinefelter's syndrome (47, XXY is the most common chromosome aneuploidy in men and is usually characterized by underdeveloped testes and sterility. The aim of the present study was to detect cellular distribution of androgen receptors (AR and aromatase in testes of patient with KS. The tissue sections were processed for morphological and immunohistochemical staining. Additionally, levels of FSH, LH, PRL, estradiol, and testosterone were measured in the plasma. Morphological analysis revealed a complete absence of spermatogenesis. No germ cells were present in seminiferous tubules. In some tubules, nests of apparently degenerating Sertoli cells were found. In the interstitium, Leydig cell hyperplasia was observed. Using immunohistochemistry, nuclear AR staining was detected in Sertoli cells and peritubular cells, whereas in Leydig cells the staining was exclusively cytoplasmic. The immunostaining of aromatase was detected in the cytoplasm of Sertoli cells and Leydig cells. Increased levels of gonadotropins and decreased level of testosterone concomitantly with the cytoplasmic localization of AR in Leydig cells might contribute to the impaired testicular function in patient with KS.

In Search of...Brain-Based Education.

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Bruer, John T.

1999-01-01

Debunks two ideas appearing in brain-based education articles: the educational significance of brain laterality (right brain versus left brain) and claims for a sensitive period of brain development in young children. Brain-based education literature provides a popular but misleading mix of fact, misinterpretation, and fantasy. (47 references (MLH)

Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay

DEFF Research Database (Denmark)

Jacobsen, Naja Wessel; Hansen, Cecilie Hurup; Nellemann, Christine

2015-01-01

shown to inhibit the aromatase enzyme in both types of aromatase assays. The IC50 values ranged from 3 to 600μM. All five SSRIs, were further investigated in the H295R cell line. All compounds altered the steroid secretion from the cells, the lowest observed effect levels were 0.9μM and 3.1μ....... In this study we investigated whether the endocrine effect due to SSRI exposure could be detected in well adopted in vitro steroidogenesis assays, two versions of the aromatase enzyme inhibition assay and the H295R cell assay. The five drugs citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, were......M for sertraline and fluvoxamine, respectively. In general the H295R cell assay was more sensitive to SSRI exposure than the two aromatase assays, up to 20 times more sensitive. This indicates that the H295R cell line is a better tool for screening endocrine disrupting effects. Our findings show that the endocrine...

Leptin, its receptor and aromatase expression in deep infiltrating endometriosis.

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Gonçalves, Helder F; Zendron, Carolina; Cavalcante, Fernanda S; Aiceles, Verônica; Oliveira, Marco Aurélio P; Manaia, Jorge Henrique M; Babinski, Márcio A; Ramos, Cristiane F

2015-08-05

The aim of this study was to evaluate the leptin levels in the serum and peritoneal fluid (PF) and the protein expression in three different peritoneal ectopic implants in patients who underwent surgery for deep infiltrating endometriosis. All patients had been treated at the Department of Gynecology of the Pedro Ernesto University Hospital, Rio de Janeiro. The study group consisted of 15 patients who underwent surgery for adnexal masses and infertility, while the control group consisted of ten women who underwent surgery for tubal ligation. Peritoneal fluid and samples tissues were collected during surgery. Serum samples were obtained before anesthesia. In this study, the leptin levels in the serum and peritoneal fluid (PF) were evaluated by ELISA. The protein expression of leptin and its receptors (ObR) and aromatase enzyme were evaluated by Western blot analysis of the intestine, uterosacral ligament and vaginal septum in the ectopic implants. The t-test and one-way ANOVA with Holm-Sìdak post-test were used, and p endometriosis = 19.2 ng/mL ± 1.84, p endometriosis = 7.71 ng/mL ± 0.59, p = 0.18). Comparing women with and without ovarian implants, the leptin levels in both the serum and PF were significantly higher in women without ovarian implants (serum: with ovarian implant = 15.85 ± 1.99; without ovarian implant = 23.14 ± 2.60; ng/mL, p = 0.04; PF: with ovarian implant = 4.28 ± 1.30; without ovarian implant = 11.18 ± 2.98;ng/mL, p = 0.048). The leptin, ObR and aromatase protein expression levels were increased in lesions in the vaginal septum and were decreased in the intestine lesions. This study reports several interesting associations between the leptin levels in serum, peritoneal fluid, and tissue samples and the localization of the ectopic endometrium. Although this study does not provide a clear picture of the role of leptin in the development and progression of peritoneal implants

Brain-Based Learning and Standards-Based Elementary Science.

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Konecki, Loretta R.; Schiller, Ellen

This paper explains how brain-based learning has become an area of interest to elementary school science teachers, focusing on the possible relationships between, and implications of, research on brain-based learning to the teaching of science education standards. After describing research on the brain, the paper looks at three implications from…

Quantitative (q)AOP for aromatase inhibition as case study to advance qAOP development practices

Science.gov (United States)

Here we describe how “read across” of a quantitative adverse outcome pathway (qAOP) developed with data for one chemical can be used to screen impacts of other chemicals. We developed a qAOP starting with inhibition of CYP19A (aromatase) in fathead minnows (FHM) as th...

Effects of Pharmaceuticals Used for Breast Cancer Treatment on Reproduction and Aromatase Activity in a Marine Fish

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Laboratory experiments were conducted with the marine fish cunner (Tautogolabrus adspersus) to evaluate whether four pharmaceuticals used in breast cancer treatment have an impact on reproduction or aromatase activity. Tamoxifen binds to estrogen receptors, while anastrozole, let...

Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, Annual Report 2009

Science.gov (United States)

2009-01-01

applications for recovering from disaster and trauma Defense and Veterans Brain Injury Center Develops and delivers advanced TBI-specifi c treatment...specifically aimed at developing cognitive and motor therapy tools using videogame technology, game-based PH outreach tools and support tools for children of...Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury Annual Report 2009 Report Documentation Page Form ApprovedOMB No

Distribution of aromatase and sex steroid receptors in the baculum during the rat life cycle: effects of estrogen during the early development of the baculum.

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Yonezawa, Tomohiro; Higashi, Mayuko; Yoshioka, Kazuki; Mutoh, Ken-ichiro

2011-07-01

The baculum, also called os penis, plays an important role during copulation. However, the hormonal regulation of its development remains to be elucidated. To determine the direct involvement of sex steroids in the development of the baculum of rats, the distributions of androgen receptors (ARs), aromatase, and estrogen receptor alpha (ESR1) were observed immunohistochemically. On Postnatal Day 1, the rudiment of the baculum expressed ARs, aromatase, and ESR1. In the proximal segment of the baculum of neonatal rats, ARs were expressed in the parosteal layer but not in the periosteum or osteoblasts. Aromatase was expressed from the parosteal layer to the endosteum, particularly in the inner osteogenic layer. ESR1 was also abundantly expressed in almost all cells from the parosteal layer to the endosteum. ARs, aromatase, and ESR1 were all abundantly expressed during the neonatal period in the hyaline cartilage of the proximal segment and in fibrocartilage of the distal segment of the baculum. Expression in all the tissues was attenuated in an age-dependent manner and became quite weak at puberty. To determine the effect of estrogen on the growth of the baculum, the aromatase inhibitor 1,4,6-androstatrien-3,17-dione (ATD) was subcutaneously injected daily into pregnant rats from Days 19 to 23 of gestation and into pups on postnatal Days 1, 3, 5, 7, and 9. On Day 10, the length of the baculum in the ATD-treated rats was significantly shorter than that in the controls, although the body weight did not change. These findings suggest that not only androgen but also locally aromatized estrogen is involved in the early growth and development of the baculum.

Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries

Energy Technology Data Exchange (ETDEWEB)

Ito, Y.; Fisher, C.R.; Simpson, E.R. (Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)); Conte, F.A.; Grumbach, M.M. (Univ. of California, San Francisco, CA (United States))

1993-11-15

The authors identified two mutations in the CYP19 gene responsible for aromatase deficiency in an 18-year-old 46,XX female with ambiguous external genitalia at birth, primary amenorrhea and sexual infantilism, and polycystic ovaries. The coding exons, namely exons II-X, of the CYP19 gene were amplified by PCR from genomic DNA and sequenced directly. Direct sequencing of the amplified DNA from the patient revealed two single-base changes, at bp 1303 (C[yields]T) and bp 1310 (G[yields]A) in exon X, which were newly found missense mutations and resulted in codon changes of R435C and C437Y, respectively. Subcloning followed by sequencing confirmed that the patient is a compound heterozygote. The results of restriction fragment length polymorphism analysis and direct sequencing of the amplified exon X DNA from the patient's mother indicate maternal inheritance of the R435C mutation. Transient expression experiments showed that the R435C mutant protein had [approx]1.1% of the activity of the wild type, whereas C437Y was totally inactive. Cysteine-437 is the conserved cysteine in the heme-binding region believed to serve as the fifth coordinating ligand of the heme iron. To the authors' knowledge, this patient is the first adult to have described the cardinal features of a syndrome of aromatase deficiency. Recognition that such defects exist will lead to a better understanding of the role of this enzyme in human development and disease.

Aromatase inhibitors in stimulated IVF cycles

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Tournaye Herman

2011-06-01

Full Text Available Abstract Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol levels

Review: neuroestrogen regulation of socio-sexual behavior of males.

Science.gov (United States)

Ubuka, Takayoshi; Tsutsui, Kazuyoshi

2014-01-01

It is thought that estrogen (neuroestrogen) synthesized by the action of aromatase in the brain from testosterone activates male socio-sexual behaviors, such as aggression and sexual behavior in birds. We recently found that gonadotropin-inhibitory hormone (GnIH), a hypothalamic neuropeptide, inhibits socio-sexual behaviors of male quail by directly activating aromatase and increasing neuroestrogen synthesis in the preoptic area (POA). The POA is thought to be the most critical site of aromatization and neuroestrogen action for the regulation of socio-sexual behavior of male birds. We concluded that GnIH inhibits socio-sexual behaviors of male quail by increasing neuroestrogen concentration beyond its optimal concentration in the brain for expression of socio-sexual behavior. On the other hand, it has been reported that dopamine and glutamate, which stimulate male socio-sexual behavior in birds and mammals, inhibit the activity of aromatase in the POA. Multiple studies also report that the activity of aromatase or neuroestrogen is negatively correlated with changes in male socio-sexual behavior in fish, birds, and mammals including humans. Here, we review previous studies that investigated the role of neuroestrogen in the regulation of male socio-sexual behavior and reconsider the hypothesis that neuroestrogen activates male socio-sexual behavior in vertebrates. It is considered that basal concentration of neuroestrogen is required for the maintenance of male socio-sexual behavior but higher concentration of neuroestrogen may inhibit male socio-sexual behavior.

Effect of a hormone-releasing intrauterine system (Mirena® on aromatase and Cox-2 expression in patients with adenomyosis submitted or not, to endometrial resection

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Maia R

2012-04-01

Full Text Available Hugo Maia Jr1,2, Clarice Haddad1, Julio Casoy1, Rebeca Maia1, Nathanael Pinheiro3, Elsimar M Coutinho11Centro de Pesquisa e Assistência em Reprodução Humana (CEPARH, 2Itaigara Memorial Day Hospital, 3IMAGEPAT, Salvador, Bahia, BrazilObjective: To investigate the effect of a levonorgestrel-releasing intrauterine system (Mirena® on aromatase and cyclooxygenase-2 (Cox-2 expression in the endometrium of patients with adenomyosis who were submitted to endometrial resection at the time of insertion, compared to a group not submitted to endometrial resection and a group of controls with adenomyosis not submitted to any previous hormonal treatment.Patients and methods: Patients with adenomyosis (n = 89 were included in this study. Twenty-two patients had been using Mirena® for 5 years but had not been submitted to endometrial resection prior to insertion of the device. Twenty-four patients were submitted to endometrial resection at the time of Mirena® insertion. The remaining 43 patients with adenomyosis had undergone no previous hormonal treatment and served as a control group. Cox-2 and aromatase expression were determined in the endometrium by immunohistochemistry.Results: Use of Mirena® for 5 years reduced aromatase expression in the endometrium; however, this reduction was significantly greater in the uteri previously submitted to endometrial resection. The reduction in Cox-2 expression was significant only in the uteri submitted to endometrial resection followed by the insertion of Mirena®.Conclusion: Endometrial resection followed by the insertion of Mirena® was associated with greater rates of amenorrhea in patients with adenomyosis, which in turn were associated with a more effective inhibition of aromatase and Cox-2 expression in the endometrium.Keywords: aromatase, Mirena®, adenomyosis, Cox-2, endometrium, levonorgestrel

Determination and confirmation of selective estrogen receptor modulators (SERMs), anti-estrogens and aromatase inhibitors in bovine and porcine urine using UHPLC-MS/MS.

Science.gov (United States)

Meijer, Thijs; Essers, Martien L; Kaklamanos, George; Sterk, Saskia S; van Ginkel, Leendert A

2017-04-01

Selective estrogen receptor modulators (SERMs), anti-estrogens and aromatase inhibitors are prohibited in human sports doping. However, they also present a risk of being used illegally in animal husbandry for fattening purposes. A method was developed and validated using UHPLC-MS/MS for the determination and confirmation of SERMs, anti-estrogens and aromatase inhibiters in bovine and porcine urine. This method was used in a survey of more than 200 bovine and porcine urine samples from Dutch farms. In 18 out of 103 porcine urine samples (17%) and two out of 114 bovine samples (2%) formestane, an aromatase inhibitor, was detected. None of the other compounds was detected. From human doping control it is known that formestane can, in some cases, be of natural origin. Analyses of reference samples from untreated bovine and porcine animals demonstrated the presence of formestane in bovine animals, but not yet in porcine animals. Future research will focus on whether the detected formestane in porcine and bovine urine is from endogenous or exogenous origin, using GC-c-IRMS.

Brain-in-Brain Artifact (BIBA) in a Patient with Hydranencepaly: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Oh, Sang Young; Kim, You Me; Lee, Seung Ha; Lee, Young Seok [College of Medicine Dankook University Hospital, Cheonan (Korea, Republic of)

2011-03-15

Hydranencephaly is a condition that is characterized by an absent brain mantle along with the subadjacent white matter, with replacement of the cerebral hemispheres by a thin-walled membranous sac containing CSF. During brain sonograpy in a neonate with hydranencephaly, we have found a brain-in-brain appearance as an unusual sonographic artifact. We report here on this interesting sonographic artifact in a neonate with hydranencephaly, and this artifact was due to multipath reflection artifact of the ultrasound beam/wave, and we explain the underlying physics

Multidimensional control using a mobile-phone based brain-muscle-computer interface.

Science.gov (United States)

Vernon, Scott; Joshi, Sanjay S

2011-01-01

Many well-known brain-computer interfaces measure signals at the brain, and then rely on the brain's ability to learn via operant conditioning in order to control objects in the environment. In our lab, we have been developing brain-muscle-computer interfaces, which measure signals at a single muscle and then rely on the brain's ability to learn neuromuscular skills via operant conditioning. Here, we report a new mobile-phone based brain-muscle-computer interface prototype for severely paralyzed persons, based on previous results from our group showing that humans may actively create specified power levels in two separate frequency bands of a single sEMG signal. Electromyographic activity on the surface of a single face muscle (Auricularis superior) is recorded with a standard electrode. This analog electrical signal is imported into an Android-based mobile phone. User-modulated power in two separate frequency band serves as two separate and simultaneous control channels for machine control. After signal processing, the Android phone sends commands to external devices via Bluetooth. Users are trained to use the device via biofeedback, with simple cursor-to-target activities on the phone screen.

Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat Part 2: Effects on reproductive parameters, on sex behavior, on memory retention and on hypothalamic expression of aromatase and 5alpha-reductases in the offspring.

Science.gov (United States)

Colciago, A; Casati, L; Mornati, O; Vergoni, A V; Santagostino, A; Celotti, F; Negri-Cesi, P

2009-08-15

The gender-specific expression pattern of aromatase and 5alpha-reductases (5alpha-R) during brain development provides neurons the right amount of estradiol and DHT to induce a dimorphic organization of the structure. Polychlorinated biphenyls (PCBs) are endocrine disruptive pollutants; exposure to PCBs through placental transfer and breast-feeding may adversely affect the organizational action of sex steroid, resulting in long-term alteration of reproductive neuroendocrinology. The study was aimed at: a) evaluating the hypothalamic expression of aromatase, 5alpha-R1 and 5alpha-R2 in fetuses (GD20), infant (PN12), weaning (PN21) and young adult (PN60) male and female rats exposed to PCBs during development; b) correlating these parameters with the time of testicular descent, puberty onset, estrous cyclicity and copulatory behavior; c) evaluating possible alterations of some non reproductive behaviors (locomotion, learning and memory, depression/anxiety behavior). A reconstituted mixture of four indicator congeners (PCB 126, 138, 153 and 180) was injected subcutaneously to dams at the dose of 10 mg/kg daily from GD15 to GD19 and then twice a week till weanling. The results indicated that developmental PCB exposure produced important changes in the dimorphic hypothalamic expression of both aromatase and the 5alpha-Rs, which were still evident in adult animals. We observed that female puberty onset occurs earlier than in control animals without cycle irregularity, while testicular descent in males was delayed. A slight but significant impairment of sexual behavior and an important alteration in memory retention were also noted specifically in males. We conclude that PCBs might affect the dimorphic neuroendocrine control of reproductive system and of other neurobiological processes.

Cardiovascular Disease After Aromatase Inhibitor Use.

Science.gov (United States)

Haque, Reina; Shi, Jiaxiao; Schottinger, Joanne E; Chung, Joanie; Avila, Chantal; Amundsen, Britta; Xu, Xiaoqing; Barac, Ana; Chlebowski, Rowan T

2016-12-01

Cardiovascular disease (CVD) is an important cause of death in older patients with breast cancer. However, limited information exists on the long-term effect of aromatase inhibitor (AI) use on CVD risk in breast cancer survivors. To this point, no other population-based studies have been able to adjust for CVD risk factors or cardiovascular medications. To determine the long-term influence of adjuvant endocrine therapies on CVD in a cohort of postmenopausal breast cancer survivors in analyses that accounted for major CVD risk factors, medication use, chemotherapy, and radiotherapy. A retrospective cohort of postmenopausal women with breast cancer diagnosed from January 1, 1991, to December 31, 2010, and followed up through December 31, 2011 (maximum, 21 years [72 886 person-years]), was evaluated using records from a managed care organization with nearly 20 community hospitals in California. A total of 13 273 postmenopausal women with hormone receptor-positive breast cancer without prior CVD were included. Cardiovascular disease incidence was compared across endocrine therapy categories. Information on demographics, comorbidity, medication, use, and CVD risk was captured from electronic health records. Multivariate Cox proportional hazards models using time-dependent endocrine drug use variables and propensity scores were conducted. Data analysis was conducted from September 15, 2014, to February 1, 2016. Women were grouped by endocrine therapy status (tamoxifen citrate only, AI only, both, or neither). Person-year rates of CVD for each therapy group. During 72 886 person-years in 13 273 women (mean [SD] age, 66.8 [8.1] years) with follow-up through 2011, we observed 3711 CVD events. In multivariable analyses (reported as hazard ratio [95% CI]), AI-only users had a similar risk of cardiac ischemia (myocardial infarction and angina) (adjusted, 0.97 [0.78-1.22]) and stroke (adjusted, 0.97 [0.70-1.33]) as tamoxifen-only users (reference). However, we found an

Near infrared spectroscopy based brain-computer interface

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Ranganatha, Sitaram; Hoshi, Yoko; Guan, Cuntai

2005-04-01

A brain-computer interface (BCI) provides users with an alternative output channel other than the normal output path of the brain. BCI is being given much attention recently as an alternate mode of communication and control for the disabled, such as patients suffering from Amyotrophic Lateral Sclerosis (ALS) or "locked-in". BCI may also find applications in military, education and entertainment. Most of the existing BCI systems which rely on the brain's electrical activity use scalp EEG signals. The scalp EEG is an inherently noisy and non-linear signal. The signal is detrimentally affected by various artifacts such as the EOG, EMG, ECG and so forth. EEG is cumbersome to use in practice, because of the need for applying conductive gel, and the need for the subject to be immobile. There is an urgent need for a more accessible interface that uses a more direct measure of cognitive function to control an output device. The optical response of Near Infrared Spectroscopy (NIRS) denoting brain activation can be used as an alternative to electrical signals, with the intention of developing a more practical and user-friendly BCI. In this paper, a new method of brain-computer interface (BCI) based on NIRS is proposed. Preliminary results of our experiments towards developing this system are reported.

Study on the effect of aromatase inhibitors and antiestrogens on the sex differentiation of broiler chicks

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E.A Valizadeh

2011-02-01

Full Text Available During the development of chick embryo, the genotype of the zygote determines the nature of the gonads, which thereafter creates the male or female phenotype. Differentiation of gonads during the period called “critical period for sexual differentiation “is accompanied with beginning of secretion of sexual hormones. Every change in the rate of steroidal hormones concentration during this critical period, affects on the structure of gonads. Therefore, injection of aromatase inhibitors (which blocks the synthesis of estrogen from testostron in 5th day of incubation into the eggs, causes the production of males with female genotype. These sex reversal females have bilateral testes with complete spermatogenesis, having normal physical appearance and behavior. In this study, 14-α-hydroxy 3,6,17, androstan-trion inhibitor (1mg/egg was injected into the eggs. Furthermore, the effect of three anti-estrogens (which blocks the estrogen receptor Tamoxifen, and Clomiphen Citrate and GAR79 were studied. Injection of aromatase inhibitors into the eggs during incubation period caused statistically significant (p

Use of MR-based trabecular bone microstructure analysis at the distal radius for osteoporosis diagnostics: a study in post-menopausal women with breast cancer and treated with aromatase inhibitor.

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Baum, Thomas; Karampinos, Dimitrios C; Seifert-Klauss, Vanadin; Pencheva, Tsvetelina D; Jungmann, Pia M; Rummeny, Ernst J; Müller, Dirk; Bauer, Jan S

2016-01-01

Treatment with aromatase inhibitor (AI) is recommended for post-menopausal women with hormone-receptor positive breast cancer. However, AI therapy is known to induce bone loss leading to osteoporosis with an increased risk for fragility fractures. The purpose of this study was to investigate whether changes of magnetic resonance (MR)-based trabecular bone microstructure parameters as advanced imaging biomarker can already be detected in subjects with AI intake but still without evidence for osteoporosis according to dual energy X-ray absorptiometry (DXA)-based bone mineral density (BMD) measurements as current clinical gold standard. Twenty-one postmenopausal women (62±6 years of age) with hormone-receptor positive breast cancer, ongoing treatment with aromatase inhibitor for 23±15 months, and no evidence for osteoporosis (current DXA T-score greater than -2.5) were recruited for this study. Eight young, healthy women (24±2 years of age) were included as controls. All subjects underwent 3 Tesla magnetic resonance imaging (MRI) of the distal radius to assess the trabecular bone microstructure. Trabecular bone microstructure parameters were not significantly (p>0.05) different between subjects with AI intake and controls, including apparent bone fraction (0.42±0.03 vs. 0.42±0.05), trabecular number (1.95±0.10 mm(-1) vs 1.89±0.15 mm(-1)), trabecular separation (0.30±0.03 mm vs 0.31±0.06 mm), trabecular thickness (0.21±0.01 mm vs 0.22±0.02 mm), and fractal dimension (1.70±0.02 vs. 1.70±0.03). These findings suggest that the initial deterioration of trabecular bone microstructure as measured by MRI and BMD loss as measured by DXA occur not sequentially but rather simultaneously. Thus, the use of MR-based trabecular bone microstructure assessment is limited as early diagnostic biomarker in this clinical setting.

Brain-Based Learning. Research Brief

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Walker, Karen

2005-01-01

What does brain-based research say about how adolescents learn? The 1990s was declared as the Decade of the Brain by President Bush and Congress. With the advancement of MRIs (Magnetic Resonance Imagining) and PET (positron emission tomography) scans, it has become much easier to study live healthy brains. As a result, the concept of…

Mapping of brain lipid binding protein (Blbp) in the brain of adult zebrafish, co-expression with aromatase B and links with proliferation.

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Diotel, Nicolas; Vaillant, Colette; Kah, Olivier; Pellegrini, Elisabeth

2016-01-01

Adult fish exhibit a strong neurogenic capacity due to the persistence of radial glial cells. In zebrafish, radial glial cells display well-established markers such as the estrogen-synthesizing enzyme (AroB) and the brain lipid binding protein (Blbp), which is known to strongly bind omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). While Blpb is mainly described in the telencephalon of adult zebrafish, its expression in the remaining regions of the brain is poorly documented. The present study was designed to further investigate Blbp expression in the brain, its co-expression with AroB, and its link with radial glial cells proliferation in zebrafish. We generated a complete and detailed mapping of Blbp expression in the whole brain and show its complete co-expression with AroB, except in some tectal and hypothalamic regions. By performing PCNA and Blbp immunohistochemistry on cyp19a1b-GFP (AroB-GFP) fish, we also demonstrated preferential Blbp expression in proliferative radial glial cells in almost all regions studied. To our knowledge, this is the first complete and detailed mapping of Blbp-expressing cells showing strong association between Blbp and radial glial cell proliferation in the adult brain of fish. Given that zebrafish is now recognized models for studying neurogenesis and brain repair, our data provide detailed characterization of Blbp in the entire brain and open up a broad field of research investigating the role of omega-3 polyunsaturated fatty acids in neural stem cell activity in fish. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of pharmacokinetics of newly discovered aromatase inhibitors by a cassette microdosing approach in healthy Japanese subjects.

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Kusuhara, Hiroyuki; Takashima, Tadayuki; Fujii, Hisako; Takashima, Tsutomu; Tanaka, Masaaki; Ishii, Akira; Tazawa, Shusaku; Takahashi, Kazuhiro; Takahashi, Kayo; Tokai, Hidekichi; Yano, Tsuneo; Kataoka, Makoto; Inano, Akihiro; Yoshida, Suguru; Hosoya, Takamitsu; Sugiyama, Yuichi; Yamashita, Shinji; Hojo, Taisuke; Watanabe, Yasuyoshi

2017-12-01

The aim of the present study is to investigate the pharmacokinetics of our newly developed aromatase inhibitors (cetrozole and TMD-322) in healthy subjects by a cassette microdose strategy. A cocktail of cetrozole and TMD-322 was administered intravenously or orally (1.98 μg for each drug) to six healthy volunteers in a crossover fashion. Anastrozole (1.98 μg) was also included in the oral cocktail. Total body clearance and bioavailability were 12.1 ± 7.1 mL/min/kg and 34.9 ± 32.3% for cetrozole, and 16.8 ± 3.5 mL/min/kg and 18.4 ± 12.2% for TMD-322, respectively. The area under the plasma concentration-time curves of cetrozole and TMD-322 after oral administration was markedly lower than that of anastrozole because of their high hepatic clearance. Two subjects out of six exhibited 4- and 17-fold larger exposure of cetrozole than the others following intravenous and oral administration, respectively. Such variation was not observed for TMD-322 and anastrozole. Extensive metabolism of cetrozole and TMD-322 was observed in the CYP2C19 expression system among the test CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). We report the first clinical investigation of our aromatase inhibitors by a cassette microdose strategy in healthy Japanese subjects. This strategy offers an optional approach for candidate selection as a phase zero study in drug development. Copyright © 2017. Published by Elsevier Ltd.

Musculoskeletal Adverse Events Associated with Adjuvant Aromatase Inhibitors

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Qamar J. Khan

2010-01-01

Full Text Available Musculoskeletal symptoms including arthralgia and myalgia occur frequently in aging women, particularly during the transition to menopause, when plasma estrogens precipitously decline. In postmenopausal women (PMW with breast cancer, third-generation aromatase inhibitors (AIs as adjuvant hormonal therapy have proven to be more effective, and to have a more predictable side effect profile, than tamoxifen. However, AIs further reduce plasma estrogens in PMW, exacerbating musculoskeletal symptoms. Clinical trial data have shown significantly higher incidences of arthralgia and myalgia with AIs compared with women on tamoxifen or placebo. Symptoms may be severe enough to significantly affect quality of life; musculoskeletal symptoms are a frequent reason for discontinuing therapy. In many cases, symptoms can be effectively managed with oral analgesics or other strategies. Early recognition and effective management of musculoskeletal symptoms can help maximize treatment compliance, enabling patients to derive optimal benefit from therapy in terms of preventing recurrence.

Short Stature in Chronic Kidney Disease Treated with Growth Hormone and an Aromatase Inhibitor

OpenAIRE

Mendley, Susan R.; Spyropoulos, Fotios; Counts, Debra R.

2015-01-01

We describe an alternative strategy for management of severe growth failure in a 14-year-old child who presented with advanced chronic kidney disease close to puberty. The patient was initially treated with growth hormone for a year until kidney transplantation, followed immediately by a year-long course of an aromatase inhibitor, anastrozole, to prevent epiphyseal fusion and prolong the period of linear growth. Outcome was excellent, with successful transplant and anticipated complete correc...

Estrogenic effects of several BPA analogs in the developing zebrafish brain

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Joel eCano-Nicolau

2016-03-01

Full Text Available Important set of studies have demonstrated the endocrine disrupting activity of Bisphenol A (BPA. The present work aimed at defining estrogenic-like activity of several BPA structural analogs, including BPS, BPF, BPAF, and BPAP, on 4-day or 7-day post-fertilization (dpf zebrafish larva as an in vivo model. We measured the induction level of the estrogen-sensitive marker cyp19a1b gene (Aromatase B, expressed in the brain, using three different in situ/in vivo strategies: 1 Quantification of cyp19a1b transcripts using RT-qPCR in wild type 7-dpf larva brains exposed to bisphenols ; 2 Detection and distribution of cyp19a1b transcripts using in situ hybridization on 7-dpf brain sections (hypothalamus; and 3 Quantification of the cyp19a1b promoter activity in live cyp19a1b-GFP transgenic zebrafish (EASZY assay at 4-dpf larval stage. These three different experimental approaches demonstrated that BPS, BPF or BPAF exposure, similarly to BPA, significantly activates the expression of the estrogenic marker in the brain of developing zebrafish. In vitro experiments using both reporter gene assay in a glial cell context and competitive ligand binding assays strongly suggested that up-regulation of cyp19a1b is largely mediated by the zebrafish estrogen nuclear receptor alpha (zfERα. Importantly, and in contrast to other tested bisphenol A analogs, the bisphenol AP (BPAP did not show estrogenic activity in our model.

Arts-based social skills interventions for adolescents with acquired brain injuries: five case reports.

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Agnihotri, Sabrina; Gray, Julia; Colantonio, Angela; Polatajko, Helene; Cameron, Deb; Wiseman-Hakes, Catherine; Rumney, Peter; Keightley, Michelle

2014-02-01

Previous research has demonstrated the value of arts-based programs for adolescents with childhood brain disorder to facilitate social skills and participation. The current study extends this work by examining the feasibility and effectiveness of an arts-based intervention for youth with acquired brain injuries (ABI). A case study approach was used with four adolescent participants and one case control. A battery of quantitative measures were administered four and one week pre-intervention, one week post-intervention, as well six to eight month post-intervention. Improvements in pragmatic communication skills and social and participation goals were observed across intervention participants. Similar improvements were not seen with the case control participant. Results support the use of an arts-based intervention for youth with ABI to facilitate social skills and participation. Findings also highlight the need for more sensitive measures of these skills for these youth. Suggested guidelines for program implementation are provided.

Template based rodent brain extraction and atlas mapping.

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Weimin Huang; Jiaqi Zhang; Zhiping Lin; Su Huang; Yuping Duan; Zhongkang Lu

2016-08-01

Accurate rodent brain extraction is the basic step for many translational studies using MR imaging. This paper presents a template based approach with multi-expert refinement to automatic rodent brain extraction. We first build the brain appearance model based on the learning exemplars. Together with the template matching, we encode the rodent brain position into the search space to reliably locate the rodent brain and estimate the rough segmentation. With the initial mask, a level-set segmentation and a mask-based template learning are implemented further to the brain region. The multi-expert fusion is used to generate a new mask. We finally combine the region growing based on the histogram distribution learning to delineate the final brain mask. A high-resolution rodent atlas is used to illustrate that the segmented low resolution anatomic image can be well mapped to the atlas. Tested on a public data set, all brains are located reliably and we achieve the mean Jaccard similarity score at 94.99% for brain segmentation, which is a statistically significant improvement compared to two other rodent brain extraction methods.

High progesterone levels during the luteal phase related to the use of an aromatase inhibitor in breast cancer patients

DEFF Research Database (Denmark)

Alviggi, C; Marci, R; Vallone, R

2017-01-01

OBJECTIVE: To evaluate the hormonal profile in three breast cancer patients who underwent controlled ovarian stimulation in the presence of the aromatase inhibitor letrozole. PATIENTS AND METHODS: In IVF University referral center, a case series of three breast cancer patients who underwent contr...

Melanoma brain metastases presenting as delirium: a case report

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Sofia Morais

Full Text Available Abstract Background Metastatic tumours sometimes present with neuropsychiatric symptoms, however psychiatric symptoms as rarely the first clinical manifestation. Cutaneous melanoma is the third most common cause of brain metastasis, with known risk factors increasing the chance of such central nervous system metastization. Objectives We present a clinical report of delirium as the first clinical manifestation of melanoma brain metastases, illustrating the relevance of an adequate and early differential diagnosis. Methods In addition to describing the clinical case, searches were undertaken in PubMed and other databases using keywords such as “brain metastasis”, “melanoma”, “agitation”, “psychiatric” and “delirium”. Results We here report the case of a 52-year-old female patient evaluated by Liaison Psychiatry after sudden onset of delirium while admitted at the Gastroenterology Department to study a hypothesis of pancreatitis. A head CT scan identified brain metastases, and after further examination, including brain biopsy, melanoma brain metastization was confirmed. Discussion Some of the diagnostic challenges of psychiatric symptoms associated with secondary brain tumours are discussed, underlining the importance of an adequate differential diagnosis when working in Psychiatry Liaison.

Gonadal expression of aromatase and estrogen receptor alpha genes in two races of Tunisian mice and their hypofertile hybrids.

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Saïd, Lamia; Delalande, Christelle; Britton-Davidian, Janice; Saïd, Khaled; Saad, Ali; Carreau, Serge

2007-07-01

House mice (Mus musculus domesticus) in Tunisia consists of two races, one carries the 40-acrocentric standard karyotypes and the other one is a robertsonian race (2n=22) homozygous for nine centric fusions (Rb). The F1 hybrids between the two chromosomal races showed a significant decrease in reproductive success and litter size. Such results can be related to the formation of meiotic trivalent in the hybrids leading to the production of viable aneuploid gametes and post-zygotic elimination of embryos due to chromosomal non disjunction events at meiosis. Moreover, testicular histology of F1 and backcross males showed in some cases a breakdown in spermatogenesis. In both females and males, androgens but also estrogens play an important role in gametogenesis. In this study, we have studied aromatase and estrogen receptor alpha (ERalpha) gene expression in the gonads of the two parental races and their chromosomal hybrids. The results showed that aromatase and ERalpha mRNAs are expressed in hybrid males of inter-racial crosses (female22Rb x male40Std and female40Std x male22Rb) and in hybrid females of inter-racial crosses (female22Rb x male40Std) as in the two parental races. However, in hybrid females of inter-racial crosses (female40Std x male22Rb) the amount of aromatase transcripts decreased sharply suggesting that this gene is involved in the breakdown of hybrid fertility in females, but not in males. However, in hybrid males, a putative post-translational modification of this enzyme, in terms of activity, should be verified.

Tuberculous brain abscess-Case report

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Veenu Gupta

2012-10-01

Full Text Available In spite of recent advances in understanding of disease, tuberculosis still remains a major health problem, particularly in developing countries. Central nervous system tuberculosis may present as commonly encountered tuberculous meningitis or tuberculous mass lesions and rare tuberculous brain abscess (TBA. We report a case of tuberculous brain abscess in a patient of chronic liver disease with pulmonary hypertension and HCV infection. A 48 years old male presented with headache and abnormal behavior. There was no history of fever, vomiting, loss of consciousness, seizures, trauma and loss of weight and appetite. On examination patient was conscious but confused. No sensory- motor deficit was revealed on neurological examination. Chest x ray showed no abnormality. Mantoux test was positive. Magnetic resonance imaging of brain showed large , well defined marginally enhancing focal mass lesion in left frontal lobe. Evacuation of brain abscess done and frank creamy pus was aspirated and was sent for gram staining, Ziehl Neelsen staining, fungal smear and culture for both pyogenic and Mycobacterium tuberculosis. Gram staining revealed no microorganisms. No growth of pyogenic organisms obtained. No fungal hypha was seen. Ziehl Neelsen staining was positive for acid fast bacilli and growth of Mycobacterium tuberculosis was obtained. Patient was put on anti tubercular treatment. Patient responded well and discharged in satisfactory condition.

Characterization and expression profile of the ovarian cytochrome P-450 aromatase (cyp19A1) gene during thermolabile sex determination in Pejerrey, Odontesthes bonariensis

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Karube, M.; Fernandino, J.I.; Strobl-Mazzulla, P.; Strussmann, C.A.; Yoshizaki, G.; Somoza, G.M.; Patino, R.

2007-01-01

Cytochrome P450 aromatase (cyp19) is an enzyme that catalyzes the conversion of androgens to estrogens and may play a role in temperature- dependent sex determination (TSD) of reptiles, amphibians, and fishes. In this study, the ovarian P450 aromatase form (cyp19A1) of pejerrey Odontesthes bonariensis, a teleost with marked TSD, was cloned and its expression profile evaluated during gonadal differentiation at feminizing (17??C, 100% females), mixed-sex producing (24 and 25??C, 73.3 and 26.7% females, respectively), and masculinizing (29??C, 0% females) temperatures. The deduced cyp19A1 amino acid sequence shared high identity (>77.8%) with that from other teleosts but had low identity (<61.8%) with brain forms (cyp19A2), including that of pejerrey itself. The tissue distribution analysis of cyp19A1 mRNA in adult fish revealed high expression in the ovary. Semi-quantitative reverse transcription polymerase chain reaction analysis of the bodies of larvae revealed that cyp19A1 expression increased before the appearance of the first histological signs of ovarian differentiation at the feminizing temperature but remained low at the masculinizing temperature. The expression levels at mixed-sex producing temperatures were bimodal rather than intermediate, showing low and high modal values similar to those at the feminizing and masculinizing temperatures, respectively. The population percentages of high and low expression levels at intermediate temperatures were proportional to the percentage of females and males, respectively, and high levels were first observed at about the time of sex differentiation of females. These results suggest that cyp19A1 is involved in the process of ovarian formation and possibly also in the TSD of pejerrey. ?? 2007 Wiley-Liss, Inc.

Informant Report of Financial Capacity for Individuals With Chronic Acquired Brain Injury: An Assessment of Informant Accuracy.

