Ovulatory effects of three oral contraceptive regimens: a randomized, open-label, descriptive trial.

PubMed

Seidman, Larry; Kroll, Robin; Howard, Brandon; Ricciotti, Nancy; Hsieh, Jennifer; Weiss, Herman

2015-06-01

This study describes ovarian activity suppression of a 21/7-active low-dose combined oral contraceptive (COC) regimen that included only ethinyl estradiol (EE) during the traditional hormone-free interval (HFI) and two commercially available 28-day regimens, a 24/4 and a 21/7 regimen. The randomized, open-label, parallel-group descriptive study was conducted at two US sites. Healthy, reproductive-aged women (n=146) were randomized to one of three groups for three consecutive 28-day cycles, as follows: treatment 1 (n=39 completed): 21/7-active COC [21 days of 150 mcg desogestrel (DSG)/20 mcg EE, followed by 7 days of 10 mcg EE (DSG/EE+7 days EE)], treatment 2 (n=39 completed): 24 days of 3mg drospirenone (DRSP)/20 mcg EE, followed by 4 placebo (PBO)-pill days (DRSP/EE+4 days PBO) and treatment 3 (n=42 completed): 21 days of 100 mcg levonorgestrel (LNG)/20 mcg EE, followed by 7 PBO-pill days (LNG/EE+7 days PBO). The primary outcome was ovarian activity suppression assessed by transvaginal ultrasound and serum hormone concentrations and classified using the Hoogland and Skouby (H/S) method. Ovarian activity rate (H/S grade 4 or 5) was low for all three treatments: 0% [95% confidence interval (CI) 0-2.8] for DSG/EE+7 days EE, 1% (95% CI 0.2-5.2) for DRSP/EE+4days PBO and 1% (95% CI 0-3.9) for LNG/EE+7 days PBO. All three treatments showed similar suppression of serum progesterone, 17β-estradiol, follicle-stimulating hormone and luteinizing hormone levels. The 21/7-active low-dose COC regimen (DSG/EE+7 days EE) showed ovarian activity suppression that was similar to the 24/4 (DRSP/EE+4 days PBO) and 21/7 (LNG/EE+7days PBO) regimens. The 21/7-active low-dose COC regimen (DSG/EE+7 days EE) that included only EE during the traditional HFI showed suppression of ovarian follicular activity that was similar to the 24/4 (DRSP/EE+4days PBO) and the 21/7 (LNG/EE+7 days PBO) comparator regimens. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel ethinyl estradiol-beta-cyclodextrin clathrate formulation does not influence the relative bioavailability of ethinyl estradiol or coadministered drospirenone.

PubMed

Blode, Hartmut; Schürmann, Rolf; Benda, Norbert

2008-03-01

A new combined oral contraceptive formulation has been developed consisting of a beta-cyclodextrin (betadex) clathrate formulation of ethinyl estradiol in combination with drospirenone (EE-betadex clathrate/drsp). In this novel EE-betadex clathrate/drsp preparation, betadex serves as an inert complexing agent to enhance stability and shelf-life. The study was conducted to investigate the relative bioavailability and pharmacokinetic parameters of EE and drsp after oral administration of EE-betadex clathrate/drsp. This was an open-label, randomized, single-dose, three-period, three-treatment, crossover study conducted in 18 healthy postmenopausal women aged 45-75 years. The women received single oral doses of 40 mcg EE/6 mg drsp formulated as EE-betadex clathrate/drsp or EE/drsp (EE as a free steroid) tablets, or as a microcrystalline suspension on three separate occasions. Serum samples were collected for pharmacokinetic analyses. The relative bioavailability of EE and drsp after EE-betadex clathrate/drsp tablet administration was comparable with that achieved with the EE/drsp tablet (107% and 101%, respectively). In addition, the inclusion of EE in a betadex clathrate does not affect the pharmacokinetics of either EE or drsp. There were no safety concerns with any of the medications. The betadex clathrate formulation of EE, when combined with DRSP, does not affect the pharmacokinetics and relative bioavailability of either EE or drsp.

The predictive capacity of perceived expressed emotion as a dynamic entity of adolescents from the general community.

PubMed

Hale, William W; Raaijmakers, Quinten A W; van Hoof, Anne; Meeus, Wim H J

2011-06-01

In previous studies, it has been demonstrated that high parental expressed emotion (EE) is predictive of depressive, aggressive and delinquency symptoms of adolescents. Two issues have received much less prominence in EE research, these being studies of adolescent perceived EE and the measurement of the EE as a dynamic, developmental construct. This 4-year, three-wave, longitudinal study of perceived EE of adolescents from the general community examines if adolescent perceived EE measured with the traditional, one-measurement EE approach as well as adolescent perceived EE measured with a repeated measured, dynamic EE approach can predict adolescent depressive, aggressive and delinquency symptoms. Dutch adolescents (N = 285; 51% girls; M = 13 years) from the general community were prospectively studied annually for 4 years. At all waves, the adolescents completed the Level of Expressed Emotion (LEE) questionnaire and at the final wave also completed self-rated measures of depressive, aggressive and delinquent symptoms. Growth models were used to predict adolescent symptoms from adolescent perceived EE. Growth models significantly predicted adolescent depressive, aggressive and delinquency symptoms from adolescent perceived EE. This study of the LEE demonstrates that developmental characteristics of EE are predictive of adolescents' symptoms. These findings hold implications for current EE intervention therapies and the conceptualization of EE.

A comparison of the pharmacokinetic profile of an ascending-dose, extended-regimen combined oral contraceptive to those of other extended regimens.

PubMed

Darwish, Mona; Bond, Mary; Ricciotti, Nancy; Hsieh, Jennifer; Fiedler-Kelly, Jill; Grasela, Thaddeus

2014-11-01

Quartette (levonorgestrel [LNG]/ethinyl estradiol [EE] and EE) is an ascending-dose, extended-regimen combined oral contraceptive (COC) that consists of a constant dose of LNG 150 µg on days 1 to 84 with EE 20 µg on days 1 to 42, 25 µg on days 43 to 63, 30 µg on days 64 to 84, and 10 µg of EE monotherapy on days 85 to 91. A population pharmacokinetic (PK) model for EE was developed using nonlinear mixed-effects modeling to characterize the PK profile of EE administered in Quartette and other extended-regimen LNG/EE COCs. Model-predicted plasma concentration-time profiles demonstrated a stepwise increase in systemic exposure to EE during the first 84 days of the cycle following each EE dose change. Lower concentrations of EE were noted during the final 7-day period of EE 10 µg. Gradual increases in EE seen with Quartette may decrease the incidence of unscheduled bleeding frequently observed during early cycles of extended-regimen COCs. © The Author(s) 2014.

Effect of protein overfeeding on energy expenditure measured in a metabolic chamber.

PubMed

Bray, George A; Redman, Leanne M; de Jonge, Lilian; Covington, Jeffrey; Rood, Jennifer; Brock, Courtney; Mancuso, Susan; Martin, Corby K; Smith, Steven R

2015-03-01

Energy expenditure (EE) increases with overfeeding, but it is unclear how rapidly this is related to changes in body composition, increased body weight, or diet. The objective was to quantify the effects of excess energy from fat or protein on energy expenditure of men and women living in a metabolic chamber. We conducted a randomized controlled trial in 25 participants who ate ∼40% excess energy for 56 d from 5%, 15%, or 25% protein diets. Twenty-four-hour EE (24EE) and sleeping EE (SleepEE) were measured on days 1, 14, and 56 of overfeeding and on day 57 while consuming the baseline diet (usually day 57). Metabolic and molecular markers of muscle metabolism were measured in skeletal muscle biopsy specimens. In the low-protein diet group whose excess energy was fat, the 24EE and SleepEE did not increase during the first day of overfeeding. When extra energy contained protein, both 24EE and SleepEE increased in relation to protein intake (r = 0.50, P = 0.02). The 24EE over 8 wk in all 3 groups was correlated with protein intake (r = 0.60, P = 0.004) but not energy intake (r = 0.16; P = 0.70). SleepEE was unchanged by overfeeding in the low-protein diet group, and baseline surface area predicted increased 24EE in this group. Protein and fat oxidation were reciprocally related during overfeeding. Observed 24EE was higher than predicted on days 1 (P ≤ 0.05), 14 (P = 0.0001), and 56 (P = 0.0007). There was no relation between change in fat mass and change in EE. Excess energy, as fat, does not acutely increase 24EE, which rises slowly as body weight increases. Excess energy as protein acutely stimulates 24EE and SleepEE. The strongest relation with change in 24EE was the change in energy expenditure in tissue other than muscle or fat-free mass. © 2015 American Society for Nutrition.

Pharmacokinetic overview of ethinyl estradiol dose and bioavailability using two transdermal contraceptive systems and a standard combined oral contraceptive

PubMed Central

Hofmann, Birte; Reinecke, Isabel; Schuett, Barbara; Merz, Martin; Zurth, Christian

2014-01-01

Objective: To determine the relative bioavailability of ethinyl estradiol (EE) and gestodene (GSD) after application of a novel transdermal contraceptive patch vs. a standard combined oral contraceptive (COC) pill (study 1), and to evaluate the pharmacokinetics (PK) of EE after application of the EE/GSD patch compared with an EE/norelgestromin (NGMN) patch (study 2). Materials: Participants were healthy, non-obese women aged 18 – 45 years (study 1) or 18 – 35 years (study 2). Compositions of study treatments were as follows: 0.55 mg EE/2.1 mg GSD (EE/GSD patch); 0.02 mg EE/0.075 mg GSD (standard COC); 0.6 mg EE/6 mg NGMN (EE/NGMN patch). Methods: In study 1, which consisted of 3 treatment periods (each followed by 7 patch- or pill-free days), treatments were administered in one of two randomized orders: either P–M–E (EE/GSD patch (P) every 7 days for 28 days → COC (M) once-daily for 21 days → two 7-day patch-wearing periods followed by one 10-day patch-wearing phase (E)), or the same treatments administered in sequence M–P–E. For study 2, participants received either the EE/GSD patch or EE/NGMN patch for seven treatment cycles (one patch per week for 3 weeks followed by a 7-day patch-free interval). Results: In study 1, average daily exposure to EE was similar for treatments P and M; the mean daily area under the concentration-time curve (AUC) ratio of treatment P vs. treatment M for EE was 1.06 (90% confidence interval (CI): 0.964 – 1.16), indicating average daily delivery similar to oral administration of 0.019 – 0.023 mg EE. For unbound GSD, average daily exposure was lower for treatment P vs. treatment M. The mean AUC ratio of treatment P vs. treatment M for unbound GSD was 0.820 (90% CI: 0.760 – 0.885), indicating average daily delivery from the patch of 0.057 – 0.066 mg GSD. Prolonged patch wearing did not result in a distinct decline in GSD and EE serum concentrations. In study 2, AUC at steady state (AUC0–168,ss), average steady-state serum concentration, and maximum steady-state serum concentration for EE was 2.0 – 2.7-fold higher for the EE/NGMN patch vs. the EE/GSD patch. The EE/GSD patch was well tolerated in both studies. Conclusions: Based on the 90% CI of the AUC ratio of oral treatment vs. patch application for unbound GSD and EE, the daily doses of GSD and EE released from the EE/GSD patch over the 7-day application period provided the same systemic exposure as those recorded after daily oral administration of a COC containing 0.02 mg EE and 0.06 mg GSD. The EE/GSD patch showed reduced EE exposure compared with the EE/NGMN patch. Together with its good tolerability, these properties support the EE/GSD patch as an effective and well-tolerated alternative to available transdermal and oral contraceptives. PMID:25295716

Thromboembolic adverse event study of combined estrogen-progestin preparations using Japanese Adverse Drug Event Report database

PubMed Central

Hasegawa, Shiori; Matsui, Toshinobu; Hane, Yuuki; Abe, Junko; Hatahira, Haruna; Motooka, Yumi; Sasaoka, Sayaka; Fukuda, Akiho; Naganuma, Misa; Hirade, Kouseki; Takahashi, Yukiko; Kinosada, Yasutomi

2017-01-01

Combined estrogen-progestin preparations (CEPs) are associated with thromboembolic (TE) side effects. The aim of this study was to evaluate the incidence of TE using the Japanese Adverse Drug Event Report (JADER) database. Adverse events recorded from April 2004 to November 2014 in the JADER database were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website (www.pmda.go.jp). We calculated the reporting odds ratios (RORs) of suspected CEPs, analyzed the time-to-onset profile, and assessed the hazard type using Weibull shape parameter (WSP). Furthermore, we used the applied association rule mining technique to discover undetected relationships such as the possible risk factors. The total number of reported cases in the JADER contained was 338,224. The RORs (95% confidential interval, CI) of drospirenone combined with ethinyl estradiol (EE, Dro-EE), norethisterone with EE (Ne-EE), levonorgestrel with EE (Lev-EE), desogestrel with EE (Des-EE), and norgestrel with EE (Nor-EE) were 56.2 (44.3–71.4), 29.1 (23.5–35.9), 42.9 (32.3–57.0), 44.7 (32.7–61.1), and 38.6 (26.3–56.7), respectively. The medians (25%–75%) of the time-to-onset of Dro-EE, Ne-EE, Lev-EE, Des-EE, and Nor-EE were 150.0 (75.3–314.0), 128.0 (27.0–279.0), 204.0 (44.0–660.0), 142.0 (41.3–344.0), and 16.5 (8.8–32.0) days, respectively. The 95% CIs of the WSP-β for Ne-EE, Lev-EE, and Nor-EE were lower and excluded 1. Association rule mining indicated that patients with anemia had a potential risk of developing a TE when using CEPs. Our results suggest that it is important to monitor patients administered CEP for TE. Careful observation is recommended, especially for those using Nor-EE, and this information may be useful for efficient therapeutic planning. PMID:28732067

Heterogeneity in Short Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Norris, Jay P.; Gehrels Neil; Scargle, Jeffrey D.

2011-01-01

We analyze the Swift/BAT sample of short gamma-ray bursts, using an objective Bayesian Block procedure to extract temporal descriptors of the bursts' initial pulse complexes (IPCs). The sample comprises 12 and 41 bursts with and without extended emission (EE) components, respectively. IPCs of non-EE bursts are dominated by single pulse structures, while EE bursts tend to have two or more pulse structures. The medians of characteristic timescales - durations, pulse structure widths, and peak intervals - for EE bursts are factors of approx 2-3 longer than for non-EE bursts. A trend previously reported by Hakkila and colleagues unifying long and short bursts - the anti-correlation of pulse intensity and width - continues in the two short burst groups, with non-EE bursts extending to more intense, narrower pulses. In addition we find that preceding and succeeding pulse intensities are anti-correlated with pulse interval. We also examine the short burst X-ray afterglows as observed by the Swift/XRT. The median flux of the initial XRT detections for EE bursts (approx 6 X 10(exp -10) erg / sq cm/ s) is approx > 20 x brighter than for non-EE bursts, and the median X-ray afterglow duration for EE bursts (approx 60,000 s) is approx 30 x longer than for non-EE bursts. The tendency for EE bursts toward longer prompt-emission timescales and higher initial X-ray afterglow fluxes implies larger energy injections powering the afterglows. The longer-lasting X-ray afterglows of EE bursts may suggest that a significant fraction explode into more dense environments than non-EE bursts, or that the sometimes-dominant EE component efficiently p()wers the afterglow. Combined, these results favor different progenitors for EE and non-EE short bursts.

Heterogeneity in Short Gamma-Ray Bursts

NASA Astrophysics Data System (ADS)

Norris, Jay P.; Gehrels, Neil; Scargle, Jeffrey D.

2011-07-01

We analyze the Swift/BAT sample of short gamma-ray bursts, using an objective Bayesian Block procedure to extract temporal descriptors of the bursts' initial pulse complexes (IPCs). The sample is comprised of 12 and 41 bursts with and without extended emission (EE) components, respectively. IPCs of non-EE bursts are dominated by single pulse structures, while EE bursts tend to have two or more pulse structures. The medians of characteristic timescales—durations, pulse structure widths, and peak intervals—for EE bursts are factors of ~2-3 longer than for non-EE bursts. A trend previously reported by Hakkila and colleagues unifying long and short bursts—the anti-correlation of pulse intensity and width—continues in the two short burst groups, with non-EE bursts extending to more intense, narrower pulses. In addition, we find that preceding and succeeding pulse intensities are anti-correlated with pulse interval. We also examine the short burst X-ray afterglows as observed by the Swift/X-Ray Telescope (XRT). The median flux of the initial XRT detections for EE bursts (~6×10-10 erg cm-2 s-1) is gsim20× brighter than for non-EE bursts, and the median X-ray afterglow duration for EE bursts (~60,000 s) is ~30× longer than for non-EE bursts. The tendency for EE bursts toward longer prompt-emission timescales and higher initial X-ray afterglow fluxes implies larger energy injections powering the afterglows. The longer-lasting X-ray afterglows of EE bursts may suggest that a significant fraction explode into denser environments than non-EE bursts, or that the sometimes-dominant EE component efficiently powers the afterglow. Combined, these results favor different progenitors for EE and non-EE short bursts.

No evidence that environmental enrichment during rearing protects against cocaine behavioral effects but as an intervention reduces an already established cocaine conditioned place preference.

PubMed

Galaj, E; Shukur, A; Manuszak, M; Newman, K; Ranaldi, R

2017-05-01

Environmental enrichment (EE) produces differential effects on psychostimulant-related behaviors. Therefore, we investigated whether the timing of EE exposure - during rearing and before cocaine exposure versus in adulthood and after cocaine exposure might be a determining factor. In Experiment 1, rats reared with EE or not (non-EE) were conditioned with cocaine (5, 10 or 20mg/kg) in one compartment of a CPP apparatus and saline in the other, and later tested for cocaine CPP. In Experiment 2, locomotor activity in response to repeated injections of saline or cocaine was measured in rats raised with EE or non-EE. In Experiment 3 we measured the effects of EE or non-EE during rearing on food-based conditioned approach learning. In Experiment 4, rats were exposed to cocaine CPP conditioning then underwent 60days of EE or non-EE treatment after which they were tested for cocaine CPP. Our results show that rearing in EE did not reduce cocaine CPP or cocaine-induced locomotor activity (Experiments 1 and 2) but significantly facilitated conditioned approach learning (Experiment 3). On the other hand, EE treatment introduced after cocaine conditioning significantly reduced the expression of cocaine CPP (Experiment 4). These findings suggest that EE does not protect against cocaine's rewarding and stimulant effects but can reduce already established cocaine effects, suggesting that EE might be an effective treatment for cocaine addiction-related behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of oral contraceptives on androgen levels and their relevance to premenstrual mood and sexual interest: a comparison of two triphasic formulations containing norgestimate and either 35 or 25 microg of ethinyl estradiol.

PubMed

Greco, Teri; Graham, Cynthia A; Bancroft, John; Tanner, Amanda; Doll, Helen A

2007-07-01

This study compared two oral contraceptives (OCs) with the same triphasic regimen of progestin (norgestimate 0.18, 0.215 and 0.25 mg) but differing doses of ethinyl estradiol (EE) - 25 and 35 microg EE - in their effects on androgens, mood and sexual interest in women starting on OCs. Total testosterone (T), free testosterone (FT), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone sulphate (DHEA-S), together with measures of mood [Beck Depression Inventory (BDI)], sexual interest [Dyadic and Solitary subscales of the Sexual Desire Inventory (SDI)] and self-reported side effects were assessed before starting on the OC and again after 3 months of use. Sixty women, all university students, were randomized to receive either the 25 microg EE (N/EE25) or the 35 microg EE (N/EE35) pill; 12 women discontinued, leaving 48 who completed the 3-month study. Their mean age was 19.7 years (18-30) and they were predominantly white and single. Both OCs produced reductions in mean T [N/EE35: from 1.33 to 0.60 nmol/L, p<.001; N/EE25: from 1.12 to 1.02 nmol/L; nonsignificant (NS)] and FT (N/EE35: from 41.3 to 4.4 pmol/L, p<.001; N/EE25: from 25.4 to 7.9 pmol/L, p<.01), but the reduction in both T and FT was significantly greater with the higher EE dose (N/EE35) (p=.05 and p=.03, respectively). DHEA-S was also reduced with both formulations (N/EE35: from 7.26 to 5.22 micromol/L); N/EE25: from 7.50 to 5.39 micromol/L), although the reduction was only significant in the N/EE35 group (p<.02). Considerable variability in changes in mood was evident with both OCs, with some women showing predominantly negative effects (10 in N/EE35, 5 in N/EE25); others, positive effects (9 in N/EE35, 17 in N/EE25) and some, no change (four in each group). Women using N/EE25 were significantly more likely to show improvement in premenstrual mood than those in the N/EE35 group (p<.02), although there was no correlation between changes in BDI and FT or DHEA-S. Sexual interest scores did not change significantly from baseline to posttreatment with either OC (N/EE35: dyadic, from 40.5 to 39.6, NS; solitary, from 5.9 to 6.4, NS; N/EE25: dyadic, from 36.7 to 37.0, NS; solitary, from 5.0 to 4.2, NS). The lower EE pill reduced FT less and was associated with greater improvement in premenstrual mood. A causal relation between these two effects is uncertain.

Predicting the implementation of environmental education in Indiana K--8 schools

NASA Astrophysics Data System (ADS)

Yang, Li-Ling

The purpose of this study was to identify the factors from the literature that influence teachers' implementation of environmental education (EE), and to predict the implementation of EE in the Indiana K--8 Schools by knowledge of these factors. By adapting two earlier instruments, a complete EE assessment instrument was developed, consisting of scales measuring teachers' implementation of EE, their pre-/in-service environmental training, their attitudes toward and competencies in teaching EE, their perceived barriers in teaching EE, and their significant life experiences related to the environment or EE. A questionnaire was sent to 1,200 randomly selected K--8 teachers in public schools throughout Indiana in April 2003, and 385 completed surveys were returned (32.1% return rate). The demographic characteristics of the respondents and the Indiana teacher population were found to be similar. Thus, the results from this study can be generalized to the Indiana teacher population. The construct validity and reliability of each scale were examined after the completion and return of the questionnaires by using factor analysis, item-test correlation analysis, and ANOVA, and also by assessing their alpha indices. It was found that all nine scales were homogeneous, valid, and reliable. Multiple regression analysis was calculated to predict the level of EE implementation in Indiana K--8 schools. Regression analyses indicated that the extent of the teachers' exposure to EE during their pre- and in-service training, the teachers' attitudes toward and competencies in teaching EE, and the barrier "EE not relevant to what I teach" were significant in the full model. This model accounted for 63% of the variance in the teachers' implementation of EE. The teachers' attitudes toward EE had the greatest effect on the teachers' EE implementation when compared to the other significant predictors in the model. The net effects of the extent of the teachers' pre-service and in-service exposure to EE, their competencies in teaching EE, and the barrier "EE not relevant to what I teach" are approximately the same. The findings of this study provide educational agencies, institutions and administrators with the information that is required to improve EE implementation in Indiana K--8 schools and teacher education programs.

Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates.

PubMed Central

Pandey, S C; Davis, J M; Pandey, G N

1995-01-01

Serotonergic neurotransmission represents a complex mechanism involving pre- and post-synaptic events and distinct 5-HT receptor subtypes. Serotonin (5-HT) receptors have been classified into several categories, and they are termed as 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 type receptors. 5-HT1 receptors have been further subdivided into 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F. 5-HT2 receptors have been divided into 5-HT2A, 5-HT2B and 5-HT2C receptors. All 5-HT2 receptor subtypes are linked to the multifunctional phosphoinositide (PI) signalling system. 5-HT3 receptors are considered ion-gated receptors and are also linked to the PI signalling system by an unknown mechanism. The 5-HT2A receptor subtype is the most widely studied of the 5-HT receptors in psychiatric disorders (for example, suicide, depression and schizophrenia) as well as in relation to the mechanism of action of antidepressant drugs. The roles of 5-HT2C and 5-HT3 receptors in psychiatric disorders are less clear. These 5-HT receptors also play an important role in alcoholism. It has been shown that 5-HT2A, 5-HT2C and 5-HT3 antagonists cause attenuation of alcohol intake in animals and humans. However, the exact mechanisms are unknown. The recent cloning of the cDNAs for 5-HT2A, 5-HT2C and 5-HT3 receptors provides the opportunity to explore the molecular mechanisms responsible for the alterations in these receptors during illness as well as pharmacotherapy. This review article will focus on the current research into the pharmacological properties, molecular biology, and clinical correlates of 5-HT2A, 5-HT2C and 5-HT3 receptors. PMID:7786883

Stereochemical diversity in lignan biosynthesis of Arctium lappa L.

PubMed

Suzuki, Shiro; Umezawa, Toshiaki; Shimada, Mikio

2002-06-01

The stereochemistry of lignan biosynthesis in Arctium lappa L. is regulated organ-specifically. (+)-Secoisolariciresinol [81% enantiomeric excess (e.e.)] was isolated from A. lappa petioles. In sharp contrast, lignans whose predominant enantiomers have the opposite absolute configuration to that of (+)-secoisolariciresinol [i.e., (-)-matairesinol (>99% e.e.), (-)-arctigenin (>99% e.e.), and (-)-secoisolariciresinol (65% e.e.)] were isolated from seeds of the species. The stereochemical diversity of secoisolariciresinol was demonstrated with enzyme preparations from A. lappa petioles and seeds. Thus, a petiole enzyme preparation catalyzed the formation of (+)-pinoresinol (33% e.e.), (+)-lariciresinol (30% e.e.), and (+)-secoisolariciresinol (20% e.e.) from achiral coniferyl alcohol in the presence of NADPH and H202, whereas that from ripening seeds catalyzed the formation of (-)-pinoresinol (22% e.e.), (-)-lariciresinol (>99% e.e.), and (-)-secoisolariciresinol (38% e.e.) under the same conditions. In addition, the ripening seed enzyme preparation mediated the selective formation of the optically pure (>99% e.e.) (-)-enantiomer of matairesinol from racemic (+/-)-secoisolariciresinols in the presence of NADP. These results indicate that the stereochemical mechanism for lignan biosynthesis in A. lappa varies with organs, suggesting that multiple lignan-synthesizing isozymes are involved in the stereochemical control of lignan formation in A. lappa.

A Comparison of Energy Expenditure Estimation of Several Physical Activity Monitors

PubMed Central

Dannecker, Kathryn L.; Sazonova, Nadezhda A.; Melanson, Edward L.; Sazonov, Edward S.; Browning, Raymond C.

2013-01-01

Accurately and precisely estimating free-living energy expenditure (EE) is important for monitoring energy balance and quantifying physical activity. Recently, single and multi-sensor devices have been developed that can classify physical activities, potentially resulting in improved estimates of EE. PURPOSE To determine the validity of EE estimation of a footwear-based physical activity monitor and to compare this validity against a variety of research and consumer physical activity monitors. METHODS Nineteen healthy young adults (10 male, 9 female), completed a four-hour stay in a room calorimeter. Participants wore a footwear-based physical activity monitor, as well as Actical, Actigraph, IDEEA, DirectLife and Fitbit devices. Each individual performed a series of postures/activities. We developed models to estimate EE from the footwear-based device, and we used the manufacturer's software to estimate EE for all other devices. RESULTS Estimated EE using the shoe-based device was not significantly different than measured EE (476(20) vs. 478(18) kcal) (Mean (SE)), respectively, and had a root mean square error (RMSE) of (29.6 kcal (6.2%)). The IDEEA and DirectLlife estimates of EE were not significantly different than the measured EE but the Actigraph and Fitbit devices significantly underestimated EE. Root mean square errors were 93.5 (19%), 62.1 kcal (14%), 88.2 kcal (18%), 136.6 kcal (27%), 130.1 kcal (26%), and 143.2 kcal (28%) for Actical, DirectLife, IDEEA, Actigraph and Fitbit respectively. CONCLUSIONS The shoe based physical activity monitor provides a valid estimate of EE while the other physical activity monitors tested have a wide range of validity when estimating EE. Our results also demonstrate that estimating EE based on classification of physical activities can be more accurate and precise than estimating EE based on total physical activity. PMID:23669877

[The pharmacological basis of the serotonin system: Application to antidepressant response].

PubMed

David, D J; Gardier, A M

2016-06-01

If serotonin (5-hydroxytryptamin [5-HT]) is well known for its role in mood regulation, it also impacts numerous physiological functions at periphery. Serotonin is synthetized at the periphery into the gut by intestinal enterochromaffin cells and in the central nervous system (CNS) in the raphe nucleus from the essential amino acid tryptophan. Physiological effects of 5-HT are mediated by about 15 serotoninergic receptors grouped into seven broad families (5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7 receptor families). Except 5-HT3 receptor, a ligand-gated ion channels, all the others are G protein-coupled receptors. Serotonin's homeostasis involves serotoninergic autoreceptor such as 5-HT1A, 5-HT1B, 5-HT1D, the enzymatic degradation of serotonin by monoamine oxidase A (MAO-A), and a transporter (serotoninergic transporter [SERT]). In the CNS, the SERT is a key target for various antidepressant drugs such as Selective Serotonin Reuptake Inhibitors (SSRI), Serotonin Norepinephrin Reuptake Inhibitors (SNRI) and tricyclics family. However, antidepressant activity of SERT inhibitors is not directly mediated by the SERT inhibition, but a consequence of postsynaptic 5-HT receptor activation following the increase in 5-HT levels in the synaptic cleft. In pharmacology, SSRIs are defined as indirect agonist of postsynaptic receptor. Among all the 5-HT receptors, 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2B and 5-HT4 receptors activation would mediate antidepressant effects. In the meanwhile, 5-HT2A, 5-HT2C, 5-HT3, 5-HT6 and 5-HT7 receptors activation would induce opposite effects. The best serotoninergic antidepressant would directly activate 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2B and 5-HT4 and would block 5-HT2A, 5-HT2C, 5-HT3, 5-HT6 and 5-HT7 receptor. If the chemical synthesis of such a compound may be compromised, SERT inhibition associated with the blockade of some but not all 5-HT receptor could shorten onset of action and/or improve antidepressant efficacy on the overall symptomatology of depression. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Eating when depressed, anxious, bored, or happy: Are emotional eating types associated with unique psychological and physical health correlates?

PubMed

Braden, Abby; Musher-Eizenman, Dara; Watford, Tanya; Emley, Elizabeth

2018-06-01

The majority of research on emotional eating has examined general emotional eating, to the exclusion of more distinct emotions such as boredom and positive emotions. The current study aimed to examine whether specific types of emotional eating (i.e., eating in response to depression (EE-D), anxiety/anger (EE-A), boredom (EE-B), and positive emotions (EE-P)) were related to a range of psychological (i.e., global psychological well-being, eating disorder symptoms, emotion regulation) and physical health variables. A sample of adults (n = 189) with overweight/obesity were recruited via Amazon Mechanical Turk. Participants self-reported height and weight and completed a battery of questionnaires. Correlational analyses showed that more frequent EE-D, EE-A, and EE-B were related to poorer psychological well-being, greater eating disorder symptoms, and more difficulties with emotion regulation. EE-P was not significantly related to outcome variables. In regression analyses, eating in response to depression (EE-D) was the type of emotional eating most closely related to psychological well-being, eating disorder symptoms, and emotion regulation difficulties. Exploratory analyses revealed associations between EE-D, EE-A, and EE-B and facets of emotion regulation and specific disordered eating symptoms. Findings suggest that unique patterns exist between specific types of emotional eating and psychological outcomes. Copyright © 2018 Elsevier Ltd. All rights reserved.

An E/e' ratio on echocardiography predicts the existence of left atrial low-voltage areas and poor outcomes after catheter ablation for atrial fibrillation.

PubMed

Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Sunaga, Akihiro; Tsujimura, Takuya; Matsuda, Yasuhiro; Ohashi, Takuya; Uematsu, Masaaki

2018-05-01

An elevated left atrial pressure has been reported to play an important role in the development of atrial remodelling in atrial fibrillation (AF) patients. The study aimed at elucidating the association between the diastolic early transmitral flow velocity/mitral annular velocity (E/e', a non-invasive surrogate of left atrial pressure) and left atrial low-voltage-area existence, and the prognostic impact of the E/e' on procedural outcomes in patients undergoing AF ablation. Total of 215 consecutive patients were divided into 3 groups based on the estimated left atrial pressure: normal (E/e' < 8.0, n = 58), undetermined (E/e' = 8.0-14.0, n = 114), and elevated (E/e' > 14.0, n = 43). Left atrial endocardial voltage mapping was performed following pulmonary vein isolation. Patients with a high E/e' more frequently had low-voltage areas (E/e' < 8.0, 31%, E/e' = 8.0-14.0, 35%; E/e' > 14.0, 67%; P = 0.0001). After adjusting for other correlates, a high E/e' was an independent predictor of low-voltage-area existence (HR = 1.11, 95% CI = 1.02-1.21, P = 0.017). During a mean follow-up period of 12 ± 6 months, recurrent atrial tachyarrhythmias occurred in 22 (10%) patients after multiple (1.4 ± 0.5) procedures. Patients with an E/e' > 14 had more frequent recurrent atrial tachyarrhythmias after multiple ablation procedures than those with an E/e' ≤ 14 (23% vs. 7%, P = 0.001). A high E/e' obtained by pre-ablation echocardiography was associated with a left atrial arrhythmogenic substrate in patients undergoing AF ablation. Furthermore, a high E/e' predicted poor procedural outcomes after pulmonary vein isolation.

Are Everolimus-Eluting Stents Associated With Better Clinical Outcomes Compared to Other Drug-Eluting Stents in Patients With Type 2 Diabetes Mellitus?

PubMed Central

Bundhun, Pravesh Kumar; Pursun, Manish; Teeluck, Abhishek Rishikesh; Long, Man-Yun

2016-01-01

Abstract Controversies still exist with the use of Everolimus-Eluting Stents (EES) compared to other Drug-Eluting Stents (DES) in patients with Type 2 Diabetes Mellitus (T2DM). Therefore, in order to solve this issue, we aim to compare the 1-year adverse clinical outcomes between EES and non-EE DES with a larger number of patients with T2DM. Medline, EMBASE, PubMed databases, as well as the Cochrane library were searched for randomized controlled trials (RCTs) and observational studies (OS) comparing EES and non-EE DES in patients with T2DM. One-year adverse outcomes were considered as the clinical endpoints in this study. Odd ratios (OR) with 95% confidence interval (CI) were used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3. Ten studies consisting of a total of 11,981 patients with T2DM (6800 patients in the EES group and 5181 in the non-EE DES group) were included in this meta-analysis. EES were associated with a significantly lower major adverse cardiac events (MACEs) with OR: 0.83, 95% CI: 0.70–0.98, P = 0.03. Revascularization including target vessel revascularization (TVR) and target lesion revascularization (TLR) were also significantly lower in the EES group with OR: 0.62, 95% CI: 0.40–0.94, P = 0.03 and OR: 0.74, 95% CI: 0.57–0.95, P = 0.02, respectively. Also, a significantly lower rate of stent thrombosis with OR: 0.63, 95% CI: 0.46–0.86, P = 0.003 was observed in the EES group. However, a similar mortality rate was reported between the EES and non-EE DES groups. During this 1-year follow-up period, EES were associated with significantly better clinical outcomes compared to non-EE DES in patients suffering from T2DM. However, further research comparing EES with non-EE DES in insulin-treated and noninsulin-treated patients with T2DM are recommended. PMID:27057888

31 CFR 351.6 - When may I redeem my Series EE savings bond?

Code of Federal Regulations, 2014 CFR

2014-07-01

... before January 1, 2003. You may redeem your Series EE savings bond at any time beginning six months after... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false When may I redeem my Series EE... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds...

31 CFR 351.6 - When may I redeem my Series EE savings bond?

Code of Federal Regulations, 2010 CFR

2010-07-01

... before January 1, 2003. You may redeem your Series EE savings bond at any time beginning six months after... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false When may I redeem my Series EE... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds...

31 CFR 351.70 - How are redemption values calculated for book-entry Series EE savings bonds?

Code of Federal Regulations, 2010 CFR

2010-07-01

... for book-entry Series EE savings bonds? 351.70 Section 351.70 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.70 How are redemption values calculated for book-entry Series EE savings bonds? We base current redemption...

31 CFR 351.70 - How are redemption values calculated for book-entry Series EE savings bonds?

Code of Federal Regulations, 2011 CFR

2011-07-01

... for book-entry Series EE savings bonds? 351.70 Section 351.70 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.70 How are redemption values calculated for book-entry Series EE savings bonds? We base current redemption...

The number distribution of weak Explosive Events observed by SUMER/SoHO

NASA Astrophysics Data System (ADS)

Mendoza-Torres, J. E.

2016-11-01

Explosive Events (EEs) observed by SUMER on SoHO at the 1393.8 Å Si IV line are analyzed. We look for EEs to study their number distribution at low energies. Eight data sets taken in June 1996 in raster observations are used. In these observations a field on the solar disk is scanned several times during a period considerably longer than the typical timelife of an EE. To look for EE, we first identified the maxima and locations of spectral line increases. The maxima that took place at inner locations of the rastered fields were considered as possible EEs. From this sample, the cases where the spectral line underwent Doppler shifts at most ±3″ from the location of the maximum were considered EEs. After a selection, the region within 5″ of the event was ignored for 5 min either side of the EE in order to conclusively select a different maxima. Based on the analysis of the locations of EEs, it was seen that the more intense EEs tend to take place at given regions while at the intermediate regions the observed EEs are less intense. Therefore we refer to them as Regions of Enhanced Emission (REE) and Quiet Regions (QR), respectively. The width of the REE regions, as seen in North-South direction is about 10-30″. In this work, a total of 487 EEs are analyzed, 266 at REE and 221 at QR. Also, Histograms are made of the maxima of the amplitude of the spectral line during EEs at both REE and QR. At the Histogram for EEs at QR the number grows as the flux decreases with a slope of -1.8. For EEs at REE the Histogram has a maximum about 1 Watts m-2 sr-1 Å-1 with a high energy slope of about -1.6. These numbers are both below the value required to give an important input of energy for coronal heating, as analyzed in the case of microflares (Hudson, 1991). The averages of the maxima of EEs at each set for the REE and QR are computed. The scatter plot of the average values indicates that there is a linear relation between them and the maximum amplitudes of EEs at REE are about two times larger than the amplitudes for EEs at QR.

The concomitant prescribing of ethinyl estradiol/drospirenone and potentially interacting drugs.

PubMed

McAdams, Mara; Staffa, Judy A; Dal Pan, Gerald J

2007-10-01

Ethinyl estradiol 0.03 mg/drospirenone 3 mg (EE/DRSP) contains a progestin drospirenone with antimineralocorticoid properties that may cause potassium retention leading to hyperkalemia. We estimated the percentage of EE/DRSP users prescribed concomitant potassium-sparing drugs [nonsteroidal antiinflammatory drugs, diuretics, angiotensin-converting enzyme inhibitors (with diuretics), angiotensin II agonists (with diuretics), and potassium chloride] between January 1, 2002, and March 31, 2005. We analyzed a population-based data set of 62,527 EE/DRSP users (Dimension Rx, Caremark). We compared the fill date and end date for each prescription (Rx) for an interacting drug to the start and end date for each EE/DRSP episode (linked Rxs). If a day of an interacting Rx overlapped with an EE/DRSP episode, concomitant prescribing was recorded. A total of 17.6% of the women concomitantly used EE/DRSP and an interacting drug. Twenty-nine percent of concomitant use occurred within a month of EE/DRSP initiation. Nonsteroidal antiinflammatory drugs and diuretics were most frequently used concomitantly with EE/DRSP. Forty percent of the women with concomitant use were 35 yearsof age or older at EE/DRSP initiation compared with 29% without concomitant use (p<.001). Obstetricians/gynecologists and family practitioners were the most common prescribers of EE/DRSP and potassium-sparing drugs, respectively. Concomitant prescribing of EE/DRSP and potassium-sparing drugs occurred frequently in our study population. As EE/DRSP becomes more widely used, physicians prescribing it should monitor patients for potassium-sparing drug use.

31 CFR 351.6 - When may I redeem my Series EE savings bond?

Code of Federal Regulations, 2012 CFR

2012-07-01

... before January 1, 2003. You may redeem your Series EE savings bond at any time beginning six months after... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false When may I redeem my Series EE savings... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds...