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Sunderaraman, Preeti; Cosentino, Stephanie; Lindgren, Karen; James, Angela; Schultheis, Maria

2018-03-29

Primarily, to investigate the association between informant report and objective performance on specific financial capacity (FC) tasks by adults with chronic, moderate to severe acquired brain injury, and to examine the nature of misestimates by the informants. Cross-sectional design. A postacute, community-based rehabilitation center. Data were obtained from 22 chronic acquired brain injury (CABI) adults, mean age of 46.6 years (SD = 8.67), mean years of education of 13.45 years (SD = 2.15), with moderate to severe acquired brain injury (86% had traumatic brain injury), with a mean postinjury period of 17.14 years (SD = 9.5). Whereas the CABI adults completed the Financial Competence Assessment Inventory interview-a combination of self-report and performance-based assessment, 22 informants completed a specifically designed parallel version of the interview. Pearson correlations and 1-sample t tests based on the discrepancy scores between informant report and CABI group's performance were used. The CABI group's performance was not associated with its informant's perceptions. One-sample t tests revealed that informants both underestimated and overestimated CABI group's performance. Results indicate lack of correspondence between self- and informant ratings. Further investigation revealed that misestimations by informants occurred in contrary directions with CABI adults' performance being inaccurately rated. These findings raise critical issues related to assuming that the informant report can be used as a "gold standard" for collecting functional data related to financial management, and the idea that obtaining objective data on financial tasks may represent a more valid method of assessing financial competency in adults with brain injury.

On the effects of testosterone on brain behavioral functions

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Peter eCelec

2015-02-01

Full Text Available Testosterone influences the brain via organizational and activational effects. Numerous relevant studies on rodents and a few on humans focusing on specific behavioral and cognitive parameters have been published. The results are, unfortunately, controversial and puzzling. Dosing, timing, even the application route seem to considerably affect the outcomes. In addition, the methods used for the assessment of psychometric parameters are a bit less than ideal regarding their validity and reproducibility. Metabolism of testosterone contributes to the complexity of its actions. Reduction to dihydrotestosterone by 5-alpha reductase increases the androgen activity; conversion to estradiol by aromatase converts the androgen to estrogen activity. Recently, the non-genomic effects of testosterone on behavior bypassing the nuclear receptors have attracted the interest of researchers. This review tries to summarize the current understanding of the complexity of the effects of testosterone on brain with special focus on their role in the known sex differences.

The Credentials of Brain-Based Learning

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Davis, Andrew

2004-01-01

This paper discusses the current fashion for brain-based learning, in which value-laden claims about learning are grounded in neurophysiology. It argues that brain science cannot have the authority about learning that some seek to give it. It goes on to discuss whether the claim that brain science is relevant to learning involves a category…

Effects of the aromatase inhibitor Letrozole on serum immunoglobulin and lysozyme levels in immunized rainbow trout (Oncorhynchus mykiss Walbaum females

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Paria Akbary

2013-12-01

Full Text Available Letrozole is a synthetic aromatase inhibitor and interfere in the committed step in the synthesis of endogenous estrogens from androgens. Also estrogens regulate the immune system in teleost. Changes of 17- β- esrtradiol (E2, serum immunoglobulin and lysozyme levels were measured using a method based on the ability of lysozyme to lyse the bacterium Micrococcus lysodeikticus, enzyme-linked immunosorbent assay (ELISA and ELISA respectively. Twelve broodstocks were injected weekly with 2.5 mg kg-1 letrozole (an endocrine disrupter component two months before spawning season and vaccinated intraperitoneally (i.p with a bacterin (inactivated L. garviae one month before spawning. Twelve broodstocks for vaccination and twelve female rainbow trout as control group were also immiunised (i.p with the bacterin and injected (i.p with PBS, respectively. In the group received 2.5 mg AI kg-1 per week, serum E2 levels were significantly lower than that of other groups. Total immunoglobulin level and lysozyme activity were significantly higher in the parents received 2.5 mg kg-1 per week and were immunized with 10-9 cells ml-1 Lactococcus garvieae  compared to the group which immunized with L. garvieae and the control (non- immunized. The present study, suggests that aromatase inhibitors such as letrozole may be a potential tool to regulate the synthesis of E2, is involved in the hormone- immune system interaction in rainbow trout.

Brain-Based Teaching/Learning and Implications for Religious Education.

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Weber, Jean Marie

2002-01-01

Argues that physical activity and water can increase brain activity, and hence, learning. Findings of neuroscientists regarding the brain can inform educators. Brain-based teaching emphasizes teamwork, cooperative learning, and global responsibility. Argues against gathering information without relevance. Connects brain-based learning concepts to…

Polymerase chain reaction amplification fails to detect aromatase cytochrome P450 transcripts in normal human endometrium or decidua.

Science.gov (United States)

Bulun, S E; Mahendroo, M S; Simpson, E R

1993-06-01

It has been proposed that the biosynthesis of estrogens by the human endometrium may be of physiological significance during the menstrual cycle. Local estrogen production was also suggested to be important in the development of endometrial cancer; however, the presence or absence of aromatase enzyme activity in normal human endometrium is controversial. To address this issue, we used a sensitive technique capable of detecting mRNA transcripts present in only very low copy number. The polymerase chain reaction linked to reverse transcription (RT-PCR) was used to evaluate the presence or absence of aromatase cytochrome P450 (P450arom) transcripts in endometrial tissues (n = 7) and endometrial stromal cells (n = 9) under various culture conditions. RNA was isolated from four proliferative and three secretory tissue samples and from cultured endometrial stromal cells isolated from seven proliferative and two secretory endometria. Five sets of cultures were treated with medroxyprogesterone acetate (MPA), estradiol (E2), and forskolin. Additionally, RNA was isolated from decidualized endometrium obtained from a patient with tubal pregnancy. A single stranded cDNA was synthesized from total RNA using Moloney murine leukemia virus reverse transcriptase and a P450arom-specific oligonucleotide. The single stranded cDNA was used as a template for PCR and was amplified for 20-35 cycles using P450arom-specific primers. RNA from adipose tissue and placenta was amplified to provide positive controls, whereas myometrial RNA was used as a negative control. In two experiments involving two endometrial tissues and three sets of cells in culture, a rat P450arom cRNA was coamplified in each sample as an internal control to demonstrate that the remote possibility of RT-PCR failures in individual test samples cannot account for our negative results. By Southern or slot blot hybridization of the amplified fragments using human and rat P450arom-specific probes, we found no evidence for

Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

Energy Technology Data Exchange (ETDEWEB)

Gorrochategui, Eva; Pérez-Albaladejo, Elisabet [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Casas, Josefina [Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain); Lacorte, Sílvia, E-mail: slbqam@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Porte, Cinta, E-mail: cinta.porte@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)

2014-06-01

The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

International Nuclear Information System (INIS)

Gorrochategui, Eva; Pérez-Albaladejo, Elisabet; Casas, Josefina; Lacorte, Sílvia; Porte, Cinta

2014-01-01

The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

GP88 (PC-Cell Derived Growth Factor, progranulin stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

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Sabnis Gauri

2011-06-01

Full Text Available Abstract Background Aromatase inhibitors (AI that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER+ breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88, also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER+ breast cancer cells Methods We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined. Results GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole. Conclusion Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer.

"Brain sex differentiation" in teleosts: Emerging concepts with potential biomarkers.

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Senthilkumaran, Balasubramanian; Sudhakumari, Cheni-Chery; Mamta, Sajwan-Khatri; Raghuveer, Kavarthapu; Swapna, Immani; Murugananthkumar, Raju

2015-09-01

"Brain sex differentiation" in teleosts is a contentious topic of research as most of the earlier reports tend to suggest that gonadal sex differentiation drives brain sex differentiation. However, identification of sex-specific marker genes in the developing brain of teleosts signifies brain-gonadal interaction during early sexual development in lower vertebrates. In this context, the influence of gonadotropin-releasing hormone (GnRH)-gonadotropin (GTH) axis on gonadal sex differentiation, if any requires in depth analysis. Presence of seabream (sb) GnRH immunoreactivity (ir-) in the brain of XY Nile tilapia was found as early as 5days post hatch (dph) followed by qualitative reduction in the preoptic area-hypothalamus region. In contrast, in the XX female brain a steady ir- of sbGnRH was evident from 15dph. Earlier studies using sea bass already implied the importance of hypothalamic gonadotropic axis completion during sex differentiation period. Such biphasic pattern of localization was also seen in pituitary GTHs using heterologous antisera in tilapia. However, more recent analysis in the same species could not detect any sexually dimorphic pattern using homologous antisera for pituitary GTHs. Detailed studies on the development of hypothalamo-hypophyseal-gonadal axis in teleosts focusing on hypothalamic monoamines (MA) and MA-related enzymes demonstrated sex-specific differential expression of tryptophan hydroxylase (Tph) in the early stages of developing male and female brains of tilapia and catfish. The changes in Tph expression was in agreement with the levels of serotonin (5-HT) and 5-hydroxytryptophan in the preoptic area-hypothalamus. Considering the stimulatory influence of 5-HT on GnRH and GTH release, it is possible to propose a network association between these correlates during early development, which may bring about brain sex dimorphism in males. A recent study from our laboratory during female brain sex development demonstrated high expression of

Signifikansi Brain Based Learning Pendidikan Anak Usia Dini

OpenAIRE

Jazariyah

2017-01-01

This study based on the reality of learning in the early childhood level and the system has not noticed the potential of the brain learners. The potential and the working system of the brain is very important in early childhood. This paper aims to reveal the importance of brain-based learning in Early Childhood Education (ECD). The problem in this study is what the nature of early childhood education and how to use the potential and work system of the brain in early childhood learning. This s...

Accuracy of radiographer reporting of paediatric brain CT

International Nuclear Information System (INIS)

Brandt, Andrew; Louw, Brand; Dekker, Gerrit; Andronikou, Savvas; Wieselthaler, Nicki; Kilborn, Tracy; Bertelsman, Jessica; Dreyer, Catherine

2007-01-01

Radiographer reporting has been studied for plain films and for ultrasonography, but not in paediatric brain CT in the emergency setting. To study the accuracy of radiographer reporting in paediatric brain CT. We prospectively collected 100 paediatric brain CT examinations. Films were read from hard copies using a prescribed tick sheet. Radiographers with 12 years' and 3 years' experience, respectively, were blinded to the history and were not trained in diagnostic film interpretation. The radiographers' results were compared with those of a consultant radiologist. Three categories were defined: abnormal scans, significant abnormalities and insignificant abnormalities. Both radiographers had an accuracy of 89.5% in reading a scan correctly as abnormal, and radiographer 1 had a sensitivity of 87.8% and radiographer 2 a sensitivity of 96%. Radiographer 1 had an accuracy in detecting a significant abnormality of 75% and radiographer 2 an accuracy of 48.6%, and the sensitivities for this category were 61.6% and 52.9%, respectively. Results for detecting the insignificant abnormalities were poorer. Selected radiographers could play an effective screening role, but lacking the sensitivity required for detecting significant abnormality, they could not be the final diagnostician. We recommend that the study be repeated after both radiographers have received formal training in interpretation of paediatric brain CT. (orig.)

Histone deacetylation during brain development is essential for permanent masculinization of sexual behavior.

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Matsuda, Ken Ichi; Mori, Hiroko; Nugent, Bridget M; Pfaff, Donald W; McCarthy, Margaret M; Kawata, Mitsuhiro

2011-07-01

Epigenetic histone modifications are emerging as important mechanisms for conveyance of and maintenance of effects of the hormonal milieu to the developing brain. We hypothesized that alteration of histone acetylation status early in development by sex steroid hormones is important for sexual differentiation of the brain. It was found that during the critical period for sexual differentiation, histones associated with promoters of essential genes in masculinization of the brain (estrogen receptor α and aromatase) in the medial preoptic area, an area necessary for male sexual behavior, were differentially acetylated between the sexes. Consistent with these findings, binding of histone deacetylase (HDAC) 2 and 4 to the promoters was higher in males than in females. To examine the involvement of histone deacetylation on masculinization of the brain at the behavioral level, we inhibited HDAC in vivo by intracerebroventricular infusion of the HDAC inhibitor trichostatin A or antisense oligodeoxynucleotide directed against the mRNA for HDAC2 and -4 in newborn male rats. Aspects of male sexual behavior in adulthood were significantly reduced by administration of either trichostatin A or antisense oligodeoxynucleotide. These results demonstrate that HDAC activity during the early postnatal period plays a crucial role in the masculinization of the brain via modifications of histone acetylation status.

Short Stature in Chronic Kidney Disease Treated with Growth Hormone and an Aromatase Inhibitor

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Susan R. Mendley

2015-01-01

Full Text Available We describe an alternative strategy for management of severe growth failure in a 14-year-old child who presented with advanced chronic kidney disease close to puberty. The patient was initially treated with growth hormone for a year until kidney transplantation, followed immediately by a year-long course of an aromatase inhibitor, anastrozole, to prevent epiphyseal fusion and prolong the period of linear growth. Outcome was excellent, with successful transplant and anticipated complete correction of height deficit. This strategy may be appropriate for children with chronic kidney disease and short stature who are in puberty.

Navigation with a passive brain based interface

NARCIS (Netherlands)

Erp, J.B.F. van; Werkhoven, P.J.; Thurlings, M.E.; Brouwer, A.-M.

2009-01-01

In this paper, we describe a Brain Computer Interface (BCI) for navigation. The system is based on detecting brain signals that are elicited by tactile stimulation on the torso indicating the desired direction.

The multiple brain abscesses associated with congenital pulmonary arteriovenous malformations: a case report.

OpenAIRE

Han, Seok; Lim, Dong-Jun; Chung, Yong-Gu; Cho, Tai-Hyoung; Lim, Seong-Jun; Kim, Woo-Jae; Park, Jung-Yul; Suh, Jung-Keun

2002-01-01

In this report, we describe a case of multiple brain abscesses associated with diffuse congenital pulmonary arteriovenous malformations (PAVM). Although the cases of brain abscesses associated with congenital PAVM are very rare, the brain abscess could be an initial clinical manifestation in asymptomatic PAVM as in the case presented in this report. PAVM may contribute to the development of a brain abscess by allowing easy bacterial access to systemic circulation through the right-to-left pul...

Brain abscess associated with ethmoidal sinus osteoma: A case report

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Hiroaki Nagashima

2014-12-01

Full Text Available Osteoma of the paranasal sinus is uncommon, and the occurrence of brain abscess associated with ethmoidal osteoma is particularly rare. We report here a case of a brain abscess complicating an ethmoidal osteoma in a 68-year-old man who presented with high-grade fever and disturbance in the level of consciousness. Computed tomography scanning and magnetic resonance imaging revealed a ring-enhancing mass in the left frontal lobe with surrounding edema and a bony mass in the ethmoidal sinus. We scheduled a two-stage operation. First, emergency aspiration and drainage of the abscess via the forehead were performed to reduce the abscess volume. These were followed by a left frontal craniotomy to totally remove both the brain abscess and the bony mass. The bony mass had breached the dura mater. After removing the bony mass, we repaired the anterior skull base using a pericranial flap. Pathological findings of the bony tumor were consistent with osteoma. The postoperative course was uneventful. In the case of a huge brain abscess associated with an ethmoidal osteoma, volume reduction by drainage followed by surgical removal of both lesions may help to control infection and achieve a cure. Use of a vascularized pericranial flap is important to prevent direct communication between the paranasal sinuses and the cranial cavity.

Applying Brain-Based Learning Principles to Athletic Training Education

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Craig, Debbie I.

2007-01-01

Objective: To present different concepts and techniques related to the application of brain-based learning principles to Athletic Training clinical education. Background: The body of knowledge concerning how our brains physically learn continues to grow. Brain-based learning principles, developed by numerous authors, offer advice on how to…

Mixed acid-base disorder secondary to topiramate use in traumatic brain injury

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S Golla

2016-01-01

Full Text Available We report a case of a man with traumatic brain injury. He was started on to prophylactic topiramate which led to a mixed acid-base disorder. He had severe metabolic acidosis secondary to renal tubular acidification defect and respiratory alkalosis secondary to hyperventilation. Withdrawal of the offending drug led to the prompt resolution of the acid-base disturbance.

Kocuria varians infection associated with brain abscess: a case report.

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Tsai, Cheng-Yu; Su, Shou-hsin; Cheng, Yu-Hsin; Chou, Yu-lin; Tsai, Tai-Hsin; Lieu, Ann-Shung

2010-04-27

Kocuria, established by Stackebrandt et al., previously was classified into Micrococcus. Only two species, K. rosea and K. kristinae are reported to be associated as pathogenic and found with catheter-related bacteremia and acute cholecystitis. We herein report the first case of brain abscess caused by Kocuria varians, a gram-positive microorganism, in a 52-year-old man. Hematogenous spread is the probable pathogenesis. This report presents a case of Kocuria varians brain abscess successfully treated with surgical excision combined with antimicrobial therapy. In addition, Vitek 2 system has been used to identify and differentiate between coagulase-negative staphylococcus.

Short-term androgen priming by use of aromatase inhibitor and hCG before controlled ovarian stimulation for IVF. A randomized controlled trial

DEFF Research Database (Denmark)

Lossl, K; Andersen, C Yding; Loft, A

2008-01-01

Temporary exposure of follicles to increased levels of androgens may augment follicular responsiveness. The present study tested whether short-term androgen priming by aromatase inhibitor and human chorionic gonadotrophin (hCG) before controlled ovarian stimulation (COS) increases the number of top......-quality embryos after IVF/ICSI....

Hemispheric asymmetry of electroencephalography-based functional brain networks.

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Jalili, Mahdi

2014-11-12

Electroencephalography (EEG)-based functional brain networks have been investigated frequently in health and disease. It has been shown that a number of graph theory metrics are disrupted in brain disorders. EEG-based brain networks are often studied in the whole-brain framework, where all the nodes are grouped into a single network. In this study, we studied the brain networks in two hemispheres and assessed whether there are any hemispheric-specific patterns in the properties of the networks. To this end, resting state closed-eyes EEGs from 44 healthy individuals were processed and the network structures were extracted separately for each hemisphere. We examined neurophysiologically meaningful graph theory metrics: global and local efficiency measures. The global efficiency did not show any hemispheric asymmetry, whereas the local connectivity showed rightward asymmetry for a range of intermediate density values for the constructed networks. Furthermore, the age of the participants showed significant direct correlations with the global efficiency of the left hemisphere, but only in the right hemisphere, with local connectivity. These results suggest that only local connectivity of EEG-based functional networks is associated with brain hemispheres.

Expression of estrogen-related gene markers in breast cancer tissue predicts aromatase inhibitor responsiveness.

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Irene Moy

Full Text Available Aromatase inhibitors (AIs are the most effective class of drugs in the endocrine treatment of breast cancer, with an approximate 50% treatment response rate. Our objective was to determine whether intratumoral expression levels of estrogen-related genes are predictive of AI responsiveness in postmenopausal women with breast cancer. Primary breast carcinomas were obtained from 112 women who received AI therapy after failing adjuvant tamoxifen therapy and developing recurrent breast cancer. Tumor ERα and PR protein expression were analyzed by immunohistochemistry (IHC. Messenger RNA (mRNA levels of 5 estrogen-related genes-AKR1C3, aromatase, ERα, and 2 estradiol/ERα target genes, BRCA1 and PR-were measured by real-time PCR. Tumor protein and mRNA levels were compared with breast cancer progression rates to determine predictive accuracy. Responsiveness to AI therapy-defined as the combined complete response, partial response, and stable disease rates for at least 6 months-was 51%; rates were 56% in ERα-IHC-positive and 14% in ERα-IHC-negative tumors. Levels of ERα, PR, or BRCA1 mRNA were independently predictive for responsiveness to AI. In cross-validated analyses, a combined measurement of tumor ERα and PR mRNA levels yielded a more superior specificity (36% and identical sensitivity (96% to the current clinical practice (ERα/PR-IHC. In patients with ERα/PR-IHC-negative tumors, analysis of mRNA expression revealed either non-significant trends or statistically significant positive predictive values for AI responsiveness. In conclusion, expression levels of estrogen-related mRNAs are predictive for AI responsiveness in postmenopausal women with breast cancer, and mRNA expression analysis may improve patient selection.

Kocuria varians infection associated with brain abscess: A case report

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Tsai Tai-Hsin

2010-04-01

Full Text Available Abstract Background Kocuria, established by Stackebrandt et al., previously was classified into Micrococcus. Only two species, K. rosea and K. kristinae are reported to be associated as pathogenic and found with catheter-related bacteremia and acute cholecystitis. Case presentation We herein report the first case of brain abscess caused by Kocuria varians, a gram-positive microorganism, in a 52-year-old man. Hematogenous spread is the probable pathogenesis. Conclusions This report presents a case of Kocuria varians brain abscess successfully treated with surgical excision combined with antimicrobial therapy. In addition, Vitek 2 system has been used to identify and differentiate between coagulase-negative staphylococcus.

Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: The BATMAN Trial.

Science.gov (United States)

Lomax, Anna J; Yee Yap, Saw; White, Karen; Beith, Jane; Abdi, Ehtesham; Broad, Adam; Sewak, Sanjeev; Lee, Chooi; Sambrook, Philip; Pocock, Nicholas; Henry, Margaret J; Yeow, Elaine G; Bell, Richard

2013-12-01

Postmenopausal women on aromatase inhibitors (AI) are at risk of aromatase inhibitor-associated bone loss (AIBL) and fractures. In 2005 Osteoporosis Australia proposed an algorithm for bisphosphonate intervention. Three hundred and three postmenopausal women with early breast cancer (EBC) were enrolled (osteoporotic, n=25; osteopaenic, n=146; normal bone mineral density (BMD), n=126). Weekly alendronate (70 mg) treatment efficacy as triggered by the algorithm in preventing bone loss was evaluated. All patients received anastrozole (1 mg daily), calcium and vitamin D. All osteoporotic patients received alendronate at baseline. Eleven out of the 146 (7.5%) osteopaenic patients commenced alendronate within 18 months of participation and eleven commenced after. One hundred and twenty four out of the 146 (84.9%) osteopaenic patients and all 126 with normal baseline BMD did not trigger the algorithm. At three years, lumbar spine mean BMD increased (15.6%, p<0.01) in the osteoporotic group. BMD in the osteopaenic group with early intervention significantly increased at three years (6.3%, p=0.02). No significant change was seen in the late intervention group. No change was observed in those with osteopaenia without alendronate. There was a significant drop in lumbar spine (-5.4%) and hip (-4.5%) mean BMD, in the normal BMD group, none of whom received alendronate. Fracture data will be presented. In postmenopausal women with endocrine-responsive EBC, BMD improved over time when a bisphosphonate is administered with anastrozole in osteoporotic patients using an osteoporosis schedule. Subjects with normal baseline BMD experienced the greatest BMD loss, although none became osteoporotic.

A human friendly reporting and database system for brain PET analysis

International Nuclear Information System (INIS)

Jamzad, M.; Ishii, Kenji; Toyama, Hinako; Senda, Michio

1996-01-01

We have developed a human friendly reporting and database system for clinical brain PET (Positron Emission Tomography) scans, which enables statistical data analysis on qualitative information obtained from image interpretation. Our system consists of a Brain PET Data (Input) Tool and Report Writing Tool. In the Brain PET Data Tool, findings and interpretations are input by selecting menu icons in a window panel instead of writing a free text. This method of input enables on-line data entry into and update of the database by means of pre-defined consistent words, which facilitates statistical data analysis. The Report Writing Tool generates a one page report of natural English sentences semi-automatically by using the above input information and the patient information obtained from our PET center's main database. It also has a keyword selection function from the report text so that we can save a set of keywords on the database for further analysis. By means of this system, we can store the data related to patient information and visual interpretation of the PET examination while writing clinical reports in daily work. The database files in our system can be accessed by means of commercially available databases. We have used the 4th Dimension database that runs on a Macintosh computer and analyzed 95 cases of 18 F-FDG brain PET studies. The results showed high specificity of parietal hypometabolism for Alzheimer's patients. (author)

Prevalence of Self-Reported Lifetime History of Traumatic Brain Injury and Associated Disability: A Statewide Population-Based Survey.

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Whiteneck, Gale G; Cuthbert, Jeffrey P; Corrigan, John D; Bogner, Jennifer A

2016-01-01

To investigate the prevalence of all severities of traumatic brain injury (TBI), regardless of treatment setting, and their associated negative outcomes. A total of 2701 adult Coloradoans. A statewide, population-based, random digit-dialed telephone survey. The lifetime history of TBI was assessed by a modification of the Ohio State University TBI Identification Method; activity limitation and life satisfaction were also assessed. The distribution of self-reported lifetime injury was as follows: 19.8%, no injury; 37.7%, injury but no TBI; 36.4%, mild TBI; and 6.0%, moderate-severe TBI. Of those reporting a TBI, 23.1% were hospitalized, 38.5% were treated in an emergency department, 9.8% were treated in a physician's office, and 27.5% did not seek medical care. A clear gradient of activity limitations and low life satisfaction was seen, with the highest proportions of these negative outcomes occurring in people reporting more severe TBI and the lowest proportions in those not reporting a TBI. Approximately twice as many people reported activity limitations and low life satisfaction after nonhospitalized TBI compared with hospitalized TBI. This investigation highlights the seriousness of TBI as a public health problem and the importance of including all severities of TBI, no matter where, or if treated, in estimating the prevalence of disability co-occurring with TBI.

The unique case-report of metachronous brain tumors of different histology

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А. М. Zaitsev

2013-01-01

Full Text Available  The case of unusual course of brain tumor process – metachronous development of breast cancer brain metastasis and then development of malignant glioma is reported. The surgical treatment for both tumors were performed with intraoperative fluorescence diagnosis and photodynamic therapy. Due to multimodality treatment the patient was alive for 15 months from diagnosis of IV stage breast cancer (brain metastasis. 

Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development.

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Bakker, J; Brock, O

2010-07-01

A central tenet of contemporary theories on mammalian brain and behavioural sexual differentiation is that an organisational action of testosterone, secreted by the male's testes, controls male-typical aspects of brain and behavioural development, whereas no active perinatal sex hormone signalling is required for female-typical sexual differentiation. Furthermore, the available evidence suggests that many, although not all, of the perinatal organisational actions of testosterone on the development of the male brain result from the cellular effects of oestradiol formed via neural aromatisation of testosterone. However, a default developmental programme for the female brain has been criticised. Indeed, we review new results obtained in aromatase knockout mice indicating that oestradiol actively contributes to the differentiation of female-typical aspects of brain and behavioural sexual differentiation. Furthermore, we propose that male-typical neural and behavioural differentiation occurs prenatally in genetic males under the influence of oestradiol, which is avoided in foetal genetic females by the neuroprotective actions of alpha-fetoprotein, whereas female-typical neural and behavioural differentiation normally occurs postnatally in genetic females under the influence of oestradiol that is presumably produced by the ovaries.

Case Report: A Case of Severe Cerebral Malaria Managed with Therapeutic Hypothermia and Other Modalities for Brain Edema.

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Gad, AbdAllah; Ali, Sajjad; Zahoor, Talal; Azarov, Nick

2018-04-01

Malarial infections are uncommon in the United States and almost all reported cases stem from recent travelers coming from endemic countries. Cerebral malaria (CM) is a severe form of the disease usually affecting children and individuals with limited immunity. Despite proper management, mortality from CM can reach up to 25%, especially when it is associated with brain edema. Inefficient management of the edema may result in brain herniation and death. Uniform guidelines for management of CM-associated brain edema are lacking. In this report, we present a case of CM with associated severe brain edema that was successfully managed using a unique combination of therapeutic hypothermia, hypertonic saline, mannitol, and hyperventilation along with the antimalarial drugs quinidine and doxycycline. Our use of hypothermia was based on its proven benefit for improving neurological outcomes in post-cardiac arrest patients and previous in vitro research, suggesting its potential inhibitory role on malaria growth.

Tuberculous meningoencephalitis associated with brain tuberculomas during pregnancy: a case report.

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Namani, Sadie; Dreshaj, Shemsedin; Berisha, Arieta Zogaj

2017-06-29

Tuberculous meningitis is globally highly prevalent and is commoner in resource-limited countries and in patients with immunosuppression. Central nervous system tuberculosis is one of the severest forms of extrapulmonary tuberculosis during pregnancy and associated brain tuberculomas have been rarely reported. With the availability of neuroimaging at our hospital center, we present the first case of tuberculous meningoencephalitis associated with brain tuberculomas during pregnancy. In this case report we present a 25-year-old, Albanian, pregnant woman living in an urban area in Kosovo, who at 24 weeks of twin pregnancy manifested signs and symptoms of meningoencephalitis with decreased level of consciousness, hemiparesis, and generalized recurrent seizures. Based on medical history, origin from a region of high prevalence of tuberculosis, clinical presentation, especially neurological examination, cytobiochemical changes in cerebrospinal fluid (mild mononuclear pleocytosis with decreased level of glucose and elevated proteins), and elevated level of interferon-gamma release assay in cerebrospinal fluid, antituberculous therapy was initiated on the fourth day of admission. After 3 weeks of treatment, at 27 weeks of pregnancy, she had a preterm delivery and both twins, with low birthweight, died after 24 and 72 hours. Although findings on chest radiography were normal, brain magnetic resonance imaging showed signs of meningoencephalitis and multiple intracerebral tuberculomas, while Koch's bacillus was isolated from urine cultures. On long-term follow-up after delivery, she was cured with no sequelae and became pregnant again without any additional complications. In countries with a high prevalence of tuberculosis, screening for central nervous system tuberculosis should be considered in the differential diagnosis of meningitis in pregnancy. Cerebral imaging is essential to establish the diagnosis of brain tuberculomas in such a case of suspected tuberculous

Functional community analysis of brain: a new approach for EEG-based investigation of the brain pathology.

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Ahmadlou, Mehran; Adeli, Hojjat

2011-09-15

Analysis of structure of the brain functional connectivity (SBFC) is a fundamental issue for understanding of the brain cognition as well as the pathology of brain disorders. Analysis of communities among sub-parts of a system is increasingly used for social, ecological, and other networks. This paper presents a new methodology for investigation of the SBFC and understanding of the brain based on graph theory and community pattern analysis of functional connectivity graph of the brain obtained from encephalograms (EEGs). The methodology consists of three main parts: fuzzy synchronization likelihood (FSL), community partitioning, and decisions based on partitions. As an example application, the methodology is applied to analysis of brain of patients with attention deficit/hyperactivity disorder (ADHD) and the problem of discrimination of ADHD EEGs from healthy (non-ADHD) EEGs. Copyright © 2011. Published by Elsevier Inc.

Inhibition of hippocampal aromatization impairs spatial memory performance in a male songbird.

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Bailey, David J; Ma, Chunqi; Soma, Kiran K; Saldanha, Colin J

2013-12-01

Recent studies have revealed the presence and regulation of aromatase at the vertebrate synapse, and identified a critical role played by presynaptic estradiol synthesis in the electrophysiological response to auditory and other social cues. However, if and how synaptic aromatization affects behavior remains to be directly tested. We have exploited 3 characteristics of the zebra finch hippocampus (HP) to test the role of synaptocrine estradiol provision on spatial memory function. Although the zebra finch HP contains abundant aromatase transcripts and enzyme activity, immunocytochemical studies reveal widespread pre- and postsynaptic, but sparse to undetectable somal, localization of this enzyme. Further, the superficial location of the avian HP makes possible the more exclusive manipulation of its neurochemical characteristics without perturbation of the neuropil and the resultant induction of astroglial aromatase. Last, as in other vertebrates, the HP is critical for spatial memory performance in this species. Here we report that local inhibition of hippocampal aromatization impairs spatial memory performance in an ecologically valid food-finding task. Local aromatase inhibition also resulted in lower levels of estradiol in the HP, but not in adjacent brain areas, and was achieved without the induction of astroglial aromatase. The observed decrement in acquisition and subsequent memory performance as a consequence of lowered aromatization was similar to that achieved by lesioning this locus. Thus, hippocampal aromatization, much of which is achieved at the synapse in this species, is critical for spatial memory performance.

Brain medical image diagnosis based on corners with importance-values.

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Gao, Linlin; Pan, Haiwei; Li, Qing; Xie, Xiaoqin; Zhang, Zhiqiang; Han, Jinming; Zhai, Xiao

2017-11-21

Brain disorders are one of the top causes of human death. Generally, neurologists analyze brain medical images for diagnosis. In the image analysis field, corners are one of the most important features, which makes corner detection and matching studies essential. However, existing corner detection studies do not consider the domain information of brain. This leads to many useless corners and the loss of significant information. Regarding corner matching, the uncertainty and structure of brain are not employed in existing methods. Moreover, most corner matching studies are used for 3D image registration. They are inapplicable for 2D brain image diagnosis because of the different mechanisms. To address these problems, we propose a novel corner-based brain medical image classification method. Specifically, we automatically extract multilayer texture images (MTIs) which embody diagnostic information from neurologists. Moreover, we present a corner matching method utilizing the uncertainty and structure of brain medical images and a bipartite graph model. Finally, we propose a similarity calculation method for diagnosis. Brain CT and MRI image sets are utilized to evaluate the proposed method. First, classifiers are trained in N-fold cross-validation analysis to produce the best θ and K. Then independent brain image sets are tested to evaluate the classifiers. Moreover, the classifiers are also compared with advanced brain image classification studies. For the brain CT image set, the proposed classifier outperforms the comparison methods by at least 8% on accuracy and 2.4% on F1-score. Regarding the brain MRI image set, the proposed classifier is superior to the comparison methods by more than 7.3% on accuracy and 4.9% on F1-score. Results also demonstrate that the proposed method is robust to different intensity ranges of brain medical image. In this study, we develop a robust corner-based brain medical image classifier. Specifically, we propose a corner detection

Predicting Adherence to Aromatase Inhibitor Therapy among Breast Cancer Survivors: An Application of the Protection Motivation Theory

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Monita Karmakar MS

2017-02-01

Full Text Available The purpose of this observational study was to determine if the Protection Motivation Theory could predict and explain adherence to aromatase inhibitor (AI therapy among breast cancer survivors. Purposive sampling was used to identify 288 survivors who had been prescribed AI therapy. A valid and reliable survey was mailed to survivors. A total of 145 survivors completed the survey. The Morisky scale was used to measure adherence to AI. The survivors reported a mean score of 6.84 (±0.66 on the scale. Nearly 4 in 10 survivors (38% were non-adherent. Adherence differed by age, marital status, insurance status, income, and presence of co-morbid conditions. Self-efficacy (r=0.485, protection motivation (r=0.310, and Response Efficacy (r=0.206 were positively and significantly correlated with adherence. Response Cost (r=-0.235 was negatively correlated with adherence. The coping appraisal constructs were statistically significant predictors medication adherence (β=0.437 with self-efficacy being the strongest significant predictor of adherence (β = 0.429.

Predicting Adherence to Aromatase Inhibitor Therapy among Breast Cancer Survivors: An Application of the Protection Motivation Theory

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Karmakar, Monita; Pinto, Sharrel L; Jordan, Timothy R; Mohamed, Iman; Holiday-Goodman, Monica

2017-01-01

The purpose of this observational study was to determine if the Protection Motivation Theory could predict and explain adherence to aromatase inhibitor (AI) therapy among breast cancer survivors. Purposive sampling was used to identify 288 survivors who had been prescribed AI therapy. A valid and reliable survey was mailed to survivors. A total of 145 survivors completed the survey. The Morisky scale was used to measure adherence to AI. The survivors reported a mean score of 6.84 (±0.66) on the scale. Nearly 4 in 10 survivors (38%) were non-adherent. Adherence differed by age, marital status, insurance status, income, and presence of co-morbid conditions. Self-efficacy (r=0.485), protection motivation (r=0.310), and Response Efficacy (r=0.206) were positively and significantly correlated with adherence. Response Cost (r=-0.235) was negatively correlated with adherence. The coping appraisal constructs were statistically significant predictors medication adherence (β=0.437) with self-efficacy being the strongest significant predictor of adherence (β = 0.429). PMID:28469437

Enhancing Student Learning with Brain-Based Research

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Bonnema, Ted R.

2009-01-01

This paper discusses brain-based learning and its relation to classroom instruction. A rapidly growing quantity of research currently exists regarding how the brain perceives, processes, and ultimately learns new information. In order to maximize their teaching efficacy, educators should have a basic understanding of key memory functions in the…

The time since last menstrual period is important as a clinical predictor for non-steroidal aromatase inhibitor-related arthralgia.

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Kanematsu, Miyuki; Morimoto, Masami; Honda, Junko; Nagao, Taeko; Nakagawa, Misako; Takahashi, Masako; Tangoku, Akira; Sasa, Mitsunori

2011-10-10

The clinical predictors of aromatase inhibitor-related arthralgia (AIA), a drug-related adverse reaction of aromatase inhibitors (AIs), remain unclear. AIA was prospectively surveyed every 4 months in 328 postmenopausal breast cancer patients administered a non-steroidal AI (anastrozole). Various clinicopathological parameters were recorded and analyzed (chi-square test, Fisher's exact test and logistic regression analysis). The mean observation period was 39.9 months. AIA manifested in 114 patients (34.8%), with peaks of onset at 4 (33.7%) and 8 months (11.4%) after starting AI administration. Some cases manifested even after 13 months. AIA tended to occur in younger patients (incidences of 46.3%, 37.4% and 28.0% for ages of 65 years, respectively (p = 0.063)) and decreased significantly with the age at menarche (53.3%, 35.3% and 15.4% for 15 years, respectively (p = 0.036)). The incidences were 45.1%, 46.3 and 25.1% for the time since the last menstrual period (LMP) 10 years, being significantly lower at > 10 years (p time since LMP > 10-year group versus the time since LMP became shorter ( 10 years since LMP. When the time since LMP was short, the onset of AIA was significantly earlier after starting AI administration.

The Brains behind Brain-Based Research: The Tale of Two Postsecondary Online Learners

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McGuckin, Dawn; Ladhani, Mubeen

2010-01-01

This paper is written from the perspective of two postsecondary students who realized the implications for brain-based learning in the online environment. This paper explores the relationship between online learning in regards to how the brain generates meaning and understanding, the role of emotions, the collaborative construction of knowledge,…

Simulation-based training in brain death determination.

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MacDougall, Benjamin J; Robinson, Jennifer D; Kappus, Liana; Sudikoff, Stephanie N; Greer, David M

2014-12-01

Despite straightforward guidelines on brain death determination by the American Academy of Neurology (AAN), substantial practice variability exists internationally, between states, and among institutions. We created a simulation-based training course on proper determination based on the AAN practice parameters to address and assess knowledge and practice gaps at our institution. Our intervention consisted of a didactic course and a simulation exercise, and was bookended by before and after multiple-choice tests. The 40-min didactic course, including a video demonstration, covered all aspects of the brain death examination. Simulation sessions utilized a SimMan 3G manikin and involved a complete examination, including an apnea test. Possible confounders and signs incompatible with brain death were embedded throughout. Facilitators evaluated performance with a 26-point checklist based on the most recent AAN guidelines. A senior neurologist conducted all aspects of the course, including the didactic session, simulation, and debriefing session. Ninety physicians from multiple specialties have participated in the didactic session, 38 of whom have completed the simulation. Pre-test scores were poor (41.4 %), with attendings scoring higher than residents (46.6 vs. 40.4 %, p = 0.07), and neurologists and neurosurgeons significantly outperforming other specialists (53.9 vs. 38.9 %, p = 0.003). Post-test scores (73.3 %) were notably higher than pre-test scores (45.4 %). Participant feedback has been uniformly positive. Baseline knowledge of brain death determination among providers was low but improved greatly after the course. Our intervention represents an effective model that can be replicated at other institutions to train clinicians in the determination of brain death according to evidence-based guidelines.

Model brain based learning (BBL and whole brain teaching (WBT in learning

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Baiq Sri Handayani

2017-08-01

Full Text Available The learning process is a process of change in behavior as a form of the result of learning. The learning model is a crucial component of the success of the learning process. The learning model is growing fastly, and each model has different characteristics. Teachers are required to be able to understand each model to teach the students optimally by matching the materials and the learning model. The best of the learning model is the model that based on the brain system in learning that are the model of Brain Based Learning (BBL and the model of Whole Brain Teaching (WBT. The purposes of this article are to obtain information related to (1 the brain’s natural learning system, (2 analyze the characteristics of the model BBL and WBT based on theory, brain sections that play a role associated with syntax, similarities, and differences, (3 explain the distinctive characteristics of both models in comparison to other models. The results of this study are: (1 the brain’s natural learning system are: (a the nerves in each hemisphere do not work independently, (b doing more activities can connect more brain nerves, (c the right hemisphere controls the left side motoric sensor of the body, and vice versa; (2 the characteristics of BBL and WBT are: (a BBL is based on the brain’s structure and function, while the model WBT is based on the instructional approach, neurolinguistic, and body language, (b the parts of the brain that work in BBL are: cerebellum, cerebral cortex, frontal lobe, limbic system, and prefrontal cortex; whereas the parts that work WBT are: prefrontal cortex, visual cortex, motor cortex, limbic system, and amygdala, (c the similarities between them are that they both rely on the brain’s system and they both promote gesture in learning, whereas the differences are on the view of the purposes of gestures and the learning theory that they rely on. BBL relies on cognitive theory while WBT relies on social theory; (3 the typical

Comparative study on individual aromatase inhibitors on cardiovascular safety profile: a network meta-analysis

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Zhao, Xihe; Liu, Lei; Li, Kai; Li, Wusheng; Zhao, Li; Zou, Huawei

2015-01-01

The third-generation aromatase inhibitors (AIs: anastrozole, letrozole, and exemestane) have now become standard adjuvant endocrine treatment for postmenopausal estrogen receptor-positive breast cancer complementing chemotherapy and surgery. Because of the absence of direct head-to-head comparisons of these AIs, an indirect comparison is needed for individual treatment choice. In this network systemic assessment, the cardiovascular (CV) side effects in using anastrozole, letrozole, and exemestane based on original studies on AIs vs placebo or tamoxifen were compared. We integrated all available direct and indirect evidences. The odds ratio (OR) of severe CV events for indirect comparisons between exemestane and anastrozole was 1.41 (95% confidence interval [CI] =0.49–2.78), letrozole and anastrozole was 1.80 (95% CI =0.40–3.92), and letrozole and exemestane was 1.46 (95% CI =0.34–3.4). OR of subgroup risk for AIs and tamoxifen were all >1 except for thrombolism risk subgroup. The results showed that the total and severe CV risk ranking is letrozole, exemestane, and anastrozole in descending order. None of the AIs showed advantages in CV events than tamoxifen except for thromboembolism event incidence. PMID:26491345

Brain meningioma with initial manifestation similar to cervical radiculopathy: a case report

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Huang YH

2014-06-01

Full Text Available Yu-Hsuan Huang,1,* Chang-Zern Hong,2,* Wei-Ting Wu,1 Kun-Ta Li,3 Li-Wei Chou1,4¹Department of Physical Medicine and Rehabilitation, China Medical University Hospital, 2Department of Physical Therapy, Hungkuang University, 3Department of Emergency Medicine, China Medical University Hospital, 4School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan*These authors contributed equally to this workAbstract: Meningiomas are the most common benign brain tumors, and are characterized by slow growth and a long asymptomatic period. Once the tumor becomes symptomatic, the various presentations may be related to the location and compression of adjacent structures. Meningioma is primarily treated through surgical intervention, and thus earlier diagnosis is likely to result in better prognosis. The symptoms of the meningioma may mimic other diseases, making precise diagnosis difficult, which will then delay treatment. We report a case of brain meningioma that showed initial signs and symptoms similar to cervical radiculopathy. The symptoms extended gradually, and the ultimate diagnosis of meningioma was confirmed based on brain-image studies. After brain-tumor excision, postoperation radiotherapy, and aggressive rehabilitation, the patient was able to perform better in daily activities.Keywords: hemiplegia, menigioma, paresthesia, radiculopathy, rehabilitation

Confounding factors in diagnosing brain death: a case report

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Login Ivan S

2002-06-01

Full Text Available Abstract Background Brain death is strictly defined medically and legally. This diagnosis depends on three cardinal neurological features: coma, absent brainstem reflexes, and apnea. The diagnosis can only be made, however, in the absence of intoxication, hypothermia, or certain medical illnesses. Case presentation A patient with severe hypoxic-ischemic brain injury met the three cardinal neurological features of brain death but concurrent profound hypothyroidism precluded the diagnosis. Our clinical and ethical decisions were further challenged by another facet of this complex case. Although her brain damage indicated a hopeless prognosis, we could not discontinue care based on futility because the only known surrogate was mentally retarded and unable to participate in medical planning. Conclusion The presence of certain medical conditions prohibits a diagnosis of brain death, which is a medicolegal diagnosis of death, not a prediction or forecast of future outcome. While prognostication is important in deciding to withdraw care, it is not a component in diagnosing brain death.

[Acid-base equilibrium and the brain].

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Rabary, O; Boussofara, M; Grimaud, D

1994-01-01

In physiological conditions, the regulation of acid-base balance in brain maintains a noteworthy stability of cerebral pH. During systemic metabolic acid-base imbalances cerebral pH is well controlled as the blood/brain barrier is slowly and poorly permeable to electrolytes (HCO3- and H+). Cerebral pH is regulated by a modulation of the respiratory drive, triggered by the early alterations of interstitial fluid pH, close to medullary chemoreceptors. As blood/brain barrier is highly permeable to Co2, CSF pH is corrected in a few hours, even in case of severe metabolic acidosis and alkalosis. Conversely, during ventilatory acidosis and alkalosis the cerebral pH varies in the same direction and in the same range than blood pH. Therefore, the brain is better protected against metabolic than ventilatory acid-base imbalances. Ventilatory acidosis and alkalosis are able to impair cerebral blood flow and brain activity through interstitial pH alterations. During respiratory acidosis, [HCO3-] increases in extracellular fluids to control cerebral pH by two main ways: a carbonic anhydrase activation at the blood/brain and blood/CSF barriers level and an increase in chloride shift in glial cells (HCO3- exchanged for Cl-). During respiratory alkalosis, [HCO3-] decreases in extracellular fluids by the opposite changes in HCO3- transport and by an increase in lactic acid synthesis by cerebral cells. The treatment of metabolic acidosis with bicarbonates may induce a cerebral acidosis and worsen a cerebral oedema during ketoacidosis. Moderate hypocapnia carried out to treat intracranial hypertension is mainly effective when cerebral blood flow is high and vascular CO2 reactivity maintained. Hypocapnia may restore an altered cerebral blood flow autoregulation. Instrumental hypocapnia requires a control of cerebral perfusion pressure and cerebral arteriovenous difference for oxygen, to select patients for whom this kind of treatment may be of benefit, to choose the optimal level of

Flexible deep brain neural probes based on a parylene tube structure

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Zhao, Zhiguo; Kim, Eric; Luo, Hao; Zhang, Jinsheng; Xu, Yong

2018-01-01

Most microfabricated neural probes have limited shank length, which prevents them from reaching many deep brain structures. This paper reports deep brain neural probes with ultra-long penetrating shanks based on a simple but novel parylene tube structure. The mechanical strength of the parylene tube shank is temporarily enhanced during implantation by inserting a metal wire. The metal wire can be removed after implantation, making the implanted probe very flexible and thus minimizing the stress caused by micromotions of brain tissues. Optogenetic stimulation and chemical delivery capabilities can be potentially integrated by taking advantage of the tube structure. Single-shank prototypes with a shank length of 18.2 mm have been developed. The microfabrication process comprises of deep reactive ion etching (DRIE) of silicon, parylene conformal coating/refilling, and XeF2 isotropic silicon etching. In addition to bench-top insertion characterization, the functionality of developed probes has been preliminarily demonstrated by implanting into the amygdala of a rat and recording neural signals.

Touch-based Brain Computer Interfaces: State of the art

NARCIS (Netherlands)

Erp, J.B.F. van; Brouwer, A.M.

2014-01-01

Brain Computer Interfaces (BCIs) rely on the user's brain activity to control equipment or computer devices. Many BCIs are based on imagined movement (called active BCIs) or the fact that brain patterns differ in reaction to relevant or attended stimuli in comparison to irrelevant or unattended

BrainBrowser: distributed, web-based neurological data visualization

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Tarek eSherif

2015-01-01

Full Text Available Recent years have seen massive, distributed datasets become the norm in neuroimaging research, and the methodologies used analyze them have, in response, become more collaborative and exploratory. Tools and infrastructure are continuously being developed and deployed to facilitate research in this context: grid computation platforms to process the data, distributed data stores to house and share them, high-speed networks to move them around and collaborative, often web-based, platforms to provide access to and sometimes manage the entire system. BrainBrowser is a lightweight, high-performance JavaScript visualization library built to provide easy-to-use, powerful, on-demand visualization of remote datasets in this new research environment. BrainBrowser leverages modern Web technologies, such as WebGL, HTML5 and Web Workers, to visualize 3D surface and volumetric neuroimaging data in any modern web browser without requiring any browser plugins. It is thus trivial to integrate BrainBrowser into any web-based platform. BrainBrowser is simple enough to produce a basic web-based visualization in a few lines of code, while at the same time being robust enough to create full-featured visualization applications. BrainBrowser can dynamically load the data required for a given visualization, so no network bandwidth needs to be waisted on data that will not be used. BrainBrowser's integration into the standardized web platform also allows users to consider using 3D data visualization in novel ways, such as for data distribution, data sharing and dynamic online publications. BrainBrowser is already being used in two major online platforms, CBRAIN and LORIS, and has been used to make the 1TB MACACC dataset openly accessible.

Brain abscess by Kocuria rosea: Case report and literature review

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Juan Esteban Muñoz Montoya

2017-03-01

Full Text Available Brain abscess is one of the most serious complications of head and neck infections (Tunkel, 2010 [1]. Defined as a focal intracranial infection that is initiated as an area of cerebritis and evolves into a collection of pus surrounded by a vascularized capsule (Tunkel and Scheld, 2011 [2]. The infectious agents depend on the pathogenesis of the infection and the presence of various predisposing conditions, however, in general: Streptococcus sp. is the most frequent microorganism (Tunkel and Scheld, 2011 [2]: Greenberg, 2010 [3]. In this article we report a case of brain abscess caused by Kocuria rosea, an entity that has not been reported previously in literature.

Use of aromatase inhibitors to treat endometriosis-related pain symptoms: a systematic review

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Venturini Pier L

2011-06-01

Full Text Available Abstract This systematic review aims to assess the efficacy of aromatase inhibitors (AIs in treating pain symptoms caused by endometriosis. A comprehensive literature search was conducted to identify all the published studies evaluating the efficacy of type II nonsteroidal aromatase inhibitors (anastrozole and letrozole in treating endometriosis-related pain symptoms. The MEDLINE, EMBASE, PubMed, and SCOPUS databases and the Cochrane System Reviews were searched up to October 2010. This review comprises of the results of 10 publications fitting the inclusion criteria; these studies included a total of 251 women. Five studies were prospective non-comparative, four were randomized controlled trials (RCTs and one was a prospective patient preference trial. Seven studies examined the efficacy of AIs in improving endometriosis-related pain symptoms, whilst three RCTs investigated the use of AIs as post-operative therapy in preventing the recurrence of pain symptoms after surgery for endometriosis. All the observational studies demonstrated that AIs combined with either progestogens or oral contraceptive pill reduce the severity of pain symptoms and improve quality of life. One patient preference study demonstrated that letrozole combined with norethisterone acetate is more effective in reducing pain and deep dyspareunia than norethisterone acetate alone. However, letrozole causes a higher incidence of adverse effects and does not improve patients' satisfaction or influence recurrence of symptoms after discontinuation of treatment. A RCT showed that combining letrozole with norethisterone acetate causes a lower incidence of adverse effects and lower discontinuation rate than combining letrozole with triptorelin. Two RCTs demonstrated that, after surgical treatment of endometriosis, the administration of AIs combined with gonadotropin releasing hormone analogue for 6 months reduces the risk of endometriosis recurrence when compared with gonadotropin

Feasibility of a skills-based substance abuse prevention program following traumatic brain injury.

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Vungkhanching, Martha; Heinemann, Allen W; Langley, Mervin J; Ridgely, Mary; Kramer, Karen M

2007-01-01

To demonstrate the feasibility of a skills-based substance abuse prevention counseling program in a community setting for adults who sustained traumatic brain injury. Convenience sample of 117 participants (mean age=35 years) with preinjury history of alcohol or other drug use. Intervention group participants (n=36) from 3 vocational rehabilitation programs; a no-intervention comparison group (n=81) from an outpatient rehabilitation service. 12 individual counseling sessions featuring skills-based intervention. Changes in self-reported alcohol and other drug use, coping skillfulness, affect, and employment status from baseline to 9 months postintervention. Significant differences were noted at baseline for the intervention and comparison groups on ethnicity, time postinjury, marital status, and employment (Pcoping skillfulness (Pskills-based intervention provides a promising approach to promoting abstinence from all substances and increasing readiness for employment for adults with traumatic brain injuries in outpatient settings.

Brain-Based Education: Its Pedagogical Implications and Research Relevance

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Laxman, Kumar; Chin, Yap Kueh

2010-01-01

The brain, being the organ of learning, must be understood if classrooms are to be places of meaningful learning. Understanding the brain has the potential to alter the foundation of education, transform traditional classrooms to interactive learning environments and promote better instructional approaches amongst teachers. Brain-based education…

Multiple brain atlas database and atlas-based neuroimaging system.

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Nowinski, W L; Fang, A; Nguyen, B T; Raphel, J K; Jagannathan, L; Raghavan, R; Bryan, R N; Miller, G A

1997-01-01

For the purpose of developing multiple, complementary, fully labeled electronic brain atlases and an atlas-based neuroimaging system for analysis, quantification, and real-time manipulation of cerebral structures in two and three dimensions, we have digitized, enhanced, segmented, and labeled the following print brain atlases: Co-Planar Stereotaxic Atlas of the Human Brain by Talairach and Tournoux, Atlas for Stereotaxy of the Human Brain by Schaltenbrand and Wahren, Referentially Oriented Cerebral MRI Anatomy by Talairach and Tournoux, and Atlas of the Cerebral Sulci by Ono, Kubik, and Abernathey. Three-dimensional extensions of these atlases have been developed as well. All two- and three-dimensional atlases are mutually preregistered and may be interactively registered with an actual patient's data. An atlas-based neuroimaging system has been developed that provides support for reformatting, registration, visualization, navigation, image processing, and quantification of clinical data. The anatomical index contains about 1,000 structures and over 400 sulcal patterns. Several new applications of the brain atlas database also have been developed, supported by various technologies such as virtual reality, the Internet, and electronic publishing. Fusion of information from multiple atlases assists the user in comprehensively understanding brain structures and identifying and quantifying anatomical regions in clinical data. The multiple brain atlas database and atlas-based neuroimaging system have substantial potential impact in stereotactic neurosurgery and radiotherapy by assisting in visualization and real-time manipulation in three dimensions of anatomical structures, in quantitative neuroradiology by allowing interactive analysis of clinical data, in three-dimensional neuroeducation, and in brain function studies.

Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

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Quan Jiang

2016-01-01

Full Text Available Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury, substantially improve functional outcome. We discuss and review state of the art magnetic resonance imaging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic.

Subcortical Brain Morphology in Schizophrenia : Descriptive analysis based on MRI findings of subcortical brain volumes

OpenAIRE

Gunleiksrud, Sindre

2009-01-01

The aim of this study was to investigate magnetic resonance images (MR) from patients with schizophrenia and healthy control subjects for difference in brain morphology with focus on subcortical brain volumes. Method: The study compared fourteen subcortical brain structure volumes of 96 patients diagnosed with schizophrenia (n=81) or schizoaffective disorder (n=15) with 106 healthy control subjects. Volume measures were obtained using voxel-based morphometry (FreeSurfer software suite) of ...

Aromatase inhibitors, efficacy and metabolic risk in the treatment of postmenopausal women with early breast cancer

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Stefano Gonnelli

2008-12-01

Full Text Available Stefano Gonnelli1, Roberto Petrioli21Department of Internal Medicine, Endocrine-Metabolic Science and Biochemistry, University of Siena, Italy (Dir. R. Nuti.; 2Department of Human Pathology and Oncology, Medical Oncology Section, University of Siena, Italy (Dir. G. FranciniAbstract: The third-generation aromatase inhibitors (AIs, letrozole, anastrozole and exemestane, are becoming the first choice endocrine drugs for post-menopausal women with breast cancer, since they present greater efficacy when compared with tamoxifen in both adjuvant and metastatic setting. In particular, several large and well designed trials have suggested an important role for AIs in the adjuvant treatment of postmenopausal women with estrogen-receptor positive breast cancer either in the upfront, sequential or extended adjuvant mode. Overall, AIs are associated with a small but significant improvement in disease free survival. The expanding use of AIs in the treatment of early breast cancer means that individual patients will be exposed to the agents for longer durations, making it increasingly important to establish their long-term safety. This review focused on the effects of AIs on bone metabolism, serum lipids and cardiovascular risk. AIs have adverse effects on bone turnover with a reduction of bone mineral density and an increase in the rate of fragility fractures. With respect to tamoxifen AIs present lower thrombotic risk and a less favorable impact on lipid profile, whereas the true effects on cardiovascular risk still remain to be clarified. An adequate monitoring of bone mineral density (BMD and lipid profile could be recommended for post-menopausal women candidate to AIs.Keywords: breast cancer, aromatase inhibitors, bone loss, lipids, cardiovascular risk

Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology.

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Wijdicks, Eelco F M; Varelas, Panayiotis N; Gronseth, Gary S; Greer, David M

2010-06-08

To provide an update of the 1995 American Academy of Neurology guideline with regard to the following questions: Are there patients who fulfill the clinical criteria of brain death who recover neurologic function? What is an adequate observation period to ensure that cessation of neurologic function is permanent? Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death? What is the comparative safety of techniques for determining apnea? Are there new ancillary tests that accurately identify patients with brain death? A systematic literature search was conducted and included a review of MEDLINE and EMBASE from January 1996 to May 2009. Studies were limited to adults. In adults, there are no published reports of recovery of neurologic function after a diagnosis of brain death using the criteria reviewed in the 1995 American Academy of Neurology practice parameter. Complex-spontaneous motor movements and false-positive triggering of the ventilator may occur in patients who are brain dead. There is insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly. Apneic oxygenation diffusion to determine apnea is safe, but there is insufficient evidence to determine the comparative safety of techniques used for apnea testing. There is insufficient evidence to determine if newer ancillary tests accurately confirm the cessation of function of the entire brain.

Adult brain abscess associated with patent foramen ovale: a case report

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Stathopoulos Georgios T

2007-08-01

Full Text Available Abstract Brain abscess results from local or metastatic septic spread to the brain. The primary infectious site is often undetected, more commonly so when it is distant. Unlike pediatric congenital heart disease, minor intracardiac right-to-left shunting due to patent foramen ovale has not been appreciated as a cause of brain abscess in adults. Here we present a case of brain abscess associated with a patent foramen ovale in a 53-year old man with dental-gingival sepsis treated in the intensive care unit. Based on this case and the relevant literature we suggest a link between a silent patent foramen ovale, paradoxic pathogen dissemination to the brain, and development of brain abscess.

A brain mass in a patient with Behcet's disease: a case report.

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Alfedaghi, Ahmad S; Masters, Y; Mourou, M; Eshak, O

2015-09-30

This case report describes an uncommon presentation of Behcet's disease which manifested as neuro-Behcet's disease. Although it is not the first reported case in the medical literature, it is a possible differential in a patient presenting with a brain tumor. Since the diagnosis of neuro-Behcet's disease depends largely on the clinical picture and medical history, it should be considered prior to opting for invasive diagnostic methods. Our patient is a 36-year-old white man from Kuwait. He presented with acute onset of headache, vomiting, and right-sided weakness. Magnetic resonance imaging of his brain showed a mass in the brain stem. He then revealed that he had a history of recurrent painful oral and genital ulcers for the past 10 years, which suggested a diagnosis of Behcet's disease. A brain biopsy was recommended by a neurosurgeon at the time, but the patient refused the procedure. After initiating steroid therapy, the mass began to regress and, eventually, was undetectable on subsequent imaging of his brain. This case of neuro-Behcet's disease reflects the need to consider this diagnosis in a patient of less than 40 years of age presenting with a suspected brain tumor. This may delay the need for invasive diagnostic methods, especially if such methods are not desired by the patient. In the management of suspected neuro-Behcet's disease, initiating steroid therapy and measuring the response is a reasonable option before seeking a definitive diagnosis via brain biopsy. If the response to steroids is minimal then a brain biopsy should be performed.

Tuberculous meningoencephalitis associated with brain tuberculomas during pregnancy: a case report

OpenAIRE

Namani, Sadie; Dreshaj, Shemsedin; Berisha, Arieta Zogaj

2017-01-01

Background Tuberculous meningitis is globally highly prevalent and is commoner in resource-limited countries and in patients with immunosuppression. Central nervous system tuberculosis is one of the severest forms of extrapulmonary tuberculosis during pregnancy and associated brain tuberculomas have been rarely reported. With the availability of neuroimaging at our hospital center, we present the first case of tuberculous meningoencephalitis associated with brain tuberculomas during pregnancy...

Complementary or alternative medicine as possible determinant of decreased persistence to aromatase inhibitor therapy among older women with non-metastatic breast cancer.

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Laetitia Huiart

Full Text Available PURPOSE: Aromatase inhibitor therapy (AI significantly improves survival in breast cancer patients. Little is known about adherence and persistence to aromatase inhibitors and about the causes of treatment discontinuation among older women. METHODS: We constituted a cohort of women over 65 receiving a first AI therapy for breast cancer between 2006 and 2008, and followed them until June 2011. Women were selected in the population-based French National Health Insurance databases, and data was collected on the basis of pharmacy refills, medical records and face-to-face interviews. Non-persistence to treatment was defined as the first treatment discontinuation lasting more than 3 consecutive months. Time to treatment discontinuation was studied using survival analysis techniques. RESULTS: Overall among the 382 selected women, non-persistence to treatment went from 8.7% (95%CI: 6.2-12.1 at 1 year, to 15.6% (95%CI: 12.2-19.8 at 2 years, 20.8% (95%CI: 16.7-25.6 at 3 years, and 24.7% (95%CI: 19.5-31.0 at 4 years. In the multivariate analysis on a sub-sample of 233 women with available data, women using complementary or alternative medicine (CAM (HR = 3.2; 95%CI: 1.5-6.9 or suffering from comorbidities (HR = 2.2; 95%CI: 1.0-4.8 were more likely to discontinue their treatment, whereas women with polypharmacy (HR = 0.4; 95%CI: 0.2-0.91 were less likely to discontinue. In addition, 13% of the women with positive hormonal receptor status did not fill any prescription for anti-hormonal therapy. CONCLUSION: AI therapy is discontinued prematurely in a substantial portion of older patients. Some patients may use CAM not as a complementary treatment, but as an alternative to conventional medicine. Improving patient-physician communication on the use of CAM may improve hormonal therapy adherence.

Complementary or alternative medicine as possible determinant of decreased persistence to aromatase inhibitor therapy among older women with non-metastatic breast cancer.

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Huiart, Laetitia; Bouhnik, Anne-Deborah; Rey, Dominique; Rousseau, Frédérique; Retornaz, Frédérique; Meresse, Mégane; Bendiane, Marc Karim; Viens, Patrice; Giorgi, Roch

2013-01-01

Aromatase inhibitor therapy (AI) significantly improves survival in breast cancer patients. Little is known about adherence and persistence to aromatase inhibitors and about the causes of treatment discontinuation among older women. We constituted a cohort of women over 65 receiving a first AI therapy for breast cancer between 2006 and 2008, and followed them until June 2011. Women were selected in the population-based French National Health Insurance databases, and data was collected on the basis of pharmacy refills, medical records and face-to-face interviews. Non-persistence to treatment was defined as the first treatment discontinuation lasting more than 3 consecutive months. Time to treatment discontinuation was studied using survival analysis techniques. Overall among the 382 selected women, non-persistence to treatment went from 8.7% (95%CI: 6.2-12.1) at 1 year, to 15.6% (95%CI: 12.2-19.8) at 2 years, 20.8% (95%CI: 16.7-25.6) at 3 years, and 24.7% (95%CI: 19.5-31.0) at 4 years. In the multivariate analysis on a sub-sample of 233 women with available data, women using complementary or alternative medicine (CAM) (HR = 3.2; 95%CI: 1.5-6.9) or suffering from comorbidities (HR = 2.2; 95%CI: 1.0-4.8) were more likely to discontinue their treatment, whereas women with polypharmacy (HR = 0.4; 95%CI: 0.2-0.91) were less likely to discontinue. In addition, 13% of the women with positive hormonal receptor status did not fill any prescription for anti-hormonal therapy. AI therapy is discontinued prematurely in a substantial portion of older patients. Some patients may use CAM not as a complementary treatment, but as an alternative to conventional medicine. Improving patient-physician communication on the use of CAM may improve hormonal therapy adherence.

Perinatal administration of aromatase inhibitors in rodents as animal models of human male homosexuality: similarities and differences.

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Olvera-Hernández, Sandra; Fernández-Guasti, Alonso

2015-01-01

In this chapter we briefly review the evidence supporting the existence of biological influences on sexual orientation. We focus on basic research studies that have affected the estrogen synthesis during the critical periods of brain sexual differentiation in male rat offspring with the use of aromatase inhibitors, such as 1,4,6-androstatriene-3,17 (ATD) and letrozole. The results after prenatal and/or postnatal treatment with ATD reveal that these animals, when adults, show female sexual responses, such as lordosis or proceptive behaviors, but retain their ability to display male sexual activity with a receptive female. Interestingly, the preference and sexual behavior of these rats vary depending upon the circadian rhythm.Recently, we have established that the treatment with low doses of letrozole during the second half of pregnancy produces male rat offspring, that when adults spend more time in the company of a sexually active male than with a receptive female in a preference test. In addition, they display female sexual behavior when forced to interact with a sexually experienced male and some typical male sexual behavior when faced with a sexually receptive female. Interestingly, these males displayed both sexual behavior patterns spontaneously, i.e., in absence of exogenous steroid hormone treatment. Most of these features correspond with those found in human male homosexuals; however, the "bisexual" behavior shown by the letrozole-treated rats may be related to a particular human population. All these data, taken together, permit to propose letrozole prenatal treatment as a suitable animal model to study human male homosexuality and reinforce the hypothesis that human sexual orientation is underlied by changes in the endocrine milieu during early development.

A high-definition fiber tracking report for patients with traumatic brain injury and their doctors.

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Chmura, Jon; Presson, Nora; Benso, Steven; Puccio, Ava M; Fissel, Katherine; Hachey, Rebecca; Braun, Emily; Okonkwo, David O; Schneider, Walter

2015-03-01

We have developed a tablet-based application, the High-Definition Fiber Tracking Report App, to enable clinicians and patients in research studies to see and understand damage from Traumatic Brain Injury (TBI) by viewing 2-dimensional and 3-dimensional images of their brain, with a focus on white matter tracts with quantitative metrics. The goal is to visualize white matter fiber tract injury like bone fractures; that is, to make the "invisible wounds of TBI" understandable for patients. Using mobile computing technology (iPad), imaging data for individual patients can be downloaded remotely within hours of a magnetic resonance imaging brain scan. Clinicians and patients can view the data in the form of images of each tract, rotating animations of the tracts, 3-dimensional models, and graphics. A growing number of tracts can be examined for asymmetry, gaps in streamline coverage, reduced arborization (branching), streamline volume, and standard quantitative metrics (e.g., Fractional Anisotropy (FA)). Novice users can learn to effectively navigate and interact with the application (explain the figures and graphs representing normal and injured brain tracts) within 15 minutes of simple orientation with high accuracy (96%). The architecture supports extensive graphics, configurable reports, provides an easy-to-use, attractive interface with a smooth user experience, and allows for securely serving cases from a database. Patients and clinicians have described the application as providing dramatic benefits in understanding their TBI and improving their lives. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Chiropractic management using a brain-based model of care for a 15-year-old adolescent boy with migraine headaches and behavioral and learning difficulties: a case report

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Kuhn, Kurt W.; Cambron, Jerrilyn

2013-01-01

Objective The purpose of this report is to describe chiropractic management, using a brain-based model of care, of a teen who had migraine headaches and several social and learning difficulties. Clinical features A 15-year-old adolescent boy with a chronic history of migraines and more than 10 years of learning and behavioral difficulties, including attention-deficit/hyperactivity disorder, obsessive compulsive disorder, and Tourette syndrome, presented for chiropractic care. Intervention and outcome The patient received spinal manipulation and was given home physical coordination activities that were contralateral to the side of the involved basal ganglia and ipsilateral to the involved cerebellum, along with interactive metronome training. Quantitative changes were noted in neurological soft signs, tests of variables of attention Conners’ Parent Rating Scale, the California Achievement Test, grade point, and reduction of medications. The patient reported qualitative improvements in tics, attention, reading, vision, health, relationships with his peers and his family, and self-esteem. Conclusion The patient with migraine headaches and learning difficulties responded well to the course of chiropractic care. This study suggests that there may be value in a brain-based model of care in the chiropractic management of conditions that are beyond musculoskeletal in nature. PMID:24396330

Idiopathic brain herniation. A report of two paediatric cases.

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Koc, Gonca; Doganay, Selim; Bayram, Ayse Kacar; Gorkem, Sureyya Burcu; Dogan, Mehmet Sait; Per, Huseyin; Coskun, Abdulhakim

2014-10-01

SUMMARY - 'Idiopathic' herniation of the brain is a rare entity previously reported in 13 cases. It may be incidentally encountered in neuroimaging studies acquired for various clinical indications. We herein describe two cases of idiopathic brain herniation that were incidentally diagnosed. A 12-year-old boy presented with a six-month history of daytime sleepiness and sudden spells of sleep. Herniation of the left inferior temporal gyrus was revealed in MRI acquired with the suspicion of epilepsy. His overnight polysomnogram and multiple sleep latency tests were compatible with the diagnosis of narcolepsy. The other case, a two-year-old girl, was transferred from an outside hospital due to partial seizures with the fever. Herniation of the precuneal gyrus was encountered in MRI acquired after controlling her seizures with the initiation of phenytoin. The brain herniations of both patients were considered to be inconsistent with their medical conditions, so that they were symptom-free with only medical treatment for following three and six months, respectively. This is a rare presentation of idiopathic brain herniation as an incidental finding that accompanied narcolepsy and epilepsy. Awareness of this entity would avoid excessive surgical and medical treatments.

Respiratory difficulty caused by an ectopic brain tissue mass in the neck of a two-month-old baby: a case report

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Aboud Mohammed J

2011-06-01

Full Text Available Abstract Introduction Neuroglial heterotopia, heterotopic brain tissue, or differentiated neural tissue outside the cranial vault is uncommon, and these anomalies most commonly occur in the nasal cavity. Case presentation We report a case of rare pure cystic heterotopic brain tissue in a two-month-old Caucasian baby girl that presented as a large cystic neck mass and was confused with a cystic hygroma. Her mother reported a progressive increase in the size of this swelling and mild respiratory difficulty when the girl was sleeping. A computed tomography scan of the brain and neck showed a large heterogeneous mass extending from the base of the skull to the left submandibular region; a cystic component was also noted. Our patient under went total excision of the cystic mass and prevention of airway obstruction by a left submandibular approach. The final gross pathology diagnosis was heterotopic brain tissue. Conclusions Pure cystic neck heterotopic brain tissue lesions are very uncommon, and a preoperative diagnosis of this lesion is difficult. Brain heterotopia is a rare, benign condition that should be considered in the differential diagnosis of the neonatal head and neck mass.

Self-Reported Cognitive Outcomes in Patients With Brain Metastases Before and After Radiation Therapy

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Cole, Ansa Maer [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany); Scherwath, Angela [Department of Medical Psychology, University Medical Centre Hamburg-Eppendorf, Hamburg (Germany); Ernst, Gundula [Department of Medical Psychology, Medical School Hannover, Hannover (Germany); Lanfermann, Heinrich [Institute for Neuroradiology, Medical School Hannover, Hannover (Germany); Bremer, Michael [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany); Steinmann, Diana, E-mail: steinmann.diana@mh-hannover.de [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany)

2013-11-15

Purpose: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. Methods and Materials: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). Results: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. Conclusion: Self-reported attention declined in

Self-Reported Cognitive Outcomes in Patients With Brain Metastases Before and After Radiation Therapy

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Cole, Ansa Maer; Scherwath, Angela; Ernst, Gundula; Lanfermann, Heinrich; Bremer, Michael; Steinmann, Diana

2013-01-01

Purpose: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. Methods and Materials: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). Results: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. Conclusion: Self-reported attention declined in

Brain-volume changes in young and middle-aged smokers: a DARTEL-based voxel-based morphometry study.

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Peng, Peng; Wang, Zhenchang; Jiang, Tao; Chu, Shuilian; Wang, Shuangkun; Xiao, Dan

2017-09-01

Many studies have reported brain volume changes in smokers. However, the volume differences of grey matter (GM) and white matter (WM) in young and middle-aged male smokers with different lifetime tobacco consumption (pack-years) remain uncertain. To examine the brain volume change, especially whether more pack-years smoking would be associated with smaller gray matter and white matter volume in young and middle-aged male smokers. We used a 3T MR scanner and performed Diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL)-based voxel-based morphometry on 53 long-term male smokers (30.72 ± 4.19 years) and 53 male healthy non-smokers (30.83 ± 5.18 years). We separated smokers to light and heavy smokers by pack-years and compared brain volume between different smoker groups and non-smokers. And then we did analysis of covariance (ANCOVA) between smokers and non-smokers by setting pack-years as covariates. Light and heavy smokers all displayed smaller GM and WM volume than non-smokers and more obviously in heavy smokers. The main smaller areas in light and heavy smokers were superior temporal gyrus, insula, middle occipital gyrus, posterior cingulate, precuneus in GM and posterior cingulate, thalamus and midbrain in WM, in addition, we also observed more pack-years smoking was associated with some certain smaller GM and WM volumes by ANCOVA. Young and middle-aged male smokers had many smaller brain areas than non-smokers. Some of these areas' volume had negative correlation with pack-years, while some had not. These may due to different pathophysiological role of smokings. © 2015 John Wiley & Sons Ltd.

Progress in EEG-Based Brain Robot Interaction Systems

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Xiaoqian Mao

2017-01-01

Full Text Available The most popular noninvasive Brain Robot Interaction (BRI technology uses the electroencephalogram- (EEG- based Brain Computer Interface (BCI, to serve as an additional communication channel, for robot control via brainwaves. This technology is promising for elderly or disabled patient assistance with daily life. The key issue of a BRI system is to identify human mental activities, by decoding brainwaves, acquired with an EEG device. Compared with other BCI applications, such as word speller, the development of these applications may be more challenging since control of robot systems via brainwaves must consider surrounding environment feedback in real-time, robot mechanical kinematics, and dynamics, as well as robot control architecture and behavior. This article reviews the major techniques needed for developing BRI systems. In this review article, we first briefly introduce the background and development of mind-controlled robot technologies. Second, we discuss the EEG-based brain signal models with respect to generating principles, evoking mechanisms, and experimental paradigms. Subsequently, we review in detail commonly used methods for decoding brain signals, namely, preprocessing, feature extraction, and feature classification, and summarize several typical application examples. Next, we describe a few BRI applications, including wheelchairs, manipulators, drones, and humanoid robots with respect to synchronous and asynchronous BCI-based techniques. Finally, we address some existing problems and challenges with future BRI techniques.

[Depersonalization syndrome after acquired brain damage. Overview based on 3 case reports and the literature and discussion of etiological models].

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Paulig, M; Böttger, S; Sommer, M; Prosiegel, M

1998-12-01

Depersonalization after brain damage is still only rarely reported and poorly understood. We describe three patients between the ages of 21 and 25 who experienced depersonalization and derealization for periods of 6 weeks to 4 months, two after traumatic brain injury, the third after surgical and radiation treatment of a pineocytoma. Each one believed to be living in a nightmare and thought about committing suicide in order to wake up. One patient developed symptoms as described in Cotard delusion. Aspects of neuroanatomy, psychodynamics, and anthropology are discussed with reference to the literature. Frontal and temporal lesions seem only to play a facilitating role but not to be a necessary condition. There is evidence for additional influence of psychological and premorbid personality factors. Summarizing the current state of information we consider depersonalization with the experience of being in a dream or being dead as a heuristic reaction to brain damage. Similar models have already been discussed in neuropsychological disorders as for instance reduplicative paramnesias, neglect, and anosognosia.

Neurosyphilis Involving Cranial Nerves in Brain Stem: 2 Case Reports

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Jang, Ji Hye [Dept. of Radiology, Kyung Hee University College of Medicine, Seoul (Korea, Republic of); Choi, Woo Suk; Kim, Eui Jong [Dept. of Radiology, Kyung Hee University Hospital, Seoul (Korea, Republic of); Yoon, Sung Sang; Heo, Sung Hyuk [Dept. of Neurology, Kyung Hee University Hospital, Seoul (Korea, Republic of)

2012-01-15

Neurosyphilis uncommonly presents with cranial neuropathies in acute syphilitic meningitis and meningovascular neurosyphilis. We now report two cases in which the meningeal form of neurosyphilis involved cranial nerves in the brain stem: the oculomotor and trigeminal nerve.

Neurosyphilis Involving Cranial Nerves in Brain Stem: 2 Case Reports

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Jang, Ji Hye; Choi, Woo Suk; Kim, Eui Jong; Yoon, Sung Sang; Heo, Sung Hyuk

2012-01-01

Neurosyphilis uncommonly presents with cranial neuropathies in acute syphilitic meningitis and meningovascular neurosyphilis. We now report two cases in which the meningeal form of neurosyphilis involved cranial nerves in the brain stem: the oculomotor and trigeminal nerve.

Current self-reported symptoms of attention deficit/hyperactivity disorder are associated with total brain volume in healthy adults.