31 CFR 351.6 - When may I redeem my Series EE savings bond?

Code of Federal Regulations, 2013 CFR

2013-07-01

... before January 1, 2003. You may redeem your Series EE savings bond at any time beginning six months after... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false When may I redeem my Series EE savings... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds...

31 CFR 351.6 - When may I redeem my Series EE savings bond?

Code of Federal Regulations, 2011 CFR

2011-07-01

... before January 1, 2003. You may redeem your Series EE savings bond at any time beginning six months after... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false When may I redeem my Series EE savings... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds...

31 CFR 351.61 - What are the denominations and prices of book-entry Series EE savings bonds?

Code of Federal Regulations, 2011 CFR

2011-07-01

... of book-entry Series EE savings bonds? 351.61 Section 351.61 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.61 What are the denominations and prices of book-entry Series EE savings bonds? Book-entry bonds are...

31 CFR 351.63 - How are redemption payments made for my redeemed book-entry Series EE savings bonds?

Code of Federal Regulations, 2010 CFR

2010-07-01

... my redeemed book-entry Series EE savings bonds? 351.63 Section 351.63 Money and Finance: Treasury... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.63 How are redemption payments made for my redeemed book-entry Series EE savings bonds? We will make...

31 CFR 351.61 - What are the denominations and prices of book-entry Series EE savings bonds?

Code of Federal Regulations, 2010 CFR

2010-07-01

... of book-entry Series EE savings bonds? 351.61 Section 351.61 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.61 What are the denominations and prices of book-entry Series EE savings bonds? Book-entry bonds are...

31 CFR 351.63 - How are redemption payments made for my redeemed book-entry Series EE savings bonds?

Code of Federal Regulations, 2011 CFR

2011-07-01

... my redeemed book-entry Series EE savings bonds? 351.63 Section 351.63 Money and Finance: Treasury... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.63 How are redemption payments made for my redeemed book-entry Series EE savings bonds? We will make...

31 CFR 351.62 - How is payment made for purchases of book-entry Series EE savings bonds?

Code of Federal Regulations, 2011 CFR

2011-07-01

... book-entry Series EE savings bonds? 351.62 Section 351.62 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.62 How is payment made for purchases of book-entry Series EE savings bonds? You may only purchase book-entry...

31 CFR 351.66 - What book-entry Series EE savings bonds are included in the computation?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What book-entry Series EE savings... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.66 What book-entry Series EE savings bonds are included in the computation? (a) We include all bonds that...

31 CFR 351.66 - What book-entry Series EE savings bonds are included in the computation?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false What book-entry Series EE savings... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.66 What book-entry Series EE savings bonds are included in the computation? (a) We include all bonds that...

31 CFR 351.62 - How is payment made for purchases of book-entry Series EE savings bonds?

Code of Federal Regulations, 2010 CFR

2010-07-01

... book-entry Series EE savings bonds? 351.62 Section 351.62 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.62 How is payment made for purchases of book-entry Series EE savings bonds? You may only purchase book-entry...

Ethinyl estradiol and levonorgestrel in a transdermal contraceptive delivery system.

PubMed

Sriprasert, Intira; Stanczyk, Frank Z; Archer, David F

2015-01-01

The new transdermal contraceptive delivery system (TCDS) developed by Agile Therapeutics containing ethinyl estradiol and levonorgestrel (EE/LNG) is a reversible contraceptive method that maintains stable serum levels of both estrogen and progestin, and has efficacy similar to that of combination oral contraceptives (COC). We provided information of this new TCDS compared with the only TCDS available on the market that contains EE and norelgestromin, and has a higher EE exposure than a COC with 35 µg of EE potentially increasing the risk of venous thromboembolism. The article will summarize finding from clinical studies Phase I, II and III of EE/LNG TCDS. The development of the lower dose EE/LNG TCDS has demonstrated less EE exposure. The serum levels of EE and LNG were stable and comparable between various application sites and daily life conditions. Moreover, the EE/LNG TCDS showed comparable efficacy among obese and non-obese users. However, the Pearl index of this EE/LNG TCDS is questionable and the problem of compliance is a potential confounder of the results. The current Phase III efficacy study will contribute to a further evaluation of compliance and efficacy and will be completed in 2016.

Enriched environment promotes remyelination and motor function recovery through modulation of HDAC1/2 in mice.

PubMed

Zheng, Jian; Ding, Weijun; Li, Baoming; Yang, Youjun

2017-08-10

Brain structure and functions are significantly affected by enriched environment (EE). Rodent and rhesus monkeys raised in EE will increase myelination in development, and these increase correlate with improved cognitive functions on learning and memory. However, whether and how EE influences remyelination in the adult remained undefined. Here, we used a cuprizone-induced demyelination mouse model demonstrate that EE significantly enhances remyelination. This EE-regulated remyelination is associated with improved motor skills. We found that histone deacetylases 1/2 (HDAC1/2) were drastically increased in EE. EE act mechanistically by inhibition of Wnt signaling pathway during remyelination through promotion of HDAC1/2. Moreover, pharmacological inhibition of HDACs promoted Wnt signaling activation and impaired remyelination in EE. These results suggested that the effect of EE is likely to be mediated, at least in part, by elevating HDAC1/2 expression and inhibiting Wnt signal pathway, which initiates 'rewiring' of the neural network and accelerates remyelination. These findings highlighted the potential of EE as a promising noninvasive strategy to accelerate remyelination and to restore motor functions for demyelination related disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Understanding the effectiveness of the entertainment-education strategy: an investigation of how audience involvement, message processing, and message design influence health information recall.

PubMed

Quintero Johnson, Jessie M; Harrison, Kristen; Quick, Brian L

2013-01-01

A growing body of evidence suggests that entertainment-education (EE) is a promising health communication strategy. The purpose of this study was to identify some of the factors that facilitate and hinder audience involvement with EE messages. Using confirmatory factor analysis, the authors introduce a construct they call experiential involvement, which describes the experience of being cognitively and emotionally involved with EE messages and is a product of transportation into an EE text and identification with EE characters. Using an experimental design, the authors also investigated how reports of experiential involvement and health information recall varied depending on the degree to which the educational content was well integrated with the narrative content in EE messages. Findings indicated that integration significantly influenced health information recall. Results indicated that experiential involvement and the perception that the health topic in EE messages was personally relevant predicted participants' systematic processing of the information in EE messages. Contrary to expectation, personal relevance did not predict experiential involvement, and systematic message processing was negatively related to health information recall. Implications for the construction of EE messages and the study of the EE strategy are discussed.

A survey of 17α-ethinylestradiol and mestranol residues in Hawkesbury River, Australia, using a highly specific enzyme-linked immunosorbent assay (ELISA) demonstrates the levels of potential biological significance.

PubMed

Uraipong, Chatchaporn; Allan, Robin D; Li, Chunhua; Kennedy, Ivan R; Wong, Victor; Lee, Nanju Alice

2017-10-01

This study reports on the potential status of 17α-ethinylestradiol (EE2) and mestranol (MeEE2) residues in aquatic environments in New South Wales (NSW), Australia, based on the analysis by a specific ELISA we developed. Polyclonal antibodies were raised against the EE2 hapten with a linker attached at the C3-position to direct the antibody binding towards the ring D of EE2/MeEE2. Using this approach, an ELISA highly specific to EE2 and MeEE2 was successfully developed, showing less than 3.1% cross-reactivity (% CR) with other major steroidal sex hormones and their derivatives. The assay performed with the limit of detection (LOD) of 0.04 ± 0.01µg/L for both EE2 and MeEE2, and the limit of quantitation (LOQ) of 0.05 ± 0.01ng/L when it was coupled with the SM2-Biobeads solid phase extraction. Prior to conducting the survey study, it was validated against the gas chromatography-mass spectrophotometry (GC-MS) method, which showed high correlation with R 2 of 0.934. Fresh surface water samples collected at different sites along Hawkesbury River in New South Wales (NSW) were analyzed for the EE2/ MeEE2 residues using the developed ELISA. The EE2/MeEE2 levels were found to range between 4.1 and 8.3ng/L in Emigrant Creek, NSW, where the primary activity was macadamia plantation, and higher levels between 15 and 29ng/L in South Creek, NSW, Greater Western Sydney at sites upstream and downstream of the municipal sewage treatment plants. Copyright © 2017 Elsevier Inc. All rights reserved.

Expression of serotonin receptors in human lower esophageal sphincter

PubMed Central

LI, HE-FEI; LIU, JUN-FENG; ZHANG, KE; FENG, YONG

2015-01-01

Serotonin (5-HT) is a neurotransmitter and vasoactive amine that is involved in the regulation of a large number of physiological functions. The wide variety of 5-HT-mediated functions is due to the existence of different classes of serotonergic receptors in the mammalian gastrointestinal tract and nervous system. The aim of this study was to explore the expression of multiple types of 5-HT receptor (5-HT1AR, 5-HT2AR, 5-HT3AR, 5-HT4R, 5-HT5AR, 5-HT6R and 5-HT7R) in sling and clasp fibers from the human lower esophageal sphincter (LES). Muscle strips of sling and clasp fibers from the LES were obtained from patients undergoing esophagogastrectomy, and circular muscle strips from the esophagus and stomach were used as controls. Reverse transcription-polymerase chain reaction (RT-PCR), quantitative PCR and western blotting were used to investigate the expression of the various 5-HT receptor types. Messenger RNA for all seven 5-HT receptor types was identified in the sling and clasp fibers of the LES. At the mRNA level, the expression levels were highest for 5-HT3AR and 5-HT4R, and lowest for 5-HT5AR, 5-HT6R and 5-HT7R. At the protein level, the expression levels were highest for 5-HT3AR and 5-HT4R, followed by 5-HT1AR and 5-HT2AR; 5-HT7R was also detected at a low level. The expression of 5-HT5AR and 5-HT6R proteins was not confirmed. The results indicate that a variety of 5-HT receptor types can be detected in the human LES and probably contribute to LES function. PMID:25452775

Characterization of a ( sub 3 H)-5-hydroxtyryptamine binding site in rabbit caudate nucleus that differs from the 5-HT sub 1A , 5-HT sub 1B , 5-HT sub 1C and 5-HT sub 1D subtypes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Wencheng; Nelson, D.L.

1989-01-01

({sup 3}H)5-HT binding sites were analyzed in membranes prepared from the rabbit caudate nucleus (CN). ({sup 3}H)5-HT labeled both 5-HT{sub 1A} and 5-HT{sub 1C} recognition sites, defined by nanomolar affinity for 8-OH-DPAT and mesulergine respectively; however, these represented only a fraction of total specific ({sup 3}H)5-HT binding. Saturation experiments of ({sup 3}H)5-HT binding in the presence of 100 nM 8-OH-DPAT and 100 nM mesulergine to block 5-HT{sub 1A} and 5-HT{sub 1C} sites revealed that non-5-HT{sub 1A}/non-5-HT{sub 1C} sites represented about 60% of the total 5-HT{sub 1} sites and that they exhibited saturable, high affinity, and homogeneous binding. The pharmacological profilemore » of the non-5-HT{sub 1A}/non-5-HT{sub 1C} sites (designated 5-HT{sub 1R}) also differed from that of 5-HT{sub 1B} and 5-HT{sub 2} sites, but was similar to that of the 5-HT{sub 1D} site. However, significant differences existed between the 5-HT{sub 1D} and 5-HT{sub 1B} sites for their K{sub i} values for spiperone, spirilene, metergoline, and methiothepin. The study of modulatory agents also showed differences between the 5-HT{sub 1R} and 5-HT{sub 1D} sites. In addition, calcium enhanced the effects of GTP on the 5-HT{sub 1R} sites, whereas calcium inhibited the GTP effect on the 5-HT{sub 1D} sites.« less

Expression and function of 5-HT4 receptors in the mouse enteric nervous system.

PubMed

Liu, Mintsai; Geddis, Matthew S; Wen, Ying; Setlik, Wanda; Gershon, Michael D

2005-12-01

The aim of the current study was to identify enteric 5-HT(4) splice variants, locate enteric 5-HT(4) receptors, determine the relationship, if any, of the 5-HT(4) receptor to 5-HT(1P) activity, and to ascertain the function of 5-HT(4) receptors in enteric neurophysiology. 5-HT(4a), 5-HT(4b), 5-HT(4e), and 5-HT(4f) isoforms were found in mouse brain and gut. The ratio of 5-HT(4) expression to that of the neural marker, synaptophysin, was higher in gut than in brain but was similar in small and large intestines. Submucosal 5-HT(4) expression was higher than myenteric. Although transcripts encoding 5-HT(4a) and 5-HT(4b) isoforms were more abundant, those encoding 5-HT(4e) and 5-HT(4f) were myenteric plexus specific. In situ hybridization revealed the presence of transcripts encoding 5-HT(4) receptors in subsets of enteric neurons, interstitial cells of Cajal, and smooth muscle cells. IgY antibodies to mouse 5-HT(4) receptors were raised, affinity purified, and characterized. Nerve fibers in the circular muscle and the neuropil in ganglia of both plexuses were highly 5-HT(4) immunoreactive, although only a small subset of neurons contained 5-HT(4) immunoreactivity. No 5-HT(4)-immunoreactive nerves were detected in the mucosa. 5-HT and 5-HT(1P) agonists evoked a G protein-mediated long-lasting inward current that was neither mimicked by 5-HT(4) agonists nor blocked by 5-HT(4) antagonists. In contrast, the 5-HT(4) agonists renzapride and tegaserod increased the amplitudes of nicotinic evoked excitatory postsynaptic currents. Enteric neuronal 5-HT(4) receptors thus are presynaptic and probably exert their prokinetic effects by strengthening excitatory neurotransmission.

Environmental enrichment facilitates cocaine-cue extinction, deters reacquisition of cocaine self-administration and alters AMPAR GluA1 expression and phosphorylation.

PubMed

Gauthier, Jamie M; Lin, Amy; Nic Dhonnchadha, Bríd Á; Spealman, Roger D; Man, Heng-Ye; Kantak, Kathleen M

2017-01-01

This study investigated the combination of environmental enrichment (EE) with cocaine-cue extinction training on reacquisition of cocaine self-administration. Rats were trained under a second-order schedule for which responses were maintained by cocaine injections and cocaine-paired stimuli. During three weekly extinction sessions, saline was substituted for cocaine but cocaine-paired stimuli were presented. Rats received 4-h periods of EE at strategic time points during extinction training, or received NoEE. Additional control rats received EE or NoEE without extinction training. One week later, reacquisition of cocaine self-administration was evaluated for 15 sessions, and then GluA1 expression, a cellular substrate for learning and memory, was measured in selected brain regions. EE provided both 24 h before and immediately after extinction training facilitated extinction learning and deterred reacquisition of cocaine self-administration for up to 13 sessions. Each intervention by itself (EE alone or extinction alone) was ineffective, as was EE scheduled at individual time points (EE 4 h or 24 h before, or EE immediately or 6 h after, each extinction training session). Under these conditions, rats rapidly reacquired baseline rates of cocaine self-administration. Cocaine self-administration alone decreased total GluA1 and/or pSer845GluA1 expression in basolateral amygdala and nucleus accumbens. Extinction training, with or without EE, opposed these changes and also increased total GluA1 in ventromedial prefrontal cortex and dorsal hippocampus. EE alone increased pSer845GluA1 and EE combined with extinction training decreased pSer845GluA1 in ventromedial prefrontal cortex. EE might be a useful adjunct to extinction therapy by enabling neuroplasticity that deters relapse to cocaine self-administration. © 2015 Society for the Study of Addiction.

Lower core body temperature and greater body fat are components of a human thrifty phenotype.

PubMed

Reinhardt, M; Schlögl, M; Bonfiglio, S; Votruba, S B; Krakoff, J; Thearle, M S

2016-05-01

In small studies, a thrifty human phenotype, defined by a greater 24-hour energy expenditure (EE) decrease with fasting, is associated with less weight loss during caloric restriction. In rodents, models of diet-induced obesity often have a phenotype including a reduced EE and decreased core body temperature. We assessed whether a thrifty human phenotype associates with differences in core body temperature or body composition. Data for this cross-sectional analysis were obtained from 77 individuals participating in one of two normal physiology studies while housed on our clinical research unit. Twenty-four-hour EE using a whole-room indirect calorimeter and 24-h core body temperature were measured during 24 h each of fasting and 200% overfeeding with a diet consisting of 50% carbohydrates, 20% protein and 30% fat. Body composition was measured by dual X-ray absorptiometry. To account for the effects of body size on EE, changes in EE were expressed as a percentage change from 24-hour EE (%EE) during energy balance. A greater %EE decrease with fasting correlated with a smaller %EE increase with overfeeding (r=0.27, P=0.02). The %EE decrease with fasting was associated with both fat mass and abdominal fat mass, even after accounting for covariates (β=-0.16 (95% CI: -0.26, -0.06) %EE per kg fat mass, P=0.003; β=-0.0004 (-0.0007, -0.00004) %EE kg(-1) abdominal fat mass, P=0.03). In men, a greater %EE decrease in response to fasting was associated with a lower 24- h core body temperature, even after adjusting for covariates (β=1.43 (0.72, 2.15) %EE per 0.1 °C, P=0.0003). Thrifty individuals, as defined by a larger EE decrease with fasting, were more likely to have greater overall and abdominal adiposity as well as lower core body temperature consistent with a more efficient metabolism.

Help-seeking in people with exceptional experiences: results from a general population sample.

PubMed

Landolt, Karin; Wittwer, Amrei; Wyss, Thomas; Unterassner, Lui; Fach, Wolfgang; Krummenacher, Peter; Brugger, Peter; Haker, Helene; Kawohl, Wolfram; Schubiger, Pius August; Folkers, Gerd; Rössler, Wulf

2014-01-01

Exceptional experiences (EE) are experiences that deviate from ordinary experiences, for example precognition, supernatural appearances, or déjà vues. In spite of the high frequency of EE in the general population, little is known about their effect on mental health and about the way people cope with EE. This study aimed to assess the quality and quantity of EE in persons from the Swiss general population, to identify the predictors of their help-seeking, and to determine how many of them approach the mental health system. An on-line survey was used to evaluate a quota sample of 1580 persons representing the Swiss general population with respect to gender, age, and level of education. Multinomial logistic regression was applied to integrate help-seeking, self-reported mental disorder, and other variables in a statistical model designed to identify predictors of help-seeking in persons with EE. Almost all participants (91%) experienced at least one EE. Generally, help-seeking was more frequent when the EE were of negative valence. Help-seeking because of EE was less frequent in persons without a self-reported mental disorder (8.6%) than in persons with a disorder (35.1%) (OR = 5.7). Even when frequency and attributes of EE were controlled for, people without a disorder sought four times less often help because of EE than expected. Persons with a self-reported diagnosis of mental disorder preferred seeing a mental health professional. Multinomial regression revealed a preference for healers in women with less education, who described themselves as believing and also having had more impressive EE. Persons with EE who do not indicate a mental disorder less often sought help because of EE than persons who indicated a mental disorder. We attribute this imbalance to a high inhibition threshold to seek professional help. Moreover, especially less educated women did not approach the mental health care system as often as other persons with EE, but preferred seeing a healer.

The effect of extending the pill-free interval on follicular activity: triphasic norgestimate/35 micro g ethinyl estradiol versus monophasic levonorgestrel/20 micro g ethinyl estradiol.

PubMed

Creinin, Mitchell D; Lippman, Joel S; Eder, Scott E; Godwin, Amy J; Olson, William

2002-09-01

This study was designed to evaluate follicular activity in women taking oral contraceptives with imposed imperfect compliance. After completing a 28-day cycle of either triphasic norgestimate/EE (NGM/EE) (Ortho Tri-Cyclen, Ortho-McNeil Pharmaceutical, Raritan, NJ) or monophasic levonorgestrel/EE (LNG/EE) (Alesse, Wyeth-Ayerst Laboratories, Philadelphia, PA), women were instructed to intentionally "miss" the first two active pills of the next pack. The first two tablets in the second treatment cycle were deliberately omitted, thereby extending the pill-free interval from 7 days to 9 days. Subjects were randomized to take NGM/EE (n = 40) or LNG/EE (n = 39) for two consecutive cycles. The mean maximum follicular diameter was significantly greater in women taking LNG/EE than in those taking NGM/EE (16.4 +/- 7.1 mm vs. 12.6 +/- 8.3 mm, p = 0.047). The LNG/EE group had significantly higher median serum estradiol concentrations compared to women taking NGM/EE on pill Days 10 [29.5 pg/mL (range: 10.0-540.0 pg/mL) vs. 2.5 pg/mL (range: 2.0-6.0 pg/mL), p < 0.001] and 14 [11.0 pg/mL (range: 2.0-416.0 pg/mL) vs. 2.0 pg/mL (range: 2.0-3.0 pg/mL), p = 0.001]. Two women in the NGM/EE group and three women in the LNG/EE group had at least one progesterone level > or =3 ng/mL; none of these women demonstrated a maximum follicular diameter >13 mm. Significantly greater follicular activity was observed after an extended pill-free interval in women taking LNG/EE compared to those taking triphasic NGM/EE. The clinical implications of these findings require further study.

A comparison of energy expenditure estimation of several physical activity monitors.

PubMed

Dannecker, Kathryn L; Sazonova, Nadezhda A; Melanson, Edward L; Sazonov, Edward S; Browning, Raymond C

2013-11-01

Accurately and precisely estimating free-living energy expenditure (EE) is important for monitoring energy balance and quantifying physical activity. Recently, single and multisensor devices have been developed that can classify physical activities, potentially resulting in improved estimates of EE. This study aimed to determine the validity of EE estimation of a footwear-based physical activity monitor and to compare this validity against a variety of research and consumer physical activity monitors. Nineteen healthy young adults (10 men, 9 women) completed a 4-h stay in a room calorimeter. Participants wore a footwear-based physical activity monitor as well as Actical, ActiGraph, IDEEA, DirectLife, and Fitbit devices. Each individual performed a series of postures/activities. We developed models to estimate EE from the footwear-based device, and we used the manufacturer's software to estimate EE for all other devices. Estimated EE using the shoe-based device was not significantly different than measured EE (mean ± SE; 476 ± 20 vs 478 ± 18 kcal, respectively) and had a root-mean-square error of 29.6 kcal (6.2%). The IDEEA and the DirectLlife estimates of EE were not significantly different than the measured EE, but the ActiGraph and the Fitbit devices significantly underestimated EE. Root-mean-square errors were 93.5 (19%), 62.1 kcal (14%), 88.2 kcal (18%), 136.6 kcal (27%), 130.1 kcal (26%), and 143.2 kcal (28%) for Actical, DirectLife, IDEEA, ActiGraph, and Fitbit, respectively. The shoe-based physical activity monitor provides a valid estimate of EE, whereas the other physical activity monitors tested have a wide range of validity when estimating EE. Our results also demonstrate that estimating EE based on classification of physical activities can be more accurate and precise than estimating EE based on total physical activity.

Combination of injectable ethinyl estradiol and drospirenone drug-delivery systems and characterization of their in vitro release.

PubMed

Nippe, Stefanie; General, Sascha

2012-11-20

Our aim was to investigate the in vitro release and combination of ethinyl estradiol (EE) and drospirenone (DRSP) drug-delivery systems. DRSP poly(lactic-co-glycolic acid) (PLGA) microparticles and organogels containing DRSP microcrystals were prepared and characterized with regard to properties influencing drug release. The morphology and release kinetics of DRSP PLGA microparticles indicated that DRSP is dispersed in the polymer. The in vitro release profiles correlated well with in vivo data. Although DRSP degradation is known to be acid-catalyzed, DRSP was relatively stable in the PLGA matrix. Aqueous DRSP PLGA microparticle suspensions were combinable with EE PLGA microparticles and EE poly(butylcyanoacrylate) (PBCA) microcapsules without interacting. EE release from PLGA microparticles was faster than DRSP release; EE release is assumed to be primarily controlled by drug diffusion. Liquid-filled EE PBCA microcapsules were shown to be more robust than air-filled EE PBCA microcapsules; the bursting of microcapsules accelerating the drug delivery was therefore delayed. The drug release profile for DRSP organogels was fairly linear with the square root of time. The system was not combinable with EE PBCA microcapsules. In contrast, incorporation of EE PLGA microparticles in organogels resulted in prolonged EE release. The drug release of EE and DRSP was thus approximated. Copyright © 2012 Elsevier B.V. All rights reserved.

Allergic sensitization modifies the pulmonary expression of 5-hydroxytryptamine receptors in guinea pigs.

PubMed

Córdoba-Rodríguez, Guadalupe; Vargas, Mario H; Ruiz, Víctor; Carbajal, Verónica; Campos-Bedolla, Patricia; Mercadillo-Herrera, Paulina; Arreola-Ramírez, José Luis; Segura-Medina, Patricia

2016-03-01

There is mounting evidence that 5-hydroxytryptamine (5-HT) plays a role in asthma. However, scarce information exists about the pulmonary expression of 5-HT receptors and its modification after allergic sensitization. In the present work, we explored the expression of 5-HT1A, 5-HT2A, 5-HT3, 5-HT4, 5-ht5a, 5-HT6, and 5-HT7 receptors in lungs from control and sensitized guinea pigs through qPCR and Western blot. In control animals, mRNA from all receptors was detectable in lung homogenates, especially from 5-HT2A and 5-HT4 receptors. Sensitized animals had decreased mRNA expression of 5-HT2A and 5-HT4 receptors and increased that of 5-HT7 receptor. In contrast, they had increased protein expression of 5-HT2A receptor in bronchial epithelium and of 5-HT4 receptor in lung parenchyma. The degree of airway response to the allergic challenge was inversely correlated with mRNA expression of the 5-HT1A receptor. In summary, our results showed that major 5-HT receptor subtypes are constitutively expressed in the guinea pig lung, and that allergic sensitization modifies the expression of 5-HT2A, 5-HT4, and 5-HT7 receptors. Copyright © 2015 Elsevier B.V. All rights reserved.

An intertemporal decision framework for electrochemical energy storage management

NASA Astrophysics Data System (ADS)

He, Guannan; Chen, Qixin; Moutis, Panayiotis; Kar, Soummya; Whitacre, Jay F.

2018-05-01

Dispatchable energy storage is necessary to enable renewable-based power systems that have zero or very low carbon emissions. The inherent degradation behaviour of electrochemical energy storage (EES) is a major concern for both EES operational decisions and EES economic assessments. Here, we propose a decision framework that addresses the intertemporal trade-offs in terms of EES degradation by deriving, implementing and optimizing two metrics: the marginal benefit of usage and the average benefit of usage. These metrics are independent of the capital cost of the EES system, and, as such, separate the value of EES use from the initial cost, which provides a different perspective on storage valuation and operation. Our framework is proved to produce the optimal solution for EES life-cycle profit maximization. We show that the proposed framework offers effective ways to assess the economic values of EES, to make investment decisions for various applications and to inform related subsidy policies.

31 CFR 351.35 - What do I need to know about interest rates, penalties, and redemption values for Series EE bonds...

Code of Federal Regulations, 2011 CFR

2011-07-01

... rates, penalties, and redemption values for Series EE bonds with issue dates of May 1, 2005, or... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates of May 1, 2005, Or Thereafter § 351.35 What do I need to know...

31 CFR 351.35 - What do I need to know about interest rates, penalties, and redemption values for Series EE bonds...

Code of Federal Regulations, 2012 CFR

2012-07-01

... rates, penalties, and redemption values for Series EE bonds with issue dates of May 1, 2005, or... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates of May 1, 2005, Or Thereafter § 351.35 What do I need to know...

31 CFR 351.35 - What do I need to know about interest rates, penalties, and redemption values for Series EE bonds...

Code of Federal Regulations, 2010 CFR

2010-07-01

... rates, penalties, and redemption values for Series EE bonds with issue dates of May 1, 2005, or... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates of May 1, 2005, Or Thereafter § 351.35 What do I need to know...

31 CFR 351.35 - What do I need to know about interest rates, penalties, and redemption values for Series EE bonds...

Code of Federal Regulations, 2014 CFR

2014-07-01

... rates, penalties, and redemption values for Series EE bonds with issue dates of May 1, 2005, or... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates of May 1, 2005, Or Thereafter § 351.35 What do I need to know...

31 CFR 351.35 - What do I need to know about interest rates, penalties, and redemption values for Series EE bonds...

Code of Federal Regulations, 2013 CFR

2013-07-01

... rates, penalties, and redemption values for Series EE bonds with issue dates of May 1, 2005, or... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates of May 1, 2005, Or Thereafter § 351.35 What do I need to know...

31 CFR 351.69 - When is a book-entry Series EE savings bond validly issued?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false When is a book-entry Series EE savings... OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.69 When is a book-entry Series EE savings bond validly issued? A book-entry bond is validly issued when it is posted to...

31 CFR 351.60 - How are book-entry Series EE savings bonds purchased and held?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false How are book-entry Series EE savings... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.60 How are book-entry Series EE savings bonds purchased and held? Book-entry bonds must be purchased and held online...

31 CFR 351.65 - What amount of book-entry Series EE savings bonds may I acquire per year?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What amount of book-entry Series EE... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.65 What amount of book-entry Series EE savings bonds may I acquire per year? The principal amount of book...

31 CFR 351.65 - What amount of book-entry Series EE savings bonds may I acquire per year?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false What amount of book-entry Series EE... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.65 What amount of book-entry Series EE savings bonds may I acquire per year? The principal amount of book...

31 CFR 351.60 - How are book-entry Series EE savings bonds purchased and held?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false How are book-entry Series EE savings... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.60 How are book-entry Series EE savings bonds purchased and held? Book-entry bonds must be purchased and held online...

31 CFR 351.69 - When is a book-entry Series EE savings bond validly issued?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false When is a book-entry Series EE... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.69 When is a book-entry Series EE savings bond validly issued? A book-entry bond is validly issued when it is posted...

31 CFR 351.60 - How are book-entry Series EE savings bonds purchased and held?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false How are book-entry Series EE savings... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.60 How are book-entry Series EE savings bonds purchased and held? Book-entry bonds must be purchased and held online...

The impact of tissue Doppler index E/e' ratio on instantaneous wave-free ratio.

PubMed

Arashi, Hiroyuki; Yamaguchi, Junichi; Ri, Tonre; Otsuki, Hisao; Nakao, Masashi; Kamishima, Kazuho; Jujo, Kentaro; Minami, Yuichiro; Ogawa, Hiroshi; Hagiwara, Nobuhisa

2018-03-01

The instantaneous wave-free ratio (iFR) is a vasodilator-free, invasive pressure wire index of the functional severity of coronary stenosis and is calculated under resting conditions. In a recent study, iFR was found to be more closely linked to coronary flow reserve (CFR) than fractional flow reserve (FFR). E/e' is a surrogate marker of left ventricular (LV) filling pressure and LV diastolic dysfunction. Coronary resting flow was found to be increased in patients with elevated E/e', and higher coronary resting flow was associated with lower CFR. Higher baseline coronary flow induces a greater loss of translesional pressure and may affect iFR. However, no reports have examined the impact of E/e' on iFR. The purpose of this study was to assess the relationship between iFR and E/e' compared with FFR. We retrospectively examined 103 consecutive patients (142 with stenosis) whose iFR, FFR, and E/e' were measured simultaneously. The mean age, LV mass index, and systolic blood pressure of patients with elevated E/e' were higher than those of patients with normal E/e'. Although no significant differences were observed in mean FFR values and % diameter stenosis, the mean iFR value in patients with elevated E/e' was significantly lower than that in patients with normal E/e'. The iFR was negatively correlated with E/e', while there was no correlation between FFR and E/e'. Multivariate analysis showed that E/e' and % diameter stenosis were independent determinants of iFR. E/e' ratio affects iFR values. Our results suggest that FFR mainly reflects the functional severity of the epicardial stenosis whereas iFR could potentially be influenced by not only epicardial stenosis but also other factors related to LV filling pressure or LV diastolic dysfunction. Further research is needed to understand the underlying mechanisms that influence the evaluation of iFR in patients with elevated E/e'. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

A comparison of bleeding patterns and cycle control using two transdermal contraceptive systems: a multicenter, open-label, randomized study.

PubMed

Gruber, D; Skřivánek, A; Serrani, M; Lanius, V; Merz, M

2015-02-01

To investigate the bleeding pattern and cycle control parameters of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a patch containing 0.6 mg EE and 6 mg norelgestromin (NGMN). In this phase III, open-label, randomized, parallel-group trial, healthy women aged 18-35 years (smokers aged 18-30 years) received either the EE/GSD patch (n=200) or the EE/NGMN patch (n=198). Treatment consisted of one patch per week for 3 weeks followed by a 7-day, patch-free interval for seven cycles. Bleeding control was assessed in two 90-day reference periods. In reference period 1, mean number of bleeding/spotting days was comparable across treatment groups (p>0.05). However, in reference period 2, there were fewer bleeding/spotting days in the EE/GSD patch group (15.7 versus 18.4; p<0.0001). Mean number of bleeding/spotting episodes was comparable across groups for both reference periods, but bleeding/spotting episodes were shorter for the EE/GSD patch than the EE/NGMN patch during reference period 1 (5.13 days versus 5.53 days, respectively; p<0.05) and reference period 2 (5.07 versus 5.66; p=0.0001). Both treatment groups showed a similar frequency of withdrawal bleeding episodes; however, across all seven cycles, the length of these episodes was consistently shorter with the EE/GSD patch (p<0.01). There were no notable treatment differences in intracyclic bleeding. Bleeding pattern and cycle control achieved with the EE/GSD patch was similar to that of the EE/NGMN patch. The paper presents data on the bleeding pattern and cycle control parameters of an investigational transdermal contraceptive patch containing EE and GSD compared with an approved contraceptive patch containing EE and NGMN. This descriptive study found that bleeding patterns associated with the EE/GSD patch were similar to those of an EE/NGMN patch providing higher EE exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

The Role of Expressed Emotion in Relationships Between Psychiatric Staff and People With a Diagnosis of Psychosis: A Review of the Literature

PubMed Central

Berry, Katherine; Barrowclough, Christine; Haddock, Gillian

2011-01-01

The concept of expressed emotion (EE) has been extended to the study of staff-patient relationships in schizophrenia. A comprehensive review of the literature identified a total of 27 studies investigating EE in this group published between 1990 and 2008. The article aims to assess whether the concept of EE is a useful and valid measure of the quality of professional caregiver and patient relationships, given that staff may be less emotionally invested in relationships than relatives. In doing so, it summarizes methods of measuring EE, the nature of professional EE compared with familial EE, associations between high EE and patient outcomes, associations between EE and both patient and staff variables, and intervention studies to reduce staff high EE. The available evidence suggests that the Camberwell Family Interview is an acceptable measure of EE in staff-patient relationships, although the Five Minute Speech Sample may provide a less resource intensive alternative. However, in contrast to familial research, neither the EE status on the Camberwell Family Interview nor the Five Minute Speech Sample show a robust relationship with outcomes. The presence or absence of a positive staff-patient relationship may have more predictive validity in this group. There is relatively consistent evidence of associations between staff criticism and poorer patient social functioning. Consistent with findings in familial research, staff attributions may play a key role in driving critical responses, and it may be possible to reduce staff high EE by modifying negative appraisals. PMID:20056685

Both pre- and post-lesion experiential therapy is beneficial in 6-hydroxydopamine dopamine-depleted female rats.

PubMed

Jadavji, N M; Metz, G A

2009-01-23

Experiential therapies, such as enriched environment (EE), have been shown to influence the neurodegenerative processes that underlie Parkinson's disease. We have previously demonstrated that EE promotes functional improvement in dopamine-depleted rats. Here we compare the influence of exposure to EE prior to versus after dopamine depletion in the 6-hydroxydopamine rat model of Parkinson's disease. Two groups of female rats were placed in an EE while two groups were housed in a standard environment (SE) for 6 weeks prior to receiving a unilateral nigrostriatal bundle infusion of the neurotoxin 6-hydroxydopamine. After the lesion, one group remained in EE, while the second EE group (Pre-Lesion EE) was moved into SE conditions. In addition, a third group of rats was now moved into EE (Post-lesion EE). A fourth group remained in SE throughout the experimental period. Rats were tested in skilled reaching and skilled walking tasks and in non-skilled motor function up to 4 weeks after lesion. The observations demonstrated beneficial effects of both pre- and post-lesion exposure to EE on skilled movement performance by promoting compensatory limb use and partial protection or restoration of skilled movement. Exposure to pre-lesion EE in particular promoted structural plasticity as indicated by increased expression of the main cytoskeletal component microtubule associated protein-2 in the lesion dorsal striatum. Continuous EE showed absence of rotational bias suggesting attenuated dopamine loss. These data indicate that enriched lifestyle before the onset of motor symptoms and rehabilitation programs after diagnosis might be beneficial in patients with Parkinson's disease.

Regulatory mechanism of CCN2 production by serotonin (5-HT) via 5-HT2A and 5-HT2B receptors in chondrocytes.

PubMed

Hori, Ayaka; Nishida, Takashi; Takashiba, Shogo; Kubota, Satoshi; Takigawa, Masaharu

2017-01-01

Serotonin (5-hydroxytryptamine: 5-HT) is recognized as a neurotransmitter in the central nerve system and as a regulator of systemic blood pressure in the peripheral tissues. Recently, it was reported that 5-HT2 receptors (5-HT2Rs) were expressed in cartilage tissues lacking both vessels and neurons, suggesting possible novel functions of 5-HT during cartilage development and regeneration. Our previous data indicated that CCN family protein 2/connective tissue growth factor (CCN2/CTGF) plays a central role in cartilage development and regeneration. Therefore, the aim of this study was to investigate the effect of 5-HT on the production of CCN2 in chondrocytes. Firstly, we showed that the mRNAs of 5-HT2R subtypes 5-HT2AR and 5-HT2BR, were expressed in a human chondrocytic cell line, HCS-2/8; however, 5-HT2CR mRNA was not detected. In addition, exogenously added 5-HT did not affect the 5-HT2AR and 5-HT2BR expressions. Next, we demonstrated that CCN2 production was increased by treatment with a 5-HT2AR agonist and the combination of 5-HT and 5-HT2BR antagonist. In contrast, treatment with a 5-HT2BR agonist and the combination of 5-HT and 5-HT2AR antagonist decreased CCN2 production. Furthermore, we showed that phosphorylation of Akt and p38 MAPK were increased by treatment with 5-HT2AR agonist, and that phosphorylation of PKCε, PKCζ, ERK1/2 and JNK were increased by treatment with 5-HT2BR agonist. Finally, we found that 5-HT2AR was localized in the growth plate, whereas 5-HT2BR was localized in the articular cartilage. These findings suggest that 5-HT promotes CCN2 production through the 5-HT2AR in growth plates, and that it represses CCN2 production through the 5-HT2BR in articular cartilage for harmonized development of long bones.

Is there unity in Europe? First survey of EUPSA delegates on the management of gastroschisis.

PubMed

Zani, Augusto; Ruttenstock, Elke; Davenport, Mark; Ade-Ajayi, Niyi

2013-02-01

To report the first European survey on the current management of gastroschisis and ascertain the degree of variability between centers. A 10-question survey was administered at the 2011 European Paediatric Surgeons' Association (EUPSA) Congress. Questionnaires were completed by 205 delegates from 39 countries. A total of 21 responses (10%) were incomplete and voided. The remaining 184 were divided on the basis of following region of practice: Western Europe (WE, n = 102), Eastern Europe (EE, n = 59), and non-European countries (n = 23). Differences between WE and EE were analyzed using contingency tests. p < 0.05 was considered significant. A total of 15% WE and 2% EE responders work in centers where antenatal magnetic resonance imaging scans are routinely used. Nonplanned delivery is the most popular approach (WE 46%, EE 58%). Primary closure is the preferred choice (WE 92%, EE 86%), and it is achieved by operative fascial closure in the majority (WE 80%, EE 75%) rather than by Bianchi technique (WE 20%, EE 25%). Staged reduction and closure is less popular (WE 8%, EE 14%), and it is achieved by custom-made silo (WE 25%, EE 12.5%), preformed silo (PFS) followed by surgical closure (WE 63%, EE 75%), or PFS followed by sutureless closure (WE 12%, EE 12.5%). Objection to PFS in WE is mainly related to surgeons' lack of confidence in the technique (40%), whereas in EE it is due to unavailability and high cost (62%, p = 0.01). In case of associated intestinal atresia, immediate resection and anastomosis is preferred by 60% of WE surgeons versus 35% of EE surgeons (p = 0.03), who equally favor primary closure and delayed surgery (33%). Nutrition is preferably delivered by peripheral long line in WE (64%) and by central line inserted in the first week of life in EE (62%, p = 0.003). Primary fascial closure is currently the preferred method of gastroschisis closure across Europe. Aspects of care such as strategy for intestinal atresia and delivery of parenteral nutrition differ significantly between WE and EE. Economic considerations appear to influence management strategy particularly in EE. A Europe-wide audit appears warranted to identify whether this survey reflects actual practice. Georg Thieme Verlag KG Stuttgart · New York.