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Martine Hoogman

Full Text Available BACKGROUND: Reduced total brain volume is a consistent finding in children with Attention Deficit/Hyperactivity Disorder (ADHD. In order to get a better understanding of the neurobiology of ADHD, we take the first step in studying the dimensionality of current self-reported adult ADHD symptoms, by looking at its relation with total brain volume. METHODOLOGY/PRINCIPAL FINDINGS: In a sample of 652 highly educated adults, the association between total brain volume, assessed with magnetic resonance imaging, and current number of self-reported ADHD symptoms was studied. The results showed an association between these self-reported ADHD symptoms and total brain volume. Post-hoc analysis revealed that the symptom domain of inattention had the strongest association with total brain volume. In addition, the threshold for impairment coincides with the threshold for brain volume reduction. CONCLUSIONS/SIGNIFICANCE: This finding improves our understanding of the biological substrates of self-reported ADHD symptoms, and suggests total brain volume as a target intermediate phenotype for future gene-finding in ADHD.

Headache, migraine, and structural brain lesions and function: population based Epidemiology of Vascular Ageing-MRI study

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Kurth, T.; Mohamed, S.; Zhu, Y.C.; Dufouil, C.; Tzourio, Ch.; Kurth, T.; Zhu, Y.C.; Dufouil, C.; Tzourio, Ch.; Kurth, T.; Maillard, P.; Mazoyer, B.; Zhu, Y.C.; Chabriat, H.; Bousser, M.G.; Tzourio, Ch.; Zhu, Y.C.; Chabriat, H.; Bousser, M.G.; Mazoyer, B.

2011-01-01

Objective: To evaluate the association of overall and specific headaches with volume of white matter hyper-intensities, brain infarcts, and cognition. Design: Population based, cross sectional study. Setting: Epidemiology of Vascular Ageing study, Nantes, France. Participants: 780 participants (mean age 69, 58.5% women) with detailed headache assessment. Main outcome measures: Brain scans were evaluated for volume of white matter hyper-intensities (by fully automated imaging processing) and for classification of infarcts (by visual reading with a standardised assessment grid). Cognitive function was assessed by a battery of tests including the mini-mental state examination. Results: 163 (20.9%) participants reported a history of severe headache and 116 had migraine, of whom 17 (14.7%) reported aura symptoms. An association was found between any history of severe headache and increasing volume of white matter hyper-intensities. The adjusted odds ratio of being in the highest third for total volume of white matter hyper-intensities was 2.0 (95% confidence interval 1.3 to 3.1, P for trend 0.002) for participants with any history of severe headache when compared with participants without severe headache being in the lowest third. The association pattern was similar for all headache types. Migraine with aura was the only headache type strongly associated with volume of deep white matter hyper-intensities (highest third odds ratio 12.4, 1.6 to 99.4, P for trend 0.005) and with brain infarcts (3.4, 1.2 to 9.3). The location of infarcts was predominantly outside the cerebellum and brain stem. Evidence was lacking for cognitive impairment for any headache type with or without brain lesions. Conclusions: In this population based study, any history of severe headache was associated with an increased volume of white matter hyper-intensities. Migraine with aura was the only headache type associated with brain infarcts. Evidence that headache of any type by itself or in

[Metronidazole-Induced Encephalopathy during Brain Abscess Treatment:Two Case Reports].

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Yokoyama, Yuka; Asaoka, Katsuyuki; Sugiyama, Taku; Uchida, Kazuki; Shimbo, Daisuke; Kobayashi, Satoshi; Itamoto, Koji

2015-10-01

Metronidazole is a widely used antibiotic against anaerobic bacteria and protozoa. We report two cases of metronidazole-induced encephalopathy(MIE)during treatment of a brain abscess with metronidazole. The patients developed mental disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case 1: A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We initiated treatment with oral metronidazole. After taking the medication, she developed mental disturbance, and her brain MRI showed a hyperintensity within the corpus callosum. We suspected metronidazole toxicity and discontinued metronidazole treatment. The symptoms resolved rapidly within a week, and the hyperintensity on the MRI disappeared. Case 2: A 22-year-old man was admitted to our hospital with a brain abscess. We initiated treatment with oral metronidazole. On day 38, he developed mental disturbance, and his MRI showed hyperintensities within the bilateral dentate nuclei and corpus callosum. These symptoms were consistent with MIE. After cessation of metronidazole, his symptoms and abnormal MRI signals completely disappeared.

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases

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Mehta, Minesh P.; Tsao, May N.; Whelan, Timothy J.; Morris, David E.; Hayman, James A.; Flickinger, John C.; Mills, Michael; Rogers, C. Leland; Souhami, Luis

2005-01-01

instrument has not been reported. All randomized trials showed improved local control with the addition of radiosurgery to whole-brain radiotherapy. For patients with multiple brain metastases, there is no overall survival benefit with the use of radiosurgery boost to whole-brain radiotherapy (Level I-III evidence). Radiosurgery boost is associated with a small risk of early or late toxicity. In patients treated with radiosurgery alone (withholding whole-brain radiotherapy) as initial treatment, there were 2 randomized trials, 2 prospective cohort studies, and 16 retrospective series. There is Level I to Level III evidence that the use of radiosurgery alone does not alter survival as compared to the use of whole-brain radiotherapy. However, there is Level I to Level III evidence that omission of whole-brain radiotherapy results in poorer intracranial disease control, both local and distant (defined as remaining brain, outside the radiosurgery field). Quality of life outcomes have not been adequately reported. Radiosurgery is associated with a small risk of early or late toxicity. Radiosurgery as salvage for patients with brain metastases was reported in zero randomized trials, one prospective study, and seven retrospective series. Conclusions: Based on Level I-III evidence, for selected patients with small (up to 4 cm) brain metastases (up to three in number and four in one randomized trial), the addition of radiosurgery boost to whole-brain radiotherapy improves brain control as compared with whole-brain radiotherapy alone. In patients with a single brain metastasis, radiosurgery boost with whole-brain radiotherapy improves survival. There is a small risk of toxicity associated with radiosurgery boost as compared with whole-brain radiotherapy alone. In selected patients treated with radiosurgery alone for newly diagnosed brain metastases, overall survival is not altered. However, local and distant brain control is significantly poorer with omission of upfront whole-brain

Parameter estimation of brain tumors using intraoperative thermal imaging based on artificial tactile sensing in conjunction with artificial neural network

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Sadeghi-Goughari, M; Mojra, A; Sadeghi, S

2016-01-01

Intraoperative Thermal Imaging (ITI) is a new minimally invasive diagnosis technique that can potentially locate margins of brain tumor in order to achieve maximum tumor resection with least morbidity. This study introduces a new approach to ITI based on artificial tactile sensing (ATS) technology in conjunction with artificial neural networks (ANN) and feasibility and applicability of this method in diagnosis and localization of brain tumors is investigated. In order to analyze validity and reliability of the proposed method, two simulations were performed. (i) An in vitro experimental setup was designed and fabricated using a resistance heater embedded in agar tissue phantom in order to simulate heat generation by a tumor in the brain tissue; and (ii) A case report patient with parafalcine meningioma was presented to simulate ITI in the neurosurgical procedure. In the case report, both brain and tumor geometries were constructed from MRI data and tumor temperature and depth of location were estimated. For experimental tests, a novel assisted surgery robot was developed to palpate the tissue phantom surface to measure temperature variations and ANN was trained to estimate the simulated tumor’s power and depth. Results affirm that ITI based ATS is a non-invasive method which can be useful to detect, localize and characterize brain tumors. (paper)

Public School Teachers' Knowledge, Perception, and Implementation of Brain-Based Learning Practices

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Wachob, David A.

2012-01-01

The purpose of this study was to determine K-12 teachers' knowledge, beliefs, and practices of brain-based learning strategies in western Pennsylvania schools. The following five research questions were explored: (a) What is the extent of knowledge K-12 public school teachers have about the indicators of brain-based learning and Brain Gym?; (b) To…

"Celebration of the Neurons": The Application of Brain Based Learning in Classroom Environment

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Duman, Bilal

2007-01-01

The purpose of this study is to investigate approaches and techniques related to how brain based learning used in classroom atmosphere. This general purpose were answered following the questions: (1) What is the aim of brain based learning? (2) What are general approaches and techniques that brain based learning used? and (3) How should be used…

Miliary Tuberculosis with Concurrent Brain and Spinal Cord Involvement: A Case Report

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Sung, Chang Keun; Na, Hyoung Il; Yu, Hyeon; Byun, Jun Soo; Youn, Young Chul; Seo, Jae Seung; Kim, Gi Hyeon

2008-01-01

Central nervous system involvement by tuberculosis is rare, and intramedullary involvement is even more rare. A patient that developed intermittent amnesia during anti-tuberculous therapy underwent brain CT and MRI and spine MRI. The latter showed multiple small enhancing nodules in the brain and spinal cord. The patient was treated with anti-tuberculous medication and steroids under the suspected diagnosis of miliary tuberculosis. Follow-up CT showed decreased nodule size and number. We report a case of miliary tuberculosis in the brain and spinal cord and present a review of the literature related to similar cases

Miliary Tuberculosis with Concurrent Brain and Spinal Cord Involvement: A Case Report

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Sung, Chang Keun; Na, Hyoung Il; Yu, Hyeon; Byun, Jun Soo; Youn, Young Chul; Seo, Jae Seung; Kim, Gi Hyeon [Chung-Ang University, Seoul (Korea, Republic of)

2008-11-15

Central nervous system involvement by tuberculosis is rare, and intramedullary involvement is even more rare. A patient that developed intermittent amnesia during anti-tuberculous therapy underwent brain CT and MRI and spine MRI. The latter showed multiple small enhancing nodules in the brain and spinal cord. The patient was treated with anti-tuberculous medication and steroids under the suspected diagnosis of miliary tuberculosis. Follow-up CT showed decreased nodule size and number. We report a case of miliary tuberculosis in the brain and spinal cord and present a review of the literature related to similar cases.

MRI-based Brain Healthcare Quotients: A bridge between neural and behavioral analyses for keeping the brain healthy.

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Nemoto, Kiyotaka; Oka, Hiroki; Fukuda, Hiroki; Yamakawa, Yoshinori

2017-01-01

Neurological and psychiatric disorders are a burden on social and economic resources. Therefore, maintaining brain health and preventing these disorders are important. While the physiological functions of the brain are well studied, few studies have focused on keeping the brain healthy from a neuroscientific viewpoint. We propose a magnetic resonance imaging (MRI)-based quotient for monitoring brain health, the Brain Healthcare Quotient (BHQ), which is based on the volume of gray matter (GM) and the fractional anisotropy (FA) of white matter (WM). We recruited 144 healthy adults to acquire structural neuroimaging data, including T1-weighted images and diffusion tensor images, and data associated with both physical (BMI, blood pressure, and daily time use) and social (subjective socioeconomic status, subjective well-being, post-materialism and Epicureanism) factors. We confirmed that the BHQ was sensitive to an age-related decline in GM volume and WM integrity. Further analysis revealed that the BHQ was critically affected by both physical and social factors. We believe that our BHQ is a simple yet highly sensitive, valid measure for brain health research that will bridge the needs of the scientific community and society and help us lead better lives in which we stay healthy, active, and sharp.

MRI-based Brain Healthcare Quotients: A bridge between neural and behavioral analyses for keeping the brain healthy.

Directory of Open Access Journals (Sweden)

Kiyotaka Nemoto

Full Text Available Neurological and psychiatric disorders are a burden on social and economic resources. Therefore, maintaining brain health and preventing these disorders are important. While the physiological functions of the brain are well studied, few studies have focused on keeping the brain healthy from a neuroscientific viewpoint. We propose a magnetic resonance imaging (MRI-based quotient for monitoring brain health, the Brain Healthcare Quotient (BHQ, which is based on the volume of gray matter (GM and the fractional anisotropy (FA of white matter (WM. We recruited 144 healthy adults to acquire structural neuroimaging data, including T1-weighted images and diffusion tensor images, and data associated with both physical (BMI, blood pressure, and daily time use and social (subjective socioeconomic status, subjective well-being, post-materialism and Epicureanism factors. We confirmed that the BHQ was sensitive to an age-related decline in GM volume and WM integrity. Further analysis revealed that the BHQ was critically affected by both physical and social factors. We believe that our BHQ is a simple yet highly sensitive, valid measure for brain health research that will bridge the needs of the scientific community and society and help us lead better lives in which we stay healthy, active, and sharp.

A network of genes, genetic disorders, and brain areas.

Directory of Open Access Journals (Sweden)

Satoru Hayasaka

Full Text Available The network-based approach has been used to describe the relationship among genes and various phenotypes, producing a network describing complex biological relationships. Such networks can be constructed by aggregating previously reported associations in the literature from various databases. In this work, we applied the network-based approach to investigate how different brain areas are associated to genetic disorders and genes. In particular, a tripartite network with genes, genetic diseases, and brain areas was constructed based on the associations among them reported in the literature through text mining. In the resulting network, a disproportionately large number of gene-disease and disease-brain associations were attributed to a small subset of genes, diseases, and brain areas. Furthermore, a small number of brain areas were found to be associated with a large number of the same genes and diseases. These core brain regions encompassed the areas identified by the previous genome-wide association studies, and suggest potential areas of focus in the future imaging genetics research. The approach outlined in this work demonstrates the utility of the network-based approach in studying genetic effects on the brain.

Learning-based meta-algorithm for MRI brain extraction.

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Shi, Feng; Wang, Li; Gilmore, John H; Lin, Weili; Shen, Dinggang

2011-01-01

Multiple-segmentation-and-fusion method has been widely used for brain extraction, tissue segmentation, and region of interest (ROI) localization. However, such studies are hindered in practice by their computational complexity, mainly coming from the steps of template selection and template-to-subject nonlinear registration. In this study, we address these two issues and propose a novel learning-based meta-algorithm for MRI brain extraction. Specifically, we first use exemplars to represent the entire template library, and assign the most similar exemplar to the test subject. Second, a meta-algorithm combining two existing brain extraction algorithms (BET and BSE) is proposed to conduct multiple extractions directly on test subject. Effective parameter settings for the meta-algorithm are learned from the training data and propagated to subject through exemplars. We further develop a level-set based fusion method to combine multiple candidate extractions together with a closed smooth surface, for obtaining the final result. Experimental results show that, with only a small portion of subjects for training, the proposed method is able to produce more accurate and robust brain extraction results, at Jaccard Index of 0.956 +/- 0.010 on total 340 subjects under 6-fold cross validation, compared to those by the BET and BSE even using their best parameter combinations.

Marked increase of final height by long-term aromatase inhibition in a boy with idiopathic short stature.

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Krebs, Andreas; Moske-Eick, Olaf; Doerfer, Jürgen; Roemer-Pergher, Cordula; van der Werf-Grohmann, Natascha; Schwab, Karl Otfried

2012-01-01

Growth hormone (GH) is the most frequently used treatment in children with idiopathic short stature (ISS). Aromatase inhibitor (AI) therapy is still in an experimental state, and both final height (FH) and long-term efficacy data in ISS have not been published. We present a 14.5-year-old boy with ISS and a height of 142.7 cm [standard deviation score (SDS) -2.79]. Based on the baseline bone age (BA) of 13.5-14 years, his predicted adult height (PAH) by Bayley/Pinneau was 154 cm (SDS -3.77)-158.2 (SDS -3.15). After a 5-year letrozole monotherapy, FH was 169 cm (SDS -1.57) showing a height difference between PAH and FH from 10.8 to 15 cm. No permanent side effects of the medication have been observed. Both a transient occurrence and a spontaneous recovery of decreased bone mineral apparent density were seen, verified by dual-energy X-ray absorptiometry. Spinal magnetic resonance imaging revealed no vertebral abnormalities. All therapy might be an effective and low-cost alternative to the use of GH. Further controlled trials should prove efficacy and safety of long-term AI therapy in boys with ISS.

Combining boundary-based methods with tensor-based morphometry in the measurement of longitudinal brain change.

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Fletcher, Evan; Knaack, Alexander; Singh, Baljeet; Lloyd, Evan; Wu, Evan; Carmichael, Owen; DeCarli, Charles

2013-02-01

Tensor-based morphometry is a powerful tool for automatically computing longitudinal change in brain structure. Because of bias in images and in the algorithm itself, however, a penalty term and inverse consistency are needed to control the over-reporting of nonbiological change. These may force a tradeoff between the intrinsic sensitivity and specificity, potentially leading to an under-reporting of authentic biological change with time. We propose a new method incorporating prior information about tissue boundaries (where biological change is likely to exist) that aims to keep the robustness and specificity contributed by the penalty term and inverse consistency while maintaining localization and sensitivity. Results indicate that this method has improved sensitivity without increased noise. Thus it will have enhanced power to detect differences within normal aging and along the spectrum of cognitive impairment.

A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole

International Nuclear Information System (INIS)

Garcia-Casado, Zaida; Cervera-Deval, Jose; Campos, Josefina; Albaladejo, Carlos Vazquez; Llombart-Bosch, Antonio; Guillem, Vicente; Lopez-Guerrero, Jose A; Guerrero-Zotano, Angel; Llombart-Cussac, Antonio; Calatrava, Ana; Fernandez-Serra, Antonio; Ruiz-Simon, Amparo; Gavila, Joaquin; Climent, Miguel A; Almenar, Sergio

2010-01-01

Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4 th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood. Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009). Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain.

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Taoka, Toshiaki; Naganawa, Shinji

2018-04-10

After Kanda's first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the 'glymphatic system', which is a coined word that combines 'gl' for glia cell and 'lymphatic' system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue.

Multiple "buy buttons" in the brain: Forecasting chocolate sales at point-of-sale based on functional brain activation using fMRI.

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Kühn, Simone; Strelow, Enrique; Gallinat, Jürgen

2016-08-01

We set out to forecast consumer behaviour in a supermarket based on functional magnetic resonance imaging (fMRI). Data was collected while participants viewed six chocolate bar communications and product pictures before and after each communication. Then self-reports liking judgement were collected. fMRI data was extracted from a priori selected brain regions: nucleus accumbens, medial orbitofrontal cortex, amygdala, hippocampus, inferior frontal gyrus, dorsomedial prefrontal cortex assumed to contribute positively and dorsolateral prefrontal cortex and insula were hypothesized to contribute negatively to sales. The resulting values were rank ordered. After our fMRI-based forecast an instore test was conducted in a supermarket on n=63.617 shoppers. Changes in sales were best forecasted by fMRI signal during communication viewing, second best by a comparison of brain signal during product viewing before and after communication and least by explicit liking judgements. The results demonstrate the feasibility of applying neuroimaging methods in a relatively small sample to correctly forecast sales changes at point-of-sale. Copyright © 2016. Published by Elsevier Inc.

Eye-gaze independent EEG-based brain-computer interfaces for communication

Science.gov (United States)

Riccio, A.; Mattia, D.; Simione, L.; Olivetti, M.; Cincotti, F.

2012-08-01

The present review systematically examines the literature reporting gaze independent interaction modalities in non-invasive brain-computer interfaces (BCIs) for communication. BCIs measure signals related to specific brain activity and translate them into device control signals. This technology can be used to provide users with severe motor disability (e.g. late stage amyotrophic lateral sclerosis (ALS); acquired brain injury) with an assistive device that does not rely on muscular contraction. Most of the studies on BCIs explored mental tasks and paradigms using visual modality. Considering that in ALS patients the oculomotor control can deteriorate and also other potential users could have impaired visual function, tactile and auditory modalities have been investigated over the past years to seek alternative BCI systems which are independent from vision. In addition, various attentional mechanisms, such as covert attention and feature-directed attention, have been investigated to develop gaze independent visual-based BCI paradigms. Three areas of research were considered in the present review: (i) auditory BCIs, (ii) tactile BCIs and (iii) independent visual BCIs. Out of a total of 130 search results, 34 articles were selected on the basis of pre-defined exclusion criteria. Thirteen articles dealt with independent visual BCIs, 15 reported on auditory BCIs and the last six on tactile BCIs, respectively. From the review of the available literature, it can be concluded that a crucial point is represented by the trade-off between BCI systems/paradigms with high accuracy and speed, but highly demanding in terms of attention and memory load, and systems requiring lower cognitive effort but with a limited amount of communicable information. These issues should be considered as priorities to be explored in future studies to meet users’ requirements in a real-life scenario.

Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report

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Stavrinou Lampis C

2011-06-01

Full Text Available Abstract Background The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. Case presentation We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. Conclusion The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report.

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Themistocleous, Marios S; Boviatsis, Efstathios J; Stavrinou, Lampis C; Stathis, Pantelis; Sakas, Damianos E

2011-06-29

The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

Total and regional brain volumes in a population-based normative sample from 4 to 18 years: the NIH MRI Study of Normal Brain Development.

Science.gov (United States)

2012-01-01

Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5-18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents.

Use of gadolinium-based magnetic resonance imaging contrast agents and awareness of brain gadolinium deposition among pediatric providers in North America

International Nuclear Information System (INIS)

Mithal, Leena B.; Patel, Payal S.; Mithal, Divakar; Palac, Hannah L.; Rozenfeld, Michael N.

2017-01-01

Numerous recent articles have reported brain gadolinium deposition when using linear but not macrocyclic gadolinium-based contrast agents (GBCAs). To determine the current landscape of gadolinium use among pediatric institutions and the knowledge base of radiologists and referring providers with regard to GBCAs and brain gadolinium deposition. We e-mailed voluntary closed surveys to 5,390 physicians in various pediatric professional societies between January 2016 and March 2016. We used chi-square and Fisher exact tests to compare response distributions among specialties. We found that 80% of surveyed pediatric hospitals use macrocyclic contrast agents. In the last year, 58% switched their agent, most commonly to gadoterate meglumine, with the most common reason being brain gadolinium deposition. Furthermore, surveys indicated that 23% of hospitals are considering switching, and, of these, 83% would switch to gadoterate meglumine; the most common reasons were brain gadolinium deposition and safety. Radiologists were more aware of brain gadolinium deposition than non-radiologist physicians (87% vs. 26%; P<0.0001). Radiologists and referring providers expressed similar levels of concern (95% and 89%). Twelve percent of radiologists and 2% of referring providers reported patients asking about brain gadolinium deposition. Radiologists were significantly more comfortable addressing patient inquiries than referring pediatric physicians (48% vs. 6%; P<0.0001). The number of MRIs requested by referring pediatric physicians correlated with their knowledge of brain gadolinium deposition, contrast agent used by their hospital, and comfort discussing brain gadolinium deposition with patients (P<0.0001). Since the discovery of brain gadolinium deposition, many pediatric hospitals have switched to or plan to switch to a more stable macrocyclic MR contrast agent, most commonly gadoterate meglumine. Despite this, there is need for substantial further education of radiologists and

Use of gadolinium-based magnetic resonance imaging contrast agents and awareness of brain gadolinium deposition among pediatric providers in North America

Energy Technology Data Exchange (ETDEWEB)

Mithal, Leena B. [Northwestern University, Feinberg School of Medicine, Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Patel, Payal S. [University of Arizona College of Medicine, Department of Pediatrics, Phoenix, AZ (United States); Mithal, Divakar [Northwestern University, Feinberg School of Medicine, Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Pediatric Neurology, Chicago, IL (United States); Palac, Hannah L. [Northwestern University, Biostatistics, Feinberg School of Medicine, Ann and Robert H. Lurie Children' s Hospital of Chicago, Chicago, IL (United States); Rozenfeld, Michael N. [University of Arizona College of Medicine, Department of Radiology, Phoenix, AZ (United States)

2017-05-15

Numerous recent articles have reported brain gadolinium deposition when using linear but not macrocyclic gadolinium-based contrast agents (GBCAs). To determine the current landscape of gadolinium use among pediatric institutions and the knowledge base of radiologists and referring providers with regard to GBCAs and brain gadolinium deposition. We e-mailed voluntary closed surveys to 5,390 physicians in various pediatric professional societies between January 2016 and March 2016. We used chi-square and Fisher exact tests to compare response distributions among specialties. We found that 80% of surveyed pediatric hospitals use macrocyclic contrast agents. In the last year, 58% switched their agent, most commonly to gadoterate meglumine, with the most common reason being brain gadolinium deposition. Furthermore, surveys indicated that 23% of hospitals are considering switching, and, of these, 83% would switch to gadoterate meglumine; the most common reasons were brain gadolinium deposition and safety. Radiologists were more aware of brain gadolinium deposition than non-radiologist physicians (87% vs. 26%; P<0.0001). Radiologists and referring providers expressed similar levels of concern (95% and 89%). Twelve percent of radiologists and 2% of referring providers reported patients asking about brain gadolinium deposition. Radiologists were significantly more comfortable addressing patient inquiries than referring pediatric physicians (48% vs. 6%; P<0.0001). The number of MRIs requested by referring pediatric physicians correlated with their knowledge of brain gadolinium deposition, contrast agent used by their hospital, and comfort discussing brain gadolinium deposition with patients (P<0.0001). Since the discovery of brain gadolinium deposition, many pediatric hospitals have switched to or plan to switch to a more stable macrocyclic MR contrast agent, most commonly gadoterate meglumine. Despite this, there is need for substantial further education of radiologists and

Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial.

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Okonkwo, David O; Shutter, Lori A; Moore, Carol; Temkin, Nancy R; Puccio, Ava M; Madden, Christopher J; Andaluz, Norberto; Chesnut, Randall M; Bullock, M Ross; Grant, Gerald A; McGregor, John; Weaver, Michael; Jallo, Jack; LeRoux, Peter D; Moberg, Dick; Barber, Jason; Lazaridis, Christos; Diaz-Arrastia, Ramon R

2017-11-01

A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study. Randomized prospective clinical trial. Ten ICUs in the United States. One hundred nineteen severe traumatic brain injury patients. Patients were randomized to treatment protocol based on intracranial pressure plus brain tissue oxygenation monitoring versus intracranial pressure monitoring alone. Brain tissue oxygenation data were recorded in the intracranial pressure -only group in blinded fashion. Tiered interventions in each arm were specified and impact on intracranial pressure and brain tissue oxygenation measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the Glasgow Outcome Scale-Extended. A management protocol based on brain tissue oxygenation and intracranial pressure monitoring reduced the proportion of time with brain tissue hypoxia after severe traumatic brain injury (0.45 in intracranial pressure-only group and 0.16 in intracranial pressure plus brain tissue oxygenation group; p injury after severe traumatic brain injury based on brain tissue oxygenation and intracranial pressure values was consistent with reduced mortality and increased proportions of patients with good recovery compared with intracranial pressure-only management; however, the study was not powered for clinical efficacy. Management of severe traumatic brain injury informed by multimodal intracranial pressure and brain tissue oxygenation monitoring reduced brain tissue hypoxia with a trend toward lower mortality and more favorable outcomes than intracranial pressure-only treatment. A Phase III randomized trial to assess

Computer- and Suggestion-based Cognitive Rehabilitation following Acquired Brain Injury

DEFF Research Database (Denmark)

Lindeløv, Jonas Kristoffer

. That is, training does not cause cognitive transfer and thus does not constitute “brain training” or “brain exercise” of any clinical relevance. A larger study found more promising results for a suggestion-based treatment in a hypnotic procedure. Patients improved to above population average in a matter...... of 4-8 hours, making this by far the most effective treatment compared to computer-based training, physical exercise, phamaceuticals, meditation, and attention process training. The contrast between computer-based methods and the hypnotic suggestion treatment may be reflect a more general discrepancy...

Early life exposure to environmental levels of the aromatase inhibitor tributyltin causes masculinisation and irreversible sperm damage in zebrafish (Danio rerio).

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McAllister, Brian G; Kime, David E

2003-11-19

To determine whether early life exposure to tributyltin (TBT), an aromatase inhibitor, impaired reproductive function in fish, Danio rerio were exposed to environmentally realistic levels (0.01-100 ng l(-1)) of TBT from 0 to 30, 30 to 60, and 0 to 70 days post-hatch, and the sex ratio and sperm motility of the adults examined 3-5 months after cessation of exposure. Fish exposed for 70 days to 0.1 ng l(-1) of TBT, a concentration presently below the detection limit in water, showed a male biased population which produced a high incidence of sperm lacking flagella. At 1 ng l(-1), the motility of sperm was significantly lower than that of control fish, while at 10 ng l(-1), all sperm lacked flagella and, at 100 ng l(-1), milt volume had increased. The effect of exposure on sex ratio was similar after exposure from 0 to 70 and 0 to 30 days, but even 100 ng l(-1) gave only 65% males after exposure from 30 to 60 days. Effects on sperm motility and morphology and on milt volume were less pronounced after 30 day than 70 day exposure. Our data suggest that screening for aromatase inhibiting activity and assessment of its risks in early life to human and wildlife fertility needs to be urgently addressed, and that the reproductive toxicity of TBT may presently be underestimated.

Electroencephalography(EEG)-based instinctive brain-control of a quadruped locomotion robot.

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Jia, Wenchuan; Huang, Dandan; Luo, Xin; Pu, Huayan; Chen, Xuedong; Bai, Ou

2012-01-01

Artificial intelligence and bionic control have been applied in electroencephalography (EEG)-based robot system, to execute complex brain-control task. Nevertheless, due to technical limitations of the EEG decoding, the brain-computer interface (BCI) protocol is often complex, and the mapping between the EEG signal and the practical instructions lack of logic associated, which restrict the user's actual use. This paper presents a strategy that can be used to control a quadruped locomotion robot by user's instinctive action, based on five kinds of movement related neurophysiological signal. In actual use, the user drives or imagines the limbs/wrists action to generate EEG signal to adjust the real movement of the robot according to his/her own motor reflex of the robot locomotion. This method is easy for real use, as the user generates the brain-control signal through the instinctive reaction. By adopting the behavioral control of learning and evolution based on the proposed strategy, complex movement task may be realized by instinctive brain-control.

[Solitary actinomycotic brain abscess: case report].

Science.gov (United States)

Takahashi, Kiyoshi; Hasegawa, Yoshihito; Nishimoto, Yo; Hayashi, Satoru; Yamasaki, Masahiro; Kuzume, Daisuke; Hashimoto, Keiko; Enzan, Hideaki

2012-06-01

Actinomycotic brain abscess is a rare condition with uncertain clinical features. Here we report the case of a 66-year-old immune-competent woman with an actinomycotic brain abscess who presented with sensory aphasia and mild right hemiparesis. She had no febrile episode or headache. Moreover, she did not have any periodontal or oto-rhino-laryngological disease, and the results of laboratory tests were normal. A computed tomography scan showed an irregular, low-density area in the left parietal lobe. Subsequent magnetic resonance imaging showed low-signal intensity in a T1 weighted image, high-signal intensity in a T2 weighted image, and mixed intensity on a diffusion weighted image. Thallium-201 chloride scintigraphy showed definite accumulation of thallium in the lesion and the patient's condition gradually deteriorated. Ten days after gadolinium administration, a T1 weighted image showed a multi- lobulated irregular mass in the left parietal lobe. The patient subsequently underwent craniotomy and evacuation of the yellowish abscess. Gram staining of the tissue showed the presence of gram-positive filamentous rods, and abscess cultures were positive for Actinomyces and Prevotella disiens. The abscess resolved after treatment with a high dose of intravenous penicillin G (24 million units/day) for 8 weeks, followed by an oral dose of amoxicillin for 4 months. The patient was discharged with a rudimentary limitation of the visual field.

Memory as the "whole brain work": a large-scale model based on "oscillations in super-synergy".

Science.gov (United States)

Başar, Erol

2005-01-01

According to recent trends, memory depends on several brain structures working in concert across many levels of neural organization; "memory is a constant work-in progress." The proposition of a brain theory based on super-synergy in neural populations is most pertinent for the understanding of this constant work in progress. This report introduces a new model on memory basing on the processes of EEG oscillations and Brain Dynamics. This model is shaped by the following conceptual and experimental steps: 1. The machineries of super-synergy in the whole brain are responsible for formation of sensory-cognitive percepts. 2. The expression "dynamic memory" is used for memory processes that evoke relevant changes in alpha, gamma, theta and delta activities. The concerted action of distributed multiple oscillatory processes provides a major key for understanding of distributed memory. It comprehends also the phyletic memory and reflexes. 3. The evolving memory, which incorporates reciprocal actions or reverberations in the APLR alliance and during working memory processes, is especially emphasized. 4. A new model related to "hierarchy of memories as a continuum" is introduced. 5. The notions of "longer activated memory" and "persistent memory" are proposed instead of long-term memory. 6. The new analysis to recognize faces emphasizes the importance of EEG oscillations in neurophysiology and Gestalt analysis. 7. The proposed basic framework called "Memory in the Whole Brain Work" emphasizes that memory and all brain functions are inseparable and are acting as a "whole" in the whole brain. 8. The role of genetic factors is fundamental in living system settings and oscillations and accordingly in memory, according to recent publications. 9. A link from the "whole brain" to "whole body," and incorporation of vegetative and neurological system, is proposed, EEG oscillations and ultraslow oscillations being a control parameter.

Traumatic primary brain stem haemorrhage

International Nuclear Information System (INIS)

Andrioli, G.C.; Zuccarello, M.; Trincia, G.; Fiore, D.L.; De Caro, R.

1983-01-01

We report 36 cases of post-traumatic 'primary brain stem haemorrhage' visualized by the CT scan and confirmed at autopsy. Clinical experience shows that many technical factors influence the inability to visualize brain stem haemorrhages. Experimental injection of fresh blood into the pons and midbrain of cadavers shows that lesions as small as 0.25 ml in volume may be visualized. The volume and the anatomical configuration of traumatic lesions of the brain stem extended over a rostro-caudal direction, and their proximity to bony structures at the base of the skull are obstacles to the visualization of brain stem haemorrhages. (Author)

A covert attention P300-based brain-computer interface: Geospell.

Science.gov (United States)

Aloise, Fabio; Aricò, Pietro; Schettini, Francesca; Riccio, Angela; Salinari, Serenella; Mattia, Donatella; Babiloni, Fabio; Cincotti, Febo

2012-01-01

The Farwell and Donchin P300 speller interface is one of the most widely used brain-computer interface (BCI) paradigms for writing text. Recent studies have shown that the recognition accuracy of the P300 speller decreases significantly when eye movement is impaired. This report introduces the GeoSpell interface (Geometric Speller), which implements a stimulation framework for a P300-based BCI that has been optimised for operation in covert visual attention. We compared the Geospell with the P300 speller interface under overt attention conditions with regard to effectiveness, efficiency and user satisfaction. Ten healthy subjects participated in the study. The performance of the GeoSpell interface in covert attention was comparable with that of the P300 speller in overt attention. As expected, the effectiveness of the spelling decreased with the new interface in covert attention. The NASA task load index (TLX) for workload assessment did not differ significantly between the two modalities. This study introduces and evaluates a gaze-independent, P300-based brain-computer interface, the efficacy and user satisfaction of which were comparable with those off the classical P300 speller. Despite a decrease in effectiveness due to the use of covert attention, the performance of the GeoSpell far exceeded the threshold of accuracy with regard to effective spelling.

Evaluating anorexia-related brain atrophy using MP2RAGE-based morphometry

International Nuclear Information System (INIS)

Boto, Jose; Loevblad, Karl-Olof; Vargas, Maria Isabel; Gkinis, Georgios; Ortiz, Nadia; Roche, Alexis; Kober, Tobias; Marechal, Benedicte; University Hospital; Ecole Polytechnique Federale de Lausanne; Lazeyras, Francois

2017-01-01

To evaluate brain atrophy in anorexic patients by automated cerebral segmentation with the magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) MRI sequence. Twenty patients (female; mean age, 27.9 years), presenting consecutively for brain MRI between August 2014-December 2016 with clinical suspicion of anorexia nervosa and BMI<18.5 kg/m 2 were included. Controls were ten healthy females (mean age, 26.5 years). Automated brain morphometry was performed based on MP2RAGE. Means of morphometric results in the two groups were compared and correlation with BMI was analysed. Significantly lower volumes of total brain, grey matter (GM), white matter (WM), cerebellum and insula were found in anorexic patients. Anorexics had higher volumes of CSF, ventricles, lateral ventricles and third ventricle. When adjusted means for weight and height were compared, the volume of WM and cerebellum were not significantly different. However, volume of WM was significantly affected by weight and positively correlated with BMI. Significant positive correlations were found between BMI and volumes of total brain, GM, cortical GM and WM. BMI was negatively correlated with volumes of CSF and third ventricle. Brain atrophy was demonstrated in anorexic patients with MP2RAGE-based automated segmentation, which seems to reliably estimate brain volume. (orig.)

Evaluating anorexia-related brain atrophy using MP2RAGE-based morphometry

Energy Technology Data Exchange (ETDEWEB)

Boto, Jose; Loevblad, Karl-Olof; Vargas, Maria Isabel [Geneva University Hospital (Switzerland). Div. of Neuroradiology and Faculty of Medicine of Geneva; Gkinis, Georgios; Ortiz, Nadia [Geneva University Hospital (Switzerland). Dept. of Mental Health and Psychiatry; Roche, Alexis; Kober, Tobias; Marechal, Benedicte [Siemens Healthcare HC CEMEA SUI DI BM PI, Lausanne (Switzerland). Siemens ACIT, Advanced Clinical Imaging Technology; University Hospital (CHUV), Lausanne (Switzerland). Dept. of Radiology; Ecole Polytechnique Federale de Lausanne (Switzerland). LTS5; Lazeyras, Francois [Geneva University Hospital (Switzerland). Div. of Radiology and Faculty of Medicine of Geneva

2017-12-15

To evaluate brain atrophy in anorexic patients by automated cerebral segmentation with the magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) MRI sequence. Twenty patients (female; mean age, 27.9 years), presenting consecutively for brain MRI between August 2014-December 2016 with clinical suspicion of anorexia nervosa and BMI<18.5 kg/m{sup 2} were included. Controls were ten healthy females (mean age, 26.5 years). Automated brain morphometry was performed based on MP2RAGE. Means of morphometric results in the two groups were compared and correlation with BMI was analysed. Significantly lower volumes of total brain, grey matter (GM), white matter (WM), cerebellum and insula were found in anorexic patients. Anorexics had higher volumes of CSF, ventricles, lateral ventricles and third ventricle. When adjusted means for weight and height were compared, the volume of WM and cerebellum were not significantly different. However, volume of WM was significantly affected by weight and positively correlated with BMI. Significant positive correlations were found between BMI and volumes of total brain, GM, cortical GM and WM. BMI was negatively correlated with volumes of CSF and third ventricle. Brain atrophy was demonstrated in anorexic patients with MP2RAGE-based automated segmentation, which seems to reliably estimate brain volume. (orig.)

Genomic risk prediction of aromatase inhibitor-related arthralgia in patients with breast cancer using a novel machine-learning algorithm.