Effects of preweaning environmental enrichment on hippocampus-dependent learning and memory in developing rats.

PubMed

Lu, Cheng-Qiu; Zhong, Le; Yan, Chong-Huai; Tian, Ying; Shen, Xiao-Ming

2017-02-15

Previous studies have shown that environmental enrichment (EE) improves learning and memory in adult animals. However, the effects of preweaning EE (preEE) on hippocampus-dependent learning and memory as well as its possible mechanisms are poorly understood. Here we report that preEE enhanced the exploratory activity in rats immediately after weaning, and the EE group showed greater performance in a passive avoidance task than the control group (p<0.05), but not in the locomotion activity. Electrophysiology analysis showed that rats exposed to preEE exhibited larger field excitatory postsynaptic potentials after long-term potentiation induction than those in the control group (p<0.05). The protein levels of phosphorylated extracellular signal-regulated kinases as well as activity-regulated cytoskeleton-associated protein were significantly upregulated in the preEE group compared to the control group (p<0.05). Our results indicate that preEE can enhance hippocampus-dependent learning and memory function as postweaning EE does, and the upregulated activation of the ERK signal transduction pathway may be the underlying molecular mechanism. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Peroxisomes, lipid droplets, and endoplasmic reticulum “hitchhike” on motile early endosomes

PubMed Central

Guimaraes, Sofia C.; Schuster, Martin; Bielska, Ewa; Dagdas, Gulay; Kilaru, Sreedhar; Meadows, Ben R.A.; Schrader, Michael

2015-01-01

Intracellular transport is mediated by molecular motors that bind cargo to be transported along the cytoskeleton. Here, we report, for the first time, that peroxisomes (POs), lipid droplets (LDs), and the endoplasmic reticulum (ER) rely on early endosomes (EEs) for intracellular movement in a fungal model system. We show that POs undergo kinesin-3– and dynein-dependent transport along microtubules. Surprisingly, kinesin-3 does not colocalize with POs. Instead, the motor moves EEs that drag the POs through the cell. PO motility is abolished when EE motility is blocked in various mutants. Most LD and ER motility also depends on EE motility, whereas mitochondria move independently of EEs. Covisualization studies show that EE-mediated ER motility is not required for PO or LD movement, suggesting that the organelles interact with EEs independently. In the absence of EE motility, POs and LDs cluster at the growing tip, whereas ER is partially retracted to subapical regions. Collectively, our results show that moving EEs interact transiently with other organelles, thereby mediating their directed transport and distribution in the cell. PMID:26620910

Shame and guilt/self-blame as predictors of expressed emotion in family members of patients with schizophrenia

PubMed Central

Wasserman, Stephanie; Weisman de Mamani, Amy; Suro, Giulia

2012-01-01

Expressed emotion (EE) is a measure of the family environment reflecting the amount of criticism and emotional over-involvement expressed by a key relative towards a family member with a disorder or impairment. Patients from high EE homes have a poorer illness prognosis than do patients from low EE homes. Despite EE's well-established predictive validity, questions remain regarding why some family members express high levels of EE attitudes while others do not. Based on indirect evidence from previous research, the current study tested whether shame and guilt/self-blame about having a relative with schizophrenia serve as predictors of EE. A sample of 72 family members of patients with schizophrenia completed the Five Minute Speech Sample to measure EE, along with questionnaires assessing self-directed emotions. In line with the hypotheses, higher levels of both shame and guilt/self-blame about having a relative with schizophrenia predicted high EE. Results of the current study elucidate the EE construct and have implications for working with families of patients with schizophrenia. PMID:22357355

The recovery of 5-HT transporter and 5-HT immunoreactivity in injured rat spinal cord.

PubMed

Saruhashi, Yasuo; Matsusue, Yoshitaka; Fujimiya, Mineko

2009-09-01

Experimental spinal cord injury. To determine the role of serotonin (5-HT) and 5-HT transporter in recovery from spinal cord injury. We examined 5-HT and 5-HT transporter of spinal cord immunohistologically and assessed locomotor recovery after extradural compression at the thoracic (T8) spinal cord in 21 rats. Eighteen rats had laminectomy and spinal cord injury, while the remaining three rats received laminectomy only. All rats were evaluated every other day for 4 weeks, using a 0-14 point scale open field test. Extradural compression markedly reduced mean hindlimbs scores from 14 to 1.5 +/- 2.0 (mean +/- standard error of mean). The rats recovered apparently normal walking by 4 weeks. The animals were perfused with fixative 1-3 days, 1, 2 and 4 weeks (three rats in each) after a spinal cord injury. The 5-HT transporter immunohistological study revealed a marked reduction of 5-HT transporter-containing terminals by 1 day after injury. By 4 weeks after injury, 5-HT transporter immunoreactive terminals returned to the control level. The 5-HT immunohistological study revealed a reduction of 5-HT-containing terminals by 1 week after injury. By 4 weeks after injury, 5-HT immunoreactive fibers and terminals returned to the control level. We estimated the recovery of 5-HT transporter and 5-HT neural elements in lumbosacral ventral horn by ranking 5-HT transporter and 5-HT staining intensity and counting 5-HT and 5-HT transporter terminals. The return of 5-HT transporter and 5-HT immunoreactivity of the lumbosacral ventral horn correlated with locomotor recovery, while 5-HT transporter showed closer relationship with locomotor recovery than 5-HT. The presence of 5-HT transporter indicates that the 5-HT fibers certainly function. This study shows that return of the function of 5-HT fibers predict the time course and extent of locomotory recovery after thoracic spinal cord injury.

Serotonin Receptor Binding Characteristics of Geissoschizine Methyl Ether, an Indole Alkaloid in Uncaria Hook

PubMed Central

Ikarashi, Yasushi; Sekiguchi, Kyoji; Mizoguchi, Kazushige

2018-01-01

Background: Geissoschizine methyl ether (GM) is one of the indole alkaloids in Uncaria hook, and an active ingredient of yokukansan (YKS) that improves behavioral and psychological symp-toms of dementia (BPSD) in patients with several types of dementia. The pharmacological action of GM has been related to various serotonin (5-HT) receptor subtypes. Objective: The aim of this article is to review the binding characteristics of GM to the 5-HT receptor sub-types in the brains using our own data and previous findings. Methods: Competitive receptor-binding and agonist/antagonist activity assays for several 5-HT receptor subtypes were performed. Moreover, the articles describing pharmacokinetics and brain distribution of GM were searched in PubMed. Results: GM bound the following 5-HT receptor subtypes: 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT4, 5-HT5A, 5-HT6, and 5-HT7. Among these receptors, GM had partial agonistic activity for 5-HT1A receptors and antagonistic activity for 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT7 receptors. Also, GM was me-tabolized by various CYP isoforms, mainly CYP3A4. Parent/unchanged GM was detected in both the blood and brain of rats after oral administration of YKS. In the brains, GM was presumed to bind to 5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT7 receptors on neuron-like large cells mainly in the frontal cor-tex. Conclusion: These results suggest that GM is a pharmacologically important alkaloid that regulates vari-ous serotonergic activities or functions by binding to multiple 5-HT receptor subtypes. Thus, this review provides recent 5-HT receptor-related evidence that GM is partly responsible for pharmacological effects of YKS. PMID:28322152

31 CFR 351.64 - What is the issue date of a book-entry Series EE savings bond?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false What is the issue date of a book-entry... OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.64 What is the issue date of a book-entry Series EE savings bond? The issue date of a book-entry Series EE savings bond...

31 CFR 351.64 - What is the issue date of a book-entry Series EE savings bond?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What is the issue date of a book... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.64 What is the issue date of a book-entry Series EE savings bond? The issue date of a book-entry Series EE savings bond...

Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors.

PubMed

Acuña-Castillo, Claudio; Villalobos, Claudio; Moya, Pablo R; Sáez, Patricio; Cassels, Bruce K; Huidobro-Toro, J Pablo

2002-06-01

The pharmacological profile of a series of (+/-)-2,5-dimethoxy-4-(X)-phenylisopropylamines (X=I, Br, NO(2), CH(3), or H) and corresponding phenylethylamines, was determined in Xenopus laevis oocytes injected with cRNA coding for rat 5-HT(2A) or 5-HT(2C) receptors. The efficacy and relative potency of these drugs were determined and compared to classical 5-HT(2) receptor agonists and antagonists. The rank order of agonist potency at the 5-HT(2A) receptor was: alpha-methyl-5-HT=5-HT>m-CPP>MK-212; at the 5-HT(2C) receptor the order was: 5-HT>alpha-methyl-5-HT>MK-212>m-CPP. All these compounds were full agonists at the 5-HT(2C) receptor, but alpha-methyl-5-HT and m-CPP showed lower efficacy at the 5-HT(2A) receptor. 4-(4-Fluorobenzoyl)-1-(4-phenylbutyl)piperidine (4F 4PP) was 200 times more potent as a 5-HT(2A) antagonist than at 5-HT(2C) receptors. Conversely, RS 102221 was 100 times more potent as a 5-HT(2C) antagonist, confirming their relative receptor selectivities. The phenylisopropylamines were partial agonists at the 5-HT(2A) receptor, with I(max) relative to 5-HT in the 22+/-7 to 58+/-15% range; the corresponding phenylethylamines had lower or undetectable efficacies. All these drugs had higher efficacies at 5-HT(2C) receptors; DOI was a full 5-HT(2C) agonist. 2C-I and the other phenylethylamines examined showed relative efficacies at the 5-HT(2C) receptor ranging from 44+/-10% to 76+/-16%. 2C-N was a 5-HT(2) receptor antagonist; the mechanism was competitive at the 5-HT(2A), but non-competitive at the 5-HT(2C) receptor. The antagonism was time-dependent at the 5-HT(2C) receptor but independent of pre-incubation time at the 5-HT(2A) receptor subtype. The alpha-methyl group determines the efficacy of these phenylalkylamines at the 5-HT(2A) and 5-HT(2C) receptors.

Environmental enrichment improves novel object recognition and enhances agonistic behavior in male mice.

PubMed

Mesa-Gresa, Patricia; Pérez-Martinez, Asunción; Redolat, Rosa

2013-01-01

Environmental enrichment (EE) is an experimental paradigm in which rodents are housed in complex environments containing objects that provide stimulation, the effects of which are expected to improve the welfare of these subjects. EE has been shown to considerably improve learning and memory in rodents. However, knowledge about the effects of EE on social interaction is generally limited and rather controversial. Thus, our aim was to evaluate both novel object recognition and agonistic behavior in NMRI mice receiving EE, hypothesizing enhanced cognition and slightly enhanced agonistic interaction upon EE rearing. During a 4-week period half the mice (n = 16) were exposed to EE and the other half (n = 16) remained in a standard environment (SE). On PND 56-57, animals performed the object recognition test, in which recognition memory was measured using a discrimination index. The social interaction test consisted of an encounter between an experimental animal and a standard opponent. Results indicated that EE mice explored the new object for longer periods than SE animals (P < .05). During social encounters, EE mice devoted more time to sociability and agonistic behavior (P < .05) than their non-EE counterparts. In conclusion, EE has been shown to improve object recognition and increase agonistic behavior in adolescent/early adulthood mice. In the future we intend to extend this study on a longitudinal basis in order to assess in more depth the effect of EE and the consistency of the above-mentioned observations in NMRI mice. Copyright © 2013 Wiley Periodicals, Inc.

Effects of oral contraceptives containing ethinylestradiol with either drospirenone or levonorgestrel on various parameters associated with well-being in healthy women: a randomized, single-blind, parallel-group, multicentre study.

PubMed

Kelly, Sue; Davies, Emyr; Fearns, Simon; McKinnon, Carol; Carter, Rick; Gerlinger, Christoph; Smithers, Andrew

2010-01-01

The combined oral contraceptive Yasmin (drospirenone 3 mg plus ethinylestradiol 30 microg [DRSP 3 mg/EE 30 microg]) has been shown to be a well tolerated and effective combination that provides high contraceptive reliability and good cycle control. Furthermore, DRSP 3 mg/EE 30 microg has been shown to have a positive effect on premenstrual symptoms and well-being/health-related quality of life, and to improve the skin condition of women with acne. To date, however, there have been relatively few studies that have compared the effects of DRSP 3 mg/EE 30 microg on the general well-being of women with those of other oral contraceptives. To compare the impact of DRSP 3 mg/EE 30 microg with that of levonorgestrel 150 microg/EE 30 microg (LNG 150 microg/EE 30 microg; Microgynon 30) on various parameters associated with well-being in healthy female subjects. This was a randomized, single-blind, parallel-group, multicentre study conducted using 21/7-day regimens of DRSP 3 mg/EE 30 microg and LNG 150 microg/EE 30 microg over seven cycles. Efficacy parameters included: changes in Menstrual Distress Questionnaire (MDQ) normative T scores; the proportion of subjects with acne; and menstrual symptoms. Cycle control and subjective well-being parameters were also assessed. Treatment with DRSP 3 mg/EE 30 microg had similar beneficial effects on symptoms of water retention and impaired concentration to LNG 150 microg/EE 30 microg, but was significantly better in alleviating negative affect symptoms during the menstrual phase (median difference in MDQ T score -3; p = 0.027; Wilcoxon rank sum test). The proportion of subjects with acne decreased from approximately 55% to approximately 45% in the DRSP 3 mg/EE 30 microg group, but remained static at approximately 60% in the LNG 150 microg/EE 30 microg group. Somatic and psychological symptoms occurred at the greatest intensity and for most subjects during the menstrual phase of the cycle in both groups. Both drugs had similar cycle control parameters with a tendency towards reduced bleeding with continued use. More subjects in the DRSP 3 mg/EE 30 microg group reported improved physical well-being (60% vs 46%; p = 0.035; chi-squared [chi2] test). Emotional well-being was reported improved in 61% and 51% of DRSP 3 mg/EE 30 microg and LNG 150 microg/EE 30 microg users, respectively (p = 0.1190; chi2 test). Adverse events were typical of oral contraceptive use and did not give rise to any safety concerns. Both products had similar beneficial effects on symptoms of water retention and impaired concentration, but DRSP 3 mg/EE 30 microg was significantly better in alleviating negative affect symptoms during the menstrual phase. The proportion of subjects with acne decreased in the DRSP 3 mg/EE 30 microg group but not in the LNG 150 microg/EE 30 microg group. More subjects in the DRSP 3 mg/EE 30 microg group reported improved physical well-being compared with the LNG 150 microg/EE 30 microg group.

Salt stress encourages proline accumulation by regulating proline biosynthesis and degradation in Jerusalem artichoke plantlets.

PubMed

Huang, Zengrong; Zhao, Long; Chen, Dandan; Liang, Mingxiang; Liu, Zhaopu; Shao, Hongbo; Long, Xiaohua

2013-01-01

Proline accumulation is an important mechanism for osmotic regulation under salt stress. In this study, we evaluated proline accumulation profiles in roots, stems and leaves of Jerusalem artichoke (Helianthus tuberosus L.) plantlets under NaCl stress. We also examined HtP5CS, HtOAT and HtPDH enzyme activities and gene expression patterns of putative HtP5CS1, HtP5CS2, HtOAT, HtPDH1, and HtPDH2 genes. The objective of our study was to characterize the proline regulation mechanisms of Jerusalem artichoke, a moderately salt tolerant species, under NaCl stress. Jerusalem artichoke plantlets were observed to accumulate proline in roots, stems and leaves during salt stress. HtP5CS enzyme activities were increased under NaCl stress, while HtOAT and HtPDH activities generally repressed. Transcript levels of HtP5CS2 increased while transcript levels of HtOAT, HtPDH1 and HtPDH2 generally decreased in response to NaCl stress. Our results supports that for Jerusalem artichoke, proline synthesis under salt stress is mainly through the Glu pathway, and HtP5CS2 is predominant in this process while HtOAT plays a less important role. Both HtPDH genes may function in proline degradation.

Extremal edges: a powerful cue to depth perception and figure-ground organization.

PubMed

Palmer, Stephen E; Ghose, Tandra

2008-01-01

Extremal edges (EEs) are projections of viewpoint-specific horizons of self-occlusion on smooth convex surfaces. An ecological analysis of viewpoint constraints suggests that an EE surface is likely to be closer to the observer than the non-EE surface on the other side of the edge. In two experiments, one using shading gradients and the other using texture gradients, we demonstrated that EEs operate as strong cues to relative depth perception and figure-ground organization. Image regions with an EE along the shared border were overwhelmingly perceived as closer than either flat or equally convex surfaces without an EE along that border. A further demonstration suggests that EEs are more powerful than classical figure-ground cues, including even the joint effects of small size, convexity, and surroundedness.

Novel Antimicrobial Peptides EeCentrocins 1, 2 and EeStrongylocin 2 from the Edible Sea Urchin Echinus esculentus Have 6-Br-Trp Post-Translational Modifications

PubMed Central

Solstad, Runar Gjerp; Li, Chun; Isaksson, Johan; Johansen, Jostein; Svenson, Johan; Stensvåg, Klara; Haug, Tor

2016-01-01

The global problem of microbial resistance to antibiotics has resulted in an urgent need to develop new antimicrobial agents. Natural antimicrobial peptides are considered promising candidates for drug development. Echinoderms, which rely on innate immunity factors in the defence against harmful microorganisms, are sources of novel antimicrobial peptides. This study aimed to isolate and characterise antimicrobial peptides from the Edible sea urchin Echinus esculentus. Using bioassay-guided purification and cDNA cloning, three antimicrobial peptides were characterised from the haemocytes of the sea urchin; two heterodimeric peptides and a cysteine-rich peptide. The peptides were named EeCentrocin 1 and 2 and EeStrongylocin 2, respectively, due to their apparent homology to the published centrocins and strongylocins isolated from the green sea urchin Strongylocentrotus droebachiensis. The two centrocin-like peptides EeCentrocin 1 and 2 are intramolecularly connected via a disulphide bond to form a heterodimeric structure, containing a cationic heavy chain of 30 and 32 amino acids and a light chain of 13 amino acids. Additionally, the light chain of EeCentrocin 2 seems to be N-terminally blocked by a pyroglutamic acid residue. The heavy chains of EeCentrocins 1 and 2 were synthesised and shown to be responsible for the antimicrobial activity of the natural peptides. EeStrongylocin 2 contains 6 cysteines engaged in 3 disulphide bonds. A fourth peptide (Ee4635) was also discovered but not fully characterised. Using mass spectrometric and NMR analyses, EeCentrocins 1 and 2, EeStrongylocin 2 and Ee4635 were all shown to contain post-translationally brominated Trp residues in the 6 position of the indole ring. PMID:27007817

A systematic review of economic evaluation in pancreatic ductal adenocarcinoma.

PubMed

Gérard, Claire; Fagnoni, Philippe; Vienot, Angélique; Borg, Christophe; Limat, Samuel; Daval, Franck; Calais, François; Vardanega, Julie; Jary, Marine; Nerich, Virginie

2017-11-01

The economic evaluation (EE) of healthcare interventions has become a necessity. However, high quality needs to be ensured in order to achieve validated results and help making informed decisions. Thus, the objective of the present study was to systematically identify and review published pancreatic ductal adenocarcinoma-related EEs and to assess their quality. Systematic literature research was conducted in PubMed and Cochrane to identify published EEs between 2000 and 2015. The quality of each selected EE was assessed by two independent reviewers, using the Drummond's checklist. Our systematic review was based on 32 EEs and showed a wide variety of methodological approaches, including different perspectives, time horizon, and cost effectiveness analyses. Nearly two-thirds of EEs are full EEs (n = 21), and about one-third of EEs had a Drummond score ≥7, synonymous with 'high quality'. Close to 50% of full EEs had a Drummond score ≥7, whereas all of partial EEs had a Drummond score <7 (n = 11). Over the past 15 years, a lot of interest has been evinced over the EE of pancreatic ductal adenocarcinoma (PDAC) and its direct impact on therapeutic advances in PDAC. To provide a framework for health care decision-making, to facilitate transferability and to lend credibility to health EEs, their quality must be improved. For the last 4 years, a tendency towards a quality improvement of these studies has been observed, probably coupled with a context of rational decision-making in health care, a better and wider spread of recommendations and thus, medical practitioners' full endorsement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential neuronal plasticity in mouse hippocampus associated with various periods of enriched environment during postnatal development.

PubMed

Hosseiny, Salma; Pietri, Mariel; Petit-Paitel, Agnès; Zarif, Hadi; Heurteaux, Catherine; Chabry, Joëlle; Guyon, Alice

2015-11-01

Enriched environment (EE) is characterized by improved conditions for enhanced exploration, cognitive activity, social interaction and physical exercise. It has been shown that EE positively regulates the remodeling of neural circuits, memory consolidation, long-term changes in synaptic strength and neurogenesis. However, the fine mechanisms by which environment shapes the brain at different postnatal developmental stages and the duration required to induce such changes are still a matter of debate. In EE, large groups of mice were housed in bigger cages and were given toys, nesting materials and other equipment that promote physical activity to provide a stimulating environment. Weaned mice were housed in EE for 4, 6 or 8 weeks and compared with matched control mice that were raised in a standard environment. To investigate the differential effects of EE on immature and mature brains, we also housed young adult mice (8 weeks old) for 4 weeks in EE. We studied the influence of onset and duration of EE housing on the structure and function of hippocampal neurons. We found that: (1) EE enhances neurogenesis in juvenile, but not young adult mice; (2) EE increases the number of synaptic contacts at every stage; (3) long-term potentiation (LTP) and spontaneous and miniature activity at the glutamatergic synapses are affected differently by EE depending on its onset and duration. Our study provides an integrative view of the role of EE during postnatal development in various mechanisms of plasticity in the hippocampus including neurogenesis, synaptic morphology and electrophysiological parameters of synaptic connectivity. This work provides an explanation for discrepancies found in the literature about the effects of EE on LTP and emphasizes the importance of environment on hippocampal plasticity.

Mathematical model for the contribution of individual organs to non-zero y-intercepts in single and multi-compartment linear models of whole-body energy expenditure.

PubMed

Kaiyala, Karl J

2014-01-01

Mathematical models for the dependence of energy expenditure (EE) on body mass and composition are essential tools in metabolic phenotyping. EE scales over broad ranges of body mass as a non-linear allometric function. When considered within restricted ranges of body mass, however, allometric EE curves exhibit 'local linearity.' Indeed, modern EE analysis makes extensive use of linear models. Such models typically involve one or two body mass compartments (e.g., fat free mass and fat mass). Importantly, linear EE models typically involve a non-zero (usually positive) y-intercept term of uncertain origin, a recurring theme in discussions of EE analysis and a source of confounding in traditional ratio-based EE normalization. Emerging linear model approaches quantify whole-body resting EE (REE) in terms of individual organ masses (e.g., liver, kidneys, heart, brain). Proponents of individual organ REE modeling hypothesize that multi-organ linear models may eliminate non-zero y-intercepts. This could have advantages in adjusting REE for body mass and composition. Studies reveal that individual organ REE is an allometric function of total body mass. I exploit first-order Taylor linearization of individual organ REEs to model the manner in which individual organs contribute to whole-body REE and to the non-zero y-intercept in linear REE models. The model predicts that REE analysis at the individual organ-tissue level will not eliminate intercept terms. I demonstrate that the parameters of a linear EE equation can be transformed into the parameters of the underlying 'latent' allometric equation. This permits estimates of the allometric scaling of EE in a diverse variety of physiological states that are not represented in the allometric EE literature but are well represented by published linear EE analyses.

Experiment 2033. Injection Test of Upper EE-3 Fracture Zone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grigsby, Charles O.

1983-09-12

This experiment is designed to investigate the apparent lithologic boundary between the low-opening-pressure fracture system (upper EE-3 fracture and Phase I system) and the high-opening-pressure fracture system (lower fracture in EE-3 and in EE-2). The experiment will test for resistence to breakthrough into the lower EE-2 fracture system at relatively low pressure and will define the veting behavior of the low pressure system.

Comparison of effects of 3 mg drospirenone plus 20 μg ethinyl estradiol alone or combined with metformin or cyproterone acetate on classic metabolic cardiovascular risk factors in nonobese women with polycystic ovary syndrome.

PubMed

Fruzzetti, Franca; Perini, Daria; Lazzarini, Veronica; Parrini, Donatella; Gambacciani, Marco; Genazzani, Andrea Riccardo

2010-10-01

To evaluate the effects of a pill with drospirenone (3 mg) plus ethinyl E(2) (20 μg) (DRP/20EE) alone or associated with metformin or cyproterone acetate (CPA) on some metabolic cardiovascular risk factors in women with polycystic ovary syndrome (PCOS). Randomized, open-label clinical trial. Academic medical clinic. Forty-eight hirsute women with PCOS. Patients were randomized to treatment with DRP/20EE or with DRP/20EE plus metformin (1,500 mg/d) or with DRP/20EE plus CPA (12.5 mg/d, 10 days per cycle) for 6 months. Blood pressure, lipid profile, and indexes of glucose tolerance and insulin sensitivity were assessed before and after 6 months of treatment. Body mass index and blood pressure were not modified by any treatment. Treatment with DRP/EE20 did not change the lipid profile; DRP/EE20 plus metformin significantly increased high-density lipoprotein cholesterol concentrations; DRP/EE20 plus CPA significantly increased triglycerides and total cholesterol. The area under the curve for insulin was significantly decreased by DRP/EE20 and DRP/EE20 plus metformin, but it was significantly increased by DRP/EE20 plus CPA. Treatment with DRP/EE20 plus CPA significantly increased the homeostasis model assessment of insulin resistance index and significantly reduced the glucose to insulin ratio index. Treatment with DRP/EE20 significantly increased the glucose to insulin ratio index. Treatment with DRP/EE20 improved insulin sensitivity in hirsute women with PCOS, with no deterioration of lipid profile. This effect was not ameliorated by the addition of metformin. The positive metabolic effects of DRP are abolished by the concomitant use of CPA. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A prospective study on the effects on hemostasis of two oral contraceptives containing drospirenone in combination with either 30 or 20 microg ethinyl estradiol and a reference containing desogestrel and 30 microg ethinyl estradiol.

PubMed

Kluft, Cornelis; Endrikat, Jan; Mulder, Simone M; Gerlinger, Christoph; Heithecker, Renate

2006-04-01

In this open-label, randomized study, we assessed the effects on hemostasis of two combined oral contraceptives containing drospirenone (DRSP) as progestogen component. Three milligrams of DRSP, a progestogen with antimineralocorticoid activity, was combined with either 30 or 20 microg ethinyl estradiol (EE) (DRSP/30EE; DRSP/20EE) and compared with a preparation containing 150 microg desogestrel (DSG) and 30 microg ethinyl estradiol (DSG/30EE). A total of 75 healthy female volunteers aged 18-35 years were enrolled. The hemostasis variables were measured in the medication-free precycle (baseline); in the first, third and sixth treatment cycle; and in the follow-up phase. The target variables for comparison were the relative changes from baseline to Cycle 6. Data of 25 volunteers in each group were valid for the per-protocol evaluation. Most changes in hemostasis variables were similar in the three treatment groups. All procoagulatory variables and the anticoagulatory variable protein C antigen increased slightly, while protein S antigen and activity decreased. For fibrinogen and protein S activity, the changes were statistically significant: less pronounced with DRSP/20EE compared to DSG/30EE at Cycle 6. There were no statistically significant differences in the changes of antifibrinolytic variables, the global clotting tests and D-dimer. All pairwise comparisons of DRSP/30EE vs. DSG/30EE yielded nonsignificant results; however, there was a trend of a lower impact of DRSP/20EE on nearly all hemostatic parameters compared to the 30EE products. All three study treatments were safe and well tolerated by the volunteers and provided adequate contraceptive reliability. The changes in the hemostatic variables for DRSP/20EE were less pronounced compared to DSG/30EE and DRSP/30EE. The results were in accordance with previous reports on effects of similar OCs.

Exploring dynamism of cultural ecosystems services through a review of environmental education research.

PubMed

Gould, Rachelle K; Coleman, Kimberly; Gluck, Sonya Buglion

2018-04-11

The field of cultural ecosystem services (CES) explores the non-material benefits that ecosystems provide to people. Human perceptions and valuations change, for many reasons and in many ways; research on CES, however, rarely accounts for this dynamism. In an almost entirely separate academic world, research on environmental education (EE) explores how EE programming affects peoples' attitudes and values toward the natural world. In this review of 119 EE research publications, we explore whether CES (and the adjacent concept of relational values) can be dynamic. We approach this via two lines of inquiry that explore whether EE may instigate this change. First, we investigate whether the EE community measures (and tries to affect) CES-related outcomes. Second, we ask: Has EE research detected changes in CES-related outcomes? We find the EE programs measure many CES outcomes (e.g., aesthetic appreciation, social connectedness), and that in most cases studies observe increases in these outcomes after EE experiences.

Help-Seeking in People with Exceptional Experiences: Results from a General Population Sample

PubMed Central

Landolt, Karin; Wittwer, Amrei; Wyss, Thomas; Unterassner, Lui; Fach, Wolfgang; Krummenacher, Peter; Brugger, Peter; Haker, Helene; Kawohl, Wolfram; Schubiger, Pius August; Folkers, Gerd; Rössler, Wulf

2014-01-01

Background: Exceptional experiences (EE) are experiences that deviate from ordinary experiences, for example precognition, supernatural appearances, or déjà vues. In spite of the high frequency of EE in the general population, little is known about their effect on mental health and about the way people cope with EE. This study aimed to assess the quality and quantity of EE in persons from the Swiss general population, to identify the predictors of their help-seeking, and to determine how many of them approach the mental health system. Methods: An on-line survey was used to evaluate a quota sample of 1580 persons representing the Swiss general population with respect to gender, age, and level of education. Multinomial logistic regression was applied to integrate help-seeking, self-reported mental disorder, and other variables in a statistical model designed to identify predictors of help-seeking in persons with EE. Results: Almost all participants (91%) experienced at least one EE. Generally, help-seeking was more frequent when the EE were of negative valence. Help-seeking because of EE was less frequent in persons without a self-reported mental disorder (8.6%) than in persons with a disorder (35.1%) (OR = 5.7). Even when frequency and attributes of EE were controlled for, people without a disorder sought four times less often help because of EE than expected. Persons with a self-reported diagnosis of mental disorder preferred seeing a mental health professional. Multinomial regression revealed a preference for healers in women with less education, who described themselves as believing and also having had more impressive EE. Conclusion: Persons with EE who do not indicate a mental disorder less often sought help because of EE than persons who indicated a mental disorder. We attribute this imbalance to a high inhibition threshold to seek professional help. Moreover, especially less educated women did not approach the mental health care system as often as other persons with EE, but preferred seeing a healer. PMID:24904915

An open label, comparative study of the effects of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol and 100 microg levonorgestrel on hemostatic, lipids, and carbohydrate metabolism variables.

PubMed

Endrikat, Jan; Klipping, C; Cronin, M; Gerlinger, C; Ruebig, A; Schmidt, W; Düsterberg, B

2002-03-01

In this open label, randomized study we compared the influence of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol (EE) and 100 microg levonorgestrel (20 EE) with a reference preparation containing 30 microg EE and 150 microg levonorgestrel (30 EE) on hemostatic, lipids, and carbohydrate metabolism variables. Data from 48 volunteers were obtained. The direction of the change (increase or decrease) in most of the hemostatic variables were similar in both treatment groups. In particular, prothrombin fragment 1 + 2 increased during treatment, reaching a median percent change of 40% in the 20 EE group and of 17% in the 30 EE group after one year. D-Dimer fibrin split products remained virtually unchanged, with no change at Cycle 13. The median HDL2 cholesterol levels decreased by 26% in the 20 EE group and by 39.8% in 30 EE group (p = 0.0045 for group difference) after one year. The median one year change for LDL cholesterol was 3.23% in the 20 EE group, compared to 25% in the 30 EE group, for VLDL 11.1% compared to 38.8%, respectively, and for total triglycerides 10.0% compared to 37.5%, respectively. The median absolute change for the area under the curve (AUC)(0-3h) for glucose at treatment Cycle 13 was 41.25 mmol/L x min in the 20 EE group and 73.50 mmol/L x min in the 30 EE group. The AUC(0-3h) insulin at treatment Cycle 13 decreased in the 20 EE group by 1635.0 pmolL x min and increased in the 30 EE group by 11797.5 pmolL x min (p = 0.0491 for group difference). Both study treatments were safe and well tolerated by the volunteers. In conclusion, the balanced one-third dose reduction in this new oral contraceptive evoked similar effects on the hemostatic variables, but favorable results for the lipid and carbohydrate profiles.

Ventriculo-arterial coupling detects occult RV dysfunction in chronic thromboembolic pulmonary vascular disease.

PubMed

Axell, Richard G; Messer, Simon J; White, Paul A; McCabe, Colm; Priest, Andrew; Statopoulou, Thaleia; Drozdzynska, Maja; Viscasillas, Jamie; Hinchy, Elizabeth C; Hampton-Till, James; Alibhai, Hatim I; Morrell, Nicholas; Pepke-Zaba, Joanna; Large, Stephen R; Hoole, Stephen P

2017-04-01

Chronic thromboembolic disease (CTED) is suboptimally defined by a mean pulmonary artery pressure (mPAP) <25 mmHg at rest in patients that remain symptomatic from chronic pulmonary artery thrombi. To improve identification of right ventricular (RV) pathology in patients with thromboembolic obstruction, we hypothesized that the RV ventriculo-arterial (Ees/Ea) coupling ratio at maximal stroke work (Ees/Ea max sw ) derived from an animal model of pulmonary obstruction may be used to identify occult RV dysfunction (low Ees/Ea) or residual RV energetic reserve (high Ees/Ea). Eighteen open chested pigs had conductance catheter RV pressure-volume (PV)-loops recorded during PA snare to determine Ees/Ea max sw This was then applied to 10 patients with chronic thromboembolic pulmonary hypertension (CTEPH) and ten patients with CTED, also assessed by RV conductance catheter and cardiopulmonary exercise testing. All patients were then restratified by Ees/Ea. The animal model determined an Ees/Ea max sw  = 0.68 ± 0.23 threshold, either side of which cardiac output and RV stroke work fell. Two patients with CTED were identified with an Ees/Ea well below 0.68 suggesting occult RV dysfunction whilst three patients with CTEPH demonstrated Ees/Ea ≥ 0.68 suggesting residual RV energetic reserve. Ees/Ea > 0.68 and Ees/Ea < 0.68 subgroups demonstrated constant RV stroke work but lower stroke volume (87.7 ± 22.1 vs. 60.1 ± 16.3 mL respectively, P  = 0.006) and higher end-systolic pressure (36.7 ± 11.6 vs. 68.1 ± 16.7 mmHg respectively, P  < 0.001). Lower Ees/Ea in CTED also correlated with reduced exercise ventilatory efficiency. Low Ees/Ea aligns with features of RV maladaptation in CTED both at rest and on exercise. Characterization of Ees/Ea in CTED may allow for better identification of occult RV dysfunction. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Characterisation of 5-HT3C, 5-HT3D and 5-HT3E receptor subunits: evolution, distribution and function.

PubMed

Holbrook, Joanna D; Gill, Catherine H; Zebda, Noureddine; Spencer, Jon P; Leyland, Rebecca; Rance, Kim H; Trinh, Han; Balmer, Gemma; Kelly, Fiona M; Yusaf, Shahnaz P; Courtenay, Nicola; Luck, Jane; Rhodes, Andrew; Modha, Sundip; Moore, Stephen E; Sanger, Gareth J; Gunthorpe, Martin J

2009-01-01

The 5-HT(3) receptor is a member of the 'Cys-loop' family of ligand-gated ion channels that mediate fast excitatory and inhibitory transmission in the nervous system. Current evidence points towards native 5-HT(3) receptors originating from homomeric assemblies of 5-HT(3A) or heteromeric assembly of 5-HT(3A) and 5-HT(3B). Novel genes encoding 5-HT(3C), 5-HT(3D), and 5-HT(3E) have recently been described but the functional importance of these proteins is unknown. In the present study, in silico analysis (confirmed by partial cloning) indicated that 5-HT(3C), 5-HT(3D), and 5-HT(3E) are not human-specific as previously reported: they are conserved in multiple mammalian species but are absent in rodents. Expression profiles of the novel human genes indicated high levels in the gastrointestinal tract but also in the brain, Dorsal Root Ganglion (DRG) and other tissues. Following the demonstration that these subunits are expressed at the cell membrane, the functional properties of the recombinant human subunits were investigated using patch clamp electrophysiology. 5-HT(3C), 5-HT(3D), and 5-HT(3E) were all non-functional when expressed alone. Co-transfection studies to determine potential novel heteromeric receptor interactions with 5-HT(3A) demonstrated that the expression or function of the receptor was modified by 5-HT(3C) and 5-HT(3E), but not 5-HT(3D). The lack of distinct effects on current rectification, kinetics or pharmacology of 5-HT(3A) receptors does not however provide unequivocal evidence to support a direct contribution of 5-HT(3C) or 5-HT(3E) to the lining of the ion channel pore of novel heteromeric receptors. The functional and pharmacological contributions of these novel subunits to human biology and diseases such as irritable bowel syndrome for which 5-HT(3) receptor antagonists have major clinical usage, therefore remains to be fully determined.

Vortioxetine dose-dependently reverses 5-HT depletion-induced deficits in spatial working and object recognition memory: a potential role for 5-HT1A receptor agonism and 5-HT3 receptor antagonism.

PubMed

du Jardin, Kristian Gaarn; Jensen, Jesper Bornø; Sanchez, Connie; Pehrson, Alan L

2014-01-01

We previously reported that the investigational multimodal antidepressant, vortioxetine, reversed 5-HT depletion-induced memory deficits while escitalopram and duloxetine did not. The present report studied the effects of vortioxetine and the potential impact of its 5-HT1A receptor agonist and 5-HT3 receptor antagonist properties on 5-HT depletion-induced memory deficits. Recognition and spatial working memory were assessed in the object recognition (OR) and Y-maze spontaneous alternation (SA) tests, respectively. 5-HT depletion was induced in female Long-Evans rats using 4-cholro-DL-phenylalanine methyl ester HCl (PCPA) and receptor occupancies were determined by ex vivo autoradiography. Rats were acutely dosed with vortioxetine, ondansetron (5-HT3 receptor antagonist) or flesinoxan (5-HT1A receptor agonist). The effects of chronic vortioxetine administration on 5-HT depletion-induced memory deficits were also assessed. 5-HT depletion reliably impaired memory performance in both the tests. Vortioxetine reversed PCPA-induced memory deficits dose-dependently with a minimal effective dose (MED) ≤0.1mg/kg (∼80% 5-HT3 receptor occupancy; OR) and ≤3.0mg/kg (5-HT1A, 5-HT1B, 5-HT3 receptor occupancy: ∼15%, 60%, 95%) in SA. Ondansetron exhibited a MED ≤3.0μg/kg (∼25% 5-HT3 receptor occupancy; OR), but was inactive in the SA test. Flesinoxan had a MED ≤1.0mg/kg (∼25% 5-HT1A receptor occupancy; SA); only 1.0mg/kg ameliorated deficits in the NOR. Chronic p.o. vortioxetine administration significantly improved memory performance in OR and occupied 95%, 66%, and 9.5% of 5-HT3, 5-HT1B, and 5-HT1A receptors, respectively. Vortioxetine's effects on SA performance may involve 5-HT1A receptor agonism, but not 5-HT3 receptor antagonism, whereas the effects on OR performance may involve 5-HT3 receptor antagonism and 5-HT1A receptor agonism. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Environmental enrichment reduces cocaine neurotoxicity during cocaine-conditioned place preference in male rats.