Science.gov (United States)

Reinbolt, Raquel E; Sonis, Stephen; Timmers, Cynthia D; Fernández-Martínez, Juan Luis; Cernea, Ana; de Andrés-Galiana, Enrique J; Hashemi, Sepehr; Miller, Karin; Pilarski, Robert; Lustberg, Maryam B

2018-01-01

Many breast cancer (BC) patients treated with aromatase inhibitors (AIs) develop aromatase inhibitor-related arthralgia (AIA). Candidate gene studies to identify AIA risk are limited in scope. We evaluated the potential of a novel analytic algorithm (NAA) to predict AIA using germline single nucleotide polymorphisms (SNP) data obtained before treatment initiation. Systematic chart review of 700 AI-treated patients with stage I-III BC identified asymptomatic patients (n = 39) and those with clinically significant AIA resulting in AI termination or therapy switch (n = 123). Germline DNA was obtained and SNP genotyping performed using the Affymetrix UK BioBank Axiom Array to yield 695,277 SNPs. SNP clusters that most closely defined AIA risk were discovered using an NAA that sequentially combined statistical filtering and a machine-learning algorithm. NCBI PhenGenI and Ensemble databases defined gene attribution of the most discriminating SNPs. Phenotype, pathway, and ontologic analyses assessed functional and mechanistic validity. Demographics were similar in cases and controls. A cluster of 70 SNPs, correlating to 57 genes, was identified. This SNP group predicted AIA occurrence with a maximum accuracy of 75.93%. Strong associations with arthralgia, breast cancer, and estrogen phenotypes were seen in 19/57 genes (33%) and were functionally consistent. Using a NAA, we identified a 70 SNP cluster that predicted AIA risk with fair accuracy. Phenotype, functional, and pathway analysis of attributed genes was consistent with clinical phenotypes. This study is the first to link a specific SNP/gene cluster to AIA risk independent of candidate gene bias. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Nordic Walking as an Exercise Intervention to Reduce Pain in Women With Aromatase Inhibitor-Associated Arthralgia: A Feasibility Study.

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Fields, Jo; Richardson, Alison; Hopkinson, Jane; Fenlon, Deborah

2016-10-01

Women taking aromatase inhibitors as treatment for breast cancer commonly experience joint pain and stiffness (aromatase inhibitor-associated arthralgia [AIAA]), which can cause problems with adherence. There is evidence that exercise might be helpful, and Nordic walking could reduce joint pain compared to normal walking. To determine the feasibility of a trial of Nordic walking as an exercise intervention for women with AIAA. A feasibility study was carried out in a sample of women with AIAA using a randomized control design. Women were randomized to exercise (six-week supervised group Nordic walking training once per week with an increasing independent element, followed by six weeks 4 × 30 minutes/week independent Nordic walking); or enhanced usual care. Data were collected on recruitment, retention, exercise adherence, safety, and acceptability. The Brief Pain Inventory, GP Physical Activity Questionnaire, and biopsychosocial measures were completed at baseline, six and 12 weeks. Forty of 159 eligible women were recruited and attrition was 10%. There was no increased lymphedema and no long-term or serious injury. Adherence was >90% for weekly supervised group Nordic walking, and during independent Nordic walking, >80% women managed one to two Nordic walking sessions per week. From baseline to study end point, overall activity levels increased and pain reduced in both the intervention and control groups. Our findings indicate that women with AIAA are prepared to take up Nordic walking, complete a six-week supervised course and maintain increased activity levels over a 12-week period with no adverse effects. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Technology-Based Rehabilitation to Improve Communication after Acquired Brain Injury

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Carrie A. Des Roches

2017-07-01

Full Text Available The utilization of technology has allowed for several advances in aphasia rehabilitation for individuals with acquired brain injury. Thirty-one previous studies that provide technology-based language or language and cognitive rehabilitation are examined in terms of the domains addressed, the types of treatments that were provided, details about the methods and the results, including which types of outcomes are reported. From this, we address questions about how different aspects of the delivery of treatment can influence rehabilitation outcomes, such as whether the treatment was standardized or tailored, whether the participants were prescribed homework or not, and whether intensity was varied. Results differed by these aspects of treatment delivery but ultimately the studies demonstrated consistent improvement on various outcome measures. With these aspects of technology-based treatment in mind, the ultimate goal of personalized rehabilitation is discussed.

Technology-Based Rehabilitation to Improve Communication after Acquired Brain Injury.

Science.gov (United States)

Des Roches, Carrie A; Kiran, Swathi

2017-01-01

The utilization of technology has allowed for several advances in aphasia rehabilitation for individuals with acquired brain injury. Thirty-one previous studies that provide technology-based language or language and cognitive rehabilitation are examined in terms of the domains addressed, the types of treatments that were provided, details about the methods and the results, including which types of outcomes are reported. From this, we address questions about how different aspects of the delivery of treatment can influence rehabilitation outcomes, such as whether the treatment was standardized or tailored, whether the participants were prescribed homework or not, and whether intensity was varied. Results differed by these aspects of treatment delivery but ultimately the studies demonstrated consistent improvement on various outcome measures. With these aspects of technology-based treatment in mind, the ultimate goal of personalized rehabilitation is discussed.

Acupuncture for central pain affecting the ribcage following traumatic brain injury and rib fractures--a case report.

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Donnellan, Clare P

2006-09-01

This case report describes the use of acupuncture in the management of chronic central pain in a 51 year old man following severe traumatic brain injury and multiple injuries including rib fractures. The patient reported rapid and significant improvements in pain and mood during a course of acupuncture treatment. Chronic pain following traumatic brain injury is a significant problem. Chronic pain after rib fractures is also commonly reported. Acupuncture is widely used in the management of pain but its use has been reported rarely in the traumatic brain injury literature. This case report suggests that acupuncture may be a useful option to consider in these patients. Outcome was assessed formally using a 0-10 verbal numerical rating scale for pain, and the Hospital Anxiety and Depression Scale (HADS) for psychological status before and after the course of treatment. These scales are widely used in clinical practice as well as in research involving patients with traumatic brain injury, although they have not been validated in this population. The changes in this patient's outcome scores were not consistent with the benefits he reported. Treatment of this patient highlighted the difficulties of using standardised self rating scales for patients with cognitive impairment. The report also discusses the effects of acupuncture on this patient's mood.

Brain-Based Indices for User System Symbiosis

NARCIS (Netherlands)

Erp, J.B.F. van; Veltman, J.A.; Grootjen, M.

2010-01-01

The future generation user system interfaces need to be user-centric which goes beyond user-friendly and includes understanding and anticipating user intentions. We introduce the concept of operator models, their role in implementing user-system symbiosis, and the usefulness of brain-based indices

Biosocial Spaces and Neurocomputational Governance: Brain-Based and Brain-Targeted Technologies in Education

Science.gov (United States)

Williamson, Ben; Pykett, Jessica; Nemorin, Selena

2018-01-01

Recently, technologies based on neuroscientific insights into brain function and structure have been promoted for application in education. The novel practices and environments produced by these technologies require new forms of "biosocial" analysis to unpack their implications for education, learning and governance. This article…

Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance.

Science.gov (United States)

Eriksen, Mette Brandt; Glintborg, Dorte; Nielsen, Michael Friberg Bruun; Jakobsen, Marianne Antonius; Brusgaard, Klaus; Tan, Qihua; Gaster, Michael

2014-09-05

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls. Glucose transport in myotubes was comparable in patients with PCOS vs. controls and was unchanged by testosterone treatment (p=0.21 PCOS vs. controls). These results suggest that testosterone treatment of myotubes increases the aromatase and androgen receptor gene expression without affecting insulin sensitivity and if testosterone is implicated in muscular insulin resistance in PCOS, this is by and indirect mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Metal-based nanoparticle interactions with the nervous system: the challenge of brain entry and the risk of retention in the organism.

Science.gov (United States)

Yokel, Robert; Grulke, Eric; MacPhail, Robert

2013-01-01

This review of metal-based nanoparticles focuses on factors influencing their distribution into the nervous system, evidence they enter brain parenchyma, and nervous system responses. Gold is emphasized as a model metal-based nanoparticle and for risk assessment in the companion review. The anatomy and physiology of the nervous system, basics of colloid chemistry, and environmental factors that influence what cells see are reviewed to provide background on the biological, physical-chemical, and internal milieu factors that influence nervous system nanoparticle uptake. The results of literature searches reveal little nanoparticle research included the nervous system, which about equally involved in vitro and in vivo methods, and very few human studies. The routes of uptake into the nervous system and mechanisms of nanoparticle uptake by cells are presented with examples. Brain nanoparticle uptake inversely correlates with size. The influence of shape has not been reported. Surface charge has not been clearly shown to affect flux across the blood-brain barrier. There is very little evidence for metal-based nanoparticle distribution into brain parenchyma. Metal-based nanoparticle disruption of the blood-brain barrier and adverse brain changes have been shown, and are more pronounced for spheres than rods. Study concentrations need to be put in exposure contexts. Work with dorsal root ganglion cells and brain cells in vitro show the potential for metal-based nanoparticles to produce toxicity. Interpretation of these results must consider the ability of nanoparticles to distribute across the barriers protecting the nervous system. Effects of the persistence of poorly soluble metal-based nanoparticles are of particular concern. Copyright © 2013 Wiley Periodicals, Inc.

High-fat diet based on dried bovine brain: an effective animal model of dyslipidemia and insulin resistance.

Science.gov (United States)

Araújo, Tiago Gomes; Leite, Ana Catarina Rezende; Martins da Fonseca, Caíque Silveira; Carvalho, Bruno Melo; Schuler, Alexandre Ricardo Pereira; Lima, Vera Lúcia de Menezes

2011-09-01

Currently, there are no reports in the literature demonstrating any animal model that ingests one of the fattiest animal food source, the bovine brain. We hypothesized that a high-fat diet (HFD), based on dried bovine brain, could be used to develop an animal model possessing a spectrum of insulin resistance-related features. The HFD was formulated with 40% dried bovine brain plus 16.4% butter fat, prepared in-house. Furthermore, the diet contained 52% calories as fat and 73% of total fatty acids were saturated. Swiss mice weighing about 40 g were assigned to two dietary groups (n=6/group), one group received a standard chow diet and the other was given HFD for 3 months. The body weight and biochemical parameters of the animals were measured initially and at monthly intervals until the end of the experiment. Animals fed on a HFD showed a significant increase in the body and adipose tissue weight, serum total cholesterol and triglyceride levels, when compared with mice fed on the control diet. Additionally, the HFD group showed higher circulating levels of liver transaminases, such as alanine aminotransferase and aspartate aminotransferase, compared with the control group. Finally, to illustrate the usefulness of this model, we report that the HFD induced mild hyperglycemia, fasting hyperinsulinemia, and increased the homeostasis model of assessment (HOMA-IR), in comparison with the control group. In conclusion, our results show that HFD, based on dried bovine brain, causes insulin resistance-related metabolic disturbances. Thus, this may be a suitable model to study disturbances in energy metabolism and their consequences.

Increased Sclerostin Levels after Further Ablation of Remnant Estrogen by Aromatase Inhibitors

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Wonjin Kim

2015-03-01

Full Text Available BackgroundSclerostin is a secreted Wnt inhibitor produced almost exclusively by osteocytes, which inhibits bone formation. Aromatase inhibitors (AIs, which reduce the conversion of steroids to estrogen, are used to treat endocrine-responsive breast cancer. As AIs lower estrogen levels, they increase bone turnover and lower bone mass. We analyzed changes in serum sclerostin levels in Korean women with breast cancer who were treated with an AI.MethodsWe included postmenopausal women with endocrine-responsive breast cancer (n=90; mean age, 57.7 years treated with an AI, and compared them to healthy premenopausal women (n=36; mean age, 28.0 years. The subjects were randomly assigned to take either 5 mg alendronate with 0.5 µg calcitriol (n=46, or placebo (n=44 for 6 months.ResultsPostmenopausal women with breast cancer had significantly higher sclerostin levels compared to those in premenopausal women (27.8±13.6 pmol/L vs. 23.1±4.8 pmol/L, P0.05.ConclusionSerum sclerostin levels increased with absolute deficiency of residual estrogens in postmenopausal women with endocrine-responsive breast cancer who underwent AI therapy with concurrent bone loss.

Traumatic brain injury due to pressure cooker explosion in a child: case report

Directory of Open Access Journals (Sweden)

Calderon-Miranda Willem Guillermo

2016-06-01

Full Text Available Traumatic brain injury is a common condition in the emergency services, affecting the pediatric and adult population significantly. Patterns of head injury as well as management principles in children are important differences compared to adults. Traumatic brain injury by Domestic pressure cooker is rare and has not been described in children, which to our knowledge is the first report in the literature of this nature.

Post-Inpatient Brain Injury Rehabilitation Outcomes: Report from the National OutcomeInfo Database

OpenAIRE

Malec, James F.; Kean, Jacob

2016-01-01

This study examined outcomes for intensive residential and outpatient/community-based post-inpatient brain injury rehabilitation (PBIR) programs compared with supported living programs. The goal of supported living programs was stable functioning (no change). Data were obtained for a large cohort of adults with acquired brain injury (ABI) from the OutcomeInfo national database, a web-based database system developed through National Institutes of Health (NIH) Small Business Technology Transfer...

Effect of rehabilitation on a patient suffering from a tuberculous brain abscess with Gerstmann's syndrome: case report

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Kuo CL

2012-05-01

Full Text Available Chih-Lan Kuo1, Sui-Foon Lo1,2, Chun-Lin Liu3, Chia-Hui Chou4, Li-Wei Chou1,2,5¹Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; ²School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 3Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan; 4Department of Infectious disease, China Medical University Hospital, Taichung, Taiwan; 5Department of Physical Therapy, China Medical University, Taichung, TaiwanAbstract: There are few reports in the literature of tuberculous brain abscess. Tuberculous brain abscess usually occurs in an immunocompromised host. Almost all previously documented cases have involved acquired immune deficiency syndrome. We encountered a 53-year-old right-handed immunocompetent male who was initially suspected of having a cerebrovascular accident due to acute-onset right hemiparesis and paresthesia. A tentative diagnosis of brain tumor versus brain abscess was made on imaging studies. The patient was finally diagnosed with a tuberculous brain abscess based upon deterioration on imaging and a positive tuberculosis culture. The tuberculous brain abscess was located in the left parietal lobe, which resulted in Gerstmann's syndrome and right-sided apraxia. Stereotactic surgery was performed. He was also given antituberculosis chemotherapy and comprehensive rehabilitation. Considerable improvement was noted after rehabilitation. The patient even returned to a normal life and work. Our case demonstrates that an aggressive intensive inpatient rehabilitation program combined with stereotactic surgery and effective antituberculosis therapy play an important role in improving the outcome for patients with tuberculous brain abscess, Gerstmann's syndrome, and right-sided apraxia.Keywords: tuberculous brain abscess, Gerstmann's syndrome, rehabilitation

Toward a brain-based theory of beauty.

Science.gov (United States)

Ishizu, Tomohiro; Zeki, Semir

2011-01-01

We wanted to learn whether activity in the same area(s) of the brain correlate with the experience of beauty derived from different sources. 21 subjects took part in a brain-scanning experiment using functional magnetic resonance imaging. Prior to the experiment, they viewed pictures of paintings and listened to musical excerpts, both of which they rated on a scale of 1-9, with 9 being the most beautiful. This allowed us to select three sets of stimuli--beautiful, indifferent and ugly--which subjects viewed and heard in the scanner, and rated at the end of each presentation. The results of a conjunction analysis of brain activity showed that, of the several areas that were active with each type of stimulus, only one cortical area, located in the medial orbito-frontal cortex (mOFC), was active during the experience of musical and visual beauty, with the activity produced by the experience of beauty derived from either source overlapping almost completely within it. The strength of activation in this part of the mOFC was proportional to the strength of the declared intensity of the experience of beauty. We conclude that, as far as activity in the brain is concerned, there is a faculty of beauty that is not dependent on the modality through which it is conveyed but which can be activated by at least two sources--musical and visual--and probably by other sources as well. This has led us to formulate a brain-based theory of beauty.

Closed Loop Brain Model of Neocortical Information Based Exchange

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James eKozloski

2016-01-01

Full Text Available Here we describe an information based exchange' model of brain function that ascribes to neocortex, basal ganglia, and thalamus distinct network functions. The model allows us to analyze whole brain system set point measures, such as the rate and heterogeneity of transitions in striatum and neocortex, in the context of neuromodulation and other perturbations. Our closed-loop model is grounded in neuroanatomical observations, proposing a novel Grand Loop through neocortex, and invokes different forms of plasticity at specific tissue interfaces and their principle cell synapses to achieve these transitions. By implementing a system for maximum information based exchange of action potentials between modeled neocortical areas, we observe changes to these measures in simulation. We hypothesize that similar dynamic set points and modulations exist in the brain's resting state activity, and that different modifications to information based exchange may shift the risk profile of different component tissues, resulting in different neurodegenerative diseases. This model is targeted for further development using IBM's Neural Tissue Simulator, which allows scalable elaboration of networks, tissues, and their neural and synaptic components towards ever greater complexity and biological realism.

Hemorrhagic brain metastases with high signal intensity on diffusion-weighted MR images. A case report

Energy Technology Data Exchange (ETDEWEB)

Mori, H.; Abe, O.; Aoki, S.; Masumoto, T.; Yoshikawa, T.; Kunimatsu, A; Hayashi, N.; Ohtomo, K. [Graduate School of Medicine, Univ. of Tokyo (Japan). Dept. of Radiology

2002-11-01

Diffusion-weighted MR imaging has been applicable to the differential diagnosis of abscesses and necrotic or cystic brain tumors. However, restricted water diffusion is not necessarily specific for brain abscess. We describe ring-enhancing metastases of lung carcinoma characterized by high signal intensity on diffusion-weighted MR images. The signal pattern probably reflected intralesional hemorrhage. The present report adds to the growing literature regarding the differential diagnosis of ring-enhancing brain lesions.

Protocol for Exercise Program in Cancer and Cognition (EPICC): A randomized controlled trial of the effects of aerobic exercise on cognitive function in postmenopausal women with breast cancer receiving aromatase inhibitor therapy.

Science.gov (United States)

Gentry, Amanda L; Erickson, Kirk I; Sereika, Susan M; Casillo, Frances E; Crisafio, Mary E; Donahue, Patrick T; Grove, George A; Marsland, Anna L; Watt, Jennifer C; Bender, Catherine M

2018-04-01

The Exercise Program in Cancer and Cognition (EPICC) Study is a randomized controlled trial designed to test the effects of moderate-intensity aerobic exercise on cognitive function in postmenopausal women with early-stage breast cancer during the first six months of aromatase inhibitor therapy. It is estimated that up to 75% of survivors of breast cancer experience cognitive impairment related to disease and treatment. At present, there are no known interventions to improve or manage cognitive function for women with breast cancer. Here, we describe a single-blinded, randomized controlled trial with allocation of 254 postmenopausal women with early-stage breast cancer to a supervised six-month aerobic exercise intervention or usual care. Prior to beginning aromatase inhibitor (AI) therapy, participants complete baseline assessments of cognitive function, cardiorespiratory fitness, blood-based biomarkers, physical activity and sleep, and symptoms (fatigue, sleep problems, depressive symptoms, anxiety). A random subset of participants (n = 150) undergoes neuroimaging procedures that include structural and functional magnetic resonance imaging assessments. All participants maintain an activity diary; physical activity and sleep monitoring is repeated three and seven months post-randomization. The remaining baseline assessments are repeated seven months post-randomization. If successful, exercise could be a low-cost method to improve cognitive function in women with breast cancer that is easily adaptable to the home or community. Clinicaltrials.govNCT02793921. Registered 20 May 2016. Copyright © 2018 Elsevier Inc. All rights reserved.

Research on segmentation based on multi-atlas in brain MR image

Science.gov (United States)

Qian, Yuejing

2018-03-01

Accurate segmentation of specific tissues in brain MR image can be effectively achieved with the multi-atlas-based segmentation method, and the accuracy mainly depends on the image registration accuracy and fusion scheme. This paper proposes an automatic segmentation method based on the multi-atlas for brain MR image. Firstly, to improve the registration accuracy in the area to be segmented, we employ a target-oriented image registration method for the refinement. Then In the label fusion, we proposed a new algorithm to detect the abnormal sparse patch and simultaneously abandon the corresponding abnormal sparse coefficients, this method is made based on the remaining sparse coefficients combined with the multipoint label estimator strategy. The performance of the proposed method was compared with those of the nonlocal patch-based label fusion method (Nonlocal-PBM), the sparse patch-based label fusion method (Sparse-PBM) and majority voting method (MV). Based on our experimental results, the proposed method is efficient in the brain MR images segmentation compared with MV, Nonlocal-PBM, and Sparse-PBM methods.

Brain hypothermia therapy for childhood acute encephalopathy based on clinical evidence

OpenAIRE

IMATAKA, GEORGE; ARISAKA, OSAMU

2015-01-01

Although previous studies have reported on the effectiveness of brain hypothermia therapy in childhood acute encephalopathy, additional studies in this field are necessary. In this review, we discussed brain hypothermia therapy methods for two clinical conditions for which sufficient evidences are currently available in the literature. The first condition is known as hypoxic-ischemic encephalopathy and occurs in newborns and the second condition is acute encephalopathy which occurs in adults ...

Local brain herniation after partial membranectomy for organized chronic subdural hematoma in an adult patient: case report and review of the literature.

Science.gov (United States)

Kusano, Yoshikazu; Horiuchi, Tetsuyoshi; Seguchi, Tatsuya; Kakizawa, Yukinari; Tanaka, Yuichiro; Hongo, Kazuhiro

2010-01-01

Local brain herniation after removal of chronic subdural haematoma is extremely rare, especially in adult patients. This study reports a case of local brain herniation after partial membranectomy for organized chronic subdural haematoma. A 77-year-old man presented with dysarthria and dysphasia caused by local brain herniation of the right frontal lobe through a defect of the inner membrane. The herniated brain was detected by magnetic resonance (MR) imaging. The patient underwent a craniotomy to release the herniated and strangulated brain, which were consistent with the MR imaging findings. The patient recovered fully within 1 month after surgery. To date, five cases of brain herniation through the internal subdural membrane have been reported as complications of chronic subdural haematomas. All but one case occurred in the paediatric population. Urgent surgery should be performed, even if an adult patient suffers from local brain herniation, for preservation of brain function. This is the sixth reported case of brain herniation through a defect of the inner membrane and the second reported case in the adult population.

Deep Learning and Texture-Based Semantic Label Fusion for Brain Tumor Segmentation.

Science.gov (United States)

Vidyaratne, L; Alam, M; Shboul, Z; Iftekharuddin, K M

2018-01-01

Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.

Deep learning and texture-based semantic label fusion for brain tumor segmentation

Science.gov (United States)

Vidyaratne, L.; Alam, M.; Shboul, Z.; Iftekharuddin, K. M.

2018-02-01

Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.

Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

Science.gov (United States)

Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

2015-01-01

Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

A subject-independent pattern-based Brain-Computer Interface

Directory of Open Access Journals (Sweden)

Andreas Markus Ray

2015-10-01

Full Text Available While earlier Brain-Computer Interface (BCI studies have mostly focused on modulating specific brain regions or signals, new developments in pattern classification of brain states are enabling real-time decoding and modulation of an entire functional network. The present study proposes a new method for real-time pattern classification and neurofeedback of brain states from electroencephalographic (EEG signals. It involves the creation of a fused classification model based on the method of Common Spatial Patterns (CSPs from data of several healthy individuals. The subject-independent model is then used to classify EEG data in real-time and provide feedback to new individuals. In a series of offline experiments involving training and testing of the classifier with individual data from 27 healthy subjects, a mean classification accuracy of 75.30% was achieved, demonstrating that the classification system at hand can reliably decode two types of imagery used in our experiments, i.e. happy emotional imagery and motor imagery. In a subsequent experiment it is shown that the classifier can be used to provide neurofeedback to new subjects, and that these subjects learn to match their brain pattern to that of the fused classification model in a few days of neurofeedback training. This finding can have important implications for future studies on neurofeedback and its clinical applications on neuropsychiatric disorders.

Brain bank of the Brazilian aging brain study group - a milestone reached and more than 1,600 collected brains.

Science.gov (United States)

Grinberg, Lea Tenenholz; Ferretti, Renata Eloah de Lucena; Farfel, José Marcelo; Leite, Renata; Pasqualucci, Carlos Augusto; Rosemberg, Sérgio; Nitrini, Ricardo; Saldiva, Paulo Hilário Nascimento; Filho, Wilson Jacob

2007-01-01

Brain banking remains a necessity for the study of aging brain processes and related neurodegenerative diseases. In the present paper, we report the methods applied at and the first results of the Brain Bank of the Brazilian Aging Brain Study Group (BBBABSG) which has two main aims: (1) To collect a large number of brains of elderly comprising non-demented subjects and a large spectrum of pathologies related to aging brain processes, (2) To provide quality material to a multidisciplinar research network unraveling multiple aspects of aging brain processes and related neurodegenerative diseases. The subjects are selected from the Sao Paulo Autopsy Service. Brain parts are frozen and fixated. CSF, carotids, kidney, heart and blood are also collected and DNA is extracted. The neuropathological examinations are carried out based on accepted criteria, using immunohistochemistry. Functional status are assessed through a collateral source based on a clinical protocol. Protocols are approved by the local ethics committee and a written informed consent form is obtained. During the first 21 months, 1,602 samples were collected and were classified by Clinical Dementia Rating as CDR0: 65.7%; CDR0.5:12.6%, CDR1:8.2%, CDR2:5.4%, and CDR3:8.1%. On average, the cost for the processing each case stood at 400 US dollars. To date, 14 laboratories have been benefited by the BBBABSG. The high percentage of non- demented subjects and the ethnic diversity of this series may be significantly contributive toward aging brain processes and related neurodegenerative diseases understanding since BBBABSG outcomes may provide investigators the answers to some additional questions.

Use of Aromatase Inhibitors in Large Cell Calcifying Sertoli Cell Tumors: Effects on Gynecomastia, Growth Velocity, and Bone Age

Science.gov (United States)

Crocker, Melissa K.; Gourgari, Evgenia; Stratakis, Constantine A.

2014-01-01

Context: Large cell calcifying Sertoli cell tumors (LCCSCT) present in isolation or, especially in children, in association with Carney Complex (CNC) or Peutz-Jeghers Syndrome (PJS). These tumors overexpress aromatase (CYP19A1), which leads to increased conversion of delta-4-androstenedione to estrone and testosterone to estradiol. Prepubertal boys may present with growth acceleration, advanced bone age, and gynecomastia. Objective: To investigate the outcomes of aromatase inhibitor therapy (AIT) in prepubertal boys with LCCSCTs. Design: Case series of a very rare tumor and chart review of cases treated at other institutions. Setting: Tertiary care and referral center. Patients: Six boys, five with PJS and one with CNC, were referred to the National Institutes of Health for treatment of LCCSCT. All patients had gynecomastia, testicular enlargement, and advanced bone ages, and were being treated by their referring physicians with AIT. Interventions: Patients were treated for a total of 6–60 months on AIT. Main Outcome Measures: Height, breast tissue mass, and testicular size were all followed; physical examination, scrotal ultrasounds, and bone ages were obtained, and hormonal concentrations and tumor markers were measured. Results: Tumor markers were negative. All patients had decreases in breast tissue while on therapy. Height percentiles declined, and predicted adult height moved closer to midparental height as bone age advancement slowed. Testicular enlargement stabilized until entry into central puberty. Only one patient required unilateral orchiectomy. Conclusions: Patients with LCCSCT benefit from AIT with reduction and/or elimination of gynecomastia and slowing of linear growth and bone age advancement. Further study of long-term outcomes and safety monitoring are needed but these preliminary data suggest that mammoplasty and/or orchiectomy may be foregone in light of the availability of medical therapy. PMID:25226294

The time since last menstrual period is important as a clinical predictor for non-steroidal aromatase inhibitor-related arthralgia

International Nuclear Information System (INIS)

Kanematsu, Miyuki; Morimoto, Masami; Honda, Junko; Nagao, Taeko; Nakagawa, Misako; Takahashi, Masako; Tangoku, Akira; Sasa, Mitsunori

2011-01-01

The clinical predictors of aromatase inhibitor-related arthralgia (AIA), a drug-related adverse reaction of aromatase inhibitors (AIs), remain unclear. AIA was prospectively surveyed every 4 months in 328 postmenopausal breast cancer patients administered a non-steroidal AI (anastrozole). Various clinicopathological parameters were recorded and analyzed (chi-square test, Fisher's exact test and logistic regression analysis). The mean observation period was 39.9 months. AIA manifested in 114 patients (34.8%), with peaks of onset at 4 (33.7%) and 8 months (11.4%) after starting AI administration. Some cases manifested even after 13 months. AIA tended to occur in younger patients (incidences of 46.3%, 37.4% and 28.0% for ages of < 55, 55-65 and > 65 years, respectively (p = 0.063)) and decreased significantly with the age at menarche (53.3%, 35.3% and 15.4% for < 12, 12-15 and > 15 years, respectively (p = 0.036)). The incidences were 45.1%, 46.3 and 25.1% for the time since the last menstrual period (LMP) < 5 years, 5-10 years and > 10 years, being significantly lower at > 10 years (p < 0.001). In logistic regression analysis, the AIA incidence was significantly lower in the time since LMP > 10-year group versus the < 5-year group (odds ratio 0.44, p = 0.002), but the age at menarche showed no association. AIA manifested significantly earlier (≤ 6 months) as the time since LMP became shorter (< 5 years). AIA tends to manifest early after starting AI, but some cases show delayed onset. The incidence was significantly lower in patients with a duration of > 10 years since LMP. When the time since LMP was short, the onset of AIA was significantly earlier after starting AI administration

Brain abscess associated with Aggregatibacter actinomycetemcomitans : case report and review of literature

NARCIS (Netherlands)

Rahamat-Langendoen, Janette C.; van Vonderen, Marit G. A.; Engstrom, Lex J.; Manson, Willem L.; van Winkelhoff, Arie Jan; Mooi-Kokenberg, Esther A. N. M.

Introduction: Aggregatibacter actinomycetemcomitans is considered a major pathogen in localized and generalized aggressive periodontitis. A. actinomycetemcomitans has been found in various extra oral infections and most frequently in endocarditis. We report a patient with multiple brain abscesses

Legal and ethical issues of using brain imaging to diagnose pain

Directory of Open Access Journals (Sweden)

Karen D. Davis

2016-10-01

Full Text Available Abstract. Pain, by definition, is a subjective experience, and as such its presence has usually been based on a self-report. However, limitations of self-reports for pain diagnostics, particularly for legal and insurance purposes, has led some to consider a brain-imaging–based objective measure of pain. This review will provide an overview of (1 differences between pain and nociception, (2 intersubject variability in pain perception and the associated brain structures and functional circuits, and (3 capabilities and limitations of current brain-imaging technologies. I then discuss how these factors impact objective proxies of pain. Finally, the ethical, privacy, and legal implications of a brain-imaging–based objective measure of pain are considered as potential future technological developments necessary to create a so-called “painometer test.”

The Global Aspects of Brain-Based Learning

Science.gov (United States)

Connell, J. Diane

2009-01-01

Brain-Based Learning (BBL) can be viewed as techniques gleaned from research in neurology and cognitive science used to enhance teacher instruction. These strategies can also be used to enhance students' ability to learn using ways in which they feel most comfortable, neurologically speaking. Jensen (1995/2000) defines BBL as "learning in…

A new microcontroller-based human brain hypothermia system.

Science.gov (United States)

Kapidere, Metin; Ahiska, Raşit; Güler, Inan

2005-10-01

Many studies show that artificial hypothermia of brain in conditions of anesthesia with the rectal temperature lowered down to 33 degrees C produces pronounced prophylactic effect protecting the brain from anoxia. Out of the methods employed now in clinical practice for reducing the oxygen consumption by the cerebral tissue, the most efficacious is craniocerebral hypothermia (CCH). It is finding even more extensive application in cardiovascular surgery, neurosurgery, neurorenimatology and many other fields of medical practice. In this study, a microcontroller-based designed human brain hypothermia system (HBHS) is designed and constructed. The system is intended for cooling and heating the brain. HBHS consists of a thermoelectric hypothermic helmet, a control and a power unit. Helmet temperature is controlled by 8-bit PIC16F877 microcontroller which is programmed using MPLAB editor. Temperature is converted to 10-bit digital and is controlled automatically by the preset values which have been already entered in the microcontroller. Calibration is controlled and the working range is tested. Temperature of helmet is controlled between -5 and +46 degrees C by microcontroller, with the accuracy of +/-0.5 degrees C.

EEG Based Inference of Spatio-Temporal Brain Dynamics

DEFF Research Database (Denmark)

Hansen, Sofie Therese

Electroencephalography (EEG) provides a measure of brain activity and has improved our understanding of the brain immensely. However, there is still much to be learned and the full potential of EEG is yet to be realized. In this thesis we suggest to improve the information gain of EEG using three...... different approaches; 1) by recovery of the EEG sources, 2) by representing and inferring the propagation path of EEG sources, and 3) by combining EEG with functional magnetic resonance imaging (fMRI). The common goal of the methods, and thus of this thesis, is to improve the spatial dimension of EEG...... recovery ability. The forward problem describes the propagation of neuronal activity in the brain to the EEG electrodes on the scalp. The geometry and conductivity of the head layers are normally required to model this path. We propose a framework for inferring forward models which is based on the EEG...

Tensor-based morphometry and stereology reveal brain pathology in the complexin1 knockout mouse.

Science.gov (United States)

Kielar, Catherine; Sawiak, Stephen J; Navarro Negredo, Paloma; Tse, Desmond H Y; Morton, A Jennifer

2012-01-01

Complexins (Cplxs) are small, soluble, regulatory proteins that bind reversibly to the SNARE complex and modulate synaptic vesicle release. Cplx1 knockout mice (Cplx1(-/-)) have the earliest known onset of ataxia seen in a mouse model, although hitherto no histopathology has been described in these mice. Nevertheless, the profound neurological phenotype displayed by Cplx1(-/-) mutants suggests that significant functional abnormalities must be present in these animals. In this study, MRI was used to automatically detect regions where structural differences were not obvious when using a traditional histological approach. Tensor-based morphometry of Cplx1(-/-) mouse brains showed selective volume loss from the thalamus and cerebellum. Stereological analysis of Cplx1(-/-) and Cplx1(+/+) mice brain slices confirmed the volume loss in the thalamus as well as loss in some lobules of the cerebellum. Finally, stereology was used to show that there was loss of cerebellar granule cells in Cplx1(-/-) mice when compared to Cplx1(+/+) animals. Our study is the first to describe pathological changes in Cplx1(-/-) mouse brain. We suggest that the ataxia in Cplx1(-/-) mice is likely to be due to pathological changes in both cerebellum and thalamus. Reduced levels of Cplx proteins have been reported in brains of patients with neurodegenerative diseases. Therefore, understanding the effects of Cplx depletion in brains from Cplx1(-/-) mice may also shed light on the mechanisms underlying pathophysiology in disorders in which loss of Cplx1 occurs.

Tensor-based morphometry and stereology reveal brain pathology in the complexin1 knockout mouse.

Directory of Open Access Journals (Sweden)

Catherine Kielar

Full Text Available Complexins (Cplxs are small, soluble, regulatory proteins that bind reversibly to the SNARE complex and modulate synaptic vesicle release. Cplx1 knockout mice (Cplx1(-/- have the earliest known onset of ataxia seen in a mouse model, although hitherto no histopathology has been described in these mice. Nevertheless, the profound neurological phenotype displayed by Cplx1(-/- mutants suggests that significant functional abnormalities must be present in these animals. In this study, MRI was used to automatically detect regions where structural differences were not obvious when using a traditional histological approach. Tensor-based morphometry of Cplx1(-/- mouse brains showed selective volume loss from the thalamus and cerebellum. Stereological analysis of Cplx1(-/- and Cplx1(+/+ mice brain slices confirmed the volume loss in the thalamus as well as loss in some lobules of the cerebellum. Finally, stereology was used to show that there was loss of cerebellar granule cells in Cplx1(-/- mice when compared to Cplx1(+/+ animals. Our study is the first to describe pathological changes in Cplx1(-/- mouse brain. We suggest that the ataxia in Cplx1(-/- mice is likely to be due to pathological changes in both cerebellum and thalamus. Reduced levels of Cplx proteins have been reported in brains of patients with neurodegenerative diseases. Therefore, understanding the effects of Cplx depletion in brains from Cplx1(-/- mice may also shed light on the mechanisms underlying pathophysiology in disorders in which loss of Cplx1 occurs.

Comparative study on individual aromatase inhibitors on cardiovascular safety profile: a network meta-analysis

Directory of Open Access Journals (Sweden)

Zhao XH

2015-09-01

Full Text Available Xihe Zhao,1 Lei Liu,2 Kai Li,1 Wusheng Li,1 Li Zhao,1 Huawei Zou1 1Department of Oncology, 2Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China Abstract: The third-generation aromatase inhibitors (AIs: anastrozole, letrozole, and exemestane have now become standard adjuvant endocrine treatment for postmenopausal estrogen receptor-positive breast cancer complementing chemotherapy and surgery. Because of the absence of direct head-to-head comparisons of these AIs, an indirect comparison is needed for individual treatment choice. In this network systemic assessment, the cardiovascular (CV side effects in using anastrozole, letrozole, and exemestane based on original studies on AIs vs placebo or tamoxifen were compared. We integrated all available direct and indirect evidences. The odds ratio (OR of severe CV events for indirect comparisons between exemestane and anastrozole was 1.41 (95% confidence interval [CI] =0.49–2.78, letrozole and anastrozole was 1.80 (95% CI =0.40–3.92, and letrozole and exemestane was 1.46 (95% CI =0.34–3.4. OR of subgroup risk for AIs and tamoxifen were all >1 except for thrombolism risk subgroup. The results showed that the total and severe CV risk ranking is letrozole, exemestane, and anastrozole in descending order. None of the AIs showed advantages in CV events than tamoxifen except for thromboembolism event incidence. Keywords: CV risk, breast cancer, AI, network meta-analysis

Validation of model-based brain shift correction in neurosurgery via intraoperative magnetic resonance imaging: preliminary results

Science.gov (United States)

Luo, Ma; Frisken, Sarah F.; Weis, Jared A.; Clements, Logan W.; Unadkat, Prashin; Thompson, Reid C.; Golby, Alexandra J.; Miga, Michael I.

2017-03-01

The quality of brain tumor resection surgery is dependent on the spatial agreement between preoperative image and intraoperative anatomy. However, brain shift compromises the aforementioned alignment. Currently, the clinical standard to monitor brain shift is intraoperative magnetic resonance (iMR). While iMR provides better understanding of brain shift, its cost and encumbrance is a consideration for medical centers. Hence, we are developing a model-based method that can be a complementary technology to address brain shift in standard resections, with resource-intensive cases as referrals for iMR facilities. Our strategy constructs a deformation `atlas' containing potential deformation solutions derived from a biomechanical model that account for variables such as cerebrospinal fluid drainage and mannitol effects. Volumetric deformation is estimated with an inverse approach that determines the optimal combinatory `atlas' solution fit to best match measured surface deformation. Accordingly, preoperative image is updated based on the computed deformation field. This study is the latest development to validate our methodology with iMR. Briefly, preoperative and intraoperative MR images of 2 patients were acquired. Homologous surface points were selected on preoperative and intraoperative scans as measurement of surface deformation and used to drive the inverse problem. To assess the model accuracy, subsurface shift of targets between preoperative and intraoperative states was measured and compared to model prediction. Considering subsurface shift above 3 mm, the proposed strategy provides an average shift correction of 59% across 2 cases. While further improvements in both the model and ability to validate with iMR are desired, the results reported are encouraging.