PubMed

Freese, Luana; Almeida, Felipe Borges; Heidrich, Nubia; Hansen, Alana Witt; Steffens, Luiza; Steinmetz, Aline; Moura, Dinara Jaqueline; Gomez, Rosane; Barros, Helena Maria Tannhauser

2018-06-01

Environmental enrichment (EE) has a neuroprotective role and prevents the development of cocaine addiction behavior in rats. Studies showing the role of EE in cocaine toxicity are nonexistent. We hypothesized that rats exposed to EE are protected from cocaine-induced changes in the redox profile and DNA damage after undergoing conditioned place preference (CPP). Ten male Wistar rats were placed in EE cages equipped with toys, a ladder and tunnels, and ten were provided clean, standard laboratory housing (non-EE). EE and non-EE rats were randomly allocated to the classical CPP cocaine vs. saline (COC/Saline) group, where cocaine (15 mg/kg; i.p.) was tested alternately with saline. Afterwards, intracellular reactive species and antioxidant enzymes were evaluated and the comet essay was performed in the prefrontal cortex and hippocampus of rats. As expected, EE rats spent less time in the cocaine-paired chamber, and as a new result, less cocaine-induced DNA damage was observed in the two brain structures. Altogether, our results demonstrate that EE decreases neurotoxicity in brain regions linked to cocaine addiction but does not extinguish it completely. Copyright © 2018. Published by Elsevier Inc.

The bioequivalence of the contraceptive steroids ethinylestradiol and drospirenone is not affected by co-administration of dehydroepiandrosterone.

PubMed

Zimmerman, Yvette; Wouters, Wout; Coelingh Bennink, Herjan J T

2013-06-01

To study the effect of co-administration of 50 mg dehydroepiandrosterone (DHEA) on the bioequivalence of ethinylestradiol (EE) and drospirenone (DRSP) in women who were using a combined oral contraceptive (COC) containing 30 μg EE and 3 mg DRSP, and to estimate whether the addition of DHEA to this COC affects the serum levels and the bioequivalence of the synthetic contraceptive steroids. This was a randomised, double-blind, two-period crossover study. Participants received two EE/DRSP COC treatment cycles in random order, one with and one without daily 50 mg DHEA , separated by a 28-day wash-out cycle during which the subjects used an EE/levonorgestrel (LNG) COC without DHEA. Serum levels of EE and DRSP were measured according to a sampling scheme allowing pharmacokinetic evaluations. Addition of DHEA to an EE/DRSP COC had no effect on serum levels of EE and DRSP. The COC regimens with and without DHEA were bioequivalent. Oestradiol levels were equally suppressed during pill intake, whether with placebo or DHEA. Adding DHEA to a COC containing EE and DRSP does not affect the pharmacokinetic properties of EE and DRSP. Therefore, it will most likely not affect its contraceptive efficacy.

Tianeptine: 5-HT uptake sites and 5-HT(1-7) receptors modulate memory formation in an autoshaping Pavlovian/instrumental task.

PubMed

Meneses, Alfredo

2002-05-01

Recent studies using invertebrate and mammal species have revealed that, endogenous serotonin (5-hydroxytryptamine, 5-HT) modulates cognitive processes, particularly learning and memory, though, at present, it is unclear the manner, where, and how long 5-HT systems are involved. Hence in this work, an attempt was made to study the effects of 5-HT endogenous on memory formation, using a 5-HT uptake facilitator (tianeptine) and, selective 5-HT(1-7) receptor antagonists to determine whether 5-HT uptake sites and which 5-HT receptors are involved, respectively. Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task, which has been useful to detect changes on memory formation elicited by drugs or aging. On interaction experiments, ketanserin (5-HT(1D/2A/2C) antagonist) slightly enhanced tianeptine effects, while WAY 100635 (5-HT(1A) antagonist), SB-224289 (5-HT(1B) inverse agonist), SB-200646 (5-HT(2B/2C) antagonist), ondansetron (5-HT(3) antagonist), GR 127487 (5-HT(4) antagonist), Ro 04-6790 (5-HT(6) antagonist), DR 4004 (5-HT(7) antagonist), or fluoxetine (an inhibitor of 5-HT reuptake) blocked the facilitatory tianeptine effect. Notably, together tianeptine and Ro 04-6790 impaired learning consolidation. Moreover, 5-HT depletion completely reversed the tianeptine effect. Tianeptine also normalized an impaired memory elicited by scopolamine (an antimuscarinic) or dizocilpine (non-competitive glutamatergic antagonist), while partially reversed that induced by TFMPP (5-HT(1B/1D/2A-2C/7) agonist/antagonist). Finally, tianeptine-fluoxetine coadministration had no effect on learning consolidation; nevertheless, administration of an acetylcholinesterase inhibitor, phenserine, potentiated subeffective tianeptine or fluoxetine doses. Collectively, these data confirmed that endogenously 5-HT modulates, via uptake sites and 5-HT(1-7) receptors, memory consolidation, and are consistent with the emerging notion that 5-HT plays a key role on memory formation.

Both exogenous 5-HT and endogenous 5-HT, released by fluoxetine, enhance distension evoked propulsion in guinea-pig ileum in vitro.

PubMed

Gwynne, Rachel M; Clarke, Amanda J; Furness, John B; Bornstein, Joel C

2014-01-01

The roles of 5-HT3 and 5-HT4 receptors in the modulation of intestinal propulsion by luminal application of 5-HT and augmentation of endogenous 5-HT effects were studied in segments of guinea-pig ileum in vitro. Persistent propulsive contractions evoked by saline distension were examined using a modified Trendelenburg method. When 5-HT (30 nM), fluoxetine (selective serotonin reuptake inhibitor; 1 nM), 2-methyl-5-HT (5-HT3 receptor agonist; 1 mM), or RS 67506 (5-HT4 receptor agonist, 1 μM) was infused into the lumen, the pressure needed to initiate persistent propulsive activity fell significantly. A specific 5-HT4 receptor antagonist, SB 207266 (10 nM in lumen), abolished the effects of 5-HT, fluoxetine, and RS 67506, but not those of 2-methyl-5-HT. Granisetron (5-HT3 receptor antagonist; 1 μM in lumen) abolished the effect of 5-HT, fluoxetine, RS 67506, and 2-methyl-5-HT. The NK3 receptor antagonist SR 142801 (100 nM in lumen) blocked the effects of 5-HT, fluoxetine, and 2-methyl-5-HT. SB 207266, granisetron, and SR 142801 had no effect by themselves. Higher concentrations of fluoxetine (100 and 300 nM) and RS 67506 (3 and 10 μM) had no effect on the distension threshold for propulsive contractions. These results indicate that luminal application of exogenous 5-HT, or increased release of endogenous mucosal 5-HT above basal levels, acts to lower the threshold for propulsive contractions in the guinea-pig ileum via activation of 5-HT3 and 5-HT4 receptors and the release of tachykinins. The results further indicate that basal release of 5-HT is insufficient to alter the threshold for propulsive motor activity.

The inhibition of cholera toxin-induced 5-HT release by the 5-HT3 receptor antagonist, granisetron, in the rat

PubMed Central

Turvill, J L; Connor, P; Farthing, M J G

2000-01-01

The secretagogue 5-hydroxytryptamine (5-HT) is implicated in the pathophysiology of cholera. 5-HT released from enterochromaffin cells after cholera toxin exposure is thought to activate non-neuronally (5-HT2 dependent) and neuronally (5-HT3 dependent) mediated water and electrolyte secretion. CT-secretion can be reduced by preventing the release of 5-HT. Enterochromaffin cells possess numerous receptors that, under basal conditions, modulate 5-HT release. These include basolateral 5-HT3 receptors, the activation of which is known to enhance 5-HT release. Until now, 5-HT3 receptor antagonists (e.g. granisetron) have been thought to inhibit cholera toxin-induced fluid secretion by blockading 5-HT3 receptors on secretory enteric neurones. Instead we postulated that they act by inhibiting cholera toxin-induced enterochromaffin cell degranulation. Isolated intestinal segments in anaesthetized male Wistar rats, pre-treated with granisetron 75 μg kg−1, lidoocaine 6 mg kg−1 or saline, were instilled with a supramaximal dose of cholera toxin or saline. Net fluid movement was determined by small intestinal perfusion or gravimetry and small intestinal and luminal fluid 5-HT levels were determined by HPLC with fluorimetric detection. Intraluminal 5-HT release was proportional to the reduction in tissue 5-HT levels and to the onset of water and electrolyte secretion, suggesting that luminal 5-HT levels reflect enterochromaffin cell activity. Both lidocaine and granisetron inhibited fluid secretion. However, granisetron alone, and proportionately, reduced 5-HT release. The simultaneous inhibition of 5-HT release and fluid secretion by granisetron suggests that 5-HT release from enterochromaffin cells is potentiated by endogenous 5-HT3 receptors. The accentuated 5-HT release promotes cholera toxin-induced fluid secretion. PMID:10882387

5-HT2 receptor blockade exhibits 5-HT vasodilator effects via nitric oxide, prostacyclin and ATP-sensitive potassium channels in rat renal vasculature.

PubMed

García-Pedraza, J A; García, M; Martín, M L; Rodríguez-Barbero, A; Morán, A

2016-04-01

The aim of this study was to determine whether orally sarpogrelate (selective 5-HT2 antagonist) treatment (30 mg/kg/day; 14 days) could modify 5-HT renal vasoconstrictor responses, characterizing 5-HT receptors and mediator mechanisms involved in serotonergic responses in the in situ autoperfused rat kidney. Intra-arterial (i.a.) injections of 5-HT (0.00000125 to 0.1 μg/kg) decreased renal perfusion pressure (RPP) but did not affect the mean blood pressure (MBP). i.a. agonists 5-CT (5-HT1/7), CGS-12066B (5-HT1B), L-694,247 (5-HT1D) or AS-19 (5-HT7) mimicked renal 5-HT vasodilator effect. However, neither 8-OH-DPAT (5-HT1A) nor 1-phenylbiguanide (5-HT3) modified RPP. Moreover: (i) GR-55562 (5-HT1B antagonist) and L-NAME (nitric oxide synthase [NOS] inhibitor) blocked CGS-12066B-induced vasodilator response, (ii) LY310762 (5-HT1D antagonist) and indomethacin (non-selective cyclooxygenase inhibitor) blocked L-694,247-induced vasodilator response; (iii) SB-258719 (5-HT7 antagonist) and glibenclamide (ATP-sensitive K+ channel blocker) blocked AS-19-induced vasodilator response; and (iv) 5-HT- or 5-CT-elicited renal vasodilation was significantly blocked by the mixture of GR-55562 + LY310762 + SB-258719. Furthermore, eNOS and iNOS proteins and prostacyclin levels are overexpressed in sarpogrelate-treated rats. Our data suggest that 5-HT exerts renal vasodilator effect in the in situ autoperfused sarpogrelate-treated rat kidney, mediated by 5-HT1D, 5-HT1B and 5-HT7 receptors, involving cyclooxygenase-derived prostacyclin, nitric oxide synthesis/release and ATP-sensitive K+ channels, respectively.

Native serotonin 5-HT3 receptors expressed in Xenopus oocytes differ from homopentameric 5-HT3 receptors.

PubMed

van Hooft, J A; Kreikamp, A P; Vijverberg, H P

1997-09-01

Efficacies of the 5-hydroxytryptamine (serotonin) 5-HT3 receptor (5-HT3R) agonists 2-methyl-5-HT, dopamine, and m-chlorophenylbiguanide on 5-HT3R native to N1E-115 cells and on homopentameric 5-HT3R expressed in Xenopus oocytes were determined relative to that of 5-HT. Efficacies of 2-methyl-5-HT and dopamine on 5-HT3R native to differentiated N1E-115 cells are high (54 and 36%) as compared with their efficacies on homopentameric 5-HT3R-A(L) and 5-HT3R-A(S) receptors expressed in oocytes (4-8%). m-Chlorophenylbiguanide does not distinguish between 5-HT3R in N1E-115 cells and in oocytes. The distinct pharmacological profile of 5-HT3R native to differentiated N1E-115 cells is conserved when poly(A)+ mRNA from these cells is expressed in oocytes. The results indicate that, apart from the known 5-HT3R subunits, N1E-115 cells express additional proteins involved in 5-HT3R function.

Reliability of symptoms and endoscopic findings for diagnosis of esophageal eosinophilia in a Japanese population.

PubMed

Shimura, Shino; Ishimura, Norihisa; Tanimura, Takashi; Yuki, Takafumi; Miyake, Tatsuya; Kushiyama, Yoshinori; Sato, Shuichi; Fujishiro, Hirofumi; Ishihara, Shunji; Komatsu, Taisuke; Kaneto, Eiji; Izumi, Akio; Ishikawa, Noriyoshi; Maruyama, Riruke; Kinoshita, Yoshikazu

2014-01-01

The clinical characteristics of esophageal eosinophilia (EE), which is essential for diagnosis of eosinophilic esophagitis (EoE), have not been fully clarified in a Japanese population. The aim of this study was to analyze the reliability of symptoms and endoscopic findings for diagnosing EE in Japanese individuals. We prospectively enrolled subjects who complained of esophageal symptoms suggesting EoE and/or those with endoscopic findings of suspected EoE at the outpatient clinics of 12 hospitals. Diagnostic utility was compared between the EE and non-EE groups using logistic regression analysis. A total of 349 patients, including 319 with symptoms and 30 with no symptoms but endoscopic findings suggesting EoE were enrolled. Of those with symptoms, 8 (2.5%) had EE, and 3 were finally diagnosed with EoE. Of those without symptoms but endoscopic findings, 4 had EE. Among 8 symptomatic patients, 7 had abnormal endoscopic findings suspicious of EoE. Although dysphagia was a major symptom in EE, none of the presenting symptoms was useful for diagnosis of EE. Among the endoscopic findings, linear furrow was the most reliable (OR = 41.583). EE is uncommon among patients with esophageal symptoms in Japanese individuals. The most useful endoscopic finding for diagnosis of EE was linear furrow, whereas subjective symptoms were not supportive. © 2014 S. Karger AG, Basel.

Ethinyl estradiol-to-desogestrel ratio impacts endothelial function in young women✩

PubMed Central

Meendering, Jessica R.; Torgrimson, Britta N.; Miller, Nicole P.; Kaplan, Paul F.; Minson, Christopher T.

2010-01-01

Background Ethinyl estradiol (EE) and progestins have the ability to alter endothelial function. The type of progestin and the ratio of EE to progestin used in oral contraceptive pills (OCPs) may determine how they affect the arterial vasculature. Study Design In this study, we investigated endothelial function across a cycle in very low dose (VLD) and low dose (LD) combination EE and desogestrel (DSG) OCP users during two phases: active (VLD=20 mcg EE/150 mcg DSG; LD=30 mcg EE/150 mcg DSG) and pill-free. Endothelial function was also measured during an EE-only hormone phase (10 mcg EE) in group VLD. Results Endothelium-dependent vasodilation was greater during the active phase compared to the pill-free phase in group LD (9.02±0.72% vs. 7.33±0.84%; p=.029). This phase difference was not observed in group VLD (5.86±0.63% vs. 6.56±0.70%; p=.108). However, endothelium-dependent vasodilation was higher during the EE-only phase, compared to the active and pill-free phases (8.92±0.47% vs. 5.86±0.63%, and 6.56±0.70%; pb.001) in group VLD. Conclusions These data suggest DSG may antagonize the vasodilatory activity of EE and that this effect is further modulated by the EE-toDSG ratio. PMID:19041440

Comparison of 2 correction methods for absolute values of esophageal pressure in subjects with acute hypoxemic respiratory failure, mechanically ventilated in the ICU.

PubMed

Guérin, Claude; Richard, Jean-Christophe

2012-12-01

A recent trial showed that setting PEEP according to end-expiratory transpulmonary pressure (P(pl,ee)) in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) might improve patient outcome. P(pl,ee) was obtained by subtracting the absolute value of esophageal pressure (P(es)) from airway pressure an invariant value of 5 cm H(2)O. The goal of the present study was to compare 2 methods for correcting absolute P(es) values in terms of resulting P(pl,ee) and recommended PEEP. Measurements collected prospectively from 42 subjects with various forms of acute hypoxemic respiratory failure receiving mechanical ventilation in ICU were analyzed. P(es) was measured at PEEP (P(es,ee)) and at relaxation volume of the respiratory system Vr (P(es,Vr)), obtained by allowing the subject to exhale into the atmosphere (zero PEEP). Two methods for correcting P(es) were compared: Talmor method (P(pl,ee,Talmor) = P(es,ee) - 5 cm H(2)O), and Vr method (P(es,ee,Vr) = P(es,ee) - P(es,Vr)). The rationale was that P(es,Vr) was a more physiologically based correction factor than an invariant value of 5 cm H(2)O applied to all subjects. Over the 42 subjects, median and interquartile range of P(es,ee) and P(es,Vr) were 11 (7-14) cm H(2)O and 8 (4-11) cm H(2)O, respectively. P(pl,ee,Talmor) was 6 (1-8) cm H(2)O, and P(es,ee,Vr) was 2 (1-5) cm H(2)O (P = .008). Two groups of subjects were defined, based on the difference between the 2 corrected values. In 28 subjects P(pl,ee,Talmor) was ≥ P(es,ee,Vr) (7 [5-9] cm H(2)O vs 2 [1-5] cm H(2)O, respectively), while in 14 subjects P(es,ee,Vr) was > P(pl,ee,Talmor) (2 [0-4] cm H(2)O vs -1 [-3 to 2] cm H(2)O, respectively). P(pl,ee,Vr) was significantly greater than P(pl,ee,Talmor) (7 [5-11] cm H(2)O vs 5 [2-7] cm H(2)O) in the former, and significantly lower in the latter (1 [-2 to 6] cm H(2)O vs 6 [4-9] cm H(2)O). Referring absolute P(es) values to Vr rather than to an invariant value would be better adapted to a patient's physiological background. Further studies are required to determine whether this correction method might improve patient outcome.

Influence of environmental enrichment on hypothalamic-pituitary-adrenal (HPA) responses to single-dose nicotine, continuous nicotine by osmotic mini-pumps, and nicotine withdrawal by mecamylamine in male and female rats

PubMed Central

Skwara, Amanda J.; Karwoski, Tracy E.; Czambel, R. Kenneth; Rubin, Robert T.; Rhodes, Michael E.

2012-01-01

In the present study, we determined the effects of environmental enrichment (EE; Kong Toys® and Nestlets®) on sexually diergic HPA axis responses to single-dose nicotine (NIC), single-dose NIC following continuous NIC administration for two weeks, and NIC withdrawal by single-dose mecamylamine (MEC) in male and female rats. Blood sampling occurred before and after MEC and NIC administrations for the determination of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Supporting and extending our previous findings, EE appeared to produce anxiolytic effects by reducing hormone responses: Male and female rats housed with EE had lower baseline ACTH and significantly lower HPA axis responses to the mild stress of saline (SAL) injection than did those housed without EE. The sexually diergic responses to single dose NIC, continuous NIC, and MEC-induced NIC withdrawal were reduced by EE in many male and female groups. ACTH responses to continuous NIC and MEC-induced NIC withdrawal were blunted to a greater extent in female EE groups than in male EE groups, suggesting that females are more sensitive to the anxiolytic effects of EE. Because EE lowered stress-responsive hormones of the HPA axis in most groups, EE may be a useful intervention for stress reduction in animal models of NIC addiction. As well, the effectiveness of EE in animal studies of NIC withdrawal may enlighten human studies addressing coping styles and tobacco cessation in men and women. PMID:22705101

Predictors of heartburn resolution and erosive esophagitis in patients with GERD.

PubMed

Orlando, Roy C; Monyak, John T; Silberg, Debra G

2009-09-01

The primary objective was to assess gastroesophageal reflux disease (GERD) symptom resolution rates with esomeprazole by erosive esophagitis (EE) status, and the secondary objective was to evaluate potential predictors of the presence of EE and heartburn resolution. Patients with GERD who have EE have higher reported symptom resolution rates than those with nonerosive reflux disease (NERD) when treated with proton pump inhibitors (PPIs). This open-label multicenter study included adults with GERD symptoms. Patients were stratified by EE status after endoscopy and received once-daily esomeprazole 40 mg for 4 weeks. Questionnaires determined symptom response rates, and baseline predictors of EE or heartburn resolution were evaluated. Potential predictors, including years with GERD, history of EE, and time to relief with antacids, were examined. Heartburn resolution rates at 4 weeks were higher for patients with EE than NERD (69% [124/179] vs. 48% [85/177]; p < 0.0001). Multivariate models had moderate predictive ability for EE (c-index, 0.76) and poor predictive ability (c-index, 0.57) for heartburn resolution. However, faster heartburn relief with antacid use, particularly within 15 min, was predictive of EE and heartburn resolution. Patients with EE have higher heartburn resolution rates than patients with NERD after treatment, although recall bias may be possible. Fast relief with antacid use is predictive of EE and heartburn resolution with a PPI and suggests that a history of antacid relief may provide corroborative evidence to empiric PPI therapy in determining whether patients with heartburn have acid reflux disease. ClinicalTrials.Gov IDENTIFIER: NCT00242736.

Residential environmental education meeting teachers' science needs and beyond: A Bradford Woods case study

NASA Astrophysics Data System (ADS)

Gatzke, Jenna M.

With the continued increase of environmental problems facing the world, the need for environmental education (EE) is greater than ever before. Residential EE centers offer unique opportunities that have the potential to increase EE in student education. The purpose of this study was to explore classroom teachers’ understandings and ideas about and what role residential EE programming and curricula play in their classroom curriculum. Using an embedded mixed methods instrumental case study design, this study worked with 58 classroom teachers attending Bradford Woods, a residential EE center. Data collection sources included an on-line survey, on-site trail observations, and semi-structured phone interviews. Results of the study indicated that teachers found multiple meanings in EE, relating the field to being about, from and in, and for the environment. Residential EE centers were seen to provide both social and academic benefits for students as well as to challenge teachers to take on new and varying roles. Results also linked connections between teachers’ values, beliefs and knowledge to their use of EE in their curriculum. Discussion and implications of the study focus on what overarching findings have been gained from the founding literature base. These findings include a detailed look at the complex role of the teacher in EE programming settings and a discussion on what little has changed in our understandings of the EE, residential EE center, and classroom milieu over the past few decades. Suggestions for future research are outlined based on these overarching findings. Finally, limitations of the study and main contributions to the research base are also presented.

Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.

PubMed

Newman-Tancredi, Adrian; Cussac, Didier; Quentric, Yann; Touzard, Manuelle; Verrièle, Laurence; Carpentier, Nathalie; Millan, Mark J

2002-11-01

Although certain antiparkinson agents interact with serotonin (5-HT) receptors, little information is available concerning functional actions. Herein, we characterized efficacies of apomorphine, bromocriptine, cabergoline, lisuride, piribedil, pergolide, roxindole, and terguride at human (h)5-HT(1A), h5-HT(1B), and h5-HT(1D) receptors [guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding], and at h5-HT(2A), h5-HT(2B), and h5-HT(2C) receptors (depletion of membrane-bound [(3)H]phosphatydilinositol). All drugs stimulated h5-HT(1A) receptors with efficacies (compared with 5-HT, 100%) ranging from modest (apomorphine, 35%) to high (cabergoline, 93%). At h5-HT(1B) receptors, efficacies varied from mild (terguride, 37%) to marked (cabergoline, 102%) and potencies were modest (pEC(50) values of 5.8-7.6): h5-HT(1D) sites were activated with a similar range of efficacies and greater potency (7.1-8.5). Piribedil and apomorphine were inactive at h5-HT(1B) and h5-HT(1D) receptors. At h5-HT(2A) receptors, terguride, lisuride, bromocriptine, cabergoline, and pergolide displayed potent (7.6-8.8) agonist properties (49-103%), whereas apomorphine and roxindole were antagonists and piribedil was inactive. Only pergolide (113%/8.2) and cabergoline (123%/8.6) displayed pronounced agonist properties at h5-HT(2B) receptors. At 5-HT(2C) receptors, lisuride, bromocriptine, pergolide, and cabergoline were efficacious (75-96%) agonists, apomorphine and terguride were antagonists, and piribedil was inactive. MDL100,907 and SB242,084, selective antagonists at 5-HT(2A) and 5-HT(2C) receptors, respectively, abolished these actions of pergolide, cabergoline, and bromocriptine. In conclusion, antiparkinson agents display markedly different patterns of agonist and antagonist properties at multiple 5-HT receptor subtypes. Although all show modest (agonist) activity at 5-HT(1A) sites, their contrasting actions at 5-HT(2A) and 5-HT(2C) sites may be of particular significance to their functional profiles in vivo.

Chronic 5-HT2 receptor blockade unmasks the role of 5-HT1F receptors in the inhibition of rat cardioaccelerator sympathetic outflow.

PubMed

García-Pedraza, José Ángel; Hernández-Abreu, Oswaldo; García, Mónica; Morán, Asunción; Villalón, Carlos M

2018-04-01

Serotonin (5-hydroxytryptamine; 5-HT) inhibits the rat cardioaccelerator sympathetic outflow by 5-HT 1B/1D/5 receptors. Because chronic blockade of sympatho-excitatory 5-HT 2 receptors is beneficial in several cardiovascular pathologies, this study investigated whether sarpogrelate (a 5-HT 2 receptor antagonist) alters the pharmacological profile of the above sympatho-inhibition. Rats were pretreated for 2 weeks with sarpogrelate in drinking water (30 mg/kg per day; sarpogrelate-treated group) or equivalent volumes of drinking water (control group). Animals were pithed and prepared for spinal stimulation (C 7 -T 1 ) of the cardioaccelerator sympathetic outflow or for intravenous (i.v.) bolus injections of noradrenaline. Both procedures produced tachycardic responses remaining unaltered after saline. Continuous i.v. infusions of 5-HT induced a cardiac sympatho-inhibition that was mimicked by the 5-HT receptor agonists 5-carboxamidotryptamine (5-CT; 5-HT 1/5A ), CP 93,129 (5-HT 1B ), or PNU 142633 (5-HT 1D ), but not by indorenate (5-HT 1A ) in both groups; whereas LY344864 (5-HT 1F ) mimicked 5-HT only in sarpogrelate-treated rats. In sarpogrelate-treated animals, i.v. GR 127935 (310 μg/kg; 5-HT 1B/1D/1F receptor antagonist) attenuated 5-CT-induced sympatho-inhibition and abolished LY344864-induced sympatho-inhibition; while GR 127935 plus SB 699551 (1 mg/kg; 5-HT 5A receptor antagonist) abolished 5-CT-induced inhibition. These results confirm the cardiac sympatho-inhibitory role of 5-HT 1B , 5-HT 1D , and 5-HT 5A receptors in both groups; nevertheless, sarpogrelate treatment specifically unmasked a cardiac sympatho-inhibition mediated by 5-HT 1F receptors.

Chronic Sarpogrelate Treatment Reveals 5-HT7 Receptor in the Serotonergic Inhibition of the Rat Vagal Bradycardia.

PubMed

García-Pedraza, José Ángel; García, Mónica; Martín, María Luisa; Eleno, Nélida; Morán, Asunción

2017-01-01

5-Hydroxytryptamine (5-HT) modulates the cardiac parasympathetic neurotransmission, inhibiting the bradyarrhythmia by 5-HT2 receptor activation. We aimed to determine whether the chronic selective 5-HT2 blockade (sarpogrelate) could modify the serotonergic modulation on vagal cardiac outflow in pithed rat. Bradycardic responses in rats treated with sarpogrelate (30 mg·kg·d; orally) were obtained by electrical stimulation of the vagal fibers (3, 6, and 9 Hz) or intravenous (IV) injections of acetylcholine (1, 5, and 10 μg/kg). 5-HT7 receptor expression was quantified by Western blot in vagus nerve and right atrium. The IV administration of 5-HT (10-200 μg/kg) dose dependently decreased the vagally induced bradycardia, and agonists 5-CT (5-HT1/7), 8-OH-DPAT (5-HT1A), or AS-19 (5-HT7) (50 μg/kg each) mimicked the 5-HT-induced inhibitory effect. Neither agonists CGS-12066B (5-HT1B), L-694,247 (5-HT1D), nor 1-phenylbiguanide (5-HT3) modified the electrically-induced bradycardic responses. Moreover, SB-258719 (5-HT7 antagonist) abolished the 5-HT-, 5-CT-, 8-OH-DPAT-, and AS-19-induced bradycardia inhibition; 5-HT or AS-19 did not modify the bradycardia induced by IV acetylcholine; and 5-HT7 receptor was expressed in both the vagus nerve and the right atrium. Our outcomes suggest that blocking chronically 5-HT2 receptors modifies the serotonergic influence on cardiac vagal neurotransmission exhibiting 5-HT as an exclusively inhibitory agent via prejunctional 5-HT7 receptor.

Do serotonin(1-7) receptors modulate short and long-term memory?

PubMed

Meneses, A

2007-05-01

Evidence from invertebrates to human studies indicates that serotonin (5-hydroxytryptamine; 5-HT) system modulates short- (STM) and long-term memory (LTM). This work is primarily focused on analyzing the contribution of 5-HT, cholinergic and glutamatergic receptors as well as protein synthesis to STM and LTM of an autoshaping learning task. It was observed that the inhibition of hippocampal protein synthesis or new mRNA did not produce a significant effect on autoshaping STM performance but it did impair LTM. Both non-contingent protein inhibition and 5-HT depletion showed no effects. It was basically the non-selective 5-HT receptor antagonist cyproheptadine, which facilitated STM. However, the blockade of glutamatergic and cholinergic transmission impaired STM. In contrast, the selective 5-HT(1B) receptor antagonist SB-224289 facilitated both STM and LTM. Selective receptor antagonists for the 5-HT(1A) (WAY100635), 5-HT(1D) (GR127935), 5-HT(2A) (MDL100907), 5-HT(2C/2B) (SB-200646), 5-HT(3) (ondansetron) or 5-HT(4) (GR125487), 5-HT(6) (Ro 04-6790, SB-399885 and SB-35713) or 5-HT(7) (SB-269970) did not impact STM. Nevertheless, WAY100635, MDL100907, SB-200646, GR125487, Ro 04-6790, SB-399885 or SB-357134 facilitated LTM. Notably, some of these changes shown to be independent of food-intake. Concomitantly, these data indicate that '5-HT tone via 5-HT(1B) receptors' might function in a serial manner from STM to LTM, whereas working in parallel using 5-HT(1A), 5-HT(2A), 5-HT(2B/2C), 5-HT(4), or 5-HT(6) receptors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stockmeier, C.A.; Kellar, K.J.

Serotonin-2 (5-HT-2) receptors in brain were measured using (/sup 3/H)ketanserin. The authors examined the effects of amitriptyline, an anti-depressant drug, of electroconvulsive shock (ECS) and of drug-induced alterations in presynaptic 5-HT function on (/sup 3/H)ketanserin binding to 5-HT-2 receptors in rat brain. The importance of intact 5-HT axons to the up-regulation of 5-HT-2 receptors by ECS was also investigated, and an attempt was made to relate the ECS-induced increase in this receptor to changes in 5-HT presynaptic mechanisms. Twelve days of ECS increased the number of 5-HT-2 receptors in frontal cortex. Neither the IC/sub 50/ nor the Hill coefficient ofmore » 5-HT in competing for (/sup 3/H)ketanserin binding sites was altered by ECS. Repeated injections of amitriptyline reduced the number of 5-HT-2 receptors in frontal cortex. Reserpine, administered daily for 12 days, caused a significant increase in 5-HT-2 receptors, but neither daily injections of p-chlorophenylalanine (PCPA) nor lesions of 5-HT axons with 5,7-dihydroxytryptamine (5,7-DHT) affected 5-HT-2 receptors. However, regulation of 5-HT-2 receptors by ECS was dependent on intact 5-HT axons since ECS could not increase the number of 5-HT-2 receptors in rats previously lesioned with 5,7-DHT. Repeated ECS, however, does not appear to affect either the high-affinity uptake of (/sup 3/H)5-HT or (/sup 3/H)imipramine binding, two presynaptic markers of 5-HT neuronal function. 5-HT-2 receptors appear to be under complex control. ECS or drug treatments such as reserpine or amitriptyline, which affect several monoamine neurotransmission systems including 5-HT, can alter 5-HT-2 receptors. 28 references, 1 figure, 7 tables.« less

Impairment of vocal expression of negative emotions in patients with Alzheimer's disease.

PubMed

Han, Kyung-Hun; Zaytseva, Yuliya; Bao, Yan; Pöppel, Ernst; Chung, Sun Yong; Kim, Jong Woo; Kim, Hyun Taek

2014-01-01

Vocal expression of emotions (EE) in retrieval of events from autobiographical memory was investigated in patients in early stages of Alzheimer's disease (AD). Twenty-one AD patients and 19 controls were interviewed, and EE of the reported memories was rated by 8 independent evaluators. The AD group had lower EE of both recent and remote memory than controls, although EE in remote memories was better preserved in both groups. We observed positive correlations between EE and indicators of cognitive competence in AD patients. AD Patients are impaired in the ability to express emotions already at early stages of the disease, and EE seems to deteriorate along with the progression of cognitive impairment.

PHARMACOLOGY OF SEROTONIN AND FEMALE SEXUAL BEHAVIOR

PubMed Central

Uphouse, Lynda

2014-01-01

In this review, first a historical perspective of serotonin’s (5-HT) involvement in female sexual behavior is presented. Then an overview of studies implicating 5-HT is presented. The effect of drugs that increase or decrease CNS levels of 5-HT is reviewed. Evidence is presented that drugs which increase 5-HT have negative effects on female sexual behavior while a decrease in 5-HT is associated with facilitation of sexual behavior. Studies with compounds that act on 5-HT1, 5-HT2 or 5-HT3 receptors are discussed. Most evidence indicates that 5-HT1A receptor agonists inhibit sexual behavior while 5-HT2 or 5-HT3 receptors may exert a positive influence. There is substantial evidence to support a role for 5-HT in the modulation of female consummatory sexual behavior, but studies on the role of 5-HT in other elements of female sexual behavior (e.g. desire, motivation, sexual appetite) are few. Future studies should be directed at determining if these additional components of female sexual behavior are also modulated by 5-HT. PMID:24239784

Eccentric exercises; why do they work, what are the problems and how can we improve them?

PubMed

Rees, J D; Wolman, R L; Wilson, A

2009-04-01

Eccentric exercises (EE) have proved successful in the management of chronic tendinopathy, particularly of the Achilles and patellar tendons, where they have been shown to be effective in controlled trials. However, numerous questions regarding EE remain. The standard protocols are time-consuming and require very motivated patients. EE are effective in some tendinopathies but not others. Furthermore, the location of the lesion can have a profound effect on efficacy; for example, standard EE in insertional lesions of the Achilles are ineffective. Until recently little was known of the effect of EE on tendinopathic tendons, although a greater understanding of this process is emerging. Additionally, recent in vivo evidence directly comparing eccentric and concentric exercises provides a possible explanation for the therapeutic benefit of EE. The challenge now is to make EE more effective. Suggestions on areas of future research are made.

Cardioprotective and hepatoprotective effects of Citrus hystrix peels extract on rats model

PubMed Central

Putri, Herwandhani; Nagadi, Standie; Larasati, Yonika Arum; Wulandari, Nindi; Hermawan, Adam

2013-01-01

Objective To observe the combination effect of doxorubicin and Citrus hystrix (kaffir lime's) peel ethanolic extract (ChEE) on blood serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity and cardio-hepato-histopathology of female Sprague Dawley rats. Methods Doxorubicin and ChEE (5 rats per group) were administered in five groups of 3 rats each for 11 d. Group I: doxorubicin (dox) 4.67 mg/kg body weight; Group II: dox+ChEE 500 mg/kg body weight; Group III: dox+ChEE 1 000 mg/kg body weight; Group IV: ChEE 1 000 mg/kg body weight; Group V: untreated (control). Results ChEE repaired cardiohistopathology profile of doxorubicin induced cardiotoxicity and hepatotoxicity rats, but did not repair neither hepatohistopathology profile nor reduce serum activity of ALT and AST. Conclusion ChEE has potency to be developed as cardioprotector agent in chemotherapy. PMID:23646300

Identification and expression analyses of a novel serotonin receptor gene, 5-HT2β, in the field cricket, Gryllus bimaculatus.

PubMed

Watanabe, T; Aonuma, H

2012-01-01

Biogenic amine serotonin (5-HT) modulates various aspects of behaviors such as aggressive behavior and circadian behavior in the cricket. In our previous report, in order to elucidate the molecular basis of the cricket 5-HT system, we identified three genes involved in 5-HT biosynthesis, as well as four 5-HT receptor genes (5-HT1A, 5-HT1B, 5-HT2α, and 5-HT7) expressed in the brain of the field cricket Gryllus bimaculatus DeGeer [7]. In the present study, we identified Gryllus 5-HT2β gene, an additional 5-HT receptor gene expressed in the cricket brain, and examined its tissue-specific distribution and embryonic stage-dependent expression. Gryllus 5-HT2β gene was ubiquitously expressed in the all examined adult tissues, and was expressed during early embryonic development, as well as during later stages. This study suggests functional differences between two 5-HT2 receptors in the cricket.

Defining Environmental Education. Workshop Resource Manual.

ERIC Educational Resources Information Center

Disinger, John F.; Monroe, Martha C.

This booklet is one in a series of resource manuals to help teacher educators conduct environmental education (EE) teacher workshops or promote EE programs. This unit is an orientation to the field of EE. It offers a definition of EE and some ways to explain its value to educators and environmental managers. The unit explains current and…

31 CFR 351.14 - When are rate announcements that apply to Series EE savings bonds announced?

Code of Federal Regulations, 2010 CFR

2010-07-01

... apply to Series EE savings bonds announced? 351.14 Section 351.14 Money and Finance: Treasury... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.14 When are rate announcements that...

31 CFR 351.14 - When are rate announcements that apply to Series EE savings bonds announced?

Code of Federal Regulations, 2014 CFR

2014-07-01

... apply to Series EE savings bonds announced? 351.14 Section 351.14 Money and Finance: Treasury... FISCAL SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.14 When are rate announcements that...

Using Smartphone Sensors for Improving Energy Expenditure Estimation

PubMed Central

Zhu, Jindan; Das, Aveek K.; Zeng, Yunze; Mohapatra, Prasant; Han, Jay J.

2015-01-01

Energy expenditure (EE) estimation is an important factor in tracking personal activity and preventing chronic diseases, such as obesity and diabetes. Accurate and real-time EE estimation utilizing small wearable sensors is a difficult task, primarily because the most existing schemes work offline or use heuristics. In this paper, we focus on accurate EE estimation for tracking ambulatory activities (walking, standing, climbing upstairs, or downstairs) of a typical smartphone user. We used built-in smartphone sensors (accelerometer and barometer sensor), sampled at low frequency, to accurately estimate EE. Using a barometer sensor, in addition to an accelerometer sensor, greatly increases the accuracy of EE estimation. Using bagged regression trees, a machine learning technique, we developed a generic regression model for EE estimation that yields upto 96% correlation with actual EE. We compare our results against the state-of-the-art calorimetry equations and consumer electronics devices (Fitbit and Nike+ FuelBand). The newly developed EE estimation algorithm demonstrated superior accuracy compared with currently available methods. The results were calibrated against COSMED K4b2 calorimeter readings. PMID:27170901

Educational storylines in entertainment television: audience reactions toward persuasive strategies in medical dramas.

PubMed

Asbeek Brusse, Elsbeth D; Fransen, Marieke L; Smit, Edith G

2015-04-01

Medical television drama series provide an important source of health information. This form of entertainment-education (E-E) can be used to influence knowledge, attitudes, and behaviors toward health-related issues. In the literature, E-E is generally regarded as a persuasive strategy in itself, whereas in an increasing number of E-E programs, several different persuasive strategies are used. An important question is how the audience ethically evaluates these strategies. The aim of the present study is to examine viewers' ethical judgments toward the use of three persuasive strategies in E-E: product placement, framing, and persuasion toward a controversial position. A survey among 525 viewers of 5 popular medical dramas demonstrates that viewers evaluate the use of the currently investigated attitudinal statements about potential persuasive strategies in E-E as being immoral and that viewers prefer neutral storylines. Adopting a strategy that viewers find inappropriate may interfere with the intended prosocial effects of E-E. A broader understanding of the appropriate and inappropriate uses of persuasive strategies in E-E is indispensable for effective E-E productions.

Energy Expenditure and Aging

PubMed Central

Manini, Todd M.

2009-01-01

The study of energy expenditure (EE) has deep roots in understanding aging and lifespan in all species. In humans, total EE decreases substantially in advanced age resulting from parallel changes in resting metabolic rate (RMR) and activity EE. For RMR, this reduction appears to be due to a reduction in organ mass and specific metabolic rates of individual tissues. However, these anatomical changes explain very little regarding the decline in activity EE, which is governed by both genetic and environmental sources. The biological control centers for activity EE are closely coupled with body mass fluctuations and seem to originate in the brain. Several candidate neuromodulators may be involved in the age-related reduction of activity EE that include: orexin, agouti-related proteins and dopaminergic pathways. Unfortunately, the existing body of research has primarily focused on how neuromodulators influence weight gain and only a few studies have been performed in aging models. Recent evidence suggests that activity EE has an important role in dictating lifespan and thus places emphasis on future research to uncover the underlying biological mechanisms. The study of EE continues to unlock clues to aging. PMID:19698803

Using Smartphone Sensors for Improving Energy Expenditure Estimation.

PubMed

Pande, Amit; Zhu, Jindan; Das, Aveek K; Zeng, Yunze; Mohapatra, Prasant; Han, Jay J

2015-01-01

Energy expenditure (EE) estimation is an important factor in tracking personal activity and preventing chronic diseases, such as obesity and diabetes. Accurate and real-time EE estimation utilizing small wearable sensors is a difficult task, primarily because the most existing schemes work offline or use heuristics. In this paper, we focus on accurate EE estimation for tracking ambulatory activities (walking, standing, climbing upstairs, or downstairs) of a typical smartphone user. We used built-in smartphone sensors (accelerometer and barometer sensor), sampled at low frequency, to accurately estimate EE. Using a barometer sensor, in addition to an accelerometer sensor, greatly increases the accuracy of EE estimation. Using bagged regression trees, a machine learning technique, we developed a generic regression model for EE estimation that yields upto 96% correlation with actual EE. We compare our results against the state-of-the-art calorimetry equations and consumer electronics devices (Fitbit and Nike+ FuelBand). The newly developed EE estimation algorithm demonstrated superior accuracy compared with currently available methods. The results were calibrated against COSMED K4b2 calorimeter readings.

A coordinated set of ecosystem research platforms open to international research in ecotoxicology, AnaEE-France.

PubMed

Mougin, Christian; Azam, Didier; Caquet, Thierry; Cheviron, Nathalie; Dequiedt, Samuel; Le Galliard, Jean-François; Guillaume, Olivier; Houot, Sabine; Lacroix, Gérard; Lafolie, François; Maron, Pierre-Alain; Michniewicz, Radika; Pichot, Christian; Ranjard, Lionel; Roy, Jacques; Zeller, Bernd; Clobert, Jean; Chanzy, André

2015-10-01

The infrastructure for Analysis and Experimentation on Ecosystems (AnaEE-France) is an integrated network of the major French experimental, analytical, and modeling platforms dedicated to the biological study of continental ecosystems (aquatic and terrestrial). This infrastructure aims at understanding and predicting ecosystem dynamics under global change. AnaEE-France comprises complementary nodes offering access to the best experimental facilities and associated biological resources and data: Ecotrons, seminatural experimental platforms to manipulate terrestrial and aquatic ecosystems, in natura sites equipped for large-scale and long-term experiments. AnaEE-France also provides shared instruments and analytical platforms dedicated to environmental (micro) biology. Finally, AnaEE-France provides users with data bases and modeling tools designed to represent ecosystem dynamics and to go further in coupling ecological, agronomical, and evolutionary approaches. In particular, AnaEE-France offers adequate services to tackle the new challenges of research in ecotoxicology, positioning its various types of platforms in an ecologically advanced ecotoxicology approach. AnaEE-France is a leading international infrastructure, and it is pioneering the construction of AnaEE (Europe) infrastructure in the field of ecosystem research. AnaEE-France infrastructure is already open to the international community of scientists in the field of continental ecotoxicology.

Influence of in line monitored fluid bed granulation process parameters on the stability of Ethinylestradiol.

PubMed

Roßteuscher-Carl, Katrin; Fricke, Sabine; Hacker, Michael C; Schulz-Siegmund, Michaela

2015-12-30

Ethinylestradiol (EE) as a highly active and low dosed compound is prone to oxidative degradation. The stability of the drug substance is therefore a critical parameter that has to be considered during drug formulation. Beside the stability of the drug substance, granule particle size and moisture are critical quality attributes (CQA) of the fluid bed granulation process which influence the tableting ability of the resulting granules. Both CQA should therefore be monitored during the production process by process analytic technology (PAT) according to ICH Q8. This work focusses on the effects of drying conditions on the stability of EE in a fluid-bed granulation process. We quantified EE degradation products 6-alpha-hydroxy-EE, 6-beta-hydroxy-EE, 9(11)-dehydro-EE and 6-oxo-EE during long time storage and accelerated conditions. PAT-tools that monitor granule particle size (Spatial filtering technology) and granule moisture (Microwave resonance technology) were applied and compared with off-line methods. We found a relevant influence of residual granule moisture and thermic stress applied during granulation on the storage stability of EE, whereas no degradation was found immediately after processing. Hence we conclude that drying parameters have a relevant influence on long term EE stability. Copyright © 2015 Elsevier B.V. All rights reserved.

Validation of Single-Item Screening Measures for Provider Burnout in a Rural Health Care Network.

PubMed

Waddimba, Anthony C; Scribani, Melissa; Nieves, Melinda A; Krupa, Nicole; May, John J; Jenkins, Paul

2016-06-01

We validated three single-item measures for emotional exhaustion (EE) and depersonalization (DP) among rural physician/nonphysician practitioners. We linked cross-sectional survey data (on provider demographics, satisfaction, resilience, and burnout) with administrative information from an integrated health care network (1 academic medical center, 6 community hospitals, 31 clinics, and 19 school-based health centers) in an eight-county underserved area of upstate New York. In total, 308 physicians and advanced-practice clinicians completed a self-administered, multi-instrument questionnaire (65.1% response rate). Significant proportions of respondents reported high EE (36.1%) and DP (9.9%). In multivariable linear mixed models, scores on EE/DP subscales of the Maslach Burnout Inventory were regressed on each single-item measure. The Physician Work-Life Study's single-item measure (classifying 32.8% of respondents as burning out/completely burned out) was correlated with EE and DP (Spearman's ρ = .72 and .41, p < .0001; Kruskal-Wallis χ(2) = 149.9 and 56.5, p < .0001, respectively). In multivariable models, it predicted high EE (but neither low EE nor low/high DP). EE/DP single items were correlated with parent subscales (Spearman's ρ = .89 and .81, p < .0001; Kruskal-Wallis χ(2) = 230.98 and 197.84, p < .0001, respectively). In multivariable models, the EE item predicted high/low EE, whereas the DP item predicted only low DP. Therefore, the three single-item measures tested varied in effectiveness as screeners for EE/DP dimensions of burnout. © The Author(s) 2015.

Occurrence of 17α-ethynylestradiol (EE2) in the environment and effect on exposed biota: a review.

PubMed

Aris, Ahmad Zaharin; Shamsuddin, Aida Soraya; Praveena, Sarva Mangala

2014-08-01

17α-ethynylestradiol (EE2) is a synthetic hormone, which is a derivative of the natural hormone, estradiol (E2). EE2 is an orally bio-active estrogen, and is one of the most commonly used medications for humans as well as livestock and aquaculture activity. EE2 has become a widespread problem in the environment due to its high resistance to the process of degradation and its tendency to (i) absorb organic matter, (ii) accumulate in sediment and (iii) concentrate in biota. Numerous studies have reported the ability of EE2 to alter sex determination, delay sexual maturity, and decrease the secondary sexual characteristics of exposed organisms even at a low concentration (ng/L) by mimicking its natural analogue, 17β-estradiol (E2). Thus, the aim of this review is to provide an overview of the science regarding EE2, the concentration levels in the environment (water, sediment and biota) and summarize the effects of this compound on exposed biota at various concentrations, stage life, sex, and species. The challenges in respect of EE2 include the extension of the limited database on the EE2 pollution profile in the environment, its fate and transport mechanism, as well as the exposure level of EE2 for better prediction and definition revision of EE2 toxicity end points, notably for the purpose of environmental risk assessment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Otolaryngologists may not be doing enough to diagnose pediatric eosinophilic esophagitis.

PubMed

Smith, Lee P; Chewaproug, Linda; Spergel, Jonathan M; Zur, Karen B

2009-11-01

To systematically evaluate the diagnosis of eosinophilic esophagitis (EE). A retrospective review of 657 patients seen at the EE center of a tertiary care children's hospital between 1994 and 2007 was performed. Charts were reviewed for the 144 patients who were also seen by the otolaryngology service. One hundred forty-four patients received 193 otolaryngology-related diagnoses. Eustachian tube dysfunction (27.5%) and sleep disordered breathing (24.9%) were the most common, followed by dysphagia (13.0%), rhinosinusitis/nasal congestion (9.3%) and airway stenosis (5.2%). Seventy-nine patients (54.9%) had a pre-existing diagnosis of EE at the time of their otolaryngology consultation. Twenty-one patients (14.6%) were referred to the gastroenterology service for evaluation for EE. Forty-four patients (30.5%) remained undiagnosed. Twenty-five of these patients presented with dysphagia, 16 of whom were not previously diagnosed with EE; only 4 of these 16 patients were referred for evaluation for EE. In one case, a child with moderate sized tonsils underwent adenotonsillectomy for dysphagia and failure to thrive; this patient was diagnosed with EE 1 month post-operatively. Twenty percent of patients with EE may require care by an otolaryngologist for a myriad of complaints. Even experienced pediatric otolaryngologists may not recognize this condition. Otolaryngologists should consider EE in patients presenting with dysphagia. A careful gastroenterology review of symptoms may also allow otolaryngologists to identify EE in patients with allergy mediated nasal complaints, or laryngeal/airway disorders.

Absence of Change in Total Daily Energy Expenditure (EE(sub TD)) in Young and Mature Rats During 14 Days of Hypergravity

NASA Technical Reports Server (NTRS)

Wade, C. E.; Moran, M. M.; Stein, T. P.; Hoban-Higgins, T. M.; Fuller, P.; Fuller, C. A.; Dalton, Bonnie P. (Technical Monitor)

1999-01-01

Effect of age on the response of EE(sub TD) to an increase in gravity was assessed in young (Y; 1.5 month old) and mature (M; 8 month old) Sprague-Dawley rats. Rats were implanted with transmitters to monitor activity, and metabolism was determined by the double labeled water technique. Daily food intake was measured. For each age, rats (n=8 per treatment) were exposed to centrifugation at 2G, or remained at 1G. There was a difference in EE(sub TD) between age groups, 182 plus or minus 11 and 143 plus or minus 5 kcal/kg/day in Y and M, respectively. This difference was attributed in part to a lower activity level in M animals, 48% of Y rats. After day 6 there was no effect on EE(sub TD) of exposure to 2G, or on food intake per 100g BW. Prior studies show a 20% increase in resting EE with hypergravity. In our study the level of activity was reduced to 41% of 1G in both age groups during 2G. For Y at 1G resting EE accounted for 78% of the EE(sub TD) and activity 22%, while at 2G resting EE was 96% of EE(sub TD) and activity 4%. M rats had similar changes. Independent of age, with exposure to hypergravity EE(sub TD) is maintained by behavioral changes.

Effectiveness of ethinylestradiol/drospirenone for premenstrual symptoms in Japanese patients with dysmenorrhea: Open-label pilot study.

PubMed

Takeda, Takashi; Kondo, Akiko; Koga, Shoko; Hayakawa, Jun; Hayakawa, Kenichi; Hiramatsu, Keizo; Yaegashi, Nobuo

2015-10-01

A combined oral contraceptive containing ethinylestradiol 20 µg plus drospirenone 3 mg (EE20 + DRSP) in a 24/4 regimen has been shown to alleviate the symptoms of premenstrual syndrome and premenstrual dysphoric disorder. This study was conducted to evaluate the efficacy of EE20 + DRSP in Japanese patients with premenstrual symptoms. A multicenter, prospective, open-label, single-arm, phase IV study was performed in Japanese women with dysmenorrhea and premenstrual symptoms. They were treated with EE20 + DRSP to alleviate the symptoms of dysmenorrhea for six treatment cycles. Premenstrual symptoms were evaluated using a Premenstrual Symptoms Questionnaire at baseline and after three and six cycles of EE20 + DRSP. The degree of dysmenorrhea was also evaluated using a visual analog scale at baseline and after one, three, and six cycles of EE20 + DRSP. Forty-eight patients were treated with EE20 + DRSP. Most of the premenstrual symptoms were alleviated significantly by three and six cycles of EE20 + DRSP treatment. EE20 + DRSP treatment significantly improved the severity of premenstrual symptoms. We also confirmed the effectiveness of EE20 + DRSP for the treatment for dysmenorrhea. This study showed that EE20 + DRSP could be a useful treatment strategy for premenstrual symptoms in Japanese women. © 2015 Japan Society of Obstetrics and Gynecology.

Activation of apoptosis by ethyl acetate fraction of ethanol extract of Dianthus superbus in HepG2 cell line.

PubMed

Yu, Jian-Qing; Yin, Yan; Lei, Jia-Chuan; Zhang, Xiu-Qiao; Chen, Wei; Ding, Cheng-Li; Wu, Shan; He, Xiao-Yu; Liu, Yan-Wen; Zou, Guo-Lin

2012-02-01

Dianthus superbus L. is commonly used as a traditional Chinese medicine. We recently showed that ethyl acetate fraction (EE-DS) from ethanol extract of D. superbus exhibited the strongest antioxidant and cytotoxic activities. In this study, we examined apoptosis of HepG2 cells induced by EE-DS, and the mechanism underlying apoptosis was also investigated. Treatment of HepG2 cells with EE-DS (20-80 μg/ml) for 48 h led to a significant dose-dependent increase in the percentage of cells in sub-G1 phase by analysis of the content of DNA in cells, and a large number of apoptotic bodies containing nuclear fragments were observed in cells treated with 80 μg/ml of EE-DS for 24 h by using Hoechst 33258 staining. These data show that EE-DS can induce apoptosis of HepG2 cells. Immunoblot analysis showed that EE-DS significantly suppressed the expressions of Bcl-2 and NF-κB. Treatment of cells with EE-DS (80 μg/ml) for 48 h resulted in significant increase of cytochrome c in the cytosol, which indicated cytochrome c release from mitochondria. Activation of caspase-9 and -3 were also determined when the cells treated with EE-DS. The results suggest that apoptosis of HepG2 cells induced by EE-DS could be through the mitochondrial intrinsic pathway. High performance liquid chromatography (HPLC) data showed that the composition of EE-DS is complicated. Further studies are needed to find the effective constituents of EE-DS. Copyright © 2011 Elsevier Ltd. All rights reserved.

Standing economy: does the heterogeneity in the energy cost of posture maintenance reside in differential patterns of spontaneous weight-shifting?

PubMed

Miles-Chan, Jennifer L; Fares, Elie-Jacques; Berkachy, Redina; Jacquet, Philippe; Isacco, Laurie; Schutz, Yves; Montani, Jean-Pierre; Dulloo, Abdul G

2017-04-01

Due to sedentarity-associated disease risks, there is much interest in methods to increase low-intensity physical activity. In this context, it is widely assumed that altering posture allocation can modify energy expenditure (EE) to impact body-weight regulation and health. However, we have recently shown the existence of two distinct phenotypes pertaining to the energy cost of standing-with most individuals having no sustained increase in EE during steady-state standing relative to sitting comfortably. Here, we investigated whether these distinct phenotypes are related to the presence/absence of spontaneous "weight-shifting", i.e. the redistribution of body-weight from one foot to the other. Using indirect calorimetry to measure EE in young adults during sitting and 10 min of steady-state standing, we examined: (i) heterogeneity in EE during standing (n = 36); (ii) EE and spontaneous weight-shifting patterns (n = 18); (iii) EE during spontaneous weight-shifting versus experimentally induced weight-shifting (n = 7), and; (iv) EE during spontaneous weight-shifting versus intermittent leg/body displacement (n = 6). Despite heterogeneity in EE response to steady-state standing, no differences were found in the amount or pattern of spontaneous weight-shifting between the two phenotypes. Whilst experimentally induced weight-shifting resulted in a mean EE increase of only 11% (range: 0-25%), intermittent leg/body displacement increased EE to >1.5 METs in all participants. Although the variability in spontaneous weight-shifting signatures between individuals does not appear to underlie heterogeneity in the energy cost of standing posture maintenance, these studies underscore the fact that leg/body displacement, rather than standing posture alone, is needed to increase EE above the currently defined sedentary threshold.

Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.

PubMed

Coelingh Bennink, Herjan J T; Zimmerman, Yvette; Laan, Ellen; Termeer, Hanneke M M; Appels, Nicole; Albert, Adelin; Fauser, Bart C J M; Thijssen, Jos H H; van Lunsen, Rik H W

2017-11-01

To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m 2 ) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC. Copyright © 2016 Pantarhei Bioscience. Published by Elsevier Inc. All rights reserved.

Mathematical Model for the Contribution of Individual Organs to Non-Zero Y-Intercepts in Single and Multi-Compartment Linear Models of Whole-Body Energy Expenditure

PubMed Central

Kaiyala, Karl J.

2014-01-01

Mathematical models for the dependence of energy expenditure (EE) on body mass and composition are essential tools in metabolic phenotyping. EE scales over broad ranges of body mass as a non-linear allometric function. When considered within restricted ranges of body mass, however, allometric EE curves exhibit ‘local linearity.’ Indeed, modern EE analysis makes extensive use of linear models. Such models typically involve one or two body mass compartments (e.g., fat free mass and fat mass). Importantly, linear EE models typically involve a non-zero (usually positive) y-intercept term of uncertain origin, a recurring theme in discussions of EE analysis and a source of confounding in traditional ratio-based EE normalization. Emerging linear model approaches quantify whole-body resting EE (REE) in terms of individual organ masses (e.g., liver, kidneys, heart, brain). Proponents of individual organ REE modeling hypothesize that multi-organ linear models may eliminate non-zero y-intercepts. This could have advantages in adjusting REE for body mass and composition. Studies reveal that individual organ REE is an allometric function of total body mass. I exploit first-order Taylor linearization of individual organ REEs to model the manner in which individual organs contribute to whole-body REE and to the non-zero y-intercept in linear REE models. The model predicts that REE analysis at the individual organ-tissue level will not eliminate intercept terms. I demonstrate that the parameters of a linear EE equation can be transformed into the parameters of the underlying ‘latent’ allometric equation. This permits estimates of the allometric scaling of EE in a diverse variety of physiological states that are not represented in the allometric EE literature but are well represented by published linear EE analyses. PMID:25068692

Enriched environment increases neurogenesis and improves social memory persistence in socially isolated adult mice.

PubMed

Monteiro, Brisa M M; Moreira, Fabrício A; Massensini, André R; Moraes, Márcio F D; Pereira, Grace S

2014-02-01

Social memory consists of the information necessary to identify and recognize cospecifics and is essential to many forms of social interaction. Social memory persistence is strongly modulated by the animal's experiences. We have shown in previous studies that social isolation (SI) in adulthood impairs social memory persistence and that an enriched environment (EE) prevents this impairment. However, the mechanisms involved in the effects of SI and EE on social memory persistence remain unknown. We hypothesized that the mechanism by which SI and EE affect social memory persistence is through their modulation of neurogenesis. To investigate this hypothesis, adult mice were submitted to 7 days of one of the following conditions: group-housing in a standard (GH) or enriched environment (GH+EE); social isolation in standard (SI) or enriched environment (SI+EE). We observed an increase in the number of newborn neurons in the dentate gyrus of the hippocampus (DG) and glomerular layer of the olfactory bulb (OB) in both GH+EE and SI+EE mice. However, this increase of newborn neurons in the granule cell layer of the OB was restricted to the GH+EE group. Furthermore, both SI and SI+EE groups showed less neurogenesis in the mitral layer of the OB. Interestingly, the performance of the SI mice in the buried food-finding task was inferior to that of the GH mice. To further analyze whether increased neurogenesis is in fact the mechanism by which the EE improves social memory persistence in SI mice, we administered the mitotic inhibitor AraC or saline directly into the lateral ventricles of the SI+EE mice. We found that the AraC treatment decreased cell proliferation in both the DG and OB, and impaired social memory persistence in the SI+EE mice. Taken together, our results strongly suggest that neurogenesis is what supports social memory persistence in socially isolated mice. © 2013 Wiley Periodicals, Inc.

Effect of the hepatitis C virus protease inhibitor faldaprevir on the pharmacokinetics of an oral contraceptive containing ethinylestradiol and levonorgestrel in healthy female volunteers.

PubMed

Sabo, John P; Lang, Benjamin; Elgadi, Mabrouk; Huang, Fenglei

2015-01-01

Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor. Faldaprevir is known to inhibit P-glycoprotein, CYP3A4, and UDP-glucuronosyltransferase 1A1. This study evaluated the effect of steady-state 240 mg faldaprevir on the pharmacokinetics (PK) of an oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) in healthy premenopausal women. In period 1, subjects received EE/LNG once daily (QD) for 14 days. Blood samples were taken on days 1, 11, and 12, with intensive PK blood sampling for EE and LNG on day 13. In period 2, subjects received EE-LNG QD and 240 mg faldaprevir QD on days 14 to 21 (240 mg faldaprevir twice daily on day 14). Blood samples were taken on days 14, 19, and 20, with PK profiling samples obtained for EE and LNG on day 21. A total of 15/16 subjects completed the study. Overall, EE and LNG exposure (assessed by the area under the curve) was approximately 1.4-fold higher when EE and LNG were coadministered with faldaprevir than when administered alone. Median t1/2 (terminal half-life in plasma at steady state) values were prolonged for both EE (2.4 h longer) and LNG (4.7 h longer) when EE and LNG were coadministered with faldaprevir. The mean oral clearance and apparent volume of distribution of both EE and LNG were lower (∼ 30%) when EE and LNG were coadministered with faldaprevir. Coadministration of faldaprevir and an oral contraceptive resulted in a moderate increase in exposure to both EE and LNG. However, this increase was not considered clinically meaningful, and no dose adjustment of oral contraceptives was deemed necessary. (This study has been registered at ClinicalTrials.gov under registration number NCT01570244.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effect of Extended 30 μg Ethinyl Estradiol with Continuous Low-Dose Ethinyl Estradiol and Cyclic 20 μg Ethinyl Estradiol Oral Contraception on Adolescent Bone Density: A Randomized Trial.

PubMed

Gersten, Janet; Hsieh, Jennifer; Weiss, Herman; Ricciotti, Nancy A

2016-12-01

To compare changes in lumbar spine bone mineral density after 12 months of a 91-day extended regimen or 28-day combined oral contraceptive with those in a healthy reference group not using hormonal contraceptives. Phase 2, multicenter, open-label, randomized, controlled study. Forty-five academic centers, clinical research centers, and community practices in the United States. Eight hundred twenty-nine postmenarcheal adolescent girls aged 12-18 years. Adolescents were randomly assigned to 91-day levonorgestrel (LNG)/ethinyl estradiol (EE) extended regimen (84 days of LNG 150 μg/EE 30 μg with 7 days of EE 10 μg [LNG/EE extended regimen]) or 28 days of LNG/EE (21 days of LNG 100 μg/EE 20 μg with 7 days of placebo [LNG/EE 21/7]) for 12 months. A reference group not seeking hormonal contraception was also evaluated. The primary end point was mean percent change in lumbar spine bone mineral density measured using dual-energy x-ray absorptiometry. Of 1361 adolescents randomized/enrolled, 829 were included in the primary analysis. Mean changes in lumbar spine bone mineral density were +2.26% with LNG/EE extended regimen, +1.45% with LNG/EE 21/7, and +2.50% in the reference group. Noninferiority of the LNG/EE extended regimen compared with the reference group was shown. A statistically significant treatment difference was found between LNG/EE 21/7 and the reference group (1.05%; 95% confidence interval, 0.61%-1.49%) but not between LNG/EE extended regimen and the reference group (0.23%; 95% confidence interval, -0.20% to 0.67%). No new safety signals were noted. Compared with the reference group, bone accrual was statistically significantly lower among LNG/EE 21/7 users but not among LNG/EE 30-μg extended regimen users. Additional research is needed to clarify the clinical relevance of these findings. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

A historical cycle control comparison of two drospirenone-containing combined oral contraceptives: ethinylestradiol 30 μg/drospirenone 3 mg administered in a 21/7 regimen versus ethinylestradiol 20 μg/drospirenone 3 mg administered in a 24/4 regimen.

PubMed

Marr, Joachim; Gerlinger, Christoph; Kunz, Michael

2012-05-01

To compare the bleeding patterns and cycle control of an oral contraceptive (OC) containing ethinylestradiol (EE) 30 μg/drospirenone (drsp) 3mg administered in a 21/7 regimen versus a lower-dose OC containing EE 20 μg/drsp 3mg administered in a 24/4 regimen, using data from two identically designed studies. In the first study, 326 healthy women (18-35 years) received EE 30 μg/drsp 3mg in a 21/7 regimen. In the second study, 1027 healthy women (17-36 years) received EE 20 μg/drsp 3mg in a 24/4 regimen. Participants recorded bleeding using daily completed diaries over 13 treatment cycles. During cycles 1-12, the prevalence of scheduled withdrawal bleeding was lower with EE 20 μg/drsp 3mg 24/4 than with EE 30 μg/drsp 3mg 21/7 (82.0-91.7% versus 94.8-100.0% of women, respectively); moreover, a higher proportion of women reported a maximum intensity of light scheduled withdrawal bleeding with EE 20 μg/drsp 3mg 24/4 than with EE 30 μg/drsp 3mg 21/7 (30.9-39.0% versus 13.8-20.5% of women, respectively). In cycles 2-13, unscheduled intracyclic bleeding was reported by 7.7-13.8% of EE 20 μg/drsp 3mg 24/4 recipients and 3.8-7.9% of EE 30 μg/drsp 3mg 21/7 recipients; these were mainly single bleeding days. During reference periods 1-4, the mean number of bleeding episodes was similar between groups (3.1-3.3 episodes with EE 20 μg/drsp 3mg 24/4 versus 3.2 episodes with EE 30 μg/drsp 3mg 21/7). A low-dose 24/4 regimen OC containing EE 20 μg/drsp 3mg is generally comparable in terms of bleeding to a higher-dose 21/7 regimen OC containing EE30 μg/drsp 3mg. Between-treatment differences in bleeding intensity and unscheduled intracyclic bleeding rates were observed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Efficacy and safety of the combined oral contraceptive ethinylestradiol/drospirenone (Yasmin) in healthy Chinese women: a randomized, open-label, controlled, multicentre trial.

PubMed

Guang-Sheng, Fan; Mei-Lu, Bian; Li-Nan, Cheng; Xiao-Ming, Cao; Zi-Rong, Huang; Zi-Yan, Han; Xiao-Ping, Jing; Jian, Li; Shu-Ying, Wu; Cheng-Liang, Xiong; Zheng-Ai, Xiong; Tian-Fu, Yue

2010-01-01

To evaluate and compare the contraceptive efficacy, bleeding pattern, side effects and other positive effects of a combined oral contraceptive (COC) containing drospirenone (DRSP) [Yasmin] with those of a COC containing desogestrel (DSG) in healthy Chinese women. This was a randomized, open-label, controlled, multicentre study of 768 healthy Chinese women requiring contraception. The subjects were randomized to ethinylestradiol (EE) 30 microg/DRSP 3 mg (n = 573) or EE 30 microg/ DSG 150 microg (n = 195), at a ratio of 3 : 1. Each individual was treated for 13 cycles. Further visits were required at cycle 4, cycle 7, cycle 10 and cycle 13 of treatment. Weight, height and body mass index were evaluated at each visit. The Menstrual Distress Questionnaire (MDQ) was administered at baseline, visit 3 (cycle 7) and visit 5 (after cycle 13). Baseline characteristics were similar between the two groups (p > 0.05). The Pearl Index (method failure) for EE/DRSP was 0.208 per 100 women-years, which was lower than that for EE/DSG (0.601 per 100 women-years). There were no significant differences between the treatment groups with regard to bleeding patterns. According to the MDQ subscale, improvements in water retention and increases in appetite during the intermenstrual period and in water retention and general well-being during the menstrual period in the EE/DRSP group (-0.297, -0.057, 0.033 and 0.150, respectively) were significantly improved compared with the EE/DSG group (-0.108, 0.023, 0.231 and -0.023, respectively) [all p < 0.05]. Other values that improved in both groups, particularly improvement in breast pain and tenderness and skin condition, were more evident in the EE/DRSP group (18.0%, 89/494; 12.6%, 62/494) than in the EE/DSG group (11.3%, 19/168; 5.4%, 9/168). Mean weight increased in the EE/DSG group (0.57 kg) while there was a significant decrease in mean weight (-0.28 kg) in the EE/DRSP group (p < 0.01). Both EE/DRSP and EE/DSG have good contraceptive efficacy and a comparable bleeding pattern. EE/DRSP had a more favourable effect on weight and premenstrual symptoms than EE/DSG.

The effects of temperature and salinity on 17-α-ethynylestradiol uptake and its relationship to oxygen consumption in the model euryhaline teleost (Fundulus heteroclitus).

PubMed

Blewett, Tamzin; MacLatchy, Deborah L; Wood, Chris M

2013-02-01

The synthetic estrogen 17-α-ethynylestradiol (EE2), a component of birth control and hormone replacement therapy, is discharged into the environment via wastewater treatment plant (WWTP) effluents. The present study employed radiolabeled EE2 to examine impacts of temperature and salinity on EE2 uptake in male killifish (Fundulus heteroclitus). Fish were exposed to a nominal concentration of 100ng/L EE2 for 2h. The rate of EE2 uptake was constant over the 2h period. Oxygen consumption rates (MO(2)), whole body uptake rates, and tissue-specific EE2 distribution were determined. In killifish acclimated to 18°C at 16ppt (50% sea water), MO(2) and EE2 uptake were both lower after 24h exposure to 10°C and 4°C, and increased after 24h exposure to 26°C. Transfer to fresh water (FW) for 24h lowered EE2 uptake rate, and long-term acclimation to fresh water reduced it by 70%. Both long-term acclimation to 100% sea water (32ppt) and a 24h transfer to 100% sea water also reduced EE2 uptake rate by 50% relative to 16ppt. Tissue-specific accumulation of EE2 was highest (40-60% of the total) in the liver plus gall bladder across all exposures, and the vast majority of this was in the bile at 2h, regardless of temperature or salinity. The carcass was the next highest accumulator (30-40%), followed by the gut (10-20%) with only small amounts in gill and spleen. Killifish chronically exposed (15 days) to 100ng/L EE2 displayed no difference in EE2 uptake rate or tissue-specific distribution. Drinking rate, measured with radiolabeled polyethylene glycol-4000, was about 25 times greater in 16ppt-acclimated killifish relative to FW-acclimated animals. However, drinking accounted for less than 30% of gut accumulation, and therefore a negligible percentage of whole body EE2 uptake rates. In general, there were strong positive relationships between EE2 uptake rates and MO(2), suggesting similar uptake pathways of these lipophilic molecules across the gills. These data will be useful in developing a predictive model of how key environmental parameter variations (salinity, temperature, dissolved oxygen) affect EE2 uptake in estuarine fish, to determine optimal timing and location of WWTP discharges. Copyright © 2012 Elsevier B.V. All rights reserved.

Synthesis and serotonergic activity of 3-[2-(pyrrolidin-1-yl)ethyl]indoles: potent agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B receptor.

PubMed

Sternfeld, F; Guiblin, A R; Jelley, R A; Matassa, V G; Reeve, A J; Hunt, P A; Beer, M S; Heald, A; Stanton, J A; Sohal, B; Watt, A P; Street, L J

1999-02-25

The design, synthesis, and biological evaluation of a novel series of 3-[2-(pyrrolidin-1-yl)ethyl]indoles with excellent selectivity for h5-HT1D (formerly 5-HT1Dalpha) receptors over h5-HT1B (formerly 5-HT1Dbeta) receptors are described. Clinically effective antimigraine drugs such as Sumatriptan show little selectivity between h5-HT1D and h5-HT1B receptors. The differential expression of h5-HT1D and h5-HT1B receptors in neural and vascular tissue prompted an investigation of whether a compound selective for the h5-HT1D subtype would have the same clinical efficacy but with reduced side effects. The pyrrolidine 3b was initially identified as having 9-fold selectivity for h5-HT1D over h5-HT1B receptors. Substitution of the pyrrolidine ring of 3b with methylbenzylamine groups gave compounds with nanomolar affinity for the h5-HT1D receptor and 100-fold selectivity with respect to h5-HT1B receptors. Modification of the indole 5-substituent led to the oxazolidinones 24a,b with up to 163-fold selectivity for the h5-HT1D subtype and improved selectivity over other serotonin receptors. The compounds were shown to be full agonists by measurement of agonist-induced [35S]GTPgammaS binding in CHO cells expressed with h5-HT receptors. This study suggests that the h5-HT1D and h5-HT1B receptors can be differentiated by appropriate substitution of the ligand in the region which binds to the aspartate residue and reveals a large binding pocket in the h5-HT1D receptor domain which is absent for the h5-HT1B receptor. The compounds described herein will be important tools to delineate the role of h5-HT1D receptors in migraine.

Molecular and pharmacological characterization of serotonin 5-HT2α and 5-HT7 receptors in the salivary glands of the blowfly Calliphora vicina.

PubMed

Röser, Claudia; Jordan, Nadine; Balfanz, Sabine; Baumann, Arnd; Walz, Bernd; Baumann, Otto; Blenau, Wolfgang

2012-01-01

Secretion in blowfly (Calliphora vicina) salivary glands is stimulated by the biogenic amine serotonin (5-hydroxytryptamine, 5-HT), which activates both inositol 1,4,5-trisphosphate (InsP(3))/Ca(2+) and cyclic adenosine 3',5'-monophosphate (cAMP) signalling pathways in the secretory cells. In order to characterize the signal-inducing 5-HT receptors, we cloned two cDNAs (Cv5-ht2α, Cv5-ht7) that share high similarity with mammalian 5-HT(2) and 5-HT(7) receptor genes, respectively. RT-PCR demonstrated that both receptors are expressed in the salivary glands and brain. Stimulation of Cv5-ht2α-transfected mammalian cells with 5-HT elevates cytosolic [Ca(2+)] in a dose-dependent manner (EC(50) = 24 nM). In Cv5-ht7-transfected cells, 5-HT produces a dose-dependent increase in [cAMP](i) (EC(50) = 4 nM). We studied the pharmacological profile for both receptors. Substances that appear to act as specific ligands of either Cv5-HT(2α) or Cv5-HT(7) in the heterologous expression system were also tested in intact blowfly salivary gland preparations. We observed that 5-methoxytryptamine (100 nM) activates only the Cv5-HT(2α) receptor, 5-carboxamidotryptamine (300 nM) activates only the Cv5-HT(7) receptor, and clozapine (1 µM) antagonizes the effects of 5-HT via Cv5-HT(7) in blowfly salivary glands, providing means for the selective activation of each of the two 5-HT receptor subtypes. This study represents the first comprehensive molecular and pharmacological characterization of two 5-HT receptors in the blowfly and permits the analysis of the physiological role of these receptors, even when co-expressed in cells, and of the modes of interaction between the Ca(2+)- and cAMP-signalling cascades.

Molecular and Pharmacological Characterization of Serotonin 5-HT2α and 5-HT7 Receptors in the Salivary Glands of the Blowfly Calliphora vicina

PubMed Central

Röser, Claudia; Jordan, Nadine; Balfanz, Sabine; Baumann, Arnd; Walz, Bernd; Baumann, Otto; Blenau, Wolfgang

2012-01-01

Secretion in blowfly (Calliphora vicina) salivary glands is stimulated by the biogenic amine serotonin (5-hydroxytryptamine, 5-HT), which activates both inositol 1,4,5-trisphosphate (InsP3)/Ca2+ and cyclic adenosine 3′,5′-monophosphate (cAMP) signalling pathways in the secretory cells. In order to characterize the signal-inducing 5-HT receptors, we cloned two cDNAs (Cv5-ht2α, Cv5-ht7) that share high similarity with mammalian 5-HT2 and 5-HT7 receptor genes, respectively. RT-PCR demonstrated that both receptors are expressed in the salivary glands and brain. Stimulation of Cv5-ht2α-transfected mammalian cells with 5-HT elevates cytosolic [Ca2+] in a dose-dependent manner (EC50 = 24 nM). In Cv5-ht7-transfected cells, 5-HT produces a dose-dependent increase in [cAMP]i (EC50 = 4 nM). We studied the pharmacological profile for both receptors. Substances that appear to act as specific ligands of either Cv5-HT2α or Cv5-HT7 in the heterologous expression system were also tested in intact blowfly salivary gland preparations. We observed that 5-methoxytryptamine (100 nM) activates only the Cv5-HT2α receptor, 5-carboxamidotryptamine (300 nM) activates only the Cv5-HT7 receptor, and clozapine (1 µM) antagonizes the effects of 5-HT via Cv5-HT7 in blowfly salivary glands, providing means for the selective activation of each of the two 5-HT receptor subtypes. This study represents the first comprehensive molecular and pharmacological characterization of two 5-HT receptors in the blowfly and permits the analysis of the physiological role of these receptors, even when co-expressed in cells, and of the modes of interaction between the Ca2+- and cAMP-signalling cascades. PMID:23145175

Vortioxetine, but not escitalopram or duloxetine, reverses memory impairment induced by central 5-HT depletion in rats: evidence for direct 5-HT receptor modulation.

PubMed

Jensen, Jesper Bornø; du Jardin, Kristian Gaarn; Song, Dekun; Budac, David; Smagin, Gennady; Sanchez, Connie; Pehrson, Alan Lars

2014-01-01

Depressed patients suffer from cognitive dysfunction, including memory deficits. Acute serotonin (5-HT) depletion impairs memory and mood in vulnerable patients. The investigational multimodal acting antidepressant vortioxetine is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and 5-HT transporter (SERT) inhibitor that enhances memory in normal rats in novel object recognition (NOR) and conditioned fear (Mørk et al., 2013). We hypothesized that vortioxetine's 5-HT receptor mechanisms are involved in its memory effects, and therefore investigated these effects in 5-HT depleted rats. Four injections of the irreversible tryptophan hydroxylase inhibitor 4-chloro-dl-phenylalanine methyl ester hydrochloride (PCPA, 86mg/kg, s.c.) induced 5-HT depletion, as measured in hippocampal homogenate and microdialysate. The effects of acute challenge with vortioxetine or the 5-HT releaser fenfluramine on extracellular 5-HT were measured in PCPA-treated and control rats. PCPA's effects on NOR and spontaneous alternation (SA) performance were assessed along with the effects of acute treatment with 5-hydroxy-l-tryptophan (5-HTP), vortioxetine, the selective 5-HT reuptake inhibitor escitalopram, or the 5-HT norepinephrine reuptake inhibitor duloxetine. SERT occupancies were estimated by ex vivo autoradiography. PCPA depleted central 5-HT by >90% in tissue and microdialysate, and impaired NOR and SA performance. Restoring central 5-HT with 5-HTP reversed these deficits. At similar SERT occupancies (>90%) vortioxetine, but not escitalopram or duloxetine, restored memory performance. Acute fenfluramine significantly increased extracellular 5-HT in control and PCPA-treated rats, while vortioxetine did so only in control rats. Thus, vortioxetine restores 5-HT depletion impaired memory performance in rats through one or more of its receptor activities. © 2013 Published by Elsevier B.V. and ECNP.

5-HT1A and 5-HT7 receptor crosstalk in the regulation of emotional memory: implications for effects of selective serotonin reuptake inhibitors.