BrainMap '95 workshop. Final report

International Nuclear Information System (INIS)

1995-01-01

The fourth annual BrainMap workshop was held at La Mansion del Rio Hotel in San Antonio December 3--4, 1995. The conference title was ''Human Brain Mapping and Modeling.'' The meeting was attended by 137 registered participants and 30 observers from 82 institutions representing 12 countries. The meeting focused on the technical issues associated with brain mapping and modeling. A total of 23 papers were presented covering the following topics: spatial normalization and registration; functional image analysis; metanalysis and modeling; and new horizons in biological databases. The full program with abstracts was available on the Research Imaging Center's web site. A book will be published by John Wiley and Sons prior to the end of 1998

"Effects of a Web-Based Intervention on Family Functioning Following Pediatric Traumatic Brain Injury"

Science.gov (United States)

Minich, Nori; Taylor, H. Gerry; Kirkwood, Michael; Brown, Tanya Maines; Stancin, Terry; Wade, Shari L

2015-01-01

Objective Investigate effectiveness of an online Counselor-Assisted Problem-Solving (CAPS) intervention on family functioning after traumatic brain injury (TBI). Methods Participants were randomized to CAPS (n = 65) or internet resource comparison (IRC; n = 67). CAPS is a counselor-assisted web-based program. IRC was given access to online resources. Outcomes were examined 6 months, 12 months, and 18 months after baseline. Injury severity, age, and SES were examined as moderators. Results A main effect of time was noted for teen-reported conflict and parent-reported problem solving. CAPS had decreased parent-reported conflict and a reduction in parental effective communication. Effects were specific to subsets of the sample. Conclusions CAPS, a family-based problem-solving intervention designed to address problem behaviors, had modest effects on some aspects of family functioning, when compared to IRC. Effects were generally limited to subsets of the families and were not evident across all follow-up assessments. PMID:26461100

Music based cognitive remediation therapy for patients with traumatic brain injury

Directory of Open Access Journals (Sweden)

Shantala eHegde

2014-03-01

Full Text Available Traumatic brain injury (TBI is one of the common causes of disability in physical, psychological and social domains of functioning leading to poor quality of life. TBI leads to impairment in sensory, motor, language and emotional processing, and also in cognitive functions such as attention, information processing, executive functions and memory. Cognitive impairment plays a central role in functional recovery in TBI. Innovative methods such as music therapy to alleviate cognitive impairments have been investigated recently. The role of music in cognitive rehabilitation is evolving, based on newer findings emerging from the fields of neuromusicology and music cognition. Research findings from these fields have contributed significantly to our understanding of music perception and cognition, and its neural underpinnings. From a neuroscientific perspective, indulging in music is considered as one of the best cognitive exercises. With ‘plasticity’ as its veritable nature, brain engages in producing music indulging an array of cognitive functions and the product, the music, in turn permits restoration and alter brain functions. With scientific findings as its basis, ‘Neurologic Music Therapy’ (NMT has been developed as a systematic treatment method to improve sensorimotor, language and cognitive domains of functioning via music. A preliminary study examining the effect of NMT in cognitive rehabilitation has reported promising results in improving executive functions along with improvement in emotional adjustment and decreasing depression and anxiety following TBI. The potential usage of music-based cognitive rehabilitation therapy in various clinical conditions including TBI is yet to be fully explored. There is a need for systematic research studies to bridge the gap between increasing theoretical understanding of usage of music in cognitive rehabilitation and application of the same in a heterogeneous condition such as TBI.

Music-based cognitive remediation therapy for patients with traumatic brain injury.

Science.gov (United States)

Hegde, Shantala

2014-01-01

Traumatic brain injury (TBI) is one of the common causes of disability in physical, psychological, and social domains of functioning leading to poor quality of life. TBI leads to impairment in sensory, motor, language, and emotional processing, and also in cognitive functions such as attention, information processing, executive functions, and memory. Cognitive impairment plays a central role in functional recovery in TBI. Innovative methods such as music therapy to alleviate cognitive impairments have been investigated recently. The role of music in cognitive rehabilitation is evolving, based on newer findings emerging from the fields of neuromusicology and music cognition. Research findings from these fields have contributed significantly to our understanding of music perception and cognition, and its neural underpinnings. From a neuroscientific perspective, indulging in music is considered as one of the best cognitive exercises. With "plasticity" as its veritable nature, brain engages in producing music indulging an array of cognitive functions and the product, the music, in turn permits restoration and alters brain functions. With scientific findings as its basis, "neurologic music therapy" (NMT) has been developed as a systematic treatment method to improve sensorimotor, language, and cognitive domains of functioning via music. A preliminary study examining the effect of NMT in cognitive rehabilitation has reported promising results in improving executive functions along with improvement in emotional adjustment and decreasing depression and anxiety following TBI. The potential usage of music-based cognitive rehabilitation therapy in various clinical conditions including TBI is yet to be fully explored. There is a need for systematic research studies to bridge the gap between increasing theoretical understanding of usage of music in cognitive rehabilitation and application of the same in a heterogeneous condition such as TBI.

Human-machine interface based on muscular and brain signals applied to a robotic wheelchair

International Nuclear Information System (INIS)

Ferreira, A; Silva, R L; Celeste, W C; Filho, T F Bastos; Filho, M Sarcinelli

2007-01-01

This paper presents a Human-Machine Interface (HMI) based on the signals generated by eye blinks or brain activity. The system structure and the signal acquisition and processing are shown. The signals used in this work are either the signal associated to the muscular movement corresponding to an eye blink or the brain signal corresponding to visual information processing. The variance is the feature extracted from such signals in order to detect the intention of the user. The classification is performed by a variance threshold which is experimentally determined for each user during the training stage. The command options, which are going to be sent to the commanded device, are presented to the user in the screen of a PDA (Personal Digital Assistant). In the experiments here reported, a robotic wheelchair is used as the device being commanded

Human-machine interface based on muscular and brain signals applied to a robotic wheelchair

Energy Technology Data Exchange (ETDEWEB)

Ferreira, A; Silva, R L; Celeste, W C; Filho, T F Bastos; Filho, M Sarcinelli [Electrical Engineering Department, Federal University of Espirito Santo (UFES), Av. Fernando Ferrari, 514, Vitoria, 29075-910 (Brazil)

2007-11-15

This paper presents a Human-Machine Interface (HMI) based on the signals generated by eye blinks or brain activity. The system structure and the signal acquisition and processing are shown. The signals used in this work are either the signal associated to the muscular movement corresponding to an eye blink or the brain signal corresponding to visual information processing. The variance is the feature extracted from such signals in order to detect the intention of the user. The classification is performed by a variance threshold which is experimentally determined for each user during the training stage. The command options, which are going to be sent to the commanded device, are presented to the user in the screen of a PDA (Personal Digital Assistant). In the experiments here reported, a robotic wheelchair is used as the device being commanded.

Regional infant brain development: an MRI-based morphometric analysis in 3 to 13 month olds.

Science.gov (United States)

Choe, Myong-Sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S; Benasich, April A; Grant, P Ellen

2013-09-01

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants' whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.

Functional outcomes of community-based brain injury rehabilitation clients.

Science.gov (United States)

Curran, Christine; Dorstyn, Diana; Polychronis, Con; Denson, Linley

2015-01-01

Community-based rehabilitation can help to maximize function following acquired brain injury (ABI); however, data on treatment outcome is limited in quantity. To describe and evaluate client outcomes of an outpatient programme for adults with moderate-to-severe traumatic and non-traumatic ABI. Two phase design involving retrospective and longitudinal study of programme completers with ABI (n = 47). Changes in functioning were measured with the Mayo-Portland Inventory (MPAI-4), administered pre- and immediately post-rehabilitation and at 3 years follow-up. Self-ratings were supplemented with MPAI-4 data from significant others (n = 32) and staff (n = 32). Injured individuals and informants reported improved physical and psychosocial functioning immediately following the completion of community rehabilitation, with medium-to-large and significant treatment gains noted on the MPAI-4 ability, adjustment and participation sub-scales (Cohen's d range = 0.31-1.10). A deterioration in individuals' adjustment was further reported at follow-up, although this was based on limited data. Issues with longer-term rehabilitation service provision were additionally noted. The data support the need for continuity of care, including ongoing emotional support, to cater to the complex and dynamic needs of the ABI population. However, these results need to be considered in the context of a small sample size and quasi-experimental design.

A Symbiotic Brain-Machine Interface through Value-Based Decision Making

Science.gov (United States)

Mahmoudi, Babak; Sanchez, Justin C.

2011-01-01

Background In the development of Brain Machine Interfaces (BMIs), there is a great need to enable users to interact with changing environments during the activities of daily life. It is expected that the number and scope of the learning tasks encountered during interaction with the environment as well as the pattern of brain activity will vary over time. These conditions, in addition to neural reorganization, pose a challenge to decoding neural commands for BMIs. We have developed a new BMI framework in which a computational agent symbiotically decoded users' intended actions by utilizing both motor commands and goal information directly from the brain through a continuous Perception-Action-Reward Cycle (PARC). Methodology The control architecture designed was based on Actor-Critic learning, which is a PARC-based reinforcement learning method. Our neurophysiology studies in rat models suggested that Nucleus Accumbens (NAcc) contained a rich representation of goal information in terms of predicting the probability of earning reward and it could be translated into an evaluative feedback for adaptation of the decoder with high precision. Simulated neural control experiments showed that the system was able to maintain high performance in decoding neural motor commands during novel tasks or in the presence of reorganization in the neural input. We then implanted a dual micro-wire array in the primary motor cortex (M1) and the NAcc of rat brain and implemented a full closed-loop system in which robot actions were decoded from the single unit activity in M1 based on an evaluative feedback that was estimated from NAcc. Conclusions Our results suggest that adapting the BMI decoder with an evaluative feedback that is directly extracted from the brain is a possible solution to the problem of operating BMIs in changing environments with dynamic neural signals. During closed-loop control, the agent was able to solve a reaching task by capturing the action and reward

A symbiotic brain-machine interface through value-based decision making.

Directory of Open Access Journals (Sweden)

Babak Mahmoudi

Full Text Available BACKGROUND: In the development of Brain Machine Interfaces (BMIs, there is a great need to enable users to interact with changing environments during the activities of daily life. It is expected that the number and scope of the learning tasks encountered during interaction with the environment as well as the pattern of brain activity will vary over time. These conditions, in addition to neural reorganization, pose a challenge to decoding neural commands for BMIs. We have developed a new BMI framework in which a computational agent symbiotically decoded users' intended actions by utilizing both motor commands and goal information directly from the brain through a continuous Perception-Action-Reward Cycle (PARC. METHODOLOGY: The control architecture designed was based on Actor-Critic learning, which is a PARC-based reinforcement learning method. Our neurophysiology studies in rat models suggested that Nucleus Accumbens (NAcc contained a rich representation of goal information in terms of predicting the probability of earning reward and it could be translated into an evaluative feedback for adaptation of the decoder with high precision. Simulated neural control experiments showed that the system was able to maintain high performance in decoding neural motor commands during novel tasks or in the presence of reorganization in the neural input. We then implanted a dual micro-wire array in the primary motor cortex (M1 and the NAcc of rat brain and implemented a full closed-loop system in which robot actions were decoded from the single unit activity in M1 based on an evaluative feedback that was estimated from NAcc. CONCLUSIONS: Our results suggest that adapting the BMI decoder with an evaluative feedback that is directly extracted from the brain is a possible solution to the problem of operating BMIs in changing environments with dynamic neural signals. During closed-loop control, the agent was able to solve a reaching task by capturing the action and

Structural brain abnormalities in women with subclinical depression, as revealed by voxel-based morphometry and diffusion tensor imaging.

Science.gov (United States)

Hayakawa, Yayoi K; Sasaki, Hiroki; Takao, Hidemasa; Mori, Harushi; Hayashi, Naoto; Kunimatsu, Akira; Aoki, Shigeki; Ohtomo, Kuni

2013-01-25

Brain structural changes accompany major depressive disorder, but whether subclinical depression is accompanied by similar changes in brain volume and white matter integrity is unknown. By using voxel-based morphometry (VBM) of the gray matter and tract-specific analysis based on diffusion tensor imaging (DTI) of the white matter, we explored the extent to which abnormalities could be identified in specific brain structures of healthy adults with subclinical depression. The subjects were 21 community-dwelling adults with subclinical depression, as measured by their Center for Epidemiologic Studies Depression Scale (CES-D) scores. They were not demented and had no neurological or psychiatric history. We collected brain magnetic resonance images of the patients and of 21 matched control subjects, and we used VBM to analyze the differences in regional gray matter volume between the two groups. Moreover, we examined the white matter integrity by using tract-specific analysis based on the gray matter volume changes revealed by VBM. VBM revealed that the volumes of both anterior cingulate gyri and the right rectal gyrus were smaller in subclinically depressed women than in control women. Calculation of DTI measures in the anterior cingulum bundle revealed a positive correlation between CES-D scale score and radial diffusivity in the right anterior cingulum in subclinically depressed women. The small sample size limits the stability of the reported findings. Gray matter volume reduction and white matter integrity change in specific frontal brain regions may be associated with depressive symptoms in women, even at a subclinical level. Copyright © 2012 Elsevier B.V. All rights reserved.

Neuro-Behçet disease mimicking brain tumor: A case report

Science.gov (United States)

Tramontini, Pedro L.; Finkelsztejn, Alessandro; Duarte, Juliana Á.; Santos, Guilherme T.; Roesler, Rafael; Isolan, Gustavo R.

2017-01-01

Background: Behçet's disease (BD) is an inflammatory multisystem disease with unknown etiology, and consists of a TRIAD comprising recurrent oral ulcers, genital ulcers, and uveitis. In some cases, the disease affects the central nervous system, called Neuro-Behçet Disease (NBD). Few cases of NBD simulating a brain tumor have been previously reported. Case Description: Here, we describe the case of a 46-year-old male patient with a previous diagnosis of brain tumor who was later diagnosed for BD. Conclusion: This case highlights the importance of differential diagnosis of lesions with tumoral features. Checking for the possibility of NBD may help avoiding biopsy in these types of cases. PMID:28695044

20 Ways To Promote Brain-Based Teaching and Learning.

Science.gov (United States)

Prigge, Debra J.

2002-01-01

Based on current knowledge about cognitive processes, this article presents strategies for preparing the learner, managing the environment to motivate students, gaining and keeping learner attention, and increasing memory and recall by making learning personally relevant to students. Resources are listed for brain-based teaching and learning. (CR)

Comparison of the effect of cortisol on aromatase activity and androgen metabolism in two human fibroblast cell lines derived from the same individual

DEFF Research Database (Denmark)

Svenstrup, B; Brünner, N; Dombernowsky, P

1990-01-01

The effect of preincubation with cortisol on estrogen and androgen metabolism was investigated in human fibroblast monolayers grown from biopsies of genital and non-genital skin of the same person. The activity in the cells of aromatase, 5 alpha-reductase, 17 beta-hydroxysteroid oxidoreductase.......5-1.0 x 10(-6) M in both cell lines. When preincubation with cortisol was omitted no estrogen synthesis was detected. The formation of androgen was not altered after preincubation with cortisol. Pronounced differences were found in estrogen and in androgen metabolism in the two cell lines suggesting...

Revisiting Einstein's brain in Brain Awareness Week.

Science.gov (United States)

Chen, Hao; Chen, Su; Zeng, Lidan; Zhou, Lin; Hou, Shengtao

2014-10-01

Albert Einstein's brain has long been an object of fascination to both neuroscience specialists and the general public. However, without records of advanced neuro-imaging of his brain, conclusions regarding Einstein's extraordinary cognitive capabilities can only be drawn based on the unique external features of his brain and through comparison of the external features with those of other human brain samples. The recent discovery of 14 previously unpublished photographs of Einstein's brain taken at unconventional angles by Dr. Thomas Stoltz Harvey, the pathologist, ignited a renewed frenzy about clues to explain Einstein's genius. Dr. Dean Falk and her colleagues, in their landmark paper published in Brain (2013; 136:1304-1327), described in such details about the unusual features of Einstein's brain, which shed new light on Einstein's intelligence. In this article, we ask what are the unique structures of his brain? What can we learn from this new information? Can we really explain his extraordinary cognitive capabilities based on these unique brain structures? We conclude that studying the brain of a remarkable person like Albert Einstein indeed provides us a better example to comprehensively appreciate the relationship between brain structures and advanced cognitive functions. However, caution must be exercised so as not to over-interpret his intelligence solely based on the understanding of the surface structures of his brain.

Control of a nursing bed based on a hybrid brain-computer interface.

Science.gov (United States)

Nengneng Peng; Rui Zhang; Haihua Zeng; Fei Wang; Kai Li; Yuanqing Li; Xiaobin Zhuang

2016-08-01

In this paper, we propose an intelligent nursing bed system which is controlled by a hybrid brain-computer interface (BCI) involving steady-state visual evoked potential (SSVEP) and P300. Specifically, the hybrid BCI includes an asynchronous brain switch based on SSVEP and P300, and a P300-based BCI. The brain switch is used to turn on/off the control system of the electric nursing bed through idle/control state detection, whereas the P300-based BCI is for operating the nursing bed. At the beginning, the user may focus on one group of flashing buttons in the graphic user interface (GUI) of the brain switch, which can simultaneously evoke SSVEP and P300, to switch on the control system. Here, the combination of SSVEP and P300 is used for improving the performance of the brain switch. Next, the user can control the nursing bed using the P300-based BCI. The GUI of the P300-based BCI includes 10 flashing buttons, which correspond to 10 functional operations, namely, left-side up, left-side down, back up, back down, bedpan open, bedpan close, legs up, legs down, right-side up, and right-side down. For instance, he/she can focus on the flashing button "back up" in the GUI of the P300-based BCI to activate the corresponding control such that the nursing bed is adjusted up. Eight healthy subjects participated in our experiment, and obtained an average accuracy of 93.75% and an average false positive rate (FPR) of 0.15 event/min. The effectiveness of our system was thus demonstrated.

Intelligent Automatic Right-Left Sign Lamp Based on Brain Signal Recognition System

Science.gov (United States)

Winda, A.; Sofyan; Sthevany; Vincent, R. S.

2017-12-01

Comfort as a part of the human factor, plays important roles in nowadays advanced automotive technology. Many of the current technologies go in the direction of automotive driver assistance features. However, many of the driver assistance features still require physical movement by human to enable the features. In this work, the proposed method is used in order to make certain feature to be functioning without any physical movement, instead human just need to think about it in their mind. In this work, brain signal is recorded and processed in order to be used as input to the recognition system. Right-Left sign lamp based on the brain signal recognition system can potentially replace the button or switch of the specific device in order to make the lamp work. The system then will decide whether the signal is ‘Right’ or ‘Left’. The decision of the Right-Left side of brain signal recognition will be sent to a processing board in order to activate the automotive relay, which will be used to activate the sign lamp. Furthermore, the intelligent system approach is used to develop authorized model based on the brain signal. Particularly Support Vector Machines (SVMs)-based classification system is used in the proposed system to recognize the Left-Right of the brain signal. Experimental results confirm the effectiveness of the proposed intelligent Automatic brain signal-based Right-Left sign lamp access control system. The signal is processed by Linear Prediction Coefficient (LPC) and Support Vector Machines (SVMs), and the resulting experiment shows the training and testing accuracy of 100% and 80%, respectively.

Anisotropic Diffusion based Brain MRI Segmentation and 3D Reconstruction

Directory of Open Access Journals (Sweden)

M. Arfan Jaffar

2012-06-01

Full Text Available In medical field visualization of the organs is very imperative for accurate diagnosis and treatment of any disease. Brain tumor diagnosis and surgery also required impressive 3D visualization of the brain to the radiologist. Detection and 3D reconstruction of brain tumors from MRI is a computationally time consuming and error-prone task. Proposed system detects and presents a 3D visualization model of the brain and tumor inside which greatly helps the radiologist to effectively diagnose and analyze the brain tumor. We proposed a multi-phase segmentation and visualization technique which overcomes the many problems of 3D volume segmentation methods like lake of fine details. In this system segmentation is done in three different phases which reduces the error chances. The system finds contours for skull, brain and tumor. These contours are stacked over and two novel methods are used to find the 3D visualization models. The results of these techniques, particularly of interpolation based, are impressive. Proposed system is tested against publically available data set [41] and MRI datasets available from MRI aamp; CT center Rawalpindi, Pakistan [42].

Plasma concentrations of estradiol and testosterone, gonadal aromatase activity and ultrastructure of the testis in Xenopus laevis exposed to estradiol or atrazine

International Nuclear Information System (INIS)

Hecker, Markus; Kim, Wan Jong; Park, June-Woo; Murphy, Margaret B.; Villeneuve, Daniel; Coady, Katherine K.; Jones, Paul D.; Solomon, Keith R.; Kraak, Glen van der; Carr, James A.; Smith, Ernest E.; Preez, Louis du; Kendall, Ronald J.; Giesy, John P.

2005-01-01

The ultrastructure of testicular cells of adult male African clawed frogs (Xenopus laevis) exposed to either estradiol (0.1 μg/L) or 2-chloro-4-ethylamino-6-isopropyl-amino-s-triazine (atrazine; 10 or 100 μg/L) was examined by electron microscopy and compared to plasma concentrations of the steroid hormones, testosterone (T) and estradiol (E2), testicular aromatase activity and gonad growth expressed as the gonado-somatic index (GSI). Exposure to E2 caused significant changes both at the sub-cellular and biochemical levels. Exposure to E2 resulted in significantly fewer sperm cells, inhibition of meiotic division of germ cells, more lipid droplets that are storage compartments for the sex steroid hormone precursor cholesterol, and lesser plasma T concentrations. Although not statistically significant, frogs exposed to E2 had slightly smaller GSI values. These results may be indicative of an inhibition of gonad growth and disrupted germ cell development by E2. Concentrations of E2 in plasma were greater in frogs exposed to E2 in water. Exposure to neither concentration of atrazine caused effects on germ cell development, testicular aromatase activity or plasma hormone concentrations. These results suggest that atrazine does not affect testicular function. In contrast, exposure of male X. laevis to E2 led to sub-cellular events that are indicative of disruption of testicular development, and demasculinization processes (decrease of androgen hormone titers). These results indicate that atrazine does not cause responses that are similar to those caused by exposure to E2

Brain Implants for Prediction and Mitigation of Epileptic Seizures - Final CRADA Report

Energy Technology Data Exchange (ETDEWEB)

Gopalsami, Nachappa

2016-09-29

This is a CRADA final report on C0100901 between Argonne National Laboratory and Flint Hills Scientific, LLC of Lawrence, Kansas. Two brain implantable probes, a surface acoustic wave probe and a miniature cooling probe, were designed, built, and tested with excellent results.

A Voxel-Based Morphometry Study of the Brain of University Students Majoring in Music and Nonmusic Disciplines.

Science.gov (United States)

Sato, Kanako; Kirino, Eiji; Tanaka, Shoji

2015-01-01

The brain changes flexibly due to various experiences during the developmental stages of life. Previous voxel-based morphometry (VBM) studies have shown volumetric differences between musicians and nonmusicians in several brain regions including the superior temporal gyrus, sensorimotor areas, and superior parietal cortex. However, the reported brain regions depend on the study and are not necessarily consistent. By VBM, we investigated the effect of musical training on the brain structure by comparing university students majoring in music with those majoring in nonmusic disciplines. All participants were right-handed healthy Japanese females. We divided the nonmusic students into two groups and therefore examined three groups: music expert (ME), music hobby (MH), and nonmusic (NM) group. VBM showed that the ME group had the largest gray matter volumes in the right inferior frontal gyrus (IFG; BA 44), left middle occipital gyrus (BA 18), and bilateral lingual gyrus. These differences are considered to be caused by neuroplasticity during long and continuous musical training periods because the MH group showed intermediate volumes in these regions.

The Influence of Medical Evaluation Board Status on Symptom Reporting Among Service Members with Traumatic Brain Injury

Science.gov (United States)

2017-04-21

MDW/SGVU SUBJECT: Professional Presentation Approvai 11APR 20 17 1. Your paper, entitled The Influence of Medical Evaluation Board Status on... influence o f medical evaluation board status on symptom reporting among service members w ith traumatic brain injury 7. FUNDING RECEIVED FOR THIS STUDY? D...Page 3 of 3 Pages Title: The influence of medical evaluation board status on symptom reporting among service members with traumatic brain injury

Understanding the Role of Neuroscience in Brain Based Products: A Guide for Educators and Consumers

Science.gov (United States)

Sylvan, Lesley J.; Christodoulou, Joanna A.

2010-01-01

The term "brain" based is often used to describe learning theories, principles, and products. Although there have been calls urging educators to be cautious in interpreting and using such material, consumers may find it challenging to understand the role of the brain and to discriminate among brain based products to determine which would be…

Assessing a Faculty Development Program for the Adoption of Brain-Based Learning Strategies

Science.gov (United States)

Lavis, Catherine C.; Williams, Kimberly A.; Fallin, Jana; Barnes, Pamela K.; Fishback, Sarah J.; Thien, Stephen

2016-01-01

Kansas State University designed a 20-month faculty development program with the goal of fostering broad, institution-wide adoption of teaching practices that focus on brain-based learning. Components of the program included annual teaching and learning workshops, reading and discussion groups based on content of a book about how the brain learns…

Manipulation of broiler chickens sex differentiation by in ovo injection of aromatase inhibitors, and garlic and tomato extracts.

Science.gov (United States)

Fazli, Nahid; Hassanabadi, Ahmad; Mottaghitalab, Majid; Hajati, Hosna

2015-11-01

The influence of in ovo administration of aromatase inhibitors, clomiphen citrate, tomoxifen, and garlic and tomato extracts on sex differentiation in broiler chickens were investigated in 2 experiments. Five hundred, and 1,000 fertile eggs from Ross 308 strain were used in experiments 1 and 2, respectively. In both experiments, eggs were divided into 5 groups: control group (DW, 0.1 mL/egg), tomoxifen (0.05 mg/egg), clomiphene citrate (0.05 mg/egg), garlic and tomato extracts (0.1 mL/egg). Eggs were sanitized and prepared for incubation in a regular automatic hatchery. Experimental preparations were injected into eggs at day 5 of the incubation period. Injection sites on the eggs were cleaned with 70% ethylic alcohol, bored by a needle, and aromatase inhibitors were injected into the white from the thin end of the eggs by insulin syringe and then sealed by melted paraffin. In experiment 1, hatched one-day-old chicks (mixed-sex) were raised till 42 days of age in 25 floor pens with a completely randomized design. Experiment 2 was designed to investigate the effects of sex and treatments on the feed-to-gain ratio of broiler chicks. In experiment 2, hatched one-day-old chicks were feather sexed and raised till 42 days of age in 50 floor pens. A completely randomized design with a 2 × 5 factorial arrangement of treatments (sex×treatment) was used. Gonads of the chicks were checked to determine their sex on day 42 by optic microscope to make sure feather sexing was correct. At the end of both experiments, on day 42, one bird from each pen was slaughtered for carcass analysis. In experiment 1, hatchability and the one-day-old weight of chicks showed no significant differences among treatments (P > 0.05). However, in ovo administration of garlic and tomato extracts caused the highest percentage of male chicks (P 0.05). © 2015 Poultry Science Association Inc.

PENGARUH PENDEKATAN BRAIN-BASED TEACHING TERHADAP HASIL BELAJAR KIMIA

Directory of Open Access Journals (Sweden)

Hermawan Agung Prasetya

2015-11-01

Full Text Available This study aimed to determine the effect of inquiry method assisted e-module on the student learning outcomes of chemistry. Population in this study is XI grader in Senior High School (SHS in Kudus, school year 2011/2012. Student learning activity is less varied, so it need to improve the variety methods to help students to be more interested in studying chemistry. The determination of the sample with cluster random sampling system obtained two classes, one class as a experiment class that are treated using the approach of Brain-Based and one as a control class who received treatment using conventional method. The data in this research obtained by documentation, tests, questionnaires, observation method. The result showed that the experimental class had an average of 85,06 and a control class had an average of 79.03. The data analysis, showed that the experimental class is better than the control class, it is shown by t count (3.159> t table (1.999. The conclusions of this research is the approach of Brain-Based Teaching gave the significant effect on student learning outcomes on colloid chemistry subject, which is indicated by the coefficient of correlation (rb  of 0.47 and the influence of 22,50%.Keyword: Brain-Based Teaching Approach

A brain-based account of "basic-level" concepts.

Science.gov (United States)

Bauer, Andrew James; Just, Marcel Adam

2017-11-01

This study provides a brain-based account of how object concepts at an intermediate (basic) level of specificity are represented, offering an enriched view of what it means for a concept to be a basic-level concept, a research topic pioneered by Rosch and others (Rosch et al., 1976). Applying machine learning techniques to fMRI data, it was possible to determine the semantic content encoded in the neural representations of object concepts at basic and subordinate levels of abstraction. The representation of basic-level concepts (e.g. bird) was spatially broad, encompassing sensorimotor brain areas that encode concrete object properties, and also language and heteromodal integrative areas that encode abstract semantic content. The representation of subordinate-level concepts (robin) was less widely distributed, concentrated in perceptual areas that underlie concrete content. Furthermore, basic-level concepts were representative of their subordinates in that they were neurally similar to their typical but not atypical subordinates (bird was neurally similar to robin but not woodpecker). The findings provide a brain-based account of the advantages that basic-level concepts enjoy in everyday life over subordinate-level concepts: the basic level is a broad topographical representation that encompasses both concrete and abstract semantic content, reflecting the multifaceted yet intuitive meaning of basic-level concepts. Copyright © 2017 Elsevier Inc. All rights reserved.

fNIRS-based brain-computer interfaces: a review

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Noman eNaseer

2015-01-01

Full Text Available A brain-computer interface (BCI is a communication system that allows the use of brain activity to control computers or other external devices. It can, by bypassing the peripheral nervous system, provide a means of communication for people suffering from severe motor disabilities or in a persistent vegetative state. In this paper, brain-signal generation tasks, noise removal methods, feature extraction/selection schemes, and classification techniques for fNIRS-based BCI are reviewed. The most common brain areas for fNIRS BCI are the primary motor cortex and the prefrontal cortex. In relation to the motor cortex, motor imagery tasks were preferred to motor execution tasks since possible proprioceptive feedback could be avoided. In relation to the prefrontal cortex, fNIRS showed a significant advantage due to no hair in detecting the cognitive tasks like mental arithmetic, music imagery, emotion induction, etc. In removing physiological noise in fNIRS data, band-pass filtering was mostly used. However, more advanced techniques like adaptive filtering, independent component analysis, multi optodes arrangement, etc. are being pursued to overcome the problem that a band-pass filter cannot be used when both brain and physiological signals occur within a close band. In extracting features related to the desired brain signal, the mean, variance, peak value, slope, skewness, and kurtosis of the noised-removed hemodynamic response were used. For classification, the linear discriminant analysis method provided simple but good performance among others: support vector machine, hidden Markov model, artificial neural network, etc. fNIRS will be more widely used to monitor the occurrence of neuro-plasticity after neuro-rehabilitation and neuro-stimulation. Technical breakthroughs in the future are expected via bundled-type probes, hybrid EEG-fNIRS BCI, and through the detection of initial dips.

Automated voxel-based analysis of brain perfusion SPECT for vasospasm after subarachnoid haemorrhage

International Nuclear Information System (INIS)

Iwabuchi, S.; Yokouchi, T.; Hayashi, M.; Kimura, H.; Tomiyama, A.; Hirata, Y.; Saito, N.; Harashina, J.; Nakayama, H.; Sato, K.; Aoki, K.; Samejima, H.; Ueda, M.; Terada, H.; Hamazaki, K.

2008-01-01

We evaluated regional cerebral blood flow (rCBF) during vasospasm after subarachnoid haemorrhage ISAH) using automated voxel-based analysis of brain perfusion single-photon emission computed tomography (SPELT). Brain perfusion SPECT was performed 7 to 10 days after onset of SAH. Automated voxel-based analysis of SPECT used a Z-score map that was calculated by comparing the patients data with a control database. In cases where computed tomography (CT) scans detected an ischemic region due to vasospasm, automated voxel-based analysis of brain perfusion SPECT revealed dramatically reduced rCBF (Z-score ≤ -4). No patients with mildly or moderately diminished rCBF (Z-score > -3) progressed to cerebral infarction. Some patients with a Z-score < -4 did not progress to cerebral infarction after active treatment with a angioplasty. Three-dimensional images provided detailed anatomical information and helped us to distinguish surgical sequelae from vasospasm. In conclusion, automated voxel-based analysis of brain perfusion SPECT using a Z-score map is helpful in evaluating decreased rCBF due to vasospasm. (author)

Bone health history in breast cancer patients on aromatase inhibitors.

Directory of Open Access Journals (Sweden)

Marilyn L Kwan

Full Text Available A cross-sectional study was performed to assess bone health history among aromatase inhibitor (AI users before breast cancer (BC diagnosis, which may impact fracture risk after AI therapy and choice of initial hormonal therapy. A total of 2,157 invasive BC patients initially treated with an AI were identified from a prospective cohort study at Kaiser Permanente Northern California (KPNC. Data on demographic and lifestyle factors were obtained from in-person interviews, and bone health history and clinical data from KPNC clinical databases. The prevalence of osteoporosis and fractures in postmenopausal AI users was assessed, compared with 325 postmenopausal TAM users. The associations of bone health history with demographic and lifestyle factors in AI users were also examined. Among all initial AI users, 11.2% had a prior history of osteoporosis, 16.3% had a prior history of any fracture, and 4.6% had a prior history of major fracture. Postmenopausal women who were taking TAM as their initial hormonal therapy had significantly higher prevalence of prior osteoporosis than postmenopausal AI users (21.5% vs. 11.8%, p<0.0001. Among initial AI users, the associations of history of osteoporosis and fracture in BC patients with demographic and lifestyle factors were, in general, consistent with those known in healthy older women. This study is one of the first to characterize AI users and risk factors for bone morbidity before BC diagnosis. In the future, this study will examine lifestyle, molecular, and genetic risk factors for AI-induced fractures.

Organoid technology for brain and therapeutics research.

Science.gov (United States)

Wang, Zhi; Wang, Shu-Na; Xu, Tian-Ying; Miao, Zhu-Wei; Su, Ding-Feng; Miao, Chao-Yu

2017-10-01

Brain is one of the most complex organs in human. The current brain research is mainly based on the animal models and traditional cell culture. However, the inherent species differences between humans and animals as well as the gap between organ level and cell level make it difficult to study human brain development and associated disorders through traditional technologies. Recently, the brain organoids derived from pluripotent stem cells have been reported to recapitulate many key features of human brain in vivo, for example recapitulating the zone of putative outer radial glia cells. Brain organoids offer a new platform for scientists to study brain development, neurological diseases, drug discovery and personalized medicine, regenerative medicine, and so on. Here, we discuss the progress, applications, advantages, limitations, and prospects of brain organoid technology in neurosciences and related therapeutics. © 2017 John Wiley & Sons Ltd.

Advances in breast cancer treatment and prevention: preclinical studies on aromatase inhibitors and new selective estrogen receptor modulators (SERMs)

International Nuclear Information System (INIS)

Schiff, Rachel; Chamness, Gary C; Brown, Powel H

2003-01-01

Intensive basic and clinical research over the past 20 years has yielded crucial molecular understanding into how estrogen and the estrogen receptor act to regulate breast cancer and has led to the development of more effective, less toxic, and safer hormonal therapy agents for breast cancer management and prevention. Selective potent aromatase inhibitors are now challenging the hitherto gold standard of hormonal therapy, the selective estrogen-receptor modulator tamoxifen. Furthermore, new selective estrogen-receptor modulators such as arzoxifene, currently under clinical development, offer the possibility of selecting one with a more ideal pharmacological profile for treatment and prevention of breast cancer. Two recent studies in preclinical model systems that evaluate mechanisms of action of these new drugs and suggestions about their optimal clinical use are discussed

Brain Chagas'disease: increasing differential diagnosis of brain mass in immunosuppressed patients - a case report and literature revision

International Nuclear Information System (INIS)

Batista, Laercio Leitao; centola, Crescencio A.P.; Kakudate, Milton Y.

1995-01-01

The authors present a case of Chagas'disease as tumor-like lesion of the brain, in a patient with Aids, simulating the lesions most frequently found in these patients, as toxoplasmosis, lymphoma and cryptococcosis. Furthermore, the case reported have peculiarity to be the only with lesion documented in cerebellum, and unusual due to be secondary by reactivation of chronic Chagas disease. Moreover, emphasize analysis of cerebrospinal fluid with realization of sorologic tests to Chagas's disease, as simple as effective method, to make use of biopsy with stereotaxia in unfinished cases and bad evolution. Finally, after a wide world literature review about Chagas'disease as a tumor-like lesion of the brain, emphasizing this publication as the first written in a radiology journal of specialty. (author). 40 refs., 3 figs., 1 tab

Region based Brain Computer Interface for a home control application.

Science.gov (United States)

Akman Aydin, Eda; Bay, Omer Faruk; Guler, Inan

2015-08-01

Environment control is one of the important challenges for disabled people who suffer from neuromuscular diseases. Brain Computer Interface (BCI) provides a communication channel between the human brain and the environment without requiring any muscular activation. The most important expectation for a home control application is high accuracy and reliable control. Region-based paradigm is a stimulus paradigm based on oddball principle and requires selection of a target at two levels. This paper presents an application of region based paradigm for a smart home control application for people with neuromuscular diseases. In this study, a region based stimulus interface containing 49 commands was designed. Five non-disabled subjects were attended to the experiments. Offline analysis results of the experiments yielded 95% accuracy for five flashes. This result showed that region based paradigm can be used to select commands of a smart home control application with high accuracy in the low number of repetitions successfully. Furthermore, a statistically significant difference was not observed between the level accuracies.

Source-based neurofeedback methods using EEG recordings: training altered brain activity in a functional brain source derived from blind source separation

Science.gov (United States)

White, David J.; Congedo, Marco; Ciorciari, Joseph

2014-01-01

A developing literature explores the use of neurofeedback in the treatment of a range of clinical conditions, particularly ADHD and epilepsy, whilst neurofeedback also provides an experimental tool for studying the functional significance of endogenous brain activity. A critical component of any neurofeedback method is the underlying physiological signal which forms the basis for the feedback. While the past decade has seen the emergence of fMRI-based protocols training spatially confined BOLD activity, traditional neurofeedback has utilized a small number of electrode sites on the scalp. As scalp EEG at a given electrode site reflects a linear mixture of activity from multiple brain sources and artifacts, efforts to successfully acquire some level of control over the signal may be confounded by these extraneous sources. Further, in the event of successful training, these traditional neurofeedback methods are likely influencing multiple brain regions and processes. The present work describes the use of source-based signal processing methods in EEG neurofeedback. The feasibility and potential utility of such methods were explored in an experiment training increased theta oscillatory activity in a source derived from Blind Source Separation (BSS) of EEG data obtained during completion of a complex cognitive task (spatial navigation). Learned increases in theta activity were observed in two of the four participants to complete 20 sessions of neurofeedback targeting this individually defined functional brain source. Source-based EEG neurofeedback methods using BSS may offer important advantages over traditional neurofeedback, by targeting the desired physiological signal in a more functionally and spatially specific manner. Having provided preliminary evidence of the feasibility of these methods, future work may study a range of clinically and experimentally relevant brain processes where individual brain sources may be targeted by source-based EEG neurofeedback. PMID

Brain-Based Learning and Educational Neuroscience: Boundary Work

NARCIS (Netherlands)

Edelenbosch, R.M.; Kupper, J.F.H.; Krabbendam, A.C.; Broerse, J.E.W.