PubMed

Eriksson, Therese M; Holst, Sarah; Stan, Tiberiu L; Hager, Torben; Sjögren, Benita; Ogren, Sven Öve; Svenningsson, Per; Stiedl, Oliver

2012-11-01

This study utilized pharmacological manipulations to analyze the role of direct and indirect activation of 5-HT(7) receptors (5-HT(7)Rs) in passive avoidance learning by assessing emotional memory in male C57BL/6J mice. Additionally, 5-HT(7)R binding affinity and 5-HT(7)R-mediated protein phosphorylation of downstream signaling targets were determined. Elevation of 5-HT by the selective serotonin reuptake inhibitor (SSRI) fluoxetine had no effect by itself, but facilitated emotional memory performance when combined with the 5-HT(1A)R antagonist NAD-299. This facilitation was blocked by the selective 5-HT(7)R antagonist SB269970, revealing excitatory effects of the SSRI via 5-HT(7)Rs. The enhanced memory retention by NAD-299 was blocked by SB269970, indicating that reduced activation of 5-HT(1A)Rs results in enhanced 5-HT stimulation of 5-HT(7)Rs. The putative 5-HT(7)R agonists LP-44 when administered systemically and AS19 when administered both systemically and into the dorsal hippocampus failed to facilitate memory. This finding is consistent with the low efficacy of LP-44 and AS19 to stimulate protein phosphorylation of 5-HT(7)R-activated signaling cascades. In contrast, increasing doses of the dual 5-HT(1A)R/5-HT(7)R agonist 8-OH-DPAT impaired memory, while co-administration with NAD-299 facilitated of emotional memory in a dose-dependent manner. This facilitation was blocked by SB269970 indicating 5-HT(7)R activation by 8-OH-DPAT. Dorsohippocampal infusion of 8-OH-DPAT impaired passive avoidance retention through hippocampal 5-HT(1A)R activation, while 5-HT(7)Rs appear to facilitate memory processes in a broader cortico-limbic network and not the hippocampus alone. Copyright © 2012 Elsevier Ltd. All rights reserved.

10 CFR 905.17 - What are the requirements for the energy efficiency and/or renewable energy report (EE/RE report...

Code of Federal Regulations, 2013 CFR

2013-01-01

... renewable energy report (EE/RE report) alternative? 905.17 Section 905.17 Energy DEPARTMENT OF ENERGY ENERGY... energy efficiency and/or renewable energy report (EE/RE report) alternative? (a) Requests to submit an EE..., including any requirements for documenting customer energy efficiency and renewable energy activities. (b...

10 CFR 905.17 - What are the requirements for the energy efficiency and/or renewable energy report (EE/RE report...

Code of Federal Regulations, 2011 CFR

2011-01-01

... renewable energy report (EE/RE report) alternative? 905.17 Section 905.17 Energy DEPARTMENT OF ENERGY ENERGY... energy efficiency and/or renewable energy report (EE/RE report) alternative? (a) Requests to submit an EE..., including any requirements for documenting customer energy efficiency and renewable energy activities. (b...

10 CFR 905.17 - What are the requirements for the energy efficiency and/or renewable energy report (EE/RE report...

Code of Federal Regulations, 2014 CFR

2014-01-01

... renewable energy report (EE/RE report) alternative? 905.17 Section 905.17 Energy DEPARTMENT OF ENERGY ENERGY... energy efficiency and/or renewable energy report (EE/RE report) alternative? (a) Requests to submit an EE..., including any requirements for documenting customer energy efficiency and renewable energy activities. (b...

10 CFR 905.17 - What are the requirements for the energy efficiency and/or renewable energy report (EE/RE report...

Code of Federal Regulations, 2012 CFR

2012-01-01

... renewable energy report (EE/RE report) alternative? 905.17 Section 905.17 Energy DEPARTMENT OF ENERGY ENERGY... energy efficiency and/or renewable energy report (EE/RE report) alternative? (a) Requests to submit an EE..., including any requirements for documenting customer energy efficiency and renewable energy activities. (b...

31 CFR 351.41 - When are definitive Series EE savings bonds validly issued?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false When are definitive Series EE savings bonds validly issued? 351.41 Section 351.41 Money and Finance: Treasury Regulations Relating to Money... OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.41 When are...

31 CFR 351.49 - How are definitive Series EE savings bonds delivered?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false How are definitive Series EE savings bonds delivered? 351.49 Section 351.49 Money and Finance: Treasury Regulations Relating to Money and... UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.49 How are definitive...

Examining the Literature to Reveal the Nature of Community EE/ESD Programs and Research

ERIC Educational Resources Information Center

Aguilar, Olivia M.

2018-01-01

Interest in community environmental education (EE) and community education for sustainable development (ESD) is increasing, as evidenced by the increase in studies examining community EE/ESD approaches and NAAEE's current development of the Community EE Guidelines for Excellence. Thus, the purpose of this paper is to: (1) provide a review of…

31 CFR 351.14 - When are rate announcements that apply to Series EE savings bonds announced?

Code of Federal Regulations, 2013 CFR

2013-07-01

... to Series EE savings bonds announced? 351.14 Section 351.14 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.14 When are rate announcements that apply to...

31 CFR 351.14 - When are rate announcements that apply to Series EE savings bonds announced?

Code of Federal Regulations, 2012 CFR

2012-07-01

... to Series EE savings bonds announced? 351.14 Section 351.14 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.14 When are rate announcements that apply to...

31 CFR 351.14 - When are rate announcements that apply to Series EE savings bonds announced?

Code of Federal Regulations, 2011 CFR

2011-07-01

... to Series EE savings bonds announced? 351.14 Section 351.14 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.14 When are rate announcements that apply to...

Early Life Stress and Sleep Restriction as Risk Factors in PTSD: An Integrative Pre-Clinical Approach

DTIC Science & Technology

2015-04-01

dDG GABAAR alpha 1 expression in both J+UWT(+),EE (J) and EE (A) rats compered to Control. In addition, EE (A) rats exhibit lower expression of BLA...GABAAR alpha 1 expression compered to Control. (*= pɘ.05,**= pɘ.01). 48 7: One way ANOVA [F (3,47)= 4.79, pɘ.01] revealed a significant main...effect for the exposure. Further Post hoc comparisons revealed increased vDG GABAAR alpha 1 expression in both J+UWT(+) and EE (A) rats compered to EE (J

The Intelligence Archipelago: The Community’s Struggle to Reform in the Globalized Era

DTIC Science & Technology

2005-05-01

operational consumers The Intelligence Archipelago: The Community’s Struggle to Reform in the Globalized Era This product has been reviewed by senior...Government Joint Military Intelligence CollegeCC ee n n tt ee rr ff oo rr St ra te gic Intelligen cc ee RR ee ss ee aa rr cc hh iii CONTENTS ...on September 11th appears to be no different than responses in the past: you don’t understand intelligence, leave us alone, we will fix it on our own

Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission.

PubMed

Sengupta, Ayesha; Bocchio, Marco; Bannerman, David M; Sharp, Trevor; Capogna, Marco

2017-02-15

The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT 2A and 5-HT 1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT 1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders. Therefore, it is essential to determine the physiological mechanisms through which 5-HT neurons in the dorsal raphe nuclei modulate amygdala circuits. Here, we combined optogenetic, electrophysiological, and pharmacological approaches to study the effects of activation of 5-HT axons in the basal nucleus of the amygdala (BA). We found that 5-HT neurons co-release 5-HT and glutamate onto BA neurons in a cell-type-specific and frequency-dependent manner. Therefore, we suggest that theories on the contribution of 5-HT neurons to amygdala function should be revised to incorporate the concept of 5-HT/glutamate cotransmission. Copyright © 2017 Sengupta et al.

Drug Discovery Targeting Serotonin G Protein-Coupled Receptors in the Treatment of Neuropsychiatric Disorders

NASA Astrophysics Data System (ADS)

Felsing, Daniel E.

Clinical data show that activation of 5-HT2C G protein-coupled receptors (GPCRs) can treat obesity (lorcaserin/BelviqRTM) and psychotic disorders (aripiprazole/Abilify.), including schizophrenia. 5-HT2C GPCRs are members of the 5-HT2 sub-family of 5-HT GPCRs, which include 5-HT2A, 5-HT2B, and 5-HT 2C GPCRs. 5-HT2C is structurally similar to 5-HT2A and 5-HT2B GPCRs, but activation of 5-HT2A and/or 5-HT 2B causes deleterious effects, including hallucinations and cardiac valvulopathy. Thus, there is a challenge to develop drugs that selectively activate only 5-HT2C. Prolonged activation of GPCRs by agonists reduces their function via a regulatory process called desensitization. This has clinical relevance, as 45% of drugs approved by the FDA target GPCRs, and agonist drugs (e.g., morphine) typically lose efficacy over time due to desensitization, which invites tolerance. Agonists that cause less desensitization may show extended clinical efficacy as well as a more acceptable clinical dose range. We hypothesized that structurally distinct agonists of the 5-HT2C receptor may cause varying degrees of desensitization by stabilizing unique 5-HT2C receptor conformations. Discovery of 5-HT2C agonists that exhibit minimal desensitization is therapeutically relevant for the pharmacotherapeutic treatment of chronic diseases such as obesity and psychotic disorders. The 5-HT7 receptor has recently been discovered as a druggable target, and selective activation of the 5-HT7 receptor has been shown to alleviate locomotor deficits in mouse models of Rett Syndrome. Additionally, buspirone has been shown to display therapeutically relevant affinity at 5-HT 1A and is currently in phase II clinical trials to treat stereotypy in children with autism. The 5-PAT chemical scaffold shows high affinity towards the 5-HT7 and 5-HT1A receptors. Modulations around the 5-phenyl moiety were able to improve selectivity in binding towards the 5-HT 7 receptor, whereas modulations of the alkyl chains bonded to the vital basic nitrogen modulated 5-HT1A selectivity. The lead candidate, (+)-o-F-5-PAT, was shown effective in attenuating three separate murine models of stereotypy and two models of drug-induced hyperlocomotion. Therefore, the 5-PAT chemical scaffold is a unique chemical scaffold enabling discrimination of therapeutic function of the 5-HT7 and 5-HT 1A receptors in vivo..

Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission

PubMed Central

Bannerman, David M.

2017-01-01

The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10–20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT2A and 5-HT1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders. Therefore, it is essential to determine the physiological mechanisms through which 5-HT neurons in the dorsal raphe nuclei modulate amygdala circuits. Here, we combined optogenetic, electrophysiological, and pharmacological approaches to study the effects of activation of 5-HT axons in the basal nucleus of the amygdala (BA). We found that 5-HT neurons co-release 5-HT and glutamate onto BA neurons in a cell-type-specific and frequency-dependent manner. Therefore, we suggest that theories on the contribution of 5-HT neurons to amygdala function should be revised to incorporate the concept of 5-HT/glutamate cotransmission. PMID:28087766

Do hormone treatments for prostate cancer cause anxiety and depression?

PubMed

Sharpley, Christopher F; Christie, David R H; Bitsika, Vicki

2014-01-01

To investigate the relationship between hormone therapy (HT) and incidence of anxiety and depression among prostate cancer patients (PCa). 526 PCa patients completed a survey about their cancer status, treatment received, anxiety, and depression status. Total scores on anxiety and depression inventories, plus symptom profiles that discriminated between patients with current HT, past HT, and never having received HT, were compiled for analysis. Patients who were currently receiving HT had significantly higher total anxiety and depression scores than patients who had previously received HT or who had never received HT. Analysis of the symptoms of anxiety and depression which distinguished between these groups of patients suggested that patients who had never received HT had significantly lower scores than current or past HT patients. Although several symptoms could be directly allocated to PCa and/or HT, symptom profiles were indicative of clinically significant anxiety and/or depression in patients who were currently receiving, or who had previously received, HT. Current HT may lead to symptoms of anxiety and/or depression which require clinical attention. These effects seem to decrease after completion of HT.

Potentiation of transient receptor potential V1 functions by the activation of metabotropic 5-HT receptors in rat primary sensory neurons

PubMed Central

Ohta, Toshio; Ikemi, Yuki; Murakami, Matsuka; Imagawa, Toshiaki; Otsuguro, Ken-ichi; Ito, Shigeo

2006-01-01

5-Hydroxytryptamine (5-HT) is one of the major chemical mediators released in injured and inflamed tissue and is capable of inducing hyperalgesia in vivo. However, the cellular mechanisms of 5-HT-induced hyperalgesia remain unclear. Transient receptor potential V1 (TRPV1) plays a pivotal role in nociceptive receptors. In the present study, we determined whether 5-HT changes TRPV1 functions in cultured dorsal root ganglion (DRG) neurons isolated from neonatal rats, using Ca2+ imaging and whole-cell patch-clamp techniques. In more than 70% of DRG neurons, 5-HT potentiated the increases of [Ca2+]i induced by capsaicin, protons and noxious heat. Capsaicin-induced current and depolarizing responses, and proton-induced currents were also augmented by 5-HT. RT-PCR analysis revealed the expression of 5-HT2A and 5-HT7 receptors in rat DRG neurons. Agonists for 5-HT2A and 5-HT7 receptors mimicked the potentiating effect of 5-HT, and their antagonists decreased it. In DRG ipsilateral to the complete Freund's adjuvant-injected inflammation side, expression levels of 5-HT2A and 5-HT7 mRNAs increased, and the potentiating effect of 5-HT was more prominent than in the contralateral control side. These results suggest that the PKC- and PKA-mediated signalling pathways are involved in the potentiating effect of 5-HT on TRPV1 functions through the activation of 5-HT2A and 5-HT7 receptors, respectively. Under inflammatory conditions, the increases of the biosynthesis of these 5-HT receptors may lead to further potentiation of TRPV1 functions, resulting in the generation of inflammatory hyperalgesia in vivo. PMID:16901936

Electrospun photosensitive nanofibers: potential for photocurrent therapy in skin regeneration.

PubMed

Jin, Guorui; Prabhakaran, Molamma P; Kai, Dan; Kotaki, Masaya; Ramakrishna, Seeram

2013-01-01

Poly(3-hexylthiophene) (P3HT) is one of the most promising photovoltaic (PV) polymers in photocurrent therapy. A novel photosensitive scaffold for skin tissue engineering was fabricated by blending P3HT with polycaprolactone (PCL) and electrospun to obtain composite PCL/P3HT nanofibers with three different weight ratios of PCL : P3HT (w/w) of 150 : 2 [PCL/P3HT(2)], 150 : 10 [PCL/P3HT(10)] and 150 : 20 [PCL/P3HT(20)]. The photosensitive properties of the blend solutions and the composite nanofibers of PCL/P3HT were investigated. The incident photon-to-electron conversion efficiencies of the PCL/P3HT(2), PCL/P3HT(10), PCL/P3HT(20) were identified as 2.0 × 10(-6), 1.6 × 10(-5) and 2.9 × 10(-5), respectively, which confirm the photosensitive ability of the P3HT-containing scaffolds. The biocompatibility of the scaffold was evaluated by culturing human dermal fibroblasts and the results showed that the proliferation of HDFs under light stimulation on PCL/P3HT(10) was 12.8%, 11.9%, and 11.6% (p ≤ 0.05) higher than the cell growth on PCL, PCL/P3HT(2) and PCL/P3HT(20), respectively. Human dermal fibroblasts cultured under light stimulation on PCL/P3HT(10) not only showed better cell proliferation but also retained cell morphology similar to the phenotype observed on tissue culture plates (control). Our experimental results suggest novel and potential application of an optimized amount of P3HT-containing scaffold, especially PCL/P3HT(10) nanofibrous scaffold in photocurrent therapy for skin regeneration.

Shifting Topographic Activation and 5-HT1A-Receptor Mediated Inhibition of Dorsal Raphe Serotonin Neurons Produced by Nicotine Exposure and Withdrawal

PubMed Central

Sperling, Robin; Commons, Kathryn G.

2011-01-01

Nicotine activates serotonin (5-HT) neurons innervating the forebrain and this is thought to reduce anxiety. Nicotine withdrawal has also been associated with an activation of 5-HT neurotransmission, although withdrawal increases anxiety. In each case, 5-HT1A receptors have been implicated in the response. To determine if there are different subgroups of 5-HT cells activated during nicotine administration and withdrawal, we mapped the appearance of Fos, a marker of neuronal activation, in 5-HT cells of the dorsal and median raphe nuclei (DR and MR). To understand the role 5-HT1A receptor feedback inhibitory pathways on 5-HT cell activity during these conditions, we administered a selective 5-HT1A-receptor antagonist and measured novel disinhibited Fos expression within 5-HT cells. Using these approaches, we found evidence that acute nicotine activates 5-HT neurons rostrally and in the lateral wings of the DR while there is 5-HT1A dependent inhibition of cells located ventrally both at rostral and mid levels. Previous chronic nicotine exposure did not modify the pattern of Fos activation produced by acute nicotine, but increased 5-HT1A-dependent inhibition of 5-HT cells in the caudal DR. This pattern was nearly reversed during nicotine withdrawal when there was evidence for caudal activation and mid- and rostral-5-HT1A-dependent inhibition. These results suggest that the distinct behavioral states produced by nicotine exposure and withdrawal correlate with reciprocal rostral-caudal patterns of activation and 5-HT1A-mediated inhibition of DR 5-HT neurons. The complimentary patterns of activation and inhibition suggest that 5-HT1A receptors may help shape distinct topographic patterns of activation within the DR. PMID:21501256

Naftopidil inhibits 5-hydroxytryptamine-induced bladder contraction in rats.

PubMed

Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

2013-01-30

Naftopidil is an α(1D) and α(1A) subtype-selective α(1)-adrenoceptor antagonist that has been used to treat lower urinary tract symptoms of benign prostatic hyperplasia. In this study, we investigated the effects of naftopidil on 5-hydroxytryptamine (5-HT)-induced rat bladder contraction (10(-8)-10(-4) M). Naftopidil (0.3, 1, and 3 μM) inhibited 5-HT-induced bladder contraction in a concentration-dependent manner. On the other hand, other α(1)-adrenoceptor antagonists, tamsulosin, silodosin or prazosin, did not inhibit 5-HT-induced bladder contraction. The 5-HT-induced bladder contraction was inhibited by both ketanserin and 4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine (RS127445), serotonin 5-HT(2A) and 5-HT(2B) receptor antagonists, respectively. In addition, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and α-methyl-5-HT, 5-HT(2A) and 5-HT(2) receptor agonists, respectively, induced bladder contraction. The 5-HT-induced bladder contraction was not inhibited by N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide (WAY-100635), [1-[2[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate (GR113808) or (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulphonyl]phenol (SB269970), 5-HT(1A), 5-HT(4) and 5-HT(7) receptor antagonists, respectively. Naftopidil inhibited both the 5-HT(2A) and 5-HT(2) receptor agonists-induced bladder contractions. Naftopidil binds to the human 5-HT(2A) and 5-HT(2B) receptors with pKi values of 6.55 and 7.82, respectively. These results suggest that naftopidil inhibits 5-HT-induced bladder contraction via blockade of the 5-HT(2A) and 5-HT(2B) receptors in rats. Furthermore, 5-HT-induced bladder contraction was enhanced in bladder strips obtained from bladder outlet obstructed rats, with this contraction inhibited by naftopidil. The beneficial effects of naftopidil on storage symptoms such as urinary frequency and nocturia in patients with benign prostatic hyperplasia may be due, in part, to the blockade of the 5-HT(2A) and 5-HT(2B) receptors in the bladder. Copyright © 2012 Elsevier B.V. All rights reserved.

The role of serotonin-2 (5-HT2) and dopamine receptors in the behavioral actions of the 5-HT2A/2C agonist, DOI, and putative 5-HT2C inverse agonist, SR46349B.

PubMed

Scarlota, Laura C; Harvey, John A; Aloyo, Vincent J

2011-02-01

Atypical antipsychotic efficacy is often attributed to actions at serotonin-2 (5-HT(2)) and dopamine receptors, indicating a potential benefit of understanding the interplay between these systems. Currently, it is known that 5-HT(2) receptors modulate dopamine release, although the role of specific dopamine receptors in 5-HT(2)-mediated behavior is not well understood. We examined the role of 5-HT(2A), 5-HT(2C), and dopamine (D1 and D2) receptors in the behavioral response to a 5-HT(2A/2C) agonist (DOI) and 5-HT(2A/2C) antagonist (SR46349B). Effects were assessed by measuring rabbit head bobs (previously characterized as 5-HT(2A) receptor-mediated) and body shakes (5-HT(2C)-mediated). As expected, DOI produced head bobs and body shakes, and these DOI-elicited behaviors were attenuated by the SR46349B pretreatment. Unexpectedly, SR46349B also induced head bobs when administered alone. However, SR46349B-elicited head bobs are distinguishable from those produced by DOI since the 5-HT(2A) antagonist, ketanserin, only attenuated DOI-elicited head bobs. Conversely, 5-HT(2C) ligands (SB242084 and SB206553) inhibited SR46349B but not DOI-induced head bobs. Furthermore, when administered alone, SB206553 (a 5-HT(2C) inverse agonist) produced head bobs, indicating the behavior can be either 5-HT(2A) or 5-HT(2C) mediated. Next, it was revealed that D1 and D2 receptors play a role in DOI-elicited head bobs, but only D1 receptors are required for SR46349B-elicited head bobs. 5-HT(2A) receptor agonism and 5-HT(2C) inverse agonism produce the same behavior, likely due to similar downstream actions at D1 receptors. Consequently, 5-HT(2C) agonism or D1 agonism may be effective therapies for disorders, such as schizophrenia, currently being treated with 5-HT(2A) antagonists.

Further investigation of the effects of 5-hydroxytryptamine, 8-OH-DPAT and DOI to mediate contraction and relaxation responses in the intestine and emesis in Suncus murinus.

PubMed

Javid, Farideh A; Afshin-Javid, Saeed; Horn, Charles C

2018-02-15

5-HT receptors are implicated in many gastrointestinal disorders. However, the precise role of 5-HT in mediating GI responses in Suncus murnius is still unclear. Therefore in this study, the effects of 5-HT and its agonists were investigated in Suncus. The involvement of 5-HT 2C receptors in mediating emesis was also investigated. The ability of 5-HT and its agonists/antagonists at 5-HT 1A and 5-HT 2 to modify GI motility was investigated in vitro and in vivo. WAY100635 (a 5-HT 1A antagonist) inhibited the contraction response to 5-HT in the proximal segments without affecting the maximum response; whilst enhancing the contraction to 5-HT (>30.0nM) in the distal intestine. The selective 5-HT 2A and 5-HT 2B receptor antagonists MDL-100907 and RS-127445 attenuated 5-HT-induced contractions (<10.0µM) in the distal segments. RS-127445 also attenuated 5-HT-induced contractions in the central segments. The selective 5-HT 2C receptor antagonist SB-242084, attenuated the responses to 5-HT (> 3.0nM) in the proximal and central but not the distal regions. 8-OH-DPAT-induced relaxation was resistant to the antagonism by 5-HT 1A/7 antagonists. DOI in the presence of 5-HT 1A/2A/2B/2C antagonists induced greater contraction responses (>1.0µM) in most tissues, whilst RS-127445, or SB-242084, reduced the responses to DOI (< 1.0µM) in some tissues. SB-242084 also suppressed emesis-induced by motion and intragastric CuSO 4 . In conclusion, within different regions of intestine, 5-HT 2 receptors are differently involved in contraction and emetic responses and that 8-OH-DPAT induces relaxation via non-5-HT 1A/7 receptors. Suncus could provide a model to investigate these diverse actions of 5-HT. Copyright © 2018 Elsevier B.V. All rights reserved.

Entertainment-Education Narrative Versus Nonnarrative Interventions to Educate and Motivate Latinas to Engage in Mammography Screening.

PubMed

Borrayo, Evelinn A; Rosales, Monica; Gonzalez, Patricia

2017-06-01

The evidence is limited comparing the effects of entertainment-education (E-E) narrative versus nonnarrative interventions to educate and motivate Latinas to engage in mammography screening. This study compared an E-E narrative intervention to two nonnarrative interventions' effects among Latinas on breast cancer knowledge and motivation, as measured by changes in self-efficacy, behavioral norms, and behavioral intentions to engage in mammography screening. A sample of 141 Spanish-speaking Latinas was randomly assigned to one of three arms: an E-E narrative video, a nonnarrative educational video, and printed educational materials. Using a repeated measures design, the influence of the E-E narrative on pretest to posttest measures was assessed and compared to the influence of the other two interventions. The E-E narrative and nonnarrative interventions significantly increased Latinas' breast cancer knowledge, mammography self-efficacy, and behavioral norms from pretest to posttest. However, the E-E narrative participants' pretest to posttest difference in mammography self-efficacy was significantly higher when compared to the difference of the other two interventions. The effect of the E-E narrative intervention on self-efficacy and behavioral norms was moderated by the participants' absorption in the story and identification with the story characters. E-E narrative and nonnarrative interventions significantly educated and motivated Latinas to engage in mammography screening. The effects on mammography self-efficacy, an important precursor to behavior change, can be more strongly influenced by E-E narratives. Although E-E narrative and nonnarrative interventions were effective, the need still exists to assess if they can ultimately influence lifesaving breast cancer screening behaviors.

Metabolic Power Method: Underestimation of Energy Expenditure in Field-Sport Movements Using a Global Positioning System Tracking System.

PubMed

Brown, Darcy M; Dwyer, Dan B; Robertson, Samuel J; Gastin, Paul B

2016-11-01

The purpose of this study was to assess the validity of a global positioning system (GPS) tracking system to estimate energy expenditure (EE) during exercise and field-sport locomotor movements. Twenty-seven participants each completed a 90-min exercise session on an outdoor synthetic futsal pitch. During the exercise session, they wore a 5-Hz GPS unit interpolated to 15 Hz and a portable gas analyzer that acted as the criterion measure of EE. The exercise session was composed of alternating 5-minute exercise bouts of randomized walking, jogging, running, or a field-sport circuit (×3) followed by 10 min of recovery. One-way analysis of variance showed significant (P < .01) and very large underestimations between GPS metabolic power- derived EE and oxygen-consumption (VO 2 ) -derived EE for all field-sport circuits (% difference ≈ -44%). No differences in EE were observed for the jog (7.8%) and run (4.8%), whereas very large overestimations were found for the walk (43.0%). The GPS metabolic power EE over the entire 90-min session was significantly lower (P < .01) than the VO 2 EE, resulting in a moderate underestimation overall (-19%). The results of this study suggest that a GPS tracking system using the metabolic power model of EE does not accurately estimate EE in field-sport movements or over an exercise session consisting of mixed locomotor activities interspersed with recovery periods; however, is it able to provide a reasonably accurate estimation of EE during continuous jogging and running.

Meta-analysis of long-term clinical outcomes of everolimus-eluting stents.

PubMed

Toyota, Toshiaki; Shiomi, Hiroki; Morimoto, Takeshi; Kimura, Takeshi

2015-07-15

The superiority of everolimus-eluting stents (EES) over sirolimus-eluting stents (SES) for long-term clinical outcomes has not been yet firmly established. We conducted a systematic review and a meta-analysis of randomized controlled trials (RCTs) comparing EES directly with SES using the longest available follow-up data. We searched PubMed, the Cochrane database, and ClinicalTrials.gov for RCTs comparing outcomes between EES and SES and identified 13,434 randomly assigned patients from 14 RCTs. EES was associated with significantly lower risks than SES for definite stent thrombosis (ST), definite/probable ST, target-lesion revascularization (TLR), and major adverse cardiac events (MACE). The risks for all-cause death and myocardial infarction were similar between EES and SES. By the stratified analysis according to the timing after stent implantation, the favorable trend of EES relative to SES for ST, TLR, and MACE was consistently observed both within and beyond 1 year. The lower risk of EES relative to SES for MACE beyond 1 year was statistically significant (pooled odds ratio 0.77, 95% confidence interval 0.61 to 0.96, p = 0.02). In conclusion, the current meta-analysis of 14 RCTs directly comparing EES with SES suggested that EES provided improvement in both safety and efficacy; EES compared with SES was associated with significantly lower risk for definite ST, definite/probable ST, TLR, and MACE. The direction and magnitude of the effect beyond 1 year were comparable with those observed within 1 year. Copyright © 2015 Elsevier Inc. All rights reserved.

CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy.

PubMed

Zhou, Zhike; Liu, Tingting; Sun, Xiaoyu; Mu, Xiaopeng; Zhu, Gang; Xiao, Ting; Zhao, Mei; Zhao, Chuansheng

2017-03-30

It has been showed that enriched environment (EE) enhances the hippocampal neurogenesis and improves the cognitive impairments, accompanied by the increased expressions of stromal cell-derived factor-1 (SDF-1) in adult rats of temporal lobe epilepsy (TLE). We examined whether the enhanced neurogenesis and improved cognitive functions induced by EE following seizures were mediated by SDF-1/CXCR4 pathway. Therefore, we investigated the effects of the EE combined with CXCR4 antagonist AMD3100 on neurogenesis, cognitive functions and the long-term seizure activity in the TLE model. Adult rats were randomly assigned as control rats, rats treated with EE, rats subjected to status epilepticus (SE), post-SE rats treated with EE, AMD3100 or EE combined with AMD3100 respectively. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the frequency and mean duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze test. EE treatment significantly, as well as improved cognitive impairments and decreased long-term seizure activity, and that these effects might be mediated through SDF-1/CXCR4 pathway during the chronic stage of TLE. Although AMD3100 reversed the effect of EE on neurogenesis, it did not abolish the cognitive improvement induced by EE following seizures. More importantly, EE combined with AMD3100 treatment significantly suppressed long-term seizure activity, which provided promising evidences to treat TLE. Copyright © 2017 Elsevier B.V. All rights reserved.

Stigma, Expressed Emotion, and Quality of Life in Caregivers of Individuals with Dementia.

PubMed

Weisman de Mamani, Amy; Weintraub, Marc J; Maura, Jessica; Martinez de Andino, Ana; Brown, Caitlin A

2017-10-15

Expressed emotion (EE) is a measure of a caregiver's critical and emotionally overinvolved (EOI; e.g., intrusive, self-sacrificing) attitudes and behaviors toward a person with a mental illness. Mounting evidence indicates that high levels of these critical and EOI attitudes and behaviors (collectively termed high EE) in family members are associated with a poorer course of illness for people with a range of disorders, including dementia (Nomura et al., 2005). However, less is known about factors that might trigger high EE and how high EE might impact dementia caregivers' own mental health. In this study we propose that caregivers who perceive stigma from their relative's illness may be more likely to be critical or intrusive (high EOI) toward their relative in an attempt to control symptomatic behaviors. We further hypothesized that high EE would partially mediate the link between stigma and quality of life (QoL) as there is some evidence that high EE is associated with poorer mental health in caregivers themselves (Safavi et al., 2015). In line with study hypotheses and using a sample of 106 dementia caregivers, we found that greater caregiver stigma was associated with both high EE (for criticism and EOI) and with poorer QoL. Mediational analyses further confirmed that high EE accounts for much of the association between stigma and poorer QoL. Study results suggest that addressing caregiver stigma in therapy could reduce levels of high EE and indirectly therefore improve caregiver QoL. Intervening directly to reduce high EE could also improve caregiver QoL. © 2017 Family Process Institute.

Evaluation of the Effect of Tofacitinib on the Pharmacokinetics of Oral Contraceptive Steroids in Healthy Female Volunteers

PubMed Central

Menon, Sujatha; Riese, Richard; Wang, Ronnie; Alvey, Christine W.; Shi, Haihong; Petit, Wendy

2016-01-01

Abstract Tofacitinib is an oral Janus kinase inhibitor. Tofacitinib metabolism is primarily mediated by cytochrome P450 3A4. This phase 1 randomized, open‐label, 2‐way crossover study (NCT01137708) evaluated the effect of tofacitinib 30 mg twice daily on the single‐dose pharmacokinetics of combination oral contraceptives ethinylestradiol (EE) and levonorgestrel (LN). EE and LN were administered as a single Microgynon 30® tablet (30 μg EE and 150 μg LN) to 19 healthy women. In the presence of tofacitinib, the area under the curve from time zero to infinity (AUC∞) increased by 6.6% and 0.9% for EE and LN, respectively. Maximal plasma concentrations decreased by 10.4% for EE and increased by 12.2% for LN when coadministered with tofacitinib. The 90% confidence intervals for the adjusted geometric mean ratios for AUC∞ fell within the 80%–125% region for both EE and LN. Mean half‐life was similar in the presence and absence of tofacitinib: 13.8 and 13.3 hours, respectively, for EE; 25.9 and 25.4 hours, respectively, for LN. Tofacitinib had no clinically relevant net inhibitory or inductive effect on the pharmacokinetics of EE and LN. Therefore, there is no evidence to suggest dose adjustments of oral contraceptive drugs containing EE or LN when coadministered with tofacitinib. PMID:27138968

Evaluation of the Effect of Tofacitinib on the Pharmacokinetics of Oral Contraceptive Steroids in Healthy Female Volunteers.

PubMed

Menon, Sujatha; Riese, Richard; Wang, Ronnie; Alvey, Christine W; Shi, Haihong; Petit, Wendy; Krishnaswami, Sriram

2016-09-01

Tofacitinib is an oral Janus kinase inhibitor. Tofacitinib metabolism is primarily mediated by cytochrome P450 3A4. This phase 1 randomized, open-label, 2-way crossover study (NCT01137708) evaluated the effect of tofacitinib 30 mg twice daily on the single-dose pharmacokinetics of combination oral contraceptives ethinylestradiol (EE) and levonorgestrel (LN). EE and LN were administered as a single Microgynon 30® tablet (30 μg EE and 150 μg LN) to 19 healthy women. In the presence of tofacitinib, the area under the curve from time zero to infinity (AUC∞ ) increased by 6.6% and 0.9% for EE and LN, respectively. Maximal plasma concentrations decreased by 10.4% for EE and increased by 12.2% for LN when coadministered with tofacitinib. The 90% confidence intervals for the adjusted geometric mean ratios for AUC∞ fell within the 80%-125% region for both EE and LN. Mean half-life was similar in the presence and absence of tofacitinib: 13.8 and 13.3 hours, respectively, for EE; 25.9 and 25.4 hours, respectively, for LN. Tofacitinib had no clinically relevant net inhibitory or inductive effect on the pharmacokinetics of EE and LN. Therefore, there is no evidence to suggest dose adjustments of oral contraceptive drugs containing EE or LN when coadministered with tofacitinib. © 2016, The American College of Clinical Pharmacology.

Do stress and support matter for caring? The role of perceived stress and social support on expressed emotion of carers of persons with first episode psychosis.

PubMed

Sadath, Anvar; Muralidhar, D; Varambally, Shivarama; Gangadhar, B N; Jose, Justin P

2017-02-01

Caring for a person with first episode psychosis (FEP) is a challenging and distressing task for the carers. The carers' stress in the early stage of psychosis can increase their expressed emotion (EE) while social support is hypothesized to decrease EE. However, the influence of stress and social support on carers' EE is not well understood in FEP. To examine how the stress and social support shape expressed emotion in the carers of FEP. Seventy one carers of the patients with non-affective FEP were recruited from the inpatient psychiatry ward of a tertiary mental health care center in South India. The family questionnaire, perceived stress scale and multidimensional scale of perceived social support were used to measure their EE, stress and social support respectively. Carers experienced high level of perceived stress, EE and poor social support. Perceived stress significantly increased EE (β=0.834; p<0.001) and social support did not significantly influence EE (β=-0.065; p>0.05). Perceived stress predicted 76 percent of the variance on EE (Adjusted R 2 =0.761). The results emphasize high level of stress and EE in carers of patients with FEP that implies the need for appropriate psychosocial interventions to manage their stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Is Obesity Associated with Altered Energy Expenditure?12

PubMed Central

Carneiro, Isabella P; Elliott, Sarah A; Siervo, Mario; Padwal, Raj; Bertoli, Simona; Battezzati, Alberto; Prado, Carla M

2016-01-01

Historically, obese individuals were believed to have lower energy expenditure (EE) rates than nonobese individuals (normal and overweight), which, in the long term, would contribute to a positive energy balance and subsequent weight gain. The aim of this review was to critically appraise studies that compared measures of EE and its components, resting EE (REE), activity EE (AEE), and diet-induced thermogenesis (DIT), in obese and nonobese adults to elucidate whether obesity is associated with altered EE. Contrary to popular belief, research has shown that obese individuals have higher absolute REE and total EE. When body composition (namely the metabolically active component, fat-free mass) is taken into account, these differences between obese and nonobese individuals disappear, suggesting that EE in obese individuals is not altered. However, an important question is whether AEE is lower in obese individuals because of a decrease in overall physical activity or because of less energy expended while performing physical activity. AEE and DIT could be reduced in obese individuals, mostly because of unhealthy behavior (low physical activity, higher intake of fat). However, the current evidence does not support the hypothesis that obesity is sustained by lower daily EE or REE. Future studies, comparing EE between obese and nonobese and assessing potential physiologic abnormalities in obese individuals, should be able to better answer the question of whether these individuals have altered energy metabolism. PMID:27184275

Maternal exposure to environmental enrichment before and during gestation influences behaviour of rat offspring in a sex-specific manner.

PubMed

Zuena, Anna Rita; Zinni, Manuela; Giuli, Chiara; Cinque, Carlo; Alemà, Giovanni Sebastiano; Giuliani, Alessandro; Catalani, Assia; Casolini, Paola; Cozzolino, Roberto

2016-09-01

The beneficial effects of Environmental Enrichment (EE) applied immediately after weaning or even in adulthood have been widely demonstrated. Less is known about the possible changes in behaviour and brain development of the progeny following the exposure of dams to EE. In order to further investigate this matter, female rats were reared in EE for 12weeks, from weaning until delivery. After having confirmed the presence of relevant behavioural effects of EE, both control and EE females underwent mating. Maternal behaviour was observed and male and female offspring were then administered a battery of behavioural test at different ages. EE mothers showed a decreased frequency of total nursing and, during the first 2days of lactation, an increase in licking/grooming behaviour. Maternal exposure to EE affected offspring behaviour in a sex-specific manner: social play behaviour and anxiety-like behaviour were increased in males but not in females and learning ability was improved only in females. As a general trend, maternal EE had a marked influence on motility in male and female offspring in both locomotor activity and swimming speed. Overall, this study highlights the importance of environmental stimulation, not only in the animals directly experiencing EE, but for their progeny too, opening the way to new hypothesis on the heritability mechanisms of behavioural traits. Copyright © 2016 Elsevier Inc. All rights reserved.

A computational model for epidural electrical stimulation of spinal sensorimotor circuits.

PubMed

Capogrosso, Marco; Wenger, Nikolaus; Raspopovic, Stanisa; Musienko, Pavel; Beauparlant, Janine; Bassi Luciani, Lorenzo; Courtine, Grégoire; Micera, Silvestro

2013-12-04

Epidural electrical stimulation (EES) of lumbosacral segments can restore a range of movements after spinal cord injury. However, the mechanisms and neural structures through which EES facilitates movement execution remain unclear. Here, we designed a computational model and performed in vivo experiments to investigate the type of fibers, neurons, and circuits recruited in response to EES. We first developed a realistic finite element computer model of rat lumbosacral segments to identify the currents generated by EES. To evaluate the impact of these currents on sensorimotor circuits, we coupled this model with an anatomically realistic axon-cable model of motoneurons, interneurons, and myelinated afferent fibers for antagonistic ankle muscles. Comparisons between computer simulations and experiments revealed the ability of the model to predict EES-evoked motor responses over multiple intensities and locations. Analysis of the recruited neural structures revealed the lack of direct influence of EES on motoneurons and interneurons. Simulations and pharmacological experiments demonstrated that EES engages spinal circuits trans-synaptically through the recruitment of myelinated afferent fibers. The model also predicted the capacity of spatially distinct EES to modulate side-specific limb movements and, to a lesser extent, extension versus flexion. These predictions were confirmed during standing and walking enabled by EES in spinal rats. These combined results provide a mechanistic framework for the design of spinal neuroprosthetic systems to improve standing and walking after neurological disorders.

Structural and biophysical characterization of an epitope-specific engineered Fab fragment and complexation with membrane proteins: implications for co-crystallization.

PubMed

Johnson, Jennifer L; Entzminger, Kevin C; Hyun, Jeongmin; Kalyoncu, Sibel; Heaner, David P; Morales, Ivan A; Sheppard, Aly; Gumbart, James C; Maynard, Jennifer A; Lieberman, Raquel L

2015-04-01

Crystallization chaperones are attracting increasing interest as a route to crystal growth and structure elucidation of difficult targets such as membrane proteins. While strategies to date have typically employed protein-specific chaperones, a peptide-specific chaperone to crystallize multiple cognate peptide epitope-containing client proteins is envisioned. This would eliminate the target-specific chaperone-production step and streamline the co-crystallization process. Previously, protein engineering and directed evolution were used to generate a single-chain variable (scFv) antibody fragment with affinity for the peptide sequence EYMPME (scFv/EE). This report details the conversion of scFv/EE to an anti-EE Fab format (Fab/EE) followed by its biophysical characterization. The addition of constant chains increased the overall stability and had a negligible impact on the antigen affinity. The 2.0 Å resolution crystal structure of Fab/EE reveals contacts with larger surface areas than those of scFv/EE. Surface plasmon resonance, an enzyme-linked immunosorbent assay, and size-exclusion chromatography were used to assess Fab/EE binding to EE-tagged soluble and membrane test proteins: namely, the β-barrel outer membrane protein intimin and α-helical A2a G protein-coupled receptor (A2aR). Molecular-dynamics simulation of the intimin constructs with and without Fab/EE provides insight into the energetic complexities of the co-crystallization approach.

Partial Sleep Deprivation Reduces the Efficacy of Orexin-A to Stimulate Physical Activity and Energy Expenditure.

PubMed

DePorter, Danielle P; Coborn, Jamie E; Teske, Jennifer A

2017-10-01

Sufficient sleep is required for weight maintenance. Sleep deprivation due to noise exposure stimulates weight gain by increasing hyperphagia and reducing energy expenditure (EE). Yet the mechanistic basis underlying the weight gain response is unclear. Orexin-A promotes arousal and negative energy balance, and orexin terminals project to the ventrolateral preoptic area (VLPO), which is involved in sleep-to-wake transitions. To determine whether sleep deprivation reduces orexin function in VLPO and to test the hypothesis that sleep deprivation would attenuate the orexin-A-stimulated increase in arousal, physical activity (PA), and EE. Electroencephalogram, electromyogram, distance traveled, and EE were determined in male Sprague-Dawley rats following orexin-A injections into VLPO both before and after acute (12-h) and chronic (8 h/d, 9 d) sleep deprivation by noise exposure. Orexin-A in the VLPO significantly increased arousal, PA, total EE, and PA-related EE and reduced sleep and respiratory quotient before sleep deprivation. In contrast to after acute sleep deprivation in which orexin-A failed to stimulate EE during PA only, orexin-A failed to significantly increase arousal, PA, fat oxidation, total EE, and PA-related EE after chronic sleep deprivation. Sleep deprivation may reduce sensitivity to endogenous stimuli that enhance EE due to PA and thus stimulate weight gain. © 2017 The Obesity Society.

An Acceptance-Based Psychoeducation Intervention to Reduce Expressed Emotion in Relatives of Bipolar Patients

ERIC Educational Resources Information Center

Eisner, Lori R.; Johnson, Sheri L.

2008-01-01

Expressed emotion (EE) is a robust predictor of outcome in bipolar disorder. Despite decades of research, interventions to reduce EE levels have had only modest effects. This study used an expanded model of EE to develop an intervention. Research has demonstrated a strong link between attributions and EE in families of patients with psychiatric…

31 CFR 351.68 - Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE...

Code of Federal Regulations, 2014 CFR

2014-07-01

... (TINs) required for registration of book-entry Series EE savings bonds? 351.68 Section 351.68 Money and... EE Savings Bonds § 351.68 Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE savings bonds? The TIN of each person named in the registration is required to...

Science Teachers' and Senior Secondary Schools Students' Perceptions of Earth and Environmental Science Topics

ERIC Educational Resources Information Center

Dawson, Vaille; Carson, Katherine

2013-01-01

This article presents an evaluation of a new upper secondary Earth and Environmental Science (EES) course in Western Australia. Twenty-seven EES teachers were interviewed and 243 students were surveyed about the degree of difficulty, relevance and interest of EES topics in the course. The impact of the course on students' views about EES topics…

Involvement of 5-HT3 receptors in the action of vortioxetine in rat brain: Focus on glutamatergic and GABAergic neurotransmission.

PubMed

Riga, Maurizio S; Sánchez, Connie; Celada, Pau; Artigas, Francesc

2016-09-01

The antidepressant vortioxetine is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin (5-HT) transporter (SERT) inhibitor. Vortioxetine occupies all targets at high therapeutic doses and only SERT and 5-HT3-R at low doses. Vortioxetine increases extracellular monoamine concentrations in rat forebrain more than selective serotonin reuptake inhibitors (SSRI) and shows pro-cognitive activity in preclinical models. Given its high affinity for 5-HT3-R (Ki = 3.7 nM), selectively expressed in GABA interneurons, we hypothesized that vortioxetine may disinhibit glutamatergic and monoaminergic neurotransmission following 5-HT3-R blockade. Here we assessed vortioxetine effect on pyramidal neuron activity and extracellular 5-HT concentration using in vivo extracellular recordings of rat medial prefrontal cortex (mPFC) pyramidal neurons and microdialysis in mPFC and ventral hippocampus (vHPC). Vortioxetine, but not escitalopram, increased pyramidal neuron discharge in mPFC. This effect was prevented by SR57227A (5-HT3-R agonist) and was mimicked by ondansetron (5-HT3-R antagonist) and by escitalopram/ondansetron combinations. In microdialysis experiments, ondansetron augmented the 5-HT-enhancing effect of escitalopram in mPFC and vHPC. Local ondansetron in vHPC augmented escitalopram effect, indicating the participation of intrinsic mechanisms. Since 5-HT neurons express GABAB receptors, we examined their putative involvement in controlling 5-HT release after 5-HT3-R blockade. Co-perfusion of baclofen (but not muscimol) reversed the increased 5-HT levels produced by vortioxetine and escitalopram/ondansetron combinations in vHPC. The present results suggest that vortioxetine increases glutamatergic and serotonergic neurotransmission in rat forebrain by blocking 5-HT3 receptors in GABA interneurons. Copyright © 2016. Published by Elsevier Ltd.

Effects of drospirenone-ethinylestradiol and/or metformin on CD4(+)CD28(null) T lymphocytes frequency in women with hyperinsulinemia having polycystic ovary syndrome: a randomized clinical trial.

PubMed

Moro, Francesca; Morciano, Andrea; Tropea, Anna; Sagnella, Francesca; Palla, Carola; Scarinci, Elisa; Ciardulli, Andrea; Martinez, Daniela; Familiari, Alessandra; Liuzzo, Giovanna; Tritarelli, Alessandra; Cosentino, Nicola; Niccoli, Giampaolo; Crea, Filippo; Lanzone, Antonio; Apa, Rosanna

2013-12-01

To evaluate the long-term effects of drospirenone (DRSP)/ethinylestradiol (EE) alone, metformin alone, and DRSP/EE-metformin on CD4(+)CD28(null) T lymphocytes frequency, a cardiovascular risk marker, in patients with hyperinsulinemic polycystic ovary syndrome (PCOS). Randomized clinical trial. Ninety three patients with hyperinsulinemic PCOS were age matched and body mass index matched and randomized to receive a 6 months daily treatment with DRSP (3 mg)/EE (0.03 mg), or metformin (1500 mg), or DRSP/EE combined with metformin. CD4(+)CD28(null) T-cell frequencies. The DRSP/EE and metformin groups did not show any significant change in the CD4(+)CD28(null) frequency compared to the baseline. Interestingly, a statistically significant decrease in CD4(+)CD28(null) frequency occurred after 6 months of DRSP/EE-metformin (median 3-1.5; P < .01). Of note, this statistically significant association was confirmed after adjusting for baseline values in DRSP/EE-metformin group by analysis of covariance (P < .05). In women with hyperinsulinemic PCOS, combined therapy with DRSP/EE and metformin may reduce cardiovascular risk.

Effects of the Menopausal Transition on Factors Related to Energy Balance. A MONET group Study

PubMed Central

Karine, Duval; Denis, Prud’homme; Rémi, Rabasa-Lhoret; Irene, Strychar; Martin, Brochu; Jean-Marc, Lavoie; Éric, Doucet

2016-01-01

Objectives Factors that influence weight gain during the menopausal transition are not fully understood. The purpose of this study was to investigate changes in energy expenditure (EE) across the menopausal transition. Methods One hundred and two premenopausal women (age: 49.9 ± 1.9 yrs; BMI: 23.3 ± 2.2 kg/m2) were followed for 5 years. Body composition (DXA), physical activity EE (accelerometer), resting EE and thermic effect of food (indirect calorimetry) were measured annually. Results Total EE decreased significantly over time in postmenopausal women (P < 0.05), which was mostly due to a decrease in physical activity EE (P < 0.05). Although average resting EE remained stable over time in postmenopausal women, a significant increase, over the 5-year period, was noted in women who were in the menopausal transition by year 5 (P < 0.05). Finally, the time spent in moderate physical activity decreased and the time spent in sedentary physical activity increased during the menopausal transition (P < 0.05). Conclusion These results suggest that menopausal transition is accompanied with a decline in EE mainly characterized by a decrease in physical activity EE and a shift to a more sedentary lifestyle. PMID:23422924

Effects of the menopausal transition on energy expenditure: a MONET Group Study.

PubMed

Duval, K; Prud'homme, D; Rabasa-Lhoret, R; Strychar, I; Brochu, M; Lavoie, J-M; Doucet, E

2013-04-01

Factors that influence weight gain during the menopausal transition are not fully understood. The purpose of this study was to investigate changes in energy expenditure (EE) across the menopausal transition. In all, 102 premenopausal women (age: 49.9 ± 1.9 years; body mass index: 23.3 ± 2.2 kg/m(2)) were followed for 5 years. Body composition (dual-energy X-ray absorptiometry), physical activity EE (accelerometer), resting EE and thermic effect of food (indirect calorimetry) were measured annually. Total EE decreased significantly over time in postmenopausal women (P<0.05), which was mostly due to a decrease in physical activity EE (P<0.05). Although average resting EE remained stable over time in postmenopausal women, a significant increase, over the 5-year period, was noted in women who were in the menopausal transition by year 5 (P<0.05). Finally, the time spent in moderate physical activity decreased and the time spent in sedentary physical activity increased during the menopausal transition (P<0.05). These results suggest that menopausal transition is accompanied with a decline in EE mainly characterized by a decrease in physical activity EE and a shift to a more sedentary lifestyle.

S-Isovaline Contained in Meteorites, Induces Enantiomeric Excess in D,L-glutamic Acid During Recrystallization

NASA Astrophysics Data System (ADS)

Kojo, Shosuke

2015-06-01

S-Isovaline (S-Iva: 6.7 mmol) and D,L-glutamic acid (Glu: 2 mmol) were dissolved in 10 ml of hot water, and the resulting solution was divided in 5 vessels. After recrystallization, the crystals were collected from each vessel, and the enantiomeric excess (ee) of Glu was determined with chemical derivatization using 1-fluoro-2,4-dinitrophenyl- 5-L-leucinamide followed by high-performance liquid chromatography. Ten crystallizations provided all D-rich Glu with ee values of 2.69 % ± 0.81 % (mean ± standard deviation), and those using R-Iva provided all L-rich Glu with ee values of 6.24 % ± 2.20 %. Five recrystallizations of D,L-Glu alone provided ee values of 0.474 % ± 0.33 %. The differences among these three ee values were statistically significant, showing that S-Iva, which was present in meteorites caused a significant induction of ee in this physiological amino acid. This is the first outcome that S-Iva induced ee changes in a physiological amino acid. S-Iva did not induce any ee changes in D,L-asparagine, leucine, valine, methionine, phenylalanine, tryptophan, glutamine, tyrosine, aspartic acid, or histidine under similar recrystallizations.

Bonding and expressed emotion: two interlinked concepts?

PubMed

Duclos, Jeanne; Maria, Anne-Solène; Dorard, Géraldine; Curt, Florence; Apfel, Alexandre; Vibert, Sarah; Rein, Zoé; Perdereau, Fabienne; Godart, Nathalie

2013-01-01

Bonding and expressed emotion (EE) are two concepts modeling family relationships. Two studies, with contradictory results, have explored whether these concepts and their corresponding instruments [the Parental Bonding Instrument (PBI) and the Camberwell Family Interview] do indeed measure the same aspects of family relationships. Our first objective was to compare the adolescents' perceptions of family relationships using the PBI, and the parental viewpoint using the Five-Minute Speech Sample (FMSS-EE). Secondly, we compared the PBI scores and EE levels of the parents. Sixty adolescent girls with anorexia nervosa completed the PBI. The FMSS and a modified version of the PBI were administered to parents separately. No significant link was identified between adolescent PBI scores and parental EE levels. However, a link between maternal 'modified' PBI scores and maternal EE was observed: when mothers registered a high Final EE, they were more likely to deny their daughter's psychological autonomy compared to mothers with lower EE. Our empirical results do not support the hypothesis of an overlap between the two concepts. Indeed bonding and EE measure the same object, i.e. the quality of family relationships, but time scales differ and so do the perspectives (patient vs. parental viewpoint). Copyright © 2012 S. Karger AG, Basel.

Expressed Emotions and Depressive Symptoms in Caregivers of Adolescents with First-Onset Anorexia Nervosa-A Long-Term Investigation over 2.5 Years.

PubMed

Schwarte, Reinhild; Timmesfeld, Nina; Dempfle, Astrid; Krei, Melanie; Egberts, Karin; Jaite, Charlotte; Fleischhaker, Christian; Wewetzer, Christoph; Herpertz-Dahlmann, Beate; Seitz, Jochen; Bühren, Katharina

2017-01-01

High levels of expressed emotions (EE) and depressive symptoms (DS) are often found in caregivers of patients with anorexia nervosa (AN). Both parameters are considered to influence AN symptoms of the patient. One hundred seventy adolescent women with AN and their caregivers were assessed at admission, discharge, at 1-year and 2.5-year follow up to evaluate AN symptoms of the patient and EE and DS of caregivers. The EE and DS were elevated at admission and decreased during treatment, criticism (as part of EE) exhibited again at the 2.5-year follow up. Caregivers of more severely ill patients reported significantly greater levels of EE and DS. Mothers were more affected than fathers. EE and DS were interrelated. Caregivers of adolescent AN patients suffer from elevated levels of EE and DS. Further studies are needed to examine whether therapeutic interventions to reduce caregivers' EE and DS might have a positive influence on treatment outcome. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Expressed Emotion in Schizophrenia: An Overview

PubMed Central

Amaresha, Anekal C.; Venkatasubramanian, Ganesan

2012-01-01

The expressed emotion (EE) is considered to be an adverse family environment, which includes the quality of interaction patterns and nature of family relationships among the family caregivers and patients of schizophrenia and other psychiatric disorders. Influence of EE has been found to be one of the robust predictors of relapse in schizophrenia. This review article aims to provide a brief description of the origins and evolution of the EE as a construct from the available literature. The EE is modulated by multiple factors–some of which include certain personality profile, attribution factors by caregivers toward patient symptoms, and patient's vulnerability to stress. The psychosocial assessment and interventions specifically focused on family psychoeducation can potentially reduce high EE and relapse of symptoms as well. However, the theory surrounded with EE undermines the caregiver's positive attitudes toward the patients. Hence, it is important that the future studies should focus on both protective and vulnerable factors within the construct of EE in schizophrenia to facilitate comprehensive care. PMID:22661801

Adsorption-induced auto-amplification of enantiomeric excess on an achiral surface

NASA Astrophysics Data System (ADS)

Yun, Yongju; Gellman, Andrew J.

2015-06-01

The homochirality of biomolecules is a signature of life on Earth and has significant implications in, for example, the production of pharmaceutical compounds. It has been suggested that biomolecular homochirality may have arisen from the amplification of a spontaneously formed small enantiomeric excess (e.e.). Many minerals exhibit naturally chiral surfaces and so adsorption has been proposed as one possible mechanism for such an amplification of e.e. Here we show that when gas-phase mixtures of D- and L-aspartic acid are exposed to an achiral Cu(111) surface, a small e.e. in the gas phase, e.e.g, leads to an amplification of the e.e. on the surface, e.e.s, under equilibrium conditions. Adsorption-induced amplification of e.e. does not require a chiral surface. The dependence of e.e.s on e.e.g has been modelled successfully using a Langmuir-like adsorption isotherm that incorporates the formation of homochiral adsorbate clusters on the surface.

Human-derived gut microbiota modulates colonic secretion in mice by regulating 5-HT3 receptor expression via acetate production.

PubMed

Bhattarai, Yogesh; Schmidt, Bradley A; Linden, David R; Larson, Eric D; Grover, Madhusudan; Beyder, Arthur; Farrugia, Gianrico; Kashyap, Purna C

2017-07-01

Serotonin [5-hydroxytryptamine (5-HT)], an important neurotransmitter and a paracrine messenger in the gastrointestinal tract, regulates intestinal secretion by its action primarily on 5-HT 3 and 5-HT 4 receptors. Recent studies highlight the role of gut microbiota in 5-HT biosynthesis. In this study, we determine whether human-derived gut microbiota affects host secretory response to 5-HT and 5-HT receptor expression. We used proximal colonic mucosa-submucosa preparation from age-matched Swiss Webster germ-free (GF) and humanized (HM; ex-GF colonized with human gut microbiota) mice. 5-HT evoked a significantly greater increase in short-circuit current (Δ I sc ) in GF compared with HM mice. Additionally, 5-HT 3 receptor mRNA and protein expression was significantly higher in GF compared with HM mice. Ondansetron, a 5-HT 3 receptor antagonist, inhibited 5-HT-evoked Δ I sc in GF mice but not in HM mice. Furthermore, a 5-HT 3 receptor-selective agonist, 2-methyl-5-hydroxytryptamine hydrochloride, evoked a significantly higher Δ I sc in GF compared with HM mice. Immunohistochemistry in 5-HT 3A -green fluorescent protein mice localized 5-HT 3 receptor expression to enterochromaffin cells in addition to nerve fibers. The significant difference in 5-HT-evoked Δ I sc between GF and HM mice persisted in the presence of tetrodotoxin (TTX) but was lost after ondansetron application in the presence of TTX. Application of acetate (10 mM) significantly lowered 5-HT 3 receptor mRNA in GF mouse colonoids. We conclude that host secretory response to 5-HT may be modulated by gut microbiota regulation of 5-HT 3 receptor expression via acetate production. Epithelial 5-HT 3 receptor may function as a mediator of gut microbiota-driven change in intestinal secretion. NEW & NOTEWORTHY We found that gut microbiota alters serotonin (5-HT)-evoked intestinal secretion in a 5-HT 3 receptor-dependent mechanism and gut microbiota metabolite acetate alters 5-HT 3 receptor expression in colonoids.View this article's corresponding video summary at https://www.youtube.com/watch?v=aOMYJMuLTcw&feature=youtu.be. Copyright © 2017 the American Physiological Society.

Measurement of cross sections of the interactions e+e- → ϕϕω and e+e- → ϕϕϕ at center-of-mass energies from 4.008 to 4.600 GeV

NASA Astrophysics Data System (ADS)

Ablikim, M.; Achasov, M. N.; Ahmed, S.; Ai, X. C.; Albayrak, O.; Albrecht, M.; Ambrose, D. J.; Amoroso, A.; An, F. F.; An, Q.; Bai, J. Z.; Bakina, O.; Baldini Ferroli, R.; Ban, Y.; Bennett, D. W.; Bennett, J. V.; Berger, N.; Bertani, M.; Bettoni, D.; Bian, J. M.; Bianchi, F.; Boger, E.; Boyko, I.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chai, J.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S.; Chen, S. J.; Chen, X.; Chen, X. R.; Chen, Y. B.; Chu, X. K.; Cibinetto, G.; Dai, H. L.; Dai, J. P.; Dbeyssi, A.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; de Mori, F.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Dou, Z. L.; Du, S. X.; Duan, P. F.; Fan, J. Z.; Fang, J.; Fang, S. S.; Fang, X.; Fang, Y.; Farinelli, R.; Fava, L.; Feldbauer, F.; Felici, G.; Feng, C. Q.; Fioravanti, E.; Fritsch, M.; Fu, C. D.; Gao, Q.; Gao, X. L.; Gao, Y.; Gao, Z.; Garzia, I.; Goetzen, K.; Gong, L.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, R. P.; Guo, Y.; Guo, Y. P.; Haddadi, Z.; Hafner, A.; Han, S.; Hao, X. Q.; Harris, F. A.; He, K. L.; Heinsius, F. H.; Held, T.; Heng, Y. K.; Holtmann, T.; Hou, Z. L.; Hu, C.; Hu, H. M.; Hu, T.; Hu, Y.; Huang, G. S.; Huang, J. S.; Huang, X. T.; Huang, X. Z.; Huang, Z. L.; Hussain, T.; Ikegami Andersson, W.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, L. W.; Jiang, X. S.; Jiang, X. Y.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Johansson, T.; Julin, A.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Ke, B. C.; Kiese, P.; Kliemt, R.; Kloss, B.; Kolcu, O. B.; Kopf, B.; Kornicer, M.; Kupsc, A.; Kühn, W.; Lange, J. S.; Lara, M.; Larin, P.; Leithoff, H.; Leng, C.; Li, C.; Li, Cheng; Li, D. M.; Li, F.; Li, F. Y.; Li, G.; Li, H. B.; Li, H. J.; Li, J. C.; Li, Jin; Li, K.; Li, K.; Li, Lei; Li, P. R.; Li, Q. Y.; Li, T.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, Y. B.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Lin, D. X.; Liu, B.; Liu, B. J.; Liu, C. X.; Liu, D.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. H.; Liu, H. H.; Liu, H. M.; Liu, J.; Liu, J. B.; Liu, J. P.; Liu, J. Y.; Liu, K.; Liu, K. Y.; Liu, L. D.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, Y. B.; Liu, Y. Y.; Liu, Z. A.; Liu, Zhiqing; Loehner, H.; Long, Y. F.; Lou, X. C.; Lu, H. J.; Lu, J. G.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lyu, X. R.; Ma, F. C.; Ma, H. L.; Ma, L. L.; Ma, M. M.; Ma, Q. M.; Ma, T.; Ma, X. N.; Ma, X. Y.; Ma, Y. M.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, Y. J.; Mao, Z. P.; Marcello, S.; Messchendorp, J. G.; Mezzadri, G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Morales Morales, C.; Morello, G.; Muchnoi, N. Yu.; Muramatsu, H.; Musiol, P.; Nefedov, Y.; Nerling, F.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, S. L.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Pan, Y.; Patteri, P.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Pettersson, J.; Ping, J. L.; Ping, R. G.; Poling, R.; Prasad, V.; Qi, H. R.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, L. Q.; Qin, N.; Qin, X. S.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Ripka, M.; Rong, G.; Rosner, Ch.; Ruan, X. D.; Sarantsev, A.; Savrié, M.; Schnier, C.; Schoenning, K.; Shan, W.; Shao, M.; Shen, C. P.; Shen, P. X.; Shen, X. Y.; Sheng, H. Y.; Song, W. M.; Song, X. Y.; Sosio, S.; Spataro, S.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. H.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Tapan, I.; Thorndike, E. H.; Tiemens, M.; Uman, I.; Varner, G. S.; Wang, B.; Wang, B. L.; Wang, D.; Wang, D. Y.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, W.; Wang, W. P.; Wang, X. F.; Wang, Y.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. H.; Wang, Z. Y.; Wang, Zongyuan; Weber, T.; Wei, D. H.; Weidenkaff, P.; Wen, S. P.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, L. J.; Wu, Z.; Xia, L.; Xia, L. G.; Xia, Y.; Xiao, D.; Xiao, H.; Xiao, Z. J.; Xie, Y. G.; Xie, Y. H.; Xiu, Q. L.; Xu, G. F.; Xu, J. J.; Xu, L.; Xu, Q. J.; Xu, Q. N.; Xu, X. P.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, Y. H.; Yang, H. J.; Yang, H. X.; Yang, L.; Yang, Y. X.; Ye, M.; Ye, M. H.; Yin, J. H.; You, Z. Y.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yuan, C. Z.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zeng, Y.; Zeng, Z.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. J.; Zhang, J. L.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, K.; Zhang, L.; Zhang, S. Q.; Zhang, X. Y.; Zhang, Y.; Zhang, Y.; Zhang, Y. H.; Zhang, Y. N.; Zhang, Y. T.; Zhang, Yu; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, J. Y.; Zhao, J. Z.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, Q. W.; Zhao, S. J.; Zhao, T. C.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, W. J.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhu, K.; Zhu, K. J.; Zhu, S.; Zhu, S. H.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zotti, L.; Zou, B. S.; Zou, J. H.; Besiii Collaboration

2017-11-01

Using data samples collected with the BESIII detector at the BEPCII collider at six center-of-mass energies between 4.008 and 4.600 GeV, we observe the processes e+e- → ϕϕω and e+e- → ϕϕϕ. The Born cross sections are measured and the ratio of the cross sections σ (e+e- → ϕϕω) / σ (e+e- → ϕϕϕ) is estimated to be 1.75 ± 0.22 ± 0.19 averaged over six energy points, where the first uncertainty is statistical and the second is systematic. The results represent first measurements of these interactions.

Hydroxytyrosol in functional hydroxytyrosol-enriched biscuits is highly bioavailable and decreases oxidised low density lipoprotein levels in humans.

PubMed

Mateos, Raquel; Martínez-López, Sara; Baeza Arévalo, Gema; Amigo-Benavent, Miryam; Sarriá, Beatriz; Bravo-Clemente, Laura

2016-08-15

Hydroxytyrosol (HT) and its derivatives in olive oil protect low-density lipoproteins (LDL) against oxidation. Biscuits could be a convenient alternative to broaden consumers' choice of HT-rich foods, although the biscuit matrix could affect HT bioavailability. We performed a crossover, randomized, double-blind study to evaluate HT bioavailability in HT-enriched biscuits (HT-B) versus non-enriched biscuits (C-B), and the effects on oxidative postprandial status. On two separate days, 13 subjects consumed 30 g of C-B or HT-B (5.25mg HT) after overnight-fasting. Blood and urine were collected at different intervals and analysed by LC-MS-QToF. After HT-B consumption, plasma metabolites peaked between 0.5 and 1h and were extensively excreted in urine. HT-sulphate and 3,4-dihydroxyphenylacetic acid (DOPAC)-sulphate were the main metabolites, followed by DOPAC and homovanillic acid (HVA). HT-glucuronide, DOPAC-glucuronide, HVA-glucuronide and HVA-sulphate were also detected. Postprandial oxidised-LDL concentrations decreased with HT-B. HT is a promising functional ingredient and, in biscuits, it is highly bioavailable and lowers postprandial oxidised-LDL levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification and expression analysis of the genes involved in serotonin biosynthesis and transduction in the field cricket Gryllus bimaculatus.

PubMed

Watanabe, T; Sadamoto, Hitoshi; Aonuma, H

2011-10-01

Serotonin (5-HT) modulates various aspects of behaviours such as aggressive behaviour and circadian behaviour in the cricket. To elucidate the molecular basis of the cricket 5-HT system, we identified 5-HT-related genes in the field cricket Gryllus bimaculatus DeGeer. Complementary DNA of tryptophan hydroxylase and phenylalanine-tryptophan hydroxylase, which convert tryptophan into 5-hydroxy-L-tryptophan (5-HTP), and that of aromatic L-amino acid decarboxylase, which converts 5-HTP into 5-HT, were isolated from a cricket brain cDNA library. In addition, four 5-HT receptor genes (5-HT(1A) , 5-HT(1B) , 5-HT(2α) , and 5-HT(7) ) were identified. Expression analysis of the tryptophan hydroxylase gene TRH and phenylalanine-tryptophan hydroxylase gene TPH, which are selectively involved in neuronal and peripheral 5-HT synthesis in Drosophila, suggested that two 5-HT synthesis pathways co-exist in the cricket neuronal tissues. The four 5-HT receptor genes were expressed in various tissues at differential expression levels, suggesting that the 5-HT system is widely distributed in the cricket. © 2011 The Authors. Insect Molecular Biology © 2011 The Royal Entomological Society.

Bioequivalence evaluation of a folate-supplemented oral contraceptive containing ethinylestradiol/drospirenone/levomefolate calcium versus ethinylestradiol/drospirenone and levomefolate calcium alone.

PubMed

Wiesinger, Herbert; Eydeler, Urte; Richard, Frank; Trummer, Dietmar; Blode, Hartmut; Rohde, Beate; Diefenbach, Konstanze

2012-10-01

Neural tube defects (NTDs) are congenital malformations that occur during early embryonic development. Suboptimal maternal folate status is a well-known risk factor for the occurrence of NTDs, and periconceptional folic acid supplementation has been shown to reduce the risk of NTDs. Folate-supplemented oral contraceptives (OCs) offer a means of improving folate status in women of childbearing potential by increasing their likelihood of having raised folate levels at the time of conception. This study aimed to demonstrate bioequivalence of ethinylestradiol (EE), drospirenone and L-5-methyl-tetrahydrofolate (L-5-methyl-THF; active moiety of levomefolate calcium) when taken as a new folate-supplemented OC containing EE/drospirenone/levomefolate calcium, with the respective OC containing EE/drospirenone and a tablet containing levomefolate calcium only. This was a randomized, open-label, three-period crossover study carried out at a single centre in Germany. The study included 45 healthy women (age range 18-38 years). The women were randomly assigned to single doses of (i) EE 0.03 mg/drospirenone 3 mg/levomefolate calcium 0.451 mg (SAFYRAL®), (ii) EE 0.03 mg/drospirenone 3 mg (Yasmin®), and (iii) levomefolate calcium 0.451 mg, administered using a crossover design, with one or more menstrual cycle washout between doses. The primary variables were maximum concentrations (C(max)) and area under the concentration versus time curve (AUC) values for EE, drospirenone and L-5-methyl-THF. The bioavailability of EE and drospirenone was similar after administration of EE/drospirenone/levomefolate calcium and EE/drospirenone. The geometric mean ratios (GMRs) and its 90% confidence intervals (CIs) for AUC values and C(max) were within the pre-specified range (80.00-125.00%) for bioequivalence for EE and drospirenone in both formulations. The bioavailability of L-5-methyl-THF was similar after administration of EE/drospirenone/levomefolate calcium and levomefolate calcium. The respective GMRs and 90% CIs of baseline-uncorrected and -corrected AUC(last) (AUC from time zero to time of last measurable concentration) and C(max) were also within the 80.00-125.00% range. The novel folate-supplemented OC EE/drospirenone/levomefolate calcium is bioequivalent to the established OC Yasmin® (EE/drospirenone components) and to levomefolate calcium (folate component).

Environmental Education in Finland--A Case Study of Environmental Education in Nature Schools

ERIC Educational Resources Information Center

Jeronen, Eila; Jeronen, Juha; Raustia, Hanna

2009-01-01

The article aims to introduce Environmental Education (EE) in Finland and to discuss how it has been taken into account in Finnish nature schools. Firstly, we present EE models used in Finland. Thereafter we describe a qualitative case study on EE in nature schools (NS). The aim of the study was to get information for the development of EE. The…

Alteration of Cingulate Long-Term Plasticity and Behavioral Sensitization to Inflammation by Environmental Enrichment

ERIC Educational Resources Information Center

Shum, Fanny W. F.; Wu, Long-Jun; Zhao, Ming-Gao; Toyoda, Hiroki; Xu, Hui; Ren, Ming; Pinaud, Raphael; Ko, Shanelle W.; Lee, Yong-Seok; Kaang, Bong-Kiun; Zhuo, Min

2007-01-01

Exposure to an enriched environment (EE) has been shown to induce cortical plasticity. Considerable amount of research is focused on the effects of EE in the hippocampus; however, effects of EE on other brain regions and the mechanisms involved are not well known. To investigate this, we induced cortical plasticity by placing mice in an EE for one…

Effects of two combined oral contraceptives containing ethinyl estradiol 30 microg combined with either gestodene or drospirenone on hemostatic parameters, lipid profiles and blood pressure.

PubMed

Yildizhan, Recep; Yildizhan, Begum; Adali, Ertan; Yoruk, Pinar; Birol, Fatih; Suer, Necdet

2009-08-01

The aim of this study is to compare the effect of ethinyl estradiol 0.03 mg/gestodene 0.075 mg (EE/GSD) with ethinylestradiol 0.03 mg/drospirenone 3 mg (EE/DRSP) administered according to conventional 21/7 regimen on body mass index (BMI), blood pressure (BP), lipid metabolism and hemostatic parameters. In this study, 160 healthy women were randomized to EE/GSD mg or EE/DRSP for 12 months. Mean differences in BMI, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), total cholesterol (TC) levels and BP compared to baseline were assessed. One hundred and forty-five (89%) of the women completed all 12 treatment cycles. The subjects randomly assigned into two treatment groups. Group EE/GSD (n = 71) and group EE/DRSP (n = 72). In group B, BMI values were significantly lower than baseline at the sixth cycle. DRSP/EE had more favorable effects on BP than GSD/EE with the mean systolic and diastolic BPs remaining lower in the DRSP/EE group. The difference between the two preparations was not statistically significant at the end of the study. TC levels remained similar in both groups throughout the study period. In both groups LDL-C levels decreased, triglyceride and HDL-C levels significantly increased from baseline levels. These changes result in increasing HDL-C/LDL-C ratio, demonstrating anti-atherogenic effect. Menstrual cycle patterns and the incidence of adverse events were similar between groups. The duration of withdrawal bleeding decreased during the study for both groups and was similar. The EE/DRSP regimen provides good cycle control with reliable contraceptive efficacy and low incidence of adverse events. Compared with the EE/GSD preparation, the EE/DRSP preparation demonstrated a more favorable effect on BMI and BP with the mean BMI and mean BP remaining lower than baseline mean. The new formulation may be especially beneficial for women susceptible to body weight gain and rise in BP.

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding

PubMed Central

Mc Mahon, Brenda; MacDonald Fisher, Patrick; Jensen, Peter Steen; Svarer, Claus; Moos Knudsen, Gitte

2016-01-01

Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [11C]SB207145 for quantification of brain 5-HT4R binding. The Buss–Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. PMID:26772668

Polymer-dielectric molecular interactions in defect-free poly(3-hexylthiophene): dependence and consequences of regioregularity on transistor charge transport properties

NASA Astrophysics Data System (ADS)

Nawaz, Ali; Cruz-Cruz, Isidro; Rego, Jessica S.; Koehler, Marlus; Gopinathan, Sreelekha P.; Kumar, Anil; Hümmelgen, Ivo A.

2017-08-01

We investigate the molecular interaction of poly(3-hexylthiophene-2,5-diyl) (P3HT) molecules with polar functional groups of the dielectric surface, and its dependence on the regioregularity of P3HT. With this aim, we consider thickness-dependent molecular order of 100% regioregular defect-free P3HT (DF-P3HT) and 93% regioregular P3HT (LT-P3HT), deposited on top of cross-linked poly(vinyl alcohol) (cr-PVA) substrates. Intimate contact of P3HT molecules and cr-PVA surface defects affects the molecular order of P3HT differently, depending on the regioregularity. Consequently, these molecular order changes on the charge transport properties of organic field-effect transistors (OFETs) are investigated using four thicknesses (20, 40, 80 and 120 nm) of P3HT. As compared to other thicknesses, μ sat for 20 nm DF-P3HT OFETs shows further improvement, while the opposite occurs for 20 nm LT-P3HT OFETs. Depending on the regioregularity (and thus the chain orientation), P3HT molecules exhibit a difference in dipole moments. Consequently, the interaction of edge-on or face-on P3HT molecules with cr-PVA surface dipoles has different contributions towards the electrostatic energetic disorder at cr-PVA/P3HT interface. This subtle difference of behavior helps one to understand the huge spread of characteristics of P3HT based transistors found in literature.

Allosteric regulation by oleamide of the binding properties of 5-hydroxytryptamine7 receptors.

PubMed

Hedlund, P B; Carson, M J; Sutcliffe, J G; Thomas, E A

1999-12-01

Oleamide belongs to a family of amidated lipids with diverse biological activities, including sleep induction and signaling modulation of several 5-hydroxytryptamine (5-HT) receptor subtypes, including 5-HT1A, 5-HT2A/2C, and 5-HT7. The 5-HT7 receptor, predominantly localized in the hypothalamus, hippocampus, and frontal cortex, stimulates cyclic AMP formation and is thought to be involved in the regulation of sleep-wake cycles. Recently, it was proposed that oleamide acts at an allosteric site on the 5-HT7 receptor to regulate cyclic AMP formation. We have further investigated the interaction between oleamide and 5-HT7 receptors by performing radioligand binding assays with HeLa cells transfected with the 5-HT7 receptor. Methiothepin, clozapine, and 5-HT all displaced specific [3H]5-HT (100 nM) binding, with pK(D) values of 7.55, 7.85, and 8.39, respectively. Oleamide also displaced [3H]5-HT binding, but the maximum inhibition was only 40% of the binding. Taking allosteric (see below) cooperativity into account, a K(D) of 2.69 nM was calculated for oleamide. In saturation binding experiments, oleamide caused a 3-fold decrease in the affinity of [3H]5-HT for the 5-HT7 receptor, without affecting the number of binding sites. A Schild analysis showed that the induced shift in affinity of [3H]5-HT reached a plateau, unlike that of a competitive inhibitor, illustrating the allosteric nature of the interaction between oleamide and the 5-HT7 receptor. Oleic acid, the product of oleamide hydrolysis, had a similar effect on [3H]5-HT binding, whereas structural analogs of oleamide, trans-9,10-octadecenamide, cis-8,9-octadecenamide, and erucamide, did not alter [3H]5-HT binding significantly. The findings support the hypothesis that oleamide acts via an allosteric site on the 5-HT7 receptor regulating receptor affinity.

Receptor⁻Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment.

PubMed

Borroto-Escuela, Dasiel O; Narváez, Manuel; Ambrogini, Patrizia; Ferraro, Luca; Brito, Ismel; Romero-Fernandez, Wilber; Andrade-Talavera, Yuniesky; Flores-Burgess, Antonio; Millon, Carmelo; Gago, Belen; Narvaez, Jose Angel; Odagaki, Yuji; Palkovits, Miklos; Diaz-Cabiale, Zaida; Fuxe, Kjell

2018-06-03

Due to the binding to a number of proteins to the receptor protomers in receptor heteromers in the brain, the term "heteroreceptor complexes" was introduced. A number of serotonin 5-HT1A heteroreceptor complexes were recently found to be linked to the ascending 5-HT pathways known to have a significant role in depression. The 5-HT1A⁻FGFR1 heteroreceptor complexes were involved in synergistically enhancing neuroplasticity in the hippocampus and in the dorsal raphe 5-HT nerve cells. The 5-HT1A protomer significantly increased FGFR1 protomer signaling in wild-type rats. Disturbances in the 5-HT1A⁻FGFR1 heteroreceptor complexes in the raphe-hippocampal 5-HT system were found in a genetic rat model of depression (Flinders sensitive line (FSL) rats). Deficits in FSL rats were observed in the ability of combined FGFR1 and 5-HT1A agonist cotreatment to produce antidepressant-like effects. It may in part reflect a failure of FGFR1 treatment to uncouple the 5-HT1A postjunctional receptors and autoreceptors from the hippocampal and dorsal raphe GIRK channels, respectively. This may result in maintained inhibition of hippocampal pyramidal nerve cell and dorsal raphe 5-HT nerve cell firing. Also, 5-HT1A⁻5-HT2A isoreceptor complexes were recently demonstrated to exist in the hippocampus and limbic cortex. They may play a role in depression through an ability of 5-HT2A protomer signaling to inhibit the 5-HT1A protomer recognition and signaling. Finally, galanin (1⁻15) was reported to enhance the antidepressant effects of fluoxetine through the putative formation of GalR1⁻GalR2⁻5-HT1A heteroreceptor complexes. Taken together, these novel 5-HT1A receptor complexes offer new targets for treatment of depression.