2015-01-01

Much attention has been given to "bridging the gap" between neuroscience and educational practice. In order to gain better understanding of the nature of this gap and of possibilities to enable the linking process, we have taken a boundary perspective on these two fields and the brain-based learning

Studying variability in human brain aging in a population-based German cohort – Rationale and design of 1000BRAINS

Directory of Open Access Journals (Sweden)

Svenja eCaspers

2014-07-01

Full Text Available The ongoing 1000 brains study (1000BRAINS is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions & language; examination of motor skills; ratings of personality, life quality, mood & daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla of the brain. The latter includes (i 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fibre tracking and for diffusion kurtosis imaging; (iii resting-state and task-based functional MRI; and (iv fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates.

Task-based core-periphery organization of human brain dynamics.

Directory of Open Access Journals (Sweden)

Danielle S Bassett

Full Text Available As a person learns a new skill, distinct synapses, brain regions, and circuits are engaged and change over time. In this paper, we develop methods to examine patterns of correlated activity across a large set of brain regions. Our goal is to identify properties that enable robust learning of a motor skill. We measure brain activity during motor sequencing and characterize network properties based on coherent activity between brain regions. Using recently developed algorithms to detect time-evolving communities, we find that the complex reconfiguration patterns of the brain's putative functional modules that control learning can be described parsimoniously by the combined presence of a relatively stiff temporal core that is composed primarily of sensorimotor and visual regions whose connectivity changes little in time and a flexible temporal periphery that is composed primarily of multimodal association regions whose connectivity changes frequently. The separation between temporal core and periphery changes over the course of training and, importantly, is a good predictor of individual differences in learning success. The core of dynamically stiff regions exhibits dense connectivity, which is consistent with notions of core-periphery organization established previously in social networks. Our results demonstrate that core-periphery organization provides an insightful way to understand how putative functional modules are linked. This, in turn, enables the prediction of fundamental human capacities, including the production of complex goal-directed behavior.

Improving the accuracy of brain tumor surgery via Raman-based technology.

Science.gov (United States)

Hollon, Todd; Lewis, Spencer; Freudiger, Christian W; Sunney Xie, X; Orringer, Daniel A

2016-03-01

Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H & E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors.

Brain waves-based index for workload estimation and mental effort engagement recognition

Science.gov (United States)

Zammouri, A.; Chraa-Mesbahi, S.; Ait Moussa, A.; Zerouali, S.; Sahnoun, M.; Tairi, H.; Mahraz, A. M.

2017-10-01

The advent of the communication systems and considering the complexity that some impose in their use, it is necessary to incorporate and equip these systems with a certain intelligence which takes into account the cognitive and mental capacities of the human operator. In this work, we address the issue of estimating the mental effort of an operator according to the cognitive tasks difficulty levels. Based on the Electroencephalogram (EEG) measurements, the proposed approach analyzes the user’s brain activity from different brain regions while performing cognitive tasks with several levels of difficulty. At a first time, we propose a variances comparison-based classifier (VCC) that makes use of the Power Spectral Density (PSD) of the EEG signal. The aim of using such a classifier is to highlight the brain regions that enter into interaction according to the cognitive task difficulty. In a second time, we present and describe a new EEG-based index for the estimation of mental efforts. The designed index is based on information recorded from two EEG channels. Results from the VCC demonstrate that powers of the Theta [4-7 Hz] (θ) and Alpha [8-12 Hz] (α) oscillations decrease while increasing the cognitive task difficulty. These decreases are mainly located in parietal and temporal brain regions. Based on the Kappa coefficients, decisions of the introduced index are compared to those obtained from an existing index. This performance assessment method revealed strong agreements. Hence the efficiency of the introduced index.

Brain-Based Learning and Educational Neuroscience: Boundary Work

Science.gov (United States)

Edelenbosch, Rosanne; Kupper, Frank; Krabbendam, Lydia; Broerse, Jacqueline E. W.

2015-01-01

Much attention has been given to "bridging the gap" between neuroscience and educational practice. In order to gain better understanding of the nature of this gap and of possibilities to enable the linking process, we have taken a boundary perspective on these two fields and the brain-based learning approach, focusing on…

Brain-machine and brain-computer interfaces.

Science.gov (United States)

Friehs, Gerhard M; Zerris, Vasilios A; Ojakangas, Catherine L; Fellows, Mathew R; Donoghue, John P

2004-11-01

The idea of connecting the human brain to a computer or machine directly is not novel and its potential has been explored in science fiction. With the rapid advances in the areas of information technology, miniaturization and neurosciences there has been a surge of interest in turning fiction into reality. In this paper the authors review the current state-of-the-art of brain-computer and brain-machine interfaces including neuroprostheses. The general principles and requirements to produce a successful connection between human and artificial intelligence are outlined and the authors' preliminary experience with a prototype brain-computer interface is reported.

Connecting Learning: Brain-Based Strategies for Linking Prior Knowledge in the Library Media Center

Science.gov (United States)

Vanderbilt, Kathi L.

2005-01-01

The brain is a complex organ and learning is a complex process. While there is not complete agreement among researchers about brain-based learning and its direct connection to neuroscience, knowledge about the brain as well as the examination of cognitive psychology, anthropology, professional experience, and educational research can provide…

Effects of virtual reality-based bilateral upper-extremity training on brain activity in post-stroke patients.

Science.gov (United States)

Lee, Su-Hyun; Kim, Yu-Mi; Lee, Byoung-Hee

2015-07-01

[Purpose] This study investigated the therapeutic effects of virtual reality-based bilateral upper-extremity training on brain activity in patients with stroke. [Subjects and Methods] Eighteen chronic stroke patients were divided into two groups: the virtual reality-based bilateral upper-extremity training group (n = 10) and the bilateral upper-limb training group (n = 8). The virtual reality-based bilateral upper-extremity training group performed bilateral upper-extremity exercises in a virtual reality environment, while the bilateral upper-limb training group performed only bilateral upper-extremity exercise. All training was conducted 30 minutes per day, three times per week for six weeks, followed by brain activity evaluation. [Results] Electroencephalography showed significant increases in concentration in the frontopolar 2 and frontal 4 areas, and significant increases in brain activity in the frontopolar 1 and frontal 3 areas in the virtual reality-based bilateral upper-extremity training group. [Conclusion] Virtual reality-based bilateral upper-extremity training can improve the brain activity of stroke patients. Thus, virtual reality-based bilateral upper-extremity training is feasible and beneficial for improving brain activation in stroke patients.

A systematic review and methodological evaluation of published cost-effectiveness analyses of aromatase inhibitors versus tamoxifen in early stage breast cancer.

Directory of Open Access Journals (Sweden)

Ava A John-Baptiste

Full Text Available BACKGROUND: A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs. For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs of five years of aromatase inhibitors (AI versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS but not overall survival (OS and indicate higher risk of fracture with AI. Policy-relevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. METHODS: We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY. We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. RESULTS: We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. CONCLUSION: Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs

MRI of neurosyphilis presenting as brain tumor: A case report

Directory of Open Access Journals (Sweden)

Yuling Xi

2015-12-01

Full Text Available Syphilis has a broad spectrum of clinical manifestations, among which cerebral gumma is a kind of neurosyphilis. However, it is rare and can be cured by penicillin. We report a case of syphilitic gumma of which the patient was first suspected of brain tumor, but confirmed by surgery to be cerebral gumma due to neurosyphilis. Magnetic resonance imaging, which is thought to be one of the potential and specific diagnostic methods for neurosyphilis, is discussed.

Towards a physiology-based measure of pain: patterns of human brain activity distinguish painful from non-painful thermal stimulation.

Directory of Open Access Journals (Sweden)

Justin E Brown

Full Text Available Pain often exists in the absence of observable injury; therefore, the gold standard for pain assessment has long been self-report. Because the inability to verbally communicate can prevent effective pain management, research efforts have focused on the development of a tool that accurately assesses pain without depending on self-report. Those previous efforts have not proven successful at substituting self-report with a clinically valid, physiology-based measure of pain. Recent neuroimaging data suggest that functional magnetic resonance imaging (fMRI and support vector machine (SVM learning can be jointly used to accurately assess cognitive states. Therefore, we hypothesized that an SVM trained on fMRI data can assess pain in the absence of self-report. In fMRI experiments, 24 individuals were presented painful and nonpainful thermal stimuli. Using eight individuals, we trained a linear SVM to distinguish these stimuli using whole-brain patterns of activity. We assessed the performance of this trained SVM model by testing it on 16 individuals whose data were not used for training. The whole-brain SVM was 81% accurate at distinguishing painful from non-painful stimuli (p<0.0000001. Using distance from the SVM hyperplane as a confidence measure, accuracy was further increased to 84%, albeit at the expense of excluding 15% of the stimuli that were the most difficult to classify. Overall performance of the SVM was primarily affected by activity in pain-processing regions of the brain including the primary somatosensory cortex, secondary somatosensory cortex, insular cortex, primary motor cortex, and cingulate cortex. Region of interest (ROI analyses revealed that whole-brain patterns of activity led to more accurate classification than localized activity from individual brain regions. Our findings demonstrate that fMRI with SVM learning can assess pain without requiring any communication from the person being tested. We outline tasks that should be

Sensorimotor rhythm-based brain-computer interface training: the impact on motor cortical responsiveness

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Pichiorri, F.; De Vico Fallani, F.; Cincotti, F.; Babiloni, F.; Molinari, M.; Kleih, S. C.; Neuper, C.; Kübler, A.; Mattia, D.

2011-04-01

The main purpose of electroencephalography (EEG)-based brain-computer interface (BCI) technology is to provide an alternative channel to support communication and control when motor pathways are interrupted. Despite the considerable amount of research focused on the improvement of EEG signal detection and translation into output commands, little is known about how learning to operate a BCI device may affect brain plasticity. This study investigated if and how sensorimotor rhythm-based BCI training would induce persistent functional changes in motor cortex, as assessed with transcranial magnetic stimulation (TMS) and high-density EEG. Motor imagery (MI)-based BCI training in naïve participants led to a significant increase in motor cortical excitability, as revealed by post-training TMS mapping of the hand muscle's cortical representation; peak amplitude and volume of the motor evoked potentials recorded from the opponens pollicis muscle were significantly higher only in those subjects who develop a MI strategy based on imagination of hand grasping to successfully control a computer cursor. Furthermore, analysis of the functional brain networks constructed using a connectivity matrix between scalp electrodes revealed a significant decrease in the global efficiency index for the higher-beta frequency range (22-29 Hz), indicating that the brain network changes its topology with practice of hand grasping MI. Our findings build the neurophysiological basis for the use of non-invasive BCI technology for monitoring and guidance of motor imagery-dependent brain plasticity and thus may render BCI a viable tool for post-stroke rehabilitation.

Hippocampal-Sparing Whole-Brain Radiotherapy: A 'How-To' Technique Using Helical Tomotherapy and Linear Accelerator-Based Intensity-Modulated Radiotherapy

International Nuclear Information System (INIS)

Gondi, Vinai; Tolakanahalli, Ranjini; Mehta, Minesh P.; Tewatia, Dinesh; Rowley, Howard; Kuo, John S.; Khuntia, Deepak; Tome, Wolfgang A.

2010-01-01

Purpose: Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases. Methods and Materials: Five anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed. The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Helical tomotherapy and linear accelerator (LINAC)-based intensity-modulated radiotherapy (IMRT) treatment plans were generated for a prescription dose of 30 Gy in 10 fractions. Results: On average, the hippocampal avoidance volume was 3.3 cm 3 , occupying 2.1% of the whole-brain planned target volume. Helical tomotherapy spared the hippocampus, with a median dose of 5.5 Gy and maximum dose of 12.8 Gy. LINAC-based IMRT spared the hippocampus, with a median dose of 7.8 Gy and maximum dose of 15.3 Gy. On a per-fraction basis, mean dose to the hippocampus (normalized to 2-Gy fractions) was reduced by 87% to 0.49 Gy 2 using helical tomotherapy and by 81% to 0.73 Gy 2 using LINAC-based IMRT. Target coverage and homogeneity was acceptable with both IMRT modalities, with differences largely attributed to more rapid dose fall-off with helical tomotherapy. Conclusion: Modern IMRT techniques allow for sparing of the hippocampus with acceptable target coverage and homogeneity. Based on compelling preclinical evidence, a Phase II cooperative group trial has been developed to test the postulated neurocognitive benefit.

Service Learning to Promote Brain-Based Learning in Undergraduate Teaching

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Nwokah, Eva E.; Leafblad, Stefanie

2013-01-01

In this study 44 undergraduate students in a language development course participated in service learning with preschool homeless and low-income children as a course requirement. Students completed a survey, questionnaires, reflective journaling, and small-group debriefing sessions. Based on current views on brain-based learning from cortical…

Factors influencing self- and parent-reporting health-related quality of life in children with brain tumors.

Science.gov (United States)

Sato, Iori; Higuchi, Akiko; Yanagisawa, Takaaki; Mukasa, Akitake; Ida, Kohmei; Sawamura, Yutaka; Sugiyama, Kazuhiko; Saito, Nobuhito; Kumabe, Toshihiro; Terasaki, Mizuhiko; Nishikawa, Ryo; Ishida, Yasushi; Kamibeppu, Kiyoko

2013-02-01

Health-related quality of life (HRQOL) is not only a degree of health but also reflects patient perceptions and expectations of health. For children with brain tumors, better understanding of HRQOL requires the use of complementary reports from parents and interviewer-administered reports for children. Here, we aimed to test whether or not the trait anxiety of children and the psychological distress of their parents influence children's and parents' responses to HRQOL questionnaires, and whether or not the report-administration method for children influences children's responses to HRQOL questionnaires. One hundred and thirty-four children aged 5-18 with brain tumors and one of their parents completed the Pediatric Quality of Life Inventory(™) (PedsQL(™)) Brain Tumor Module questionnaires. In addition, the children also completed the State-Trait Anxiety Inventory for Children (STAIC), and the parents also completed the Kessler-10 (K10) and health and sociodemographic characteristics questionnaires. The child questionnaires were administered either by the child (self-administered) or an interviewer. Rater-dependent perceptions about HRQOL were derived from the subscales scores of the PedsQL(™) Brain Tumor Module using structural equation modeling based on a multitrait-multimethod model. The STAIC trait-anxiety score, K10 score, report-administration method, and other health and sociodemographic factors related to each child's or parent's perceptions were identified through multiple linear regression analyses of the questionnaire responses. We used a path analysis to estimate the change in a PedsQL(™) child-reported score that occurs when interviewer-administration changes the child's perception about HRQOL. Surveys for 89 children were self-administered while those for 45 were interviewer-administered. The perceptions of the children and parents were calculated by fitting data to the model (chi-squared P = 0.087, normed fit index = 0.932, comparative fit

Are previous episodes of bacterial vaginosis a predictor for vaginal symptoms in breast cancer patients treated with aromatase inhibitors?

DEFF Research Database (Denmark)

Gade, Malene R; Goukasian, Irina; Panduro, Nathalie

2018-01-01

Objective To estimate the prevalence of vaginal symptoms in postmenopausal women with breast cancer exposed to aromatase inhibitors, and to investigate if the risk of vaginal symptoms is associated with previous episodes of bacterial vaginosis. Methods Patients from Rigshospitalet and Herlev...... University Hospital, Denmark, were identified through the register of Danish Breast Cancer Cooperation Group and 78 patients participated in the study. Semiquantitave questionnaires and telephone interview were used to assess the prevalence of vaginal symptoms and previous episode(s) of bacterial vaginosis....... Multivariable logistic regression models were used to assess the association between vaginal symptoms and previous episodes of bacterial vaginosis. Results Moderate to severe symptoms due to vaginal itching/irritation were experienced by 6.4% (95% CI: 2.8-14.1%), vaginal dryness by 28.4% (95% CI: 19...

Brain injuries due to neonatal hypoglycemia: case report

International Nuclear Information System (INIS)

Kim, Dae Bong; Song, Chang Joon; Chang, Mae Young; Youn, Hyae Won

2003-01-01

Although hypoglycemia may be common among neonates, brain injuries resulting from isolated neonatal hypoglycemia are rare. The condition may cause neurological symptoms such as stupor, jitteriness, and seizures, though in their absence, diagnosis delayed or difficult. Hypoglycemia was diagnosed in a three-day-old neonate after he visited the emergency department with loose stool, poor oral intake, and decreased activity, first experienced two days earlier. Two days after his visity, several episodes of seizure occurred. T2 and diffusion-weighted magnetic resonance (MR) scanning, performed at 11 days of age, revealed bilateral and symmetrical high signal intensity lesions in occipital, parietal, and temporal lobes. We report the MR findings of hypoglycemic encephalopathy in a neonate

The brain's silent messenger: using selective attention to decode human thought for brain-based communication.

Science.gov (United States)

Naci, Lorina; Cusack, Rhodri; Jia, Vivian Z; Owen, Adrian M

2013-05-29

The interpretation of human thought from brain activity, without recourse to speech or action, is one of the most provoking and challenging frontiers of modern neuroscience. In particular, patients who are fully conscious and awake, yet, due to brain damage, are unable to show any behavioral responsivity, expose the limits of the neuromuscular system and the necessity for alternate forms of communication. Although it is well established that selective attention can significantly enhance the neural representation of attended sounds, it remains, thus far, untested as a response modality for brain-based communication. We asked whether its effect could be reliably used to decode answers to binary (yes/no) questions. Fifteen healthy volunteers answered questions (e.g., "Do you have brothers or sisters?") in the fMRI scanner, by selectively attending to the appropriate word ("yes" or "no"). Ninety percent of the answers were decoded correctly based on activity changes within the attention network. The majority of volunteers conveyed their answers with less than 3 min of scanning, suggesting that this technique is suited for communication in a reasonable amount of time. Formal comparison with the current best-established fMRI technique for binary communication revealed improved individual success rates and scanning times required to detect responses. This novel fMRI technique is intuitive, easy to use in untrained participants, and reliably robust within brief scanning times. Possible applications include communication with behaviorally nonresponsive patients.

The Development of Female Sexual Behavior Requires Prepubertal Estradiol

NARCIS (Netherlands)

Brock, O.; Baum, M.J.; Bakker, J.

2011-01-01

The classic view of brain and behavioral sexual differentiation holds that the neural mechanisms controlling sexual behavior in female rodents develop in the absence ofovarian sex hormone actions. However,inaprevious study, female aromatase knock-out (ArKO) mice, which cannot convert testosterone to

Sex Change in Clownfish: Molecular Insights from Transcriptome Analysis

KAUST Repository

Casas, Laura; Saborido-Rey, Fran; Ryu, Tae Woo; Michell, Craig; Ravasi, Timothy; Irigoien, Xabier

2016-01-01

steroidogenic machinery during sex change in clownfish, with the aromatase gene playing a central role, both in the brain and the gonad. This work constitutes the first genome-wide study in a social sex-changing species and provides insights into the genetic

Salmonella enterica serovar Enteritidis brain abscess mimicking meningitis after surgery for glioblastoma multiforme: a case report and review of the literature.

Science.gov (United States)

Luciani, Léa; Dubourg, Grégory; Graillon, Thomas; Honnorat, Estelle; Lepidi, Hubert; Drancourt, Michel; Seng, Piseth; Stein, Andreas

2016-07-07

Salmonella brain abscess associated with brain tumor is rare. Only 11 cases have been reported to date. Here we report a case of brain abscess caused by Salmonella enterica serovar Enteritidis mimicking post-surgical meningitis in a patient with glioblastoma multiforme. A 60-year-old Algerian woman was admitted through an emergency department for a 4-day history of headache, nausea and vomiting, and behavioral disorders. Surgery for cerebral tumor excision was performed and histopathological analysis revealed glioblastoma multiforme. On the seventh day post-surgery, she presented a sudden neurological deterioration with a meningeal syndrome, confusion, and fever of 39.8°C. Her cerebrospinal fluid sample and blood cultures were positive for S. enterica Enteritidis. She was treated with ceftriaxone and ciprofloxacin. On the 17th day post-surgery, she presented a new neurological disorder and purulent discharge from the surgical wound. Brain computed tomography revealed a large cerebral abscess located at the operative site. Surgical drainage of the abscess was performed and microbial cultures of surgical deep samples were positive for the same S. enterica Enteritidis isolate. She recovered and was discharged 6 weeks after admission. In this case report, a brain abscess was initially diagnosed as Salmonella post-surgical meningitis before the imaging diagnosis of the brain abscess. The diagnosis of brain abscess should be considered in all cases of non-typhoidal Salmonella meningitis after surgery for brain tumor. Surgical brain abscess drainage followed by prolonged antibiotic treatment remains a major therapeutic option.

Biodistribution of ultra small gadolinium-based nanoparticles as theranostic agent: application to brain tumors.

Science.gov (United States)

Miladi, Imen; Duc, Géraldine Le; Kryza, David; Berniard, Aurélie; Mowat, Pierre; Roux, Stéphane; Taleb, Jacqueline; Bonazza, Pauline; Perriat, Pascal; Lux, François; Tillement, Olivier; Billotey, Claire; Janier, Marc

2013-09-01

Gadolinium-based nanoparticles are novel objects with interesting physical properties, allowing their use for diagnostic and therapeutic applications. Gadolinium-based nanoparticles were imaged following intravenous injection in healthy rats and rats grafted with 9L gliosarcoma tumors using magnetic resonance imaging and scintigraphic imaging. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles were rapidly cleared essentially by renal excretion. Accumulation of these nanoparticles in 9L gliosarcoma tumors implanted in the rat brain was quantitated. This passive and long-duration accumulation of gadolinium-based nanoparticles in tumor, which is related to disruption of the blood-brain barrier, is in good agreement with the use of these nanoparticles as radiosensitizers for brain tumors.

A flocking based method for brain tractography.

Science.gov (United States)

Aranda, Ramon; Rivera, Mariano; Ramirez-Manzanares, Alonso

2014-04-01

We propose a new method to estimate axonal fiber pathways from Multiple Intra-Voxel Diffusion Orientations. Our method uses the multiple local orientation information for leading stochastic walks of particles. These stochastic particles are modeled with mass and thus they are subject to gravitational and inertial forces. As result, we obtain smooth, filtered and compact trajectory bundles. This gravitational interaction can be seen as a flocking behavior among particles that promotes better and robust axon fiber estimations because they use collective information to move. However, the stochastic walks may generate paths with low support (outliers), generally associated to incorrect brain connections. In order to eliminate the outlier pathways, we propose a filtering procedure based on principal component analysis and spectral clustering. The performance of the proposal is evaluated on Multiple Intra-Voxel Diffusion Orientations from two realistic numeric diffusion phantoms and a physical diffusion phantom. Additionally, we qualitatively demonstrate the performance on in vivo human brain data. Copyright © 2014 Elsevier B.V. All rights reserved.

Brain order disorder 2nd group report of f-EEG

Science.gov (United States)

Lalonde, Francois; Gogtay, Nitin; Giedd, Jay; Vydelingum, Nadarajen; Brown, David; Tran, Binh Q.; Hsu, Charles; Hsu, Ming-Kai; Cha, Jae; Jenkins, Jeffrey; Ma, Lien; Willey, Jefferson; Wu, Jerry; Oh, Kenneth; Landa, Joseph; Lin, C. T.; Jung, T. P.; Makeig, Scott; Morabito, Carlo Francesco; Moon, Qyu; Yamakawa, Takeshi; Lee, Soo-Young; Lee, Jong-Hwan; Szu, Harold H.; Kaur, Balvinder; Byrd, Kenneth; Dang, Karen; Krzywicki, Alan; Familoni, Babajide O.; Larson, Louis; Harkrider, Susan; Krapels, Keith A.; Dai, Liyi

2014-05-01

Since the Brain Order Disorder (BOD) group reported on a high density Electroencephalogram (EEG) to capture the neuronal information using EEG to wirelessly interface with a Smartphone [1,2], a larger BOD group has been assembled, including the Obama BRAIN program, CUA Brain Computer Interface Lab and the UCSD Swartz Computational Neuroscience Center. We can implement the pair-electrodes correlation functions in order to operate in a real time daily environment, which is of the computation complexity of O(N3) for N=102~3 known as functional f-EEG. The daily monitoring requires two areas of focus. Area #(1) to quantify the neuronal information flow under arbitrary daily stimuli-response sources. Approach to #1: (i) We have asserted that the sources contained in the EEG signals may be discovered by an unsupervised learning neural network called blind sources separation (BSS) of independent entropy components, based on the irreversible Boltzmann cellular thermodynamics(ΔS function. (i) Although the entropy itself is not the information per se, but the concurrence of the entropy sources is the information flow as a functional-EEG, sketched in this 2nd BOD report. Area #(2) applying EEG bio-feedback will improve collective decision making (TBD). Approach to #2: We introduce a novel performance quality metrics, in terms of the throughput rate of faster (Δt) & more accurate (ΔA) decision making, which applies to individual, as well as team brain dynamics. Following Nobel Laureate Daniel Kahnmen's novel "Thinking fast and slow", through the brainwave biofeedback we can first identify an individual's "anchored cognitive bias sources". This is done in order to remove the biases by means of individually tailored pre-processing. Then the training effectiveness can be maximized by the collective product Δt * ΔA. For Area #1, we compute a spatiotemporally windowed EEG in vitro average using adaptive time-window sampling. The sampling rate depends on the type of neuronal

Errors in MR-based attenuation correction for brain imaging with PET/MR scanners

International Nuclear Information System (INIS)

Rota Kops, Elena; Herzog, Hans

2013-01-01

Aim: Attenuation correction of PET data acquired by hybrid MR/PET scanners remains a challenge, even if several methods for brain and whole-body measurements have been developed recently. A template-based attenuation correction for brain imaging proposed by our group is easy to handle and delivers reliable attenuation maps in a short time. However, some potential error sources are analyzed in this study. We investigated the choice of template reference head among all the available data (error A), and possible skull anomalies of the specific patient, such as discontinuities due to surgery (error B). Materials and methods: An anatomical MR measurement and a 2-bed-position transmission scan covering the whole head and neck region were performed in eight normal subjects (4 females, 4 males). Error A: Taking alternatively one of the eight heads as reference, eight different templates were created by nonlinearly registering the images to the reference and calculating the average. Eight patients (4 females, 4 males; 4 with brain lesions, 4 w/o brain lesions) were measured in the Siemens BrainPET/MR scanner. The eight templates were used to generate the patients' attenuation maps required for reconstruction. ROI and VOI atlas-based comparisons were performed employing all the reconstructed images. Error B: CT-based attenuation maps of two volunteers were manipulated by manually inserting several skull lesions and filling a nasal cavity. The corresponding attenuation coefficients were substituted with the water's coefficient (0.096/cm). Results: Error A: The mean SUVs over the eight templates pairs for all eight patients and all VOIs did not differ significantly one from each other. Standard deviations up to 1.24% were found. Error B: After reconstruction of the volunteers' BrainPET data with the CT-based attenuation maps without and with skull anomalies, a VOI-atlas analysis was performed revealing very little influence of the skull lesions (less than 3%), while the filled

Errors in MR-based attenuation correction for brain imaging with PET/MR scanners

Science.gov (United States)

Rota Kops, Elena; Herzog, Hans

2013-02-01

AimAttenuation correction of PET data acquired by hybrid MR/PET scanners remains a challenge, even if several methods for brain and whole-body measurements have been developed recently. A template-based attenuation correction for brain imaging proposed by our group is easy to handle and delivers reliable attenuation maps in a short time. However, some potential error sources are analyzed in this study. We investigated the choice of template reference head among all the available data (error A), and possible skull anomalies of the specific patient, such as discontinuities due to surgery (error B). Materials and methodsAn anatomical MR measurement and a 2-bed-position transmission scan covering the whole head and neck region were performed in eight normal subjects (4 females, 4 males). Error A: Taking alternatively one of the eight heads as reference, eight different templates were created by nonlinearly registering the images to the reference and calculating the average. Eight patients (4 females, 4 males; 4 with brain lesions, 4 w/o brain lesions) were measured in the Siemens BrainPET/MR scanner. The eight templates were used to generate the patients' attenuation maps required for reconstruction. ROI and VOI atlas-based comparisons were performed employing all the reconstructed images. Error B: CT-based attenuation maps of two volunteers were manipulated by manually inserting several skull lesions and filling a nasal cavity. The corresponding attenuation coefficients were substituted with the water's coefficient (0.096/cm). ResultsError A: The mean SUVs over the eight templates pairs for all eight patients and all VOIs did not differ significantly one from each other. Standard deviations up to 1.24% were found. Error B: After reconstruction of the volunteers' BrainPET data with the CT-based attenuation maps without and with skull anomalies, a VOI-atlas analysis was performed revealing very little influence of the skull lesions (less than 3%), while the filled nasal

Goal selection versus process control in a brain-computer interface based on sensorimotor rhythms.

Science.gov (United States)

Royer, Audrey S; He, Bin

2009-02-01

In a brain-computer interface (BCI) utilizing a process control strategy, the signal from the cortex is used to control the fine motor details normally handled by other parts of the brain. In a BCI utilizing a goal selection strategy, the signal from the cortex is used to determine the overall end goal of the user, and the BCI controls the fine motor details. A BCI based on goal selection may be an easier and more natural system than one based on process control. Although goal selection in theory may surpass process control, the two have never been directly compared, as we are reporting here. Eight young healthy human subjects participated in the present study, three trained and five naïve in BCI usage. Scalp-recorded electroencephalograms (EEG) were used to control a computer cursor during five different paradigms. The paradigms were similar in their underlying signal processing and used the same control signal. However, three were based on goal selection, and two on process control. For both the trained and naïve populations, goal selection had more hits per run, was faster, more accurate (for seven out of eight subjects) and had a higher information transfer rate than process control. Goal selection outperformed process control in every measure studied in the present investigation.

Salmonella enterica serovar Enteritidis brain abscess mimicking meningitis after surgery for glioblastoma multiforme: a case report and review of the literature

OpenAIRE

Luciani, L?a; Dubourg, Gr?gory; Graillon, Thomas; Honnorat, Estelle; Lepidi, Hubert; Drancourt, Michel; Seng, Piseth; Stein, Andreas

2016-01-01

Background Salmonella brain abscess associated with brain tumor is rare. Only 11 cases have been reported to date. Here we report a case of brain abscess caused by Salmonella enterica serovar Enteritidis mimicking post-surgical meningitis in a patient with glioblastoma multiforme. Case presentation A 60-year-old Algerian woman was admitted through an emergency department for a 4-day history of headache, nausea and vomiting, and behavioral disorders. Surgery for cerebral tumor excision was per...

Fun cube based brain gym cognitive function assessment system.

Science.gov (United States)

Zhang, Tao; Lin, Chung-Chih; Yu, Tsang-Chu; Sun, Jing; Hsu, Wen-Chuin; Wong, Alice May-Kuen

2017-05-01

The aim of this study is to design and develop a fun cube (FC) based brain gym (BG) cognitive function assessment system using the wireless sensor network and multimedia technologies. The system comprised (1) interaction devices, FCs and a workstation used as interactive tools for collecting and transferring data to the server, (2) a BG information management system responsible for managing the cognitive games and storing test results, and (3) a feedback system used for conducting the analysis of cognitive functions to assist caregivers in screening high risk groups with mild cognitive impairment. Three kinds of experiments were performed to evaluate the developed FC-based BG cognitive function assessment system. The experimental results showed that the Pearson correlation coefficient between the system's evaluation outcomes and the traditional Montreal Cognitive Assessment scores was 0.83. The average Technology Acceptance Model 2 score was close to six for 31 elderly subjects. Most subjects considered that the brain games are interesting and the FC human-machine interface is easy to learn and operate. The control group and the cognitive impairment group had statistically significant difference with respect to the accuracy of and the time taken for the brain cognitive function assessment games, including Animal Naming, Color Search, Trail Making Test, Change Blindness, and Forward / Backward Digit Span. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diffusion Tensor Imaging (DTI Correlates of Self-Reported Sleep Quality and Depression Following Mild Traumatic Brain Injury

Directory of Open Access Journals (Sweden)

Adam C. Raikes

2018-06-01

Full Text Available Background: Mild traumatic brain injuries (mTBIs are a significant social, sport, and military health issue. In spite of advances in the clinical management of these injuries, the underlying pathophysiology is not well-understood. There is a critical need to advance objective biomarkers, allowing the identification and tracking of the long-term evolution of changes resulting from mTBI. Diffusion-weighted imaging (DWI allows for the assessment of white-matter properties in the brain and shows promise as a suitable biomarker of mTBI pathophysiology.Methods: 34 individuals within a year of an mTBI (age: 24.4 ± 7.4 and 18 individuals with no history of mTBI (age: 23.2 ± 3.4 participated in this study. Participants completed self-report measures related to functional outcomes, psychological health, post-injury symptoms, and sleep, and underwent a neuroimaging session that included DWI. Whole-brain white matter was skeletonized using tract-based spatial statistics (TBSS and compared between groups as well as correlated within-group with the self-report measures.Results: There were no statistically significant anatomical differences between the two groups. After controlling for time since injury, fractional anisotropy (FA demonstrated a negative correlation with sleep quality scores (higher FA was associated with better sleep quality and increasing depressive symptoms in the mTBI participants. Conversely, mean (MD and radial diffusivity (RD demonstrated positive correlations with sleep quality scores (higher RD was associated with worse sleep quality and increasing depressive symptoms. These correlations were observed bilaterally in the internal capsule (anterior and posterior limbs, corona radiata (anterior and superior, fornix, and superior fronto-occipital fasciculi.Conclusion: The results of this study indicate that the clinical presentation of mTBI, particularly with respect to depression and sleep, is associated with reduced white

Potential predictors for the amount of intra-operative brain shift during deep brain stimulation surgery

Science.gov (United States)

Datteri, Ryan; Pallavaram, Srivatsan; Konrad, Peter E.; Neimat, Joseph S.; D'Haese, Pierre-François; Dawant, Benoit M.

2011-03-01

A number of groups have reported on the occurrence of intra-operative brain shift during deep brain stimulation (DBS) surgery. This has a number of implications for the procedure including an increased chance of intra-cranial bleeding and complications due to the need for more exploratory electrodes to account for the brain shift. It has been reported that the amount of pneumocephalus or air invasion into the cranial cavity due to the opening of the dura correlates with intraoperative brain shift. Therefore, pre-operatively predicting the amount of pneumocephalus expected during surgery is of interest toward accounting for brain shift. In this study, we used 64 DBS patients who received bilateral electrode implantations and had a post-operative CT scan acquired immediately after surgery (CT-PI). For each patient, the volumes of the pneumocephalus, left ventricle, right ventricle, third ventricle, white matter, grey matter, and cerebral spinal fluid were calculated. The pneumocephalus was calculated from the CT-PI utilizing a region growing technique that was initialized with an atlas-based image registration method. A multi-atlas-based image segmentation method was used to segment out the ventricles of each patient. The Statistical Parametric Mapping (SPM) software package was utilized to calculate the volumes of the cerebral spinal fluid (CSF), white matter and grey matter. The volume of individual structures had a moderate correlation with pneumocephalus. Utilizing a multi-linear regression between the volume of the pneumocephalus and the statistically relevant individual structures a Pearson's coefficient of r = 0.4123 (p = 0.0103) was found. This study shows preliminary results that could be used to develop a method to predict the amount of pneumocephalus ahead of the surgery.

Development of representative magnetic resonance imaging-based atlases of the canine brain and evaluation of three methods for atlas-based segmentation.

Science.gov (United States)

Milne, Marjorie E; Steward, Christopher; Firestone, Simon M; Long, Sam N; O'Brien, Terrence J; Moffat, Bradford A

2016-04-01

To develop representative MRI atlases of the canine brain and to evaluate 3 methods of atlas-based segmentation (ABS). 62 dogs without clinical signs of epilepsy and without MRI evidence of structural brain disease. The MRI scans from 44 dogs were used to develop 4 templates on the basis of brain shape (brachycephalic, mesaticephalic, dolichocephalic, and combined mesaticephalic and dolichocephalic). Atlas labels were generated by segmenting the brain, ventricular system, hippocampal formation, and caudate nuclei. The MRI scans from the remaining 18 dogs were used to evaluate 3 methods of ABS (manual brain extraction and application of a brain shape-specific template [A], automatic brain extraction and application of a brain shape-specific template [B], and manual brain extraction and application of a combined template [C]). The performance of each ABS method was compared by calculation of the Dice and Jaccard coefficients, with manual segmentation used as the gold standard. Method A had the highest mean Jaccard coefficient and was the most accurate ABS method assessed. Measures of overlap for ABS methods that used manual brain extraction (A and C) ranged from 0.75 to 0.95 and compared favorably with repeated measures of overlap for manual extraction, which ranged from 0.88 to 0.97. Atlas-based segmentation was an accurate and repeatable method for segmentation of canine brain structures. It could be performed more rapidly than manual segmentation, which should allow the application of computer-assisted volumetry to large data sets and clinical cases and facilitate neuroimaging research and disease diagnosis.

MR imaging of the brain in large cohort studies: feasibility report of the population- and patient-based BiDirect study

International Nuclear Information System (INIS)

Teuber, Anja; Berger, Klaus; Wersching, Heike; Sundermann, Benedikt; Kugel, Harald; Schwindt, Wolfram; Heindel, Walter; Minnerup, Jens; Dannlowski, Udo

2017-01-01

To describe the implementation and protocol of cerebral magnetic resonance imaging (MRI) in the longitudinal BiDirect study and to report rates of study participation as well as management of incidental findings. Data came from the BiDirect study that investigates the relationship between depression and arteriosclerosis and comprises 2258 participants in three cohorts: 999 patients with depression, 347 patients with manifest cardiovascular disease (CVD) and 912 population-based controls. The study program includes MRI of the brain. Reasons for non-participation were systematically collected. Incidental findings were categorized and disclosed according to clinical relevance. At baseline 2176 participants were offered MRI, of whom 1453 (67 %) completed it. Reasons for non-participation differed according to cohort, age and gender with controls showing the highest participation rate of 79 %. Patient cohorts had higher refusal rates and CVD patients a high prevalence of contraindications. In the first follow-up examination 69 % of participating subjects completed MRI. Incidental findings were disclosed to 246 participants (17 %). The majority of incidental findings were extensive white matter hyperintensities requiring further diagnostic work-up. Knowledge about subjects and sensible definition of incidental findings are crucial for large-scale imaging projects. Our data offer practical and concrete information for the design of future studies. (orig.)