Effects of prenatal stress and monoaminergic perturbations on the expression of serotonin 5-HT₄ and adrenergic β₂ receptors in the embryonic mouse telencephalon.

PubMed

Chen, Angela; Kelley, Lauren D S; Janušonis, Skirmantas

2012-06-12

The serotonin 5-HT(4) receptor (5-HT(4)R) is coded by a complex gene that produces four mRNA splice variants in mice (5-HT(4(a))R, 5-HT(4(b))R, 5-HT(4(e))R, 5-HT(4(f))R). This receptor has highly dynamic expression in brain development and its splice variants differ in their developmental trajectories. Since 5-HT(4)Rs are important in forebrain function (including forebrain control of serotonergic activity in the brainstem), we investigated the susceptibility of 5-HT(4)R expression in the mouse embryonic telencephalon to prenatal maternal stress and altered serotonin (5-hydroxytryptamine, 5-HT) levels. Because the gene coding the adrenergic β(2) receptor (β(2)AR) is embedded in the 5-HT(4)R gene, we also investigated whether 5-HT(4)R mRNA levels were modulated by selective β(2)AR agents. Timed-pregnant C57BL/6 mice were treated beginning at embryonic day (E) 14 and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to assess the mRNA levels of all 5-HT(4)R splice variants and β(2)AR in the embryonic telencephalon at E17. Maternal prenatal stress and 5-HT depletion with pCPA, a tryptophan hydroxylase inhibitor, reduced the levels of the 5-HT(4(b))R splice variant. Terbutaline (a selective β(2)AR agonist) and ICI 118,551 (a selective β(2)AR antagonist) had no effect on β(2)AR and 5-HT(4)R mRNA levels. These results show that prenatal stress and reduced 5-HT levels can alter 5-HT(4)R expression in the developing forebrain and that some 5-HT(4)R splice variants may be more susceptible than others. Copyright © 2012 Elsevier B.V. All rights reserved.

No contractile effect for 5-HT1D and 5-HT1F receptor agonists in human and bovine cerebral arteries: similarity with human coronary artery

PubMed Central

Bouchelet, Isabelle; Case, Bruce; Olivier, André; Hamel, Edith

2000-01-01

Using subtype-selective 5-HT1 receptor agonists and/or the 5-HT1 receptor antagonist GR127935, we characterized in vitro the 5-HT receptor that mediates the contraction of human and bovine cerebral arteries. Further, we investigated which sumatriptan-sensitive receptors are present in human coronary artery by reverse-transcriptase polymerase chain reaction (RT–PCR). Agonists with affinity at the 5-HT1B receptor, such as sumatriptan, alniditan and/or IS-159, elicited dose-dependent contraction in both human and bovine cerebral arteries. They behaved as full agonists at the sumatriptan-sensitive 5-HT1 receptors in both species. In contrast, PNU-109291 and LY344864, selective agonists at 5-HT1D and 5-HT1F receptors, respectively, were devoid of any significant vasocontractile activity in cerebral arteries, or did not affect the sumatriptan-induced vasocontraction. The rank order of agonist potency was similar in both species and could be summarized as 5-HT=alniditan>sumatriptan=IS-159>>>PNU-109291=LY344864. In bovine cerebral arteries, the 5-HT1 receptor antagonist GR127935 dose-dependently inhibited the vasoconstrictions elicited by both 5-HT and sumatriptan, with respective pA2 values of 8.0 and 8.6. RT–PCR studies in human coronary arteries showed a strong signal for the 5-HT1B receptor while message for the 5-HT1F receptor was weak and less frequently detected. Expression of 5-HT1D receptor mRNA was not detected in any sample. The present results demonstrate that the triptan-induced contraction in brain vessels is mediated exclusively by the 5-HT1B receptor, which is also present in a majority of human coronary arteries. These results suggest that selective 5-HT1D and 5-HT1F receptor agonists might represent new antimigraine drugs devoid of cerebro- and cardiovascular effects. PMID:10711348

5HT-1A receptors and anxiety-like behaviours: studies in rats with constitutionally upregulated/downregulated serotonin transporter.

PubMed

Bordukalo-Niksic, Tatjana; Mokrovic, Gordana; Stefulj, Jasminka; Zivin, Marko; Jernej, Branimir; Cicin-Sain, Lipa

2010-12-01

Altered activity of brain serotonergic (5HT) system has been implicated in a wide range of behaviours and behavioural disorders, including anxiety. Functioning of 5HT-1A receptor has been suggested as a modulator of emotional balance in both, normal and pathological forms of anxiety. Here, we studied serotonergic modulation of anxiety-like behaviour using a genetic rat model with constitutional differences in 5HT homeostasis, named Wistar-Zagreb 5HT (WZ-5HT) rats. The model, consisting of high-5HT and low-5HT sublines, was developed by selective breeding of animals for extreme activities of peripheral (platelet) 5HT transporter, but selection process had affected also central 5HT homeostasis, as evidenced from neurochemical and behavioural studies. Anxiety-like behaviour in WZ-5HT rats was evaluated by two commonly used paradigms: open field and elevated-plus maze. The involvement of 5HT-1A receptors in behavioural response was assessed by measuring mRNA expression in cell bodies (raphe nuclei) and projection regions (frontal cortex, hippocampus) by use of RT-PCR and in situ hybridization, and by measuring functionality of cortical 5HT-1A receptors by use of [(3)H]8-OH-DPAT radioligand binding. Animals from the high-5HT subline exhibit increased anxiety-like behaviour and decreased exploratory activity when exposed to novel environment. No measurable differences in constitutional (baseline) functionality or expression of 5HT-1A receptors between sublines were found. The results support contribution of increased serotonergic functioning to the anxiety-like behaviour. They also validate the high-5HT subline of WZ-5HT rats as a potential model to study mechanisms of anxiety, especially of its nonpathological form, while the low-5HT subline may be useful to model sensation seeking phenotype. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Allergen and ozone exacerbate serotonin-induced increases in airway smooth muscle contraction in a model of childhood asthma.

PubMed

Moore, Brian D; Hyde, Dallas; Miller, Lisa; Wong, Emily; Frelinger, Jessica; Schelegle, Edward S

2012-01-01

Serotonin (5-HT) modulates cholinergic neurotransmission and exacerbates airway smooth muscle (ASM) contraction in normal animal and nonasthmatic human tissue. Exposure to house dust mite allergen (HDMA) and ozone (O(3)) leads to airway hyperreactivity and 5-HT-positive cells in the airway epithelium of infant rhesus monkeys. Research shows that concomitant exposure in allergic animals has an additive effect on airway hyperreactivity. In this study, the hypothesis is that the exposure of allergic infant rhesus monkeys to HDMA, O(3) and in combination, acting through 5-HT receptors, enhances 5-HT modulation of postganglionic cholinergic ASM contraction. Twenty-four HDMA-sensitized infant monkeys were split into 4 groups at the age of 1 month, and were exposed to filtered air (FA), HDMA, O(3) or in combination (HDMA+O(3)). At the age of 6 months, airway rings were harvested and postganglionic, and parasympathetic-mediated ASM contraction was evaluated using electrical-field stimulation (EFS). 5-HT exacerbated the EFS response within all exposure groups, but had no effect in the FA group. 5-HT(2), 5-HT(3) and 5-HT(4) receptor agonists exacerbated the response. 5-HT concentration-response curves performed after incubation with specific receptor antagonists confirmed the involvement of 5-HT(2), 5-HT(3) and 5-HT(4) receptors. Conversely, a 5-HT(1) receptor agonist attenuated the tension across all groups during EFS, and in ASM contracted via exogenous acetylcholine. HDMA, O(3) and HDMA+O(3) exposure in a model of childhood allergic asthma enhances 5-HT exacerbation of EFS-induced ASM contraction through 5-HT(2), 5-HT(3) and 5-HT(4) receptors. A nonneurogenic inhibitory pathway exists, unaffected by exposure, mediated by 5-HT(1) receptors located on ASM. Copyright © 2012 S. Karger AG, Basel.

Preclinical and clinical characterization of the selective 5-HT(1A) receptor antagonist DU-125530 for antidepressant treatment.

PubMed

Scorza, M C; Lladó-Pelfort, L; Oller, S; Cortés, R; Puigdemont, D; Portella, M J; Pérez-Egea, R; Alvarez, E; Celada, P; Pérez, V; Artigas, F

2012-11-01

The antidepressant efficacy of selective 5-HT reuptake inhibitors (SSRI) and other 5-HT-enhancing drugs is compromised by a negative feedback mechanism involving 5-HT(1A) autoreceptor activation by the excess 5-HT produced by these drugs in the somatodendritic region of 5-HT neurones. 5-HT(1A) receptor antagonists augment antidepressant-like effects in rodents by preventing this negative feedback, and the mixed β-adrenoceptor/5-HT(1A) receptor antagonist pindolol improves clinical antidepressant effects by preferentially interacting with 5-HT(1A) autoreceptors. However, it is unclear whether 5-HT(1A) receptor antagonists not discriminating between pre- and post-synaptic 5-HT(1A) receptors would be clinically effective. We characterized the pharmacological properties of the 5-HT(1A) receptor antagonist DU-125530 using receptor autoradiography, intracerebral microdialysis and electrophysiological recordings. Its capacity to accelerate/enhance the clinical effects of fluoxetine was assessed in a double-blind, randomized, 6 week placebo-controlled trial in 50 patients with major depression (clinicaltrials.gov identifier NCT01119430). DU-125530 showed equal (low nM) potency to displace agonist and antagonist binding to pre- and post-synaptic 5-HT(1A) receptors in rat and human brain. It antagonized suppression of 5-hydroxytryptaminergic activity evoked by 8-OH-DPAT and SSRIs in vivo. DU-125530 augmented SSRI-induced increases in extracellular 5-HT as effectively as in mice lacking 5-HT(1A) receptors, indicating a silent, maximal occupancy of pre-synaptic 5-HT(1A) receptors at the dose used. However, DU-125530 addition to fluoxetine did not accelerate nor augment its antidepressant effects. DU-125530 is an excellent pre- and post-synaptic 5-HT(1A) receptor antagonist. However, blockade of post-synaptic 5- HT(1A) receptors by DU-125530 cancels benefits obtained by enhancing pre-synaptic 5-hydroxytryptaminergic function. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

5-HT2A receptor activation is necessary for CO2-induced arousal

PubMed Central

Smith, Haleigh R.; MacAskill, Amanda; Richerson, George B.

2015-01-01

Hypercapnia-induced arousal from sleep is an important protective mechanism pertinent to a number of diseases. Most notably among these are the sudden infant death syndrome, obstructive sleep apnea and sudden unexpected death in epilepsy. Serotonin (5-HT) plays a significant role in hypercapnia-induced arousal. The mechanism of 5-HT's role in this protective response is unknown. Here we sought to identify the specific 5-HT receptor subtype(s) involved in this response. Wild-type mice were pretreated with antagonists against 5-HT receptor subtypes, as well as antagonists against adrenergic, cholinergic, histaminergic, dopaminergic, and orexinergic receptors before challenge with inspired CO2 or hypoxia. Antagonists of 5-HT2A receptors dose-dependently blocked CO2-induced arousal. The 5-HT2C receptor antagonist, RS-102221, and the 5-HT1A receptor agonist, 8-OH-DPAT, attenuated but did not completely block CO2-induced arousal. Blockade of non-5-HT receptors did not affect CO2-induced arousal. None of these drugs had any effect on hypoxia-induced arousal. 5-HT2 receptor agonists were given to mice in which 5-HT neurons had been genetically eliminated during embryonic life (Lmx1bf/f/p) and which are known to lack CO2-induced arousal. Application of agonists to 5-HT2A, but not 5-HT2C, receptors, dose-dependently restored CO2-induced arousal in these mice. These data identify the 5-HT2A receptor as an important mediator of CO2-induced arousal and suggest that, while 5-HT neurons can be independently activated to drive CO2-induced arousal, in the absence of 5-HT neurons and endogenous 5-HT, 5-HT receptor activation can act in a permissive fashion to facilitate CO2-induced arousal via another as yet unidentified chemosensor system. PMID:25925320

Electrochemical detection of a powerful estrogenic endocrine disruptor: ethinylestradiol in water samples through bioseparation procedure.

PubMed

Martínez, Noelia A; Pereira, Sirley V; Bertolino, Franco A; Schneider, Rudolf J; Messina, Germán A; Raba, Julio

2012-04-20

The synthetic estrogen ethinylestradiol (EE2) is an active component of oral contraceptives (OCs), considered as an endocrine disrupting compound (EDC). It is excreted from humans and released via sewage treatment plant effluents into aquatic environments. EDCs are any environmental pollutant chemical that, once incorporated into an organism, affects the hormonal balance of various species including humans. Its presence in the environment is becoming of great importance in water quality. This paper describes the development of an accurate, sensitive and selective method for capture, preconcentration and determination of EE2 present in water samples using: magnetic particles (MPs) as bioaffinity support for the capture and preconcentration of EE2 and a glassy carbon electrode modified with multi-walled carbon nanotubes (MWCNTs/GCE) as detection system. The capture procedure was based on the principle of immunoaffinity, the EE2 being extracted from the sample using the anti-EE2 antibodies (anti-EE2 Ab) which were previously immobilized on MPs. Subsequently the analyte desorption was done employing a sulfuric acid solution and the determination of the EE2 in the pre-concentrated solution was carried out by square wave voltammetry (SWV). This method can be used to determine EE2 in the range of 0.035-70 ng L(-1) with a detection limit (LOD) of 0.01 ng L(-1) and R.S.D.<4.20%. The proposed method has been successfully applied to the determination of EE2 in water samples and it has promising analytical applications for the direct determination of EE2 at trace levels. Copyright © 2012 Elsevier B.V. All rights reserved.

Hey Teacher, Don't Leave Them Kids Alone: Action Is Better for Memory than Reading.

PubMed

Hainselin, Mathieu; Picard, Laurence; Manolli, Patrick; Vankerkore-Candas, Sophie; Bourdin, Béatrice

2017-01-01

There is no consensus on how the enactment effect (EE), although it is robust, enhances memory. Researchers are currently investigating the cognitive processes underlying this effect, mostly during adulthood; the link between EE and crucial function identified in adulthood such as episodic memory and binding process remains elusive. Therefore, this study aims to verify the existence of EE in 6-10 years old and assess cognitive functions potentially linked to this effect in order to shed light on the mechanisms underlying the EE during childhood. Thirty-five children (15 second graders and 20 fifth graders) were included in this study. They encoded 24 action phrases from a protocol adapted from Hainselin et al. (2014). Encoding occurred under four conditions: Verbal Task, Listening Task, Experimenter-Performed Task, and Subject-Performed Task. Memory performance was assessed for free and cued recall, as well as source memory abilities. ANOVAS were conducted to explore age-related effects on the different scores according to encoding conditions. Correlations between EE scores (Subject-Performed Task/Listening Task) and binding memory scores (short-term binding and episodic memory) were run. Both groups benefited from EE. However, in both groups, performance did not significantly differ between Subject-Performed Task and Experimenter-Performed Task. A positive correlation was found between EE and episodic memory score for second graders and a moderate negative correlation was found between EE and binding scores for fifth graders. Our results confirm the existence of EE in 6 and 10 year olds, but they do not support the multimodal theory (Engelkamp, 2001) or the "glue" theory (Kormi-Nouri and Nilsson, 2001). This suggests instead that episodic memory might not underlie EE during early childhood.

Estrogens Can Disrupt Amphibian Mating Behavior

PubMed Central

Hoffmann, Frauke; Kloas, Werner

2012-01-01

The main component of classical contraceptives, 17α-ethinylestradiol (EE2), has high estrogenic activity even at environmentally relevant concentrations. Although estrogenic endocrine disrupting compounds are assumed to contribute to the worldwide decline of amphibian populations by adverse effects on sexual differentiation, evidence for EE2 affecting amphibian mating behaviour is lacking. In this study, we demonstrate that EE2 exposure at five different concentrations (0.296 ng/L, 2.96 ng/L, 29.64 ng/L, 2.96 µg/L and 296.4 µg/L) can disrupt the mating behavior of adult male Xenopus laevis. EE2 exposure at all concentrations lowered male sexual arousal, indicated by decreased proportions of advertisement calls and increased proportions of the call type rasping, which characterizes a sexually unaroused state of a male. Additionally, EE2 at all tested concentrations affected temporal and spectral parameters of the advertisement calls, respectively. The classical and highly sensitive biomarker vitellogenin, on the other hand, was only induced at concentrations equal or higher than 2.96 µg/L. If kept under control conditions after a 96 h EE2 exposure (2.96 µg/L), alterations of male advertisement calls vanish gradually within 6 weeks and result in a lower sexual attractiveness of EE2 exposed males toward females as demonstrated by female choice experiments. These findings indicate that exposure to environmentally relevant EE2 concentrations can directly disrupt male mate calling behavior of X. laevis and can indirectly affect the mating behavior of females. The results suggest the possibility that EE2 exposure could reduce the reproductive success of EE2 exposed animals and these effects might contribute to the global problem of amphibian decline. PMID:22355410

What do faculty feel about teaching in this school? assessment of medical education environment by teachers.

PubMed

Shehnaz, Syed Ilyas; Arifulla, Mohamed; Sreedharan, Jayadevan; Gomathi, Kadayam Guruswami

2017-01-01

Faculty members are major stakeholders in curriculum delivery, and positive student learning outcomes can only be expected in an educational environment (EE) conducive to learning. EE experienced by teachers includes all conditions affecting teaching and learning activities. As the EE of teachers indirectly influences the EE of students, assessment of teachers' perceptions of EE can highlight issues affecting student learning. These perceptions can also serve as a valuable tool for identifying faculty development needs. In this study, we have used the Assessment of Medical Education Environment by Teachers (AMEET) inventory as a tool to assess medical teachers' perceptions of the EE. The AMEET inventory was used to assess perceptions regarding various domains of EE by teachers teaching undergraduate students at the College of Medicine, Gulf Medical University, Ajman, United Arab Emirates. Median total, domain, and individual statement scores were compared between groups using Wilcoxon rank-sum test. Teaching-learning activities, learning atmosphere, collaborative atmosphere, and professional self-perceptions were identified as strengths of the EE while time allocated for various teaching-learning activities, preparedness of students, levels of student stress, learning atmosphere in hospital, and support system for stressed faculty members were areas necessitating improvement. The scores of faculty members teaching in basic medical sciences were found to be significantly higher than those in clinical sciences. The EE of this medical college was generally perceived as being positive by faculty although a few areas of concern were highlighted. Strengths and weaknesses of the EE from the teachers' point of view provide important feedback to curriculum planners, which can be used to improve the working environment of the faculty as well as facilitate a better direction and focus to faculty development programs being planned for the future.

Interrelations of maternal expressed emotion, maltreatment, and separation/divorce and links to family conflict and children's externalizing behavior.

PubMed

Narayan, Angela; Cicchetti, Dante; Rogosch, Fred A; Toth, Sheree L

2015-02-01

Research has documented that maternal expressed emotion-criticism (EE-Crit) from the Five-Minute Speech Sample (FMSS) predicts family conflict and children's externalizing behavior in clinical and community samples. However, studies have not examined EE-Crit in maltreating or separated/divorced families, or whether these family risks exacerbate the links between EE-Crit and family conflict and externalizing behavior. The current study examined the associations between maternal EE-Crit, maltreatment, and separation/divorce, and whether maltreatment and separation/divorce moderated associations between EE-Crit and children's externalizing problems, and EE-Crit and family conflict. Participants included 123 children (M = 8.01 years, SD = 1.58; 64.2 % males) from maltreating (n = 83) or low-income, comparison (n = 40) families, and 123 mothers (n = 48 separated/divorced). Mothers completed the FMSS for EE-Crit and the Family Environment Scale for family conflict. Maltreatment was coded with the Maltreatment Classification System using information from official Child Protection Services (CPS) reports from the Department of Human Services (DHS). Trained summer camp counselors rated children's externalizing behavior. Maltreatment was directly associated with higher externalizing problems, and separation/divorce, but not maltreatment, moderated the association between EE-Crit and externalizing behavior. Analyses pertaining to family conflict were not significant. Findings indicate that maltreatment is a direct risk factor for children's externalizing behavior and separation/divorce is a vulnerability factor for externalizing behavior in family contexts with high maternal EE-Crit. Intervention, prevention, and policy efforts to promote resilience in high-risk families may be effective in targeting maltreating and critical parents, especially those with co-occurring separation/divorce. Key Words: expressed emotion, EE-Crit, Five-Minute Speech Sample; maltreatment, divorce, externalizing behavior.

The predictive role of E/e' on ischemic stroke and atrial fibrillation in Japanese patients without atrial fibrillation.

PubMed

Arai, Riku; Suzuki, Shinya; Semba, Hiroaki; Arita, Takuto; Yagi, Naoharu; Otsuka, Takayuki; Sagara, Koichi; Sasaki, Kenichi; Kano, Hiroto; Matsuno, Shunsuke; Kato, Yuko; Uejima, Tokuhisa; Oikawa, Yuji; Kunihara, Takashi; Yajima, Junji; Yamashita, Takeshi

2018-07-01

The predictive role of E/e' on ischemic stroke (IS) and atrial fibrillation (AF) in Japanese patients without AF are unclear. Shinken database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. E/e' has been routinely measured since 2007. Patients without AF for whom E/e' was measured at the initial visit between 2007 and 2014 (n=11 477, mean age 57.2 years old, men 59.5%) were divided into E/e' tertiles (<8.04, 8.04-11.00, >11.00). During the mean follow-up period of 1.8 years, 58 IS and 140 new appearances of AF were observed. High E/e' tertile was associated with more prevalence of atherothrombotic risks. The cumulative incidence of IS events and new appearance of AF at 6 years in low, middle, and high E/e' tertiles were 0.5%, 1.4%, and 3.0%/year (log-rank test, p<0.001), and 2.5%, 2.9%, and 4.2%/year (log-rank test, p=0.007), respectively. In multivariate analysis, high E/e' tertile was independently associated with IS (HR, 2.857, 95%CI 1.257-6.495, p=0.012). Although high E/e' tertile was independently associated with new appearance of AF when adjusted for coexistence of atherothrombotic risk factors (HR, 1.694, 95%CI, 1.097-2.616, p=0.017), the association was attenuated after adjustment for left atrial dimension. E/e' was significantly associated with incidence of IS and new appearance of AF in non-AF patients. Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Is the etiology of eosinophilic esophagitis in adults a response to allergy or reflux injury? Study of cellular proliferation markers.

PubMed

Lewis, C J; Lamb, C A; Kanakala, V; Pritchard, S; Armstrong, G R; Attwood, S E A

2009-01-01

Recent research suggests that allergy may be the key factor in the etiology of eosinophilic esophagitis (EE); however, historically, the condition was hypothesized as related to reflux injury to the esophageal mucosa. We studied this hypothesis by comparing markers of inflammation and cellular proliferation in EE and reflux esophagitis. Lower esophageal biopsies of adult patients with EE (n = 10), reflux esophagitis (n = 8), and normal controls (n = 13) were assessed quantitatively for the expression of the cyclooxygenase-2 (COX-2) enzyme, cellular proliferation, and oncogenic resistance to apoptosis using monoclonal antibodies for COX-2, Ki-67, and Bcl-2, respectively. Normal esophageal epithelium demonstrated weak diffuse uptake of COX-2 stain in the basal layer. No COX-2 expression was demonstrated in the EE group, significantly less than the control and reflux groups (P < 0.01 and P < 0.001, respectively). Cellular proliferation measured by Ki-67 expression was higher in EE and reflux compared with control (P < 0.001 and P < 0.01). Ki-67 expression, and thus degree of hyperplasia, appeared greater in EE than reflux, but was not statistically significant (P = 0.228). The degree of apoptosis was similar in all study groups. EE and reflux esophagitis are proliferative conditions expressing Ki-67 in higher concentrations than control. Mucosal proliferation in reflux esophagitis is COX-2 dependent. This novel research in EE has demonstrated downregulation of COX-2 expression compared with reflux esophagitis and control. We hypothesize that the allergy-related cytokine IL-13 known to inhibit COX-2 expression and found in high concentrations in EE as responsible for this. The pathogenesis of EE is likely dependent on allergy rather than reflux injury to the esophagus.

Energy expenditure during an exercise training session for cardiac patients.

PubMed

Santa-Clara, Helena; Melo, Xavier; Willi, Romina; Pinto, Rita; Santos, Vanessa; Almeida, José P; Martins, Rodrigo; Clijsen, Ron; Mendes, Miguel; Fernhall, Bo

2018-03-01

Increasing energy expenditure (EE) in cardiac patients remains a challenge. Exercise approaches in cardiac rehabilitation/secondary prevention programs (CR/SP) have consistently resulted in minimal weight loss, due in part to the low exercise-related EE. The purpose of this study was to measure the EE among patients participating in a routine exercise session of Phase III maintenance CR/SP, where a recreational activity was introduced. Twelve overweight/obese male patients with coronary artery disease (aged 62.6 ± 8.5 years) had their total EE measured during a combined aerobic (circuit workout (ACW) and recreational activity) and resistance training (RT) session using a portable gas analyzer. Subjects were instructed to exercise at 60%-70% of heart rate reserve. Activity EE was calculated from total EE and resting EE. The duration of the session was 75.3 ± 1.5 min, of which 59.7 ± 8.8 min were above moderate intensity (3-6 METs). Activity EE was 309 ± 76 kcal, concurring to a total EE of 457 ± 80 kcal (3.9 ± 0.8 METs-h). ACW, recreational activity, and RT fulfilled 34.4% ± 6.4%, 25.0% ± 5.3%, and 14.2% ± 2.7% of the activity EE, respectively. Absolute intensities (METs) were significantly different between the RT (3.9 ± 1.0) and the ACW (6.9 ± 1.8) and recreational activity (5.9 ± 0.8). In conclusion, a combined aerobic and resistance training following standard exercise prescription practices, coupled with a recreational activity, is an effective tool to promote exercise above moderate intensity in male coronary artery disease patients. Clinicians can adopt concepts from recreational activity to develop CR/SP sessions.

Ethinyl estradiol-drospirenone vs ethinyl estradiol-drospirenone plus metformin in the treatment of lean women with polycystic ovary syndrome.

PubMed

Cinar, Nese; Harmanci, Ayla; Bayraktar, Miyase; Yildiz, Bulent O

2013-03-01

Oral contraceptive use might be associated with cardiometabolic risk in PCOS. We aimed to compare the effects of ethinyl estradiol-drospirenone (EE/DRSP) alone vs EE/DRSP plus metformin on clinical and cardiometabolic parameters in PCOS. Prospective observational study. Forty-five lean patients with PCOS who received EE/DRSP (30 μg/3 mg) (n = 25) or EE/DRSP plus metformin (1700 mg/day) (n = 20) and 45 BMI-matched healthy controls. BMI, waist-to-hip ratio (WHR), hirsutism scores, androgens, lipids, glucose and insulin levels during an OGTT were measured before and after 6 months of treatment in patients and compared to controls. At baseline, patients with PCOS showed similar glucose, insulin and lipids but increased 2 h glucose values compared to controls. Hirsutism scores and free androgen index decreased in both treatment groups. BMI and WHR did not show any change in the EE/DRSP group, while metformin addition resulted in a decrease in BMI. Lipid levels increased in both groups. Glucose and insulin parameters did not change in any group, but metformin addition compared to EE/DRSP alone significantly decreased waist circumference, fasting insulin and HOMA-IR. After-treatment values for both EE/DRSP alone and in combination with metformin compared to the control group showed increased 2 h glucose and increased lipids in patients with PCOS. EE/DRSP alone or in combination with metformin improves clinical and biochemical hyperandrogenism in lean PCOS. Both treatments similarly alter lipid profile. EE/DRSP alone does not affect insulin sensitivity, whereas combining EE/DRSP with metformin might improve it. © 2012 Blackwell Publishing Ltd.

Gestational and lactational exposure to ethinyl estradiol, but not bisphenol A, decreases androgen-dependent reproductive organ weights and epididymal sperm abundance in the male long evans hooded rat.

PubMed

Howdeshell, Kembra L; Furr, Johnathan; Lambright, Christy R; Wilson, Vickie S; Ryan, Bryce C; Gray, L Earl

2008-04-01

Many chemicals released into the environment are capable of disrupting normal sex steroid balance, including the oral contraceptive ethinyl estradiol (EE) and the plastic monomer bisphenol A (BPA). EE and BPA are reported to impair reproductive organ development in laboratory animals; however, effects of lower doses of these chemicals have been debated. The goal of the current study was to determine whether relatively low oral doses of EE or BPA would alter male reproductive morphology and associated hormone levels of Long Evans hooded rat. Dams were gavaged with corn oil vehicle, EE (0.05-50 mug/kg/day) or BPA (2, 20, and 200 mug/kg/day) during pregnancy through lactation from gestational day 7 to postnatal day (PND) 18. Anogenital distance was measured at PND2 and nipple retention was measured at PND14 in male pups. Male offspring were euthanized beginning at PND150, and sera and organs were collected for analyses. Adult body weight was significantly decreased in males exposed to 50 mug EE/kg/day. Developmental EE exposure reduced androgen-dependent tissue weights in a dose-dependent fashion; for example, seminal vesicle and paired testes weights were reduced with >/= 5 mug EE/kg/day. Epididymal sperm counts were also significantly decreased with 50 mug EE/kg/day. In contrast, treatment with 2, 20, or 200 mug BPA/kg/day or EE at 0.05-1.5 mug/kg/day did not significantly affect any male endpoint in the current study. These results demonstrate that developmental exposure to oral micromolar doses of EE can permanently disrupt the reproductive tract of the male rat.

Hippocampal 5-HT1A Receptor and Spatial Learning and Memory

PubMed Central

Glikmann-Johnston, Yifat; Saling, Michael M.; Reutens, David C.; Stout, Julie C.

2015-01-01

Spatial cognition is fundamental for survival in the topographically complex environments inhabited by humans and other animals. The hippocampus, which has a central role in spatial cognition, is characterized by high concentration of serotonin (5-hydroxytryptamine; 5-HT) receptor binding sites, particularly of the 1A receptor (5-HT1A) subtype. This review highlights converging evidence for the role of hippocampal 5-HT1A receptors in spatial learning and memory. We consider studies showing that activation or blockade of the 5-HT1A receptors using agonists or antagonists, respectively, lead to changes in spatial learning and memory. For example, pharmacological manipulation to induce 5-HT release, or to block 5-HT uptake, have indicated that increased extracellular 5-HT concentrations maintain or improve memory performance. In contrast, reduced levels of 5-HT have been shown to impair spatial memory. Furthermore, the lack of 5-HT1A receptor subtype in single gene knockout mice is specifically associated with spatial memory impairments. These findings, along with evidence from recent cognitive imaging studies using positron emission tomography (PET) with 5-HT1A receptor ligands, and studies of individual genetic variance in 5-HT1A receptor availability, strongly suggests that 5-HT, mediated by the 5-HT1A receptor subtype, plays a key role in spatial learning and memory. PMID:26696889

Schizophrenic Patients' Perceptions of Stress, Expressed Emotion, and Sensitivity To Criticism

PubMed Central

Cutting, Linda P.; Aakre, Jennifer M.; Docherty, Nancy M.

2006-01-01

This study was designed to get an “insider's view” of expressed emotion (EE) from the perspective of schizophrenic patients. Thirty-two patient and “influential other” pairs participated in the study. Patients' perceptions of EE attitudes in influential others were examined to determine whether they corresponded with actual EE ratings. Patients also rated how “stressed” they felt when interacting with their influential others, and patients' general sensitivity to criticism (STC) was assessed. As predicted, patients' perceptions of critical attitudes were related to actual EE ratings of criticism, although patients' perceptions of emotional overinvolvement (EOI) were not related to EOI ratings. Patients reported feeling more stressed when interacting with high-EE influential others, supporting an “EE as stressor” hypothesis. Finally, patients' STC influenced the level of stress they reported. PMID:16731686

A Comparative Study of Exceptional Experiences of Clients Seeking Advice and of Subjects in an Ordinary Population

PubMed Central

Fach, W.; Atmanspacher, H.; Landolt, K.; Wyss, T.; Rössler, W.

2012-01-01

Exceptional experiences (EE) occur frequently within the populations of many countries and across various socio-cultural contexts. Although some EE show similarities with mental disorders, it would be a mistake to identify them in general as disorders. In fact, the vast number of individuals reporting EE includes subclinical and completely healthy subjects. We conducted a comparative empirical study of several characteristics of EE for two samples – one from ordinary population and the other from clients seeking advice. We found surprisingly similar phenomenological patterns of EE in both samples, but the frequency and intensity of EE for clients seeking advice significantly exceeded those for the ordinary population. Our results support the hypothesis of a continuous spectrum between mental health and mental disorder for the types of experiences analyzed. PMID:23423775

Transgenerational effects of environmental enrichment on repetitive motor behavior development.

PubMed

Bechard, Allison R; Lewis, Mark H

2016-07-01

The favorable consequences of environmental enrichment (EE) on brain and behavior development are well documented. Much less is known, however, about transgenerational benefits of EE on non-enriched offspring. We explored whether transgenerational effects of EE might extend to the development of repetitive motor behaviors in deer mice. Repetitive motor behaviors are invariant patterns of movement that, across species, can be reduced by EE. We found that EE not only attenuated the development of repetitive behavior in dams, but also in their non-enriched offspring. Moreover, maternal behavior did not seem to mediate the transgenerational effect we found, although repetitive behavior was affected by reproductive experience. These data support a beneficial transgenerational effect of EE on repetitive behavior development and suggest a novel benefit of reproductive experience. Copyright © 2016 Elsevier B.V. All rights reserved.

Bridging the gap: using microsociological theory to understand how expressed emotion predicts clinical outcomes.

PubMed

Stanhope, Victoria; Solomon, Phyllis

2007-06-01

Research has shown that expressed emotion (EE) among families is a strong predictor of relapse for people with severe mental illness. Recent studies have also found the presence of EE in consumer-provider relationships. Despite high consistency in the findings related to EE and relapse, the concept has weak validity as little is known about how exactly it triggers relapse. Microsociological theory provides a framework with which to analyze social interaction and, more specifically, understand how interactions relate to the emotions of pride and shame. By identifying the components of interaction rituals, the theory provides insight into the key processes underlying EE and demonstrates how methodologies based on direct observation have the potential to measure EE with greater validity. This article describes how microsociological theory can be applied to the concept of EE.

Effects of ethynylestradiol on vitellogenin synthesis and sex differentiation in juvenile grey mullet (Mugil cephalus) persist after long-term exposure to a clean environment.

PubMed

Aoki, Jun-ya; Hatsuyama, Ayaka; Hiramatsu, Naoshi; Soyano, Kiyoshi

2011-11-01

We investigated the continuing effects of exposure to ethynylestradiol (EE(2)) in juvenile grey mullet after transfer to a clean environment. Eleven-month-old juvenile fish containing immature phenotype gonad were fed dry diets; the low and high EE(2)-treated groups were fed diets with 0.04 and 4 μg EE(2)/g body weight for 4 weeks, respectively. After treatment, they were transferred to clean seawater, and reared with an EE(2) free diet for 350 days. Vitellogenin (VTG) was not detected in the serum of the control group throughout the experimental period. However, in both treatment groups, abnormal values of serum VTG were detected until approximately 100 days after transfer to a clean environment. In the control group, sex differentiation was not confirmed until 206 days after transfer to a clean environment. However, some of the fish in the 0.04 μg EE(2)-treated group had ovarian cavity and oocytes at 26 days. In most of the fish in the 4 μg EE(2)-treated group, the ovarian cavity had already appeared at the end of EE(2) treatment (0 day), and oocytes were observed at 26 days, suggesting that EE(2) accelerates ovarian differentiation. These results suggest that previous exposure to EE(2) has long-term effects on VTG synthesis and gonadal development. Copyright © 2011 Elsevier Inc. All rights reserved.

The impact of familial expressed emotion on clinical and personal recovery among patients with psychiatric disorders: The mediating roles of self-stigma content and process.

PubMed

Chan, Kevin Ka Shing; Lam, Chun Bun

2018-05-24

The present study examined the associations of familial expressed emotion (EE) with clinical and personal recovery among patients with psychiatric disorders, as well as the potential mechanisms underlying these associations. Guided by the content-process theory of self-stigma, we hypothesized that EE would be negatively associated with clinical and personal recovery and that these associations would be mediated by self-stigma content and process. A total of 311 patients with psychiatric disorders completed questionnaires on their perceptions of EE, self-stigma, and recovery. Structural equation modeling demonstrated that EE was positively associated with self-stigma content and process, which were in turn negatively associated with clinical and personal recovery. The indirect effects of EE on clinical and personal recovery, via self-stigma content and process, were also significant. Multigroup analyses further demonstrated that the impact of EE on self-stigma and recovery was generalizable across patients with psychotic and nonpsychotic disorders. Theoretically, our findings revealed the potential pathways through which EE may adversely affect psychiatric recovery. Practically, our findings highlighted the importance of designing multipronged intervention programs to reduce familial EE and its potential harmful impact on psychiatric patients. In addition to helping family members improve their knowledge about psychiatric disorders and adjust their communication styles, practitioners should help psychiatric patients develop resilience against EE, mitigate self-stigma, and achieve recovery. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Haemostatic and metabolic impact of estradiol pills and drospirenone-containing ethinylestradiol pills vs. levonorgestrel-containing ethinylestradiol pills: A literature review.

PubMed

Lete, Iñaki; Chabbert-Buffet, Nathalie; Jamin, Christian; Lello, Stefano; Lobo, Paloma; Nappi, Rossella E; Pintiaux, Axelle

2015-01-01

Since its introduction 50 years ago, the contraceptive pill has continuously evolved to decrease the risk of venous thromboembolism (VTE) associated with its use. An increased risk of VTE still remains, however. Other concerns, such as effects on lipid and carbohydrate metabolism, have also been reported. In this study we compared two reference combined oral contraceptives (COCs) containing ethinylestradiol (EE)/levonorgestrel (LNG) and EE/drospirenone (DRSP) with COCs containing estradiol (E2) (estradiol valerate [E2V]/dienogest [DNG] and E2/nomegestrol acetate [NOMAC]). They were evaluated according to their influence on recognised haemostatic and metabolic markers. A literature search of the MEDLINE/PubMed database was conducted for head-to-head studies. EE/LNG was chosen as the comparator pill. The haemostatic impact of E2 pills and EE/LNG has been extensively compared, in contrast to that of EE/DRSP and EE/LNG. Changes in haemostatic and metabolic marker levels between EE/LNG and E2V/DNG were generally not statistically significant. E2/NOMAC showed statistically significantly favourable results on haemostatic markers and had a neutral effect on carbohydrate and lipid metabolism when compared with EE/LNG. E2/NOMAC exhibits less haemostatic and metabolic impact than EE/LNG and other COCs, suggesting that it may be a promising candidate to reduce residual VTE risk associated with COC use. Confirmation from a well-powered prospective clinical trial is, however, needed.

Effects of environmental enrichment on the incubation of cocaine craving

PubMed Central

Chauvet, Claudia; Goldberg, Steven R.; Jaber, Mohamed; Solinas, Marcello

2012-01-01

Recent studies have demonstrated that exposure to environmental enrichment (EE) during withdrawal periods reduces the risks of relapse to drug-seeking behavior. In this study, we investigated whether EE could prevent the development of time-dependent increases in cocaine-seeking behavior (incubation of craving). In addition, we investigated whether EE could eliminate already developed incubation and whether the effects of EE would last when enrichment is discontinued. For this, we allowed rats to self-administer cocaine for 10 daily 6h sessions and measured cocaine seeking 1, 30 and 60 days after the last self-administration session. In between these tests, rats were kept in forced abstinence and housed either in EE or standard environments (SE). Between day 30 and 60 of withdrawal, half of the rats in each group were maintained in their original environmental condition and the other half was switched to the other environmental condition. We found that exposure to EE prevents development of incubation of cocaine craving and eliminates already developed incubation. In addition, contrary to our expectations, when EE was discontinued, its positive effects on incubation of craving disappeared. These results indicate that EE can reduce cocaine seeking but only temporarily and questions the hypothesis that EE can permanently eliminate the neural consequences of exposure to drugs of abuse. Therefore, stimulating environments could have positive effects on the treatment