MR imaging of the brain in large cohort studies: feasibility report of the population- and patient-based BiDirect study

Energy Technology Data Exchange (ETDEWEB)

Teuber, Anja; Berger, Klaus; Wersching, Heike [University of Muenster, Institute of Epidemiology and Social Medicine, Muenster (Germany); Sundermann, Benedikt; Kugel, Harald; Schwindt, Wolfram; Heindel, Walter [University Hospital Muenster, Department of Clinical Radiology, Muenster (Germany); Minnerup, Jens [University Hospital Muenster, Department of Neurology, Muenster (Germany); Dannlowski, Udo [University of Muenster, Department of Psychiatry, Muenster (Germany); University of Marburg, Department of Psychiatry, Marburg (Germany)

2017-01-15

To describe the implementation and protocol of cerebral magnetic resonance imaging (MRI) in the longitudinal BiDirect study and to report rates of study participation as well as management of incidental findings. Data came from the BiDirect study that investigates the relationship between depression and arteriosclerosis and comprises 2258 participants in three cohorts: 999 patients with depression, 347 patients with manifest cardiovascular disease (CVD) and 912 population-based controls. The study program includes MRI of the brain. Reasons for non-participation were systematically collected. Incidental findings were categorized and disclosed according to clinical relevance. At baseline 2176 participants were offered MRI, of whom 1453 (67 %) completed it. Reasons for non-participation differed according to cohort, age and gender with controls showing the highest participation rate of 79 %. Patient cohorts had higher refusal rates and CVD patients a high prevalence of contraindications. In the first follow-up examination 69 % of participating subjects completed MRI. Incidental findings were disclosed to 246 participants (17 %). The majority of incidental findings were extensive white matter hyperintensities requiring further diagnostic work-up. Knowledge about subjects and sensible definition of incidental findings are crucial for large-scale imaging projects. Our data offer practical and concrete information for the design of future studies. (orig.)

Brain hemorrhage after electrical burn injury: Case report and probable mechanism.

Science.gov (United States)

Axayacalt, Gutierrez Aceves Guillermo; Alejandro, Ceja Espinosa; Marcos, Rios Alanis; Inocencio, Ruiz Flores Milton; Alfredo, Herrera Gonzalez Jose

2016-01-01

High-voltage electric injury may induce lesion in different organs. In addition to the local tissue damage, electrical injuries may lead to neurological deficits, musculoskeletal damage, and cardiovascular injury. Severe vascular damage may occur making the blood vessels involved prone to thrombosis and spontaneous rupture. Here, we present the case of a 39-year-old male who suffered an electrical burn with high tension wire causing intracranial bleeding. He presented with an electrical burn in the parietal area (entry zone) and the left forearm (exit zone). The head tomography scan revealed an intraparenchimatous bleeding in the left parietal area. In this case, the electric way was the scalp, cranial bone, blood vessels and brain, upper limb muscle, and skin. The damage was different according to the dielectric property in each tissue. The injury was in the scalp, cerebral blood vessel, skeletal muscle, and upper limb skin. The main damage was in brain's blood vessels because of the dielectric and geometric features that lead to bleeding, high temperature, and gas delivering. This is a report of a patient with an electric brain injury that can be useful to elucidate the behavior of the high voltage electrical current flow into the nervous system.

[A 53-year-old man with herpes encephalitis showing acceleration of improvement in higher brain function after general anesthesia with sevoflurane: a case report].

Science.gov (United States)

Togashi, Naohiko; Kaida, Kenichi; Hongo, Yu; Ogawa, Go; Ishikawa, Yukinobu; Takeda, Katsuhiko; Kamakura, Keiko

2014-01-01

We experienced a right-handed 53-year-old man who presented with disturbance of consciousness and fever. Herpes simplex encephalitis (HSE) was diagnosed based on the detection of herpes simplex virus DNA in the cerebrospinal fluid. The administration of acyclovir for 42 days improved his consciousness level. Drowsiness, fever and seizures reappeared 20 days after stopping acyclovir treatment (day 67) and he responded well to vidarabine and methylprednisolone pulse therapy. An assessment of aphasia on day 98 revealed transcortical sensory aphasia. Brain MRI showed lesion in the left temporal lobe, bilateral insular cortexes and bilateral frontal lobe. His higher brain dysfunction continued. On day 156, he underwent hip replacement arthroplasty under general anesthesia sevoflurane. His higher brain dysfunction rapidly improved thereafter. We concluded that the accelerated improvement in our patient's higher brain function was related to the protective effect of sevoflurane. Some reports also show the protective effects of sevoflurane in experimental allergic encephalomyelitis by inhibition of T cell activation. These protective and anti-inflammatory effects may explain the accelerated improvement in higher brain function after general anesthesia.

Deep penetrating brain injury with 20 years asymptomatic survival. Case report

International Nuclear Information System (INIS)

Buczek, M.; Pieninski, A.

1993-01-01

Authors report the case of penetrating injury of the head with large metallic fragment embedded to the brain with 20 years asymptomatic survival. Patient sustained head injury during work, 20 years ago and for these period of time was not aware of having foreign body intracranially with excellent general condition and no signs of neurological deficit. Metal nail was detected incidentally by plain skull X-ray films( and subsequent CT scan) during routine procedures when patient was admitted for surgical procedure. In our opinion presented case is uncommon because of asymptomatic course. Most of penetrating head injuries are considered as life threatening due to sudden onset, severe general patient condition and possible deterioration according to the type of injury and extent of cerebral destruction. For those reasons earliest possible neurosurgical treatment is recommended. We emphasize the role of debridement for most of brain penetration injuries. (author)

Neuromyelitis optica with linear enhancement of corpus callosum in brain magnetic resonance imaging with contrast: a case report.

Science.gov (United States)

Sahraian, Mohammad Ali; Moghadasi, Abdorreza Naser; Owji, Mahsa; Naghshineh, Hoda; Minagar, Alireza

2015-06-10

Neuromyelitis optica is a demyelinating disease of the central nervous system with various patterns of brain lesions. Corpus callosum may be involved in both multiple sclerosis and neuromyelitis optica. Previous case reports have demonstrated that callosal lesions in neuromyelitis optica are usually large and edematous and have a heterogeneous intensity showing a "marbled pattern" in the acute phase. Their size and intensity may reduce with time or disappear in the chronic stages. In this report, we describe a case of a 25-year-old Caucasian man with neuromyelitis optica who presented clinically with optic neuritis and myelitis. His brain magnetic resonance imaging demonstrated linear enhancement of the corpus callosum. Brain images with contrast agent added also showed linear ependymal layer enhancement of the lateral ventricles, which has been reported in this disease previously. Linear enhancement of corpus callosum in magnetic resonance imaging with contrast agent could help in diagnosing neuromyelitis optica and differentiating it from other demyelinating disease, especially multiple sclerosis.

Draft evidence report : traumatic brain injury and commercial motor vehicle driver safety (comprehensive review).

Science.gov (United States)

2009-03-30

Purpose of this evidence report is to address several key questions posed by the Federal Motor Carrier Safety Administration : Key question 1: What is the impact of traumatic brain injury on crash risk/driving performance? Key question 2: What factor...

Systematic review of self-reported prognosis in adults after mild traumatic brain injury

DEFF Research Database (Denmark)

Cassidy, John David; Cancelliere, Carol; Carroll, Linda J

2014-01-01

accepted and form our evidence base of prognostic studies. Of these, 23 addressed self-reported outcomes in adults, including 2 of the 3 original ICoMP research studies. These studies show that common postconcussion symptoms are not specific to MTBI/concussion and occur after other injuries as well. Poor...... recovery after MTBI is associated with poorer premorbid mental and physical health status and with more injury-related stress. Most recover over 1 year, but persistent symptoms are more likely in those with more acute symptoms and more emotional stress. CONCLUSIONS: Common subjective symptoms after MTBI......OBJECTIVE: To update the mild traumatic brain injury (MTBI) prognosis review published by the World Health Organization Task Force in 2004. DATA SOURCES: MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were searched from 2001 to 2012. We included published, peer-reviewed studies with more than...

Brain abscess mimicking lung cancer metastases; a case report.

Science.gov (United States)

Asano, Michiko; Fujimoto, Nobukazu; Fuchimoto, Yasuko; Ono, Katsuichiro; Ozaki, Shinji; Kimura, Fumiaki; Kishimoto, Takumi

2013-01-01

A 76-year-old woman came to us because of staggering, fever, dysarthria, and appetite loss. Magnetic resonance imaging (MRI) of the brain revealed multiple masses with surrounding edema. Chest X-ray and computed tomography demonstrated a mass-like lesion in the left lung and left pleural effusion. Lung cancer and multiple brain metastases were suspected. However, the brain lesions demonstrated a high intensity through diffusion-weighted MRI. The finding was an important key to differentiate brain abscesses from lung cancer metastases. Copyright © 2013 Elsevier Inc. All rights reserved.

The standard-based open workflow system in GeoBrain (Invited)

Science.gov (United States)

Di, L.; Yu, G.; Zhao, P.; Deng, M.

2013-12-01

GeoBrain is an Earth science Web-service system developed and operated by the Center for Spatial Information Science and Systems, George Mason University. In GeoBrain, a standard-based open workflow system has been implemented to accommodate the automated processing of geospatial data through a set of complex geo-processing functions for advanced production generation. The GeoBrain models the complex geoprocessing at two levels, the conceptual and concrete. At the conceptual level, the workflows exist in the form of data and service types defined by ontologies. The workflows at conceptual level are called geo-processing models and cataloged in GeoBrain as virtual product types. A conceptual workflow is instantiated into a concrete, executable workflow when a user requests a product that matches a virtual product type. Both conceptual and concrete workflows are encoded in Business Process Execution Language (BPEL). A BPEL workflow engine, called BPELPower, has been implemented to execute the workflow for the product generation. A provenance capturing service has been implemented to generate the ISO 19115-compliant complete product provenance metadata before and after the workflow execution. The generation of provenance metadata before the workflow execution allows users to examine the usability of the final product before the lengthy and expensive execution takes place. The three modes of workflow executions defined in the ISO 19119, transparent, translucent, and opaque, are available in GeoBrain. A geoprocessing modeling portal has been developed to allow domain experts to develop geoprocessing models at the type level with the support of both data and service/processing ontologies. The geoprocessing models capture the knowledge of the domain experts and are become the operational offering of the products after a proper peer review of models is conducted. An automated workflow composition has been experimented successfully based on ontologies and artificial

Brain imaging and brain function

International Nuclear Information System (INIS)

Sokoloff, L.

1985-01-01

This book is a survey of the applications of imaging studies of regional cerebral blood flow and metabolism to the investigation of neurological and psychiatric disorders. Contributors review imaging techniques and strategies for measuring regional cerebral blood flow and metabolism, for mapping functional neural systems, and for imaging normal brain functions. They then examine the applications of brain imaging techniques to the study of such neurological and psychiatric disorders as: cerebral ischemia; convulsive disorders; cerebral tumors; Huntington's disease; Alzheimer's disease; depression and other mood disorders. A state-of-the-art report on magnetic resonance imaging of the brain and central nervous system rounds out the book's coverage

A preliminary report on the use of functional magnetic resonance imaging with simultaneous urodynamics to record brain activity during micturition.

Science.gov (United States)

Krhut, Jan; Tintera, Jaroslav; Holý, Petr; Zachoval, Roman; Zvara, Peter

2012-08-01

We mapped brain activity during micturition using functional magnetic resonance imaging with simultaneous recording of urodynamic properties during slow bladder filling and micturition. We evaluated 12 healthy female volunteers 20 to 68 years old. Eight subjects could urinate while supine. Meaningful data were obtained on 6 of these subjects. Brain activity was recorded continuously during bladder filling and micturition. Functional magnetic resonance imaging measurements made during the micturition phase were used for the final analysis. Using group statistics we identified clusters of brain activity in the parahippocampal gyrus, anterior cingulate gyrus, inferior temporal gyrus and inferior frontal gyrus during micturition. At the individual level we also observed activation in the upper pontine region, thalamus and posterior cingulum. In subjects unable to void brain activation was documented in the frontal lobe and posterior cingulate gyrus but not in the pons, thalamus or anterior cingulate gyrus. In 5 subjects we identified a relevant pattern of brain activity during the terminal portion of the filling phase when the patient reported a strong desire to urinate. This new protocol allows for the localization of brain structures that are active during micturition. Data suggest that additional validation studies are needed. Future studies will test modifications that include more detailed monitoring of bladder sensation, stratifying subjects based on age and gender, and increasing the number of data points by adding subjects and the number of micturitions recorded in a single subject. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Landmark-based deep multi-instance learning for brain disease diagnosis.

Science.gov (United States)

Liu, Mingxia; Zhang, Jun; Adeli, Ehsan; Shen, Dinggang

2018-01-01

In conventional Magnetic Resonance (MR) image based methods, two stages are often involved to capture brain structural information for disease diagnosis, i.e., 1) manually partitioning each MR image into a number of regions-of-interest (ROIs), and 2) extracting pre-defined features from each ROI for diagnosis with a certain classifier. However, these pre-defined features often limit the performance of the diagnosis, due to challenges in 1) defining the ROIs and 2) extracting effective disease-related features. In this paper, we propose a landmark-based deep multi-instance learning (LDMIL) framework for brain disease diagnosis. Specifically, we first adopt a data-driven learning approach to discover disease-related anatomical landmarks in the brain MR images, along with their nearby image patches. Then, our LDMIL framework learns an end-to-end MR image classifier for capturing both the local structural information conveyed by image patches located by landmarks and the global structural information derived from all detected landmarks. We have evaluated our proposed framework on 1526 subjects from three public datasets (i.e., ADNI-1, ADNI-2, and MIRIAD), and the experimental results show that our framework can achieve superior performance over state-of-the-art approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

Brain-Based Learning and Classroom Practice: A Study Investigating Instructional Methodologies of Urban School Teachers

Science.gov (United States)

Morris, Lajuana Trezette

2010-01-01

The purpose of this study was to examine the implementation of brain-based instructional strategies by teachers serving at Title I elementary, middle, and high schools within the Memphis City School District. This study was designed to determine: (a) the extent to which Title I teachers applied brain-based strategies, (b) the differences in…

Semi-supervised adaptation in ssvep-based brain-computer interface using tri-training

DEFF Research Database (Denmark)

Bender, Thomas; Kjaer, Troels W.; Thomsen, Carsten E.

2013-01-01

This paper presents a novel and computationally simple tri-training based semi-supervised steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI). It is implemented with autocorrelation-based features and a Naïve-Bayes classifier (NBC). The system uses nine characters...

African Journal of Biotechnology - Vol 11, No 48 (2012)

African Journals Online (AJOL)

... brain aromatase-induction of monosodium glutamate in estrogen-responsive mosaic transgenic zebra fish Danio rerio · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Tamer Said Abdelkader, Chang Seo-Na, Kim Tae-Hyun, Song Juha, Kim Dongso, Jae-Hak Park ...

EKG-based detection of deep brain stimulation in fMRI studies.

Science.gov (United States)

Fiveland, Eric; Madhavan, Radhika; Prusik, Julia; Linton, Renee; Dimarzio, Marisa; Ashe, Jeffrey; Pilitsis, Julie; Hancu, Ileana

2018-04-01

To assess the impact of synchronization errors between the assumed functional MRI paradigm timing and the deep brain stimulation (DBS) on/off cycling using a custom electrocardiogram-based triggering system METHODS: A detector for measuring and predicting the on/off state of cycling deep brain stimulation was developed and tested in six patients in office visits. Three-electrode electrocardiogram measurements, amplified by a commercial bio-amplifier, were used as input for a custom electronics box (e-box). The e-box transformed the deep brain stimulation waveforms into transistor-transistor logic pulses, recorded their timing, and propagated it in time. The e-box was used to trigger task-based deep brain stimulation functional MRI scans in 5 additional subjects; the impact of timing accuracy on t-test values was investigated in a simulation study using the functional MRI data. Following locking to each patient's individual waveform, the e-box was shown to predict stimulation onset with an average absolute error of 112 ± 148 ms, 30 min after disconnecting from the patients. The subsecond accuracy of the e-box in predicting timing onset is more than adequate for our slow varying, 30-/30-s on/off stimulation paradigm. Conversely, the experimental deep brain stimulation onset prediction accuracy in the absence of the e-box, which could be off by as much as 4 to 6 s, could significantly decrease activation strength. Using this detector, stimulation can be accurately synchronized to functional MRI acquisitions, without adding any additional hardware in the MRI environment. Magn Reson Med 79:2432-2439, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

The Effectiveness of the Brain Based Teaching Approach in Enhancing Scientific Understanding of Newtonian Physics among Form Four Students

Science.gov (United States)

Saleh, Salmiza

2012-01-01

The aim of this study was to assess the effectiveness of Brain Based Teaching Approach in enhancing students' scientific understanding of Newtonian Physics in the context of Form Four Physics instruction. The technique was implemented based on the Brain Based Learning Principles developed by Caine & Caine (1991, 2003). This brain compatible…

Influence of Signal Intensity Non-Uniformity on Brain Volumetry Using an Atlas-Based Method

International Nuclear Information System (INIS)

Takao, Hidemasa; Kunimatsu, Akira; Mori, Harushi

2012-01-01

Many studies have reported pre-processing effects for brain volumetry; however, no study has investigated whether non-parametric non-uniform intensity normalization (N3) correction processing results in reduced system dependency when using an atlas-based method. To address this shortcoming, the present study assessed whether N3 correction processing provides reduced system dependency in atlas-based volumetry. Contiguous sagittal T1-weighted images of the brain were obtained from 21 healthy participants, by using five magnetic resonance protocols. After image preprocessing using the Statistical Parametric Mapping 5 software, we measured the structural volume of the segmented images with the WFU-PickAtlas software. We applied six different bias-correction levels (Regularization 10, Regularization 0.0001, Regularization 0, Regularization 10 with N3, Regularization 0.0001 with N3, and Regularization 0 with N3) to each set of images. The structural volume change ratio (%) was defined as the change ratio (%) = (100 X[measured volume - mean volume of five magnetic resonance protocols] / mean volume of five magnetic resonance protocols) for each bias-correction level. A low change ratio was synonymous with lower system dependency. The results showed that the images with the N3 correction had a lower change ratio compared with those without the N3 correction. The present study is the first atlas-based volumetry study to show that the precision of atlas-based volumetry improves when using N3-corrected images. Therefore, correction for signal intensity non-uniformity is strongly advised for multi-scanner or multi-site imaging trials.

Influence of signal intensity non-uniformity on brain volumetry using an atlas-based method.

Science.gov (United States)

Goto, Masami; Abe, Osamu; Miyati, Tosiaki; Kabasawa, Hiroyuki; Takao, Hidemasa; Hayashi, Naoto; Kurosu, Tomomi; Iwatsubo, Takeshi; Yamashita, Fumio; Matsuda, Hiroshi; Mori, Harushi; Kunimatsu, Akira; Aoki, Shigeki; Ino, Kenji; Yano, Keiichi; Ohtomo, Kuni

2012-01-01

Many studies have reported pre-processing effects for brain volumetry; however, no study has investigated whether non-parametric non-uniform intensity normalization (N3) correction processing results in reduced system dependency when using an atlas-based method. To address this shortcoming, the present study assessed whether N3 correction processing provides reduced system dependency in atlas-based volumetry. Contiguous sagittal T1-weighted images of the brain were obtained from 21 healthy participants, by using five magnetic resonance protocols. After image preprocessing using the Statistical Parametric Mapping 5 software, we measured the structural volume of the segmented images with the WFU-PickAtlas software. We applied six different bias-correction levels (Regularization 10, Regularization 0.0001, Regularization 0, Regularization 10 with N3, Regularization 0.0001 with N3, and Regularization 0 with N3) to each set of images. The structural volume change ratio (%) was defined as the change ratio (%) = (100 × [measured volume - mean volume of five magnetic resonance protocols] / mean volume of five magnetic resonance protocols) for each bias-correction level. A low change ratio was synonymous with lower system dependency. The results showed that the images with the N3 correction had a lower change ratio compared with those without the N3 correction. The present study is the first atlas-based volumetry study to show that the precision of atlas-based volumetry improves when using N3-corrected images. Therefore, correction for signal intensity non-uniformity is strongly advised for multi-scanner or multi-site imaging trials.

Influence of Signal Intensity Non-Uniformity on Brain Volumetry Using an Atlas-Based Method

Energy Technology Data Exchange (ETDEWEB)

Takao, Hidemasa; Kunimatsu, Akira; Mori, Harushi [University of Tokyo Hospital, Tokyo (Japan); and others

2012-07-15

Many studies have reported pre-processing effects for brain volumetry; however, no study has investigated whether non-parametric non-uniform intensity normalization (N3) correction processing results in reduced system dependency when using an atlas-based method. To address this shortcoming, the present study assessed whether N3 correction processing provides reduced system dependency in atlas-based volumetry. Contiguous sagittal T1-weighted images of the brain were obtained from 21 healthy participants, by using five magnetic resonance protocols. After image preprocessing using the Statistical Parametric Mapping 5 software, we measured the structural volume of the segmented images with the WFU-PickAtlas software. We applied six different bias-correction levels (Regularization 10, Regularization 0.0001, Regularization 0, Regularization 10 with N3, Regularization 0.0001 with N3, and Regularization 0 with N3) to each set of images. The structural volume change ratio (%) was defined as the change ratio (%) = (100 X[measured volume - mean volume of five magnetic resonance protocols] / mean volume of five magnetic resonance protocols) for each bias-correction level. A low change ratio was synonymous with lower system dependency. The results showed that the images with the N3 correction had a lower change ratio compared with those without the N3 correction. The present study is the first atlas-based volumetry study to show that the precision of atlas-based volumetry improves when using N3-corrected images. Therefore, correction for signal intensity non-uniformity is strongly advised for multi-scanner or multi-site imaging trials.

Longitudinal volumetric changes following traumatic brain injury: a tensor-based morphometry study.

Science.gov (United States)

Farbota, Kimberly D M; Sodhi, Aparna; Bendlin, Barbara B; McLaren, Donald G; Xu, Guofan; Rowley, Howard A; Johnson, Sterling C

2012-11-01

After traumatic injury, the brain undergoes a prolonged period of degenerative change that is paradoxically accompanied by cognitive recovery. The spatiotemporal pattern of atrophy and the specific relationships of atrophy to cognitive changes are ill understood. The present study used tensor-based morphometry and neuropsychological testing to examine brain volume loss in 17 traumatic brain injury (TBI) patients and 13 controls over a 4-year period. Patients were scanned at 2 months, 1 year, and 4 years post-injury. High-dimensional warping procedures were used to create change maps of each subject's brain for each of the two intervals. TBI patients experienced volume loss in both cortical areas and white matter regions during the first interval. We also observed continuing volume loss in extensive regions of white matter during the second interval. Neuropsychological correlations indicated that cognitive tasks were associated with subsequent volume loss in task-relevant regions. The extensive volume loss in brain white matter observed well beyond the first year post-injury suggests that the injured brain remains malleable for an extended period, and the neuropsychological relationships suggest that this volume loss may be associated with subtle cognitive improvements.

Near-infrared spectroscopy (NIRS - electroencephalography (EEG based brain-state dependent electrotherapy (BSDE: A computational approach based on excitation-inhibition balance hypothesis

Directory of Open Access Journals (Sweden)

Snigdha Dagar

2016-08-01

Full Text Available Stroke is the leading cause of severe chronic disability and the second cause of death worldwide with 15 million new cases and 50 million stroke survivors. The post stroke chronic disability may be ameliorated with early neuro rehabilitation where non-invasive brain stimulation (NIBS techniques can be used as an adjuvant treatment to hasten the effects. However, the heterogeneity in the lesioned brain will require individualized NIBS intervention where innovative neuroimaging technologies of portable electroencephalography (EEG and functional-near-infrared spectroscopy (fNIRS can be leveraged for Brain State Dependent Electrotherapy (BSDE. In this hypothesis and theory article, we propose a computational approach based on excitation-inhibition (E-I balance hypothesis to objectively quantify the post stroke individual brain state using online fNIRS-EEG joint imaging. One of the key events that occurs following Stroke is the imbalance in local excitation-inhibition (that is the ratio of Glutamate/GABA which may be targeted with NIBS using a computational pipeline that includes individual forward models to predict current flow patterns through the lesioned brain or brain target region. The current flow will polarize the neurons which can be captured with excitation-inhibition based brain models. Furthermore, E-I balance hypothesis can be used to find the consequences of cellular polarization on neuronal information processing which can then be implicated in changes in function. We first review evidence that shows how this local imbalance between excitation-inhibition leading to functional dysfunction can be restored in targeted sites with NIBS (Motor Cortex, Somatosensory Cortex resulting in large scale plastic reorganization over the cortex, and probably facilitating recovery of functions. Secondly, we show evidence how BSDE based on inhibition–excitation balance hypothesis may target a specific brain site or network as an adjuvant treatment

Aromatase inhibitors for prevention of breast cancer in postmenopausal women: a narrative review.

Science.gov (United States)

Behan, Lucy Ann; Amir, Eitan; Casper, Robert F

2015-03-01

The increasing incidence of breast cancer (BC) worldwide has resulted in widespread interest in primary prevention therapies. A number of large randomized trials have shown that selective estrogen receptor modulators can reduce the relative risk for BC by 30% to 40% in high-risk women. In early-stage BC, aromatase inhibitors (AIs) showed a 35% relative reduction in the risk of contralateral BCs compared with tamoxifen. In this narrative review, we discuss the role of AIs in the primary prevention of BC and novel research on combination hormone therapy-medical therapy for the primary prevention of BC. Using PubMed/Medline, we comprehensively searched for studies of BC primary prevention using AIs, including studies of novel methods of prevention using combination hormone therapy-BC prevention. Two large multicenter, prospective, randomized, placebo-controlled trials have evaluated AIs--anastrozole (International Breast Cancer Intervention Study II) and exemestane (Mammary Prevention 3)--for BC risk reduction in women at increased risk for BC, which we summarize. We identified five studies (three completed and two ongoing) of combination AI-hormone therapy that are undergoing investigation for BC risk reduction. AIs are effective at BC risk reduction, although long-term follow-up data are required to assess whether this risk reduction will result in reduced mortality. Combination hormone therapy-AI for BC risk reduction is experimental and warrants further investigation.

PET/MRI for Oncologic Brain Imaging

DEFF Research Database (Denmark)

Rausch, Ivo; Rischka, Lucas; Ladefoged, Claes N

2017-01-01

The aim of this study was to compare attenuation-correction (AC) approaches for PET/MRI in clinical neurooncology.Methods:Forty-nine PET/MRI brain scans were included: brain tumor studies using18F-fluoro-ethyl-tyrosine (18F-FET) (n= 31) and68Ga-DOTANOC (n= 7) and studies of healthy subjects using18...... by Siemens Healthcare). As a reference, AC maps were derived from patient-specific CT images (CTref). PET data were reconstructed using standard settings after AC with all 4 AC methods. We report changes in diagnosis for all brain tumor patients and the following relative differences values (RDs...... of the whole brain and 10 anatomic regions segmented on MR images.Results:For brain tumor imaging (A and B), the standard PET-based diagnosis was not affected by any of the 3 MR-AC methods. For A, the average RDs of SUVmeanwere -10%, -4%, and -3% and of the VOIs 1%, 2%, and 7% for DIXON, UTE, and BD...

Brain Based Learning in Science Education in Turkey: Descriptive Content and Meta Analysis of Dissertations

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Yasar, M. Diyaddin

2017-01-01

This study aimed at performing content analysis and meta-analysis on dissertations related to brain-based learning in science education to find out the general trend and tendency of brain-based learning in science education and find out the effect of such studies on achievement and attitude of learners with the ultimate aim of raising awareness…

Effect of cocaine on structural changes in brain: MRI volumetry using tensor-based morphometry.

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Narayana, Ponnada A; Datta, Sushmita; Tao, Guozhi; Steinberg, Joel L; Moeller, F Gerard

2010-10-01

Magnetic resonance imaging (MRI) was performed in cocaine-dependent subjects to determine the structural changes in brain compared to non-drug using controls. Cocaine-dependent subjects and controls were carefully screened to rule out brain pathology of undetermined origin. Magnetic resonance images were analyzed using tensor-based morphometry (TBM) and voxel-based morphometry (VBM) without and with modulation to adjust for volume changes during normalization. For TBM analysis, unbiased atlases were generated using two different inverse consistent and diffeomorphic nonlinear registration techniques. Two different control groups were used for generating unbiased atlases. Independent of the nonlinear registration technique and normal cohorts used for creating the unbiased atlases, our analysis failed to detect any statistically significant effect of cocaine on brain volumes. These results show that cocaine-dependent subjects do not show differences in regional brain volumes compared to non-drug using controls. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Virtual reality-based prospective memory training program for people with acquired brain injury.

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Yip, Ben C B; Man, David W K

2013-01-01

Acquired brain injuries (ABI) may display cognitive impairments and lead to long-term disabilities including prospective memory (PM) failure. Prospective memory serves to remember to execute an intended action in the future. PM problems would be a challenge to an ABI patient's successful community reintegration. While retrospective memory (RM) has been extensively studied, treatment programs for prospective memory are rarely reported. The development of a treatment program for PM, which is considered timely, can be cost-effective and appropriate to the patient's environment. A 12-session virtual reality (VR)-based cognitive rehabilitation program was developed using everyday PM activities as training content. 37 subjects were recruited to participate in a pretest-posttest control experimental study to evaluate its treatment effectiveness. Results suggest that significantly better changes were seen in both VR-based and real-life PM outcome measures, related cognitive attributes such as frontal lobe functions and semantic fluency. VR-based training may be well accepted by ABI patients as encouraging improvement has been shown. Large-scale studies of a virtual reality-based prospective memory (VRPM) training program are indicated.

Covert orienting in the split brain: Right hemisphere specialization for object-based attention.

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Kingstone, Alan

2015-12-18

The present paper takes as its starting point Phil Bryden's long-standing interest in human attention and the role it can play in laterality effects. Past split-brain research has suggested that object-based attention is lateralized to the left hemisphere [e.g., Egly, R., Rafal, R. D., Driver, J., & Starreveld, Y. (1994). Covert orienting in the split brain reveals hemispheric specialization for object-based attention. Psychological Science, 5(6), 380-382]. The task used to isolate object-based attention in that previous work, however, has been found wanting [Vecera, S. P. (1994). Grouped locations and object-based attention: Comment on Egly, Driver, and Rafal (1994). Journal of Experimental Psychology: General, 123(3), 316-320]; and indeed, subsequent research with healthy participants using a different task has suggested that object-based attention is lateralized to the opposite right hemisphere (RH) [Valsangkar-Smyth, M. A., Donovan, C. L., Sinnett, S., Dawson, M. R., & Kingstone, A. (2004). Hemispheric performance in object-based attention. Psychonomic Bulletin & Review, 11(1), 84-91]. The present study tested the same split-brain as Egly, Rafal, et al. (1994) but used the object-based attention task introduced by Valsangkar-Smyth et al. (2004). The results confirm that object-based attention is lateralized to the RH. They also suggest that subcortical interhemispheric competition may occur and be dominated by the RH.

Brain Migration Revisited

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Vinokur, Annie

2006-01-01

The "brain drain/brain gain" debate has been going on for the past 40 years, with irresolvable theoretical disputes and unenforceable policy recommendations that economists commonly ascribe to the lack of reliable empirical data. The recent report of the World Bank, "International migration, remittances and the brain drain", documents the…

Automated brain structure segmentation based on atlas registration and appearance models

DEFF Research Database (Denmark)

van der Lijn, Fedde; de Bruijne, Marleen; Klein, Stefan

2012-01-01

Accurate automated brain structure segmentation methods facilitate the analysis of large-scale neuroimaging studies. This work describes a novel method for brain structure segmentation in magnetic resonance images that combines information about a structure’s location and appearance. The spatial...... with different magnetic resonance sequences, in which the hippocampus and cerebellum were segmented by an expert. Furthermore, the method is compared to two other segmentation techniques that were applied to the same data. Results show that the atlas- and appearance-based method produces accurate results...

Validation of In Vitro Cell-Based Human Blood-Brain Barrier Model Using Clinical Positron Emission Tomography Radioligands To Predict In Vivo Human Brain Penetration

International Nuclear Information System (INIS)

Mabondzo, A.; Guyot, A.C.; Bottlaender, M.; Deverre, J.R.; Tsaouin, K.; Balimane, P.V.

2010-01-01

We have evaluated a novel in vitro cell-based human blood-brain barrier (BBB) model that could predict in vivo human brain penetration for compounds with different BBB permeabilities using the clinical positron emission tomography (PET) data. Comparison studies were also performed to demonstrate that the in vitro cell-based human BBB model resulted in better predictivity over the traditional permeability model in discovery organizations, Caco-2 cells. We evaluated the in vivo BBB permeability of [ 18 F] and [ 11 C]-compounds in humans by PET imaging. The in vivo plasma-brain exchange parameters used for comparison were determined in humans by PET using a kinetic analysis of the radiotracer binding. For each radiotracer, the parameters were determined by fitting the brain kinetics of the radiotracer using a two-tissue compartment model of the ligand-receptor interaction. Bidirectional transport studies with the same compounds as in in vivo studies were carried out using the in vitro cell-based human BBB model as well as Caco-2 cells. The in vitro cell-based human BBB model has important features of the BBB in vivo and is suitable for discriminating between CNS and non-CNS marketed drugs. A very good correlation (r 2 =0.90; P≤0.001) was demonstrated between in vitro BBB permeability and in vivo permeability coefficient. In contrast, a poor correlation (r 2 = 0.17) was obtained between Caco-2 data and in vivo human brain penetration. This study highlights the potential of this in vitro cell-based human BBB model in drug discovery and shows that it can be an extremely effective screening tool for CNS programs. (authors)

Individualized prediction of schizophrenia based on the whole-brain pattern of altered white matter tract integrity.

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Chen, Yu-Jen; Liu, Chih-Min; Hsu, Yung-Chin; Lo, Yu-Chun; Hwang, Tzung-Jeng; Hwu, Hai-Gwo; Lin, Yi-Tin; Tseng, Wen-Yih Isaac

2018-01-01

A schizophrenia diagnosis relies on characteristic symptoms identified by trained physicians, and is thus prone to subjectivity. This study developed a procedure for the individualized prediction of schizophrenia based on whole-brain patterns of altered white matter tract integrity. The study comprised training (108 patients and 144 controls) and testing (60 patients and 60 controls) groups. Male and female participants were comparable in each group and were analyzed separately. All participants underwent diffusion spectrum imaging of the head, and the data were analyzed using the tract-based automatic analysis method to generate a standardized two-dimensional array of white matter tract integrity, called the connectogram. Unique patterns in the connectogram that most accurately identified schizophrenia were systematically reviewed in the training group. Then, the diagnostic performance of the patterns was individually verified in the testing group by using receiver-operating characteristic curve analysis. The performance was high in men (accuracy = 0.85) and satisfactory in women (accuracy = 0.75). In men, the pattern was located in discrete fiber tracts, as has been consistently reported in the literature; by contrast, the pattern was widespread over all tracts in women. These distinct patterns suggest that there is a higher variability in the microstructural alterations in female patients than in male patients. The individualized prediction of schizophrenia is feasible based on the different whole-brain patterns of tract integrity. The optimal masks and their corresponding regions in the fiber tracts could serve as potential imaging biomarkers for schizophrenia. Hum Brain Mapp 39:575-587, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A Review of EEG-Based Brain-Computer Interfaces as Access Pathways for Individuals with Severe Disabilities

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Moghimi, Saba; Kushki, Azadeh; Guerguerian, Anne Marie; Chau, Tom

2013-01-01

Electroencephalography (EEG) is a non-invasive method for measuring brain activity and is a strong candidate for brain-computer interface (BCI) development. While BCIs can be used as a means of communication for individuals with severe disabilities, the majority of existing studies have reported BCI evaluations by able-bodied individuals.…

Nocardia Farcinica brain abscess in an immunocompetent old patient: A case report and review of literature

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Dinesh Mohan Chaudhari

2017-01-01

Full Text Available By definition, a brain abscess is an intraparenchymal collection of pus. Nocardia shows to have a special tropism for the neural tissue. Solitary abscess represents the most common manifestation in the central nervous system, accounting for 1%–2% of all cerebral abscesses. In this report, we present a case of primary multiple brain abscesses due to Nocardia farcinica in an immune competent patient. Early diagnosis and surgical intervention is significant for the patient.

Assessing paedophilia based on the haemodynamic brain response to face images

DEFF Research Database (Denmark)

Ponseti, Jorge; Granert, Oliver; Van Eimeren, Thilo

2016-01-01

that human face processing is tuned to sexual age preferences. This observation prompted us to test whether paedophilia can be inferred based on the haemodynamic brain responses to adult and child faces. METHODS: Twenty-four men sexually attracted to prepubescent boys or girls (paedophiles) and 32 men......OBJECTIVES: Objective assessment of sexual preferences may be of relevance in the treatment and prognosis of child sexual offenders. Previous research has indicated that this can be achieved by pattern classification of brain responses to sexual child and adult images. Our recent research showed...... sexually attracted to men or women (teleiophiles) were exposed to images of child and adult, male and female faces during a functional magnetic resonance imaging (fMRI) session. RESULTS: A cross-validated, automatic pattern classification algorithm of brain responses to facial stimuli yielded four...

Analysis of a human brain transcriptome map

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Greene Jonathan R

2002-04-01

Full Text Available Abstract Background Genome wide transcriptome maps can provide tools to identify candidate genes that are over-expressed or silenced in certain disease tissue and increase our understanding of the structure and organization of the genome. Expressed Sequence Tags (ESTs from the public dbEST and proprietary Incyte LifeSeq databases were used to derive a transcript map in conjunction with the working draft assembly of the human genome sequence. Results Examination of ESTs derived from brain tissues (excluding brain tumor tissues suggests that these genes are distributed on chromosomes in a non-random fashion. Some regions on the genome are dense with brain-enriched genes while some regions lack brain-enriched genes, suggesting a significant correlation between distribution of genes along the chromosome and tissue type. ESTs from brain tumor tissues have also been mapped to the human genome working draft. We reveal that some regions enriched in brain genes show a significant decrease in gene expression in brain tumors, and, conversely that some regions lacking in brain genes show an increased level of gene expression in brain tumors. Conclusions This report demonstrates a novel approach for tissue specific transcriptome mapping using EST-based quantitative assessment.

Personality Trait and Facial Expression Filter-Based Brain-Computer Interface

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Seongah Chin

2013-02-01

Full Text Available In this paper, we present technical approaches that bridge the gap in the research related to the use of brain-computer interfaces for entertainment and facial expressions. Such facial expressions that reflect an individual's personal traits can be used to better realize artificial facial expressions in a gaming environment based on a brain-computer interface. First, an emotion extraction filter is introduced in order to classify emotions on the basis of the users' brain signals in real time. Next, a personality trait filter is defined to classify extrovert and introvert types, which manifest as five traits: very extrovert, extrovert, medium, introvert and very introvert. In addition, facial expressions derived from expression rates are obtained by an extrovert-introvert fuzzy model through its defuzzification process. Finally, we confirm this validation via an analysis of the variance of the personality trait filter, a k-fold cross validation of the emotion extraction filter, an accuracy analysis, a user study of facial synthesis and a test case game.

Lower gingival squamous cell carcinoma with brain metastasis during long-term cetuximab treatment: A case report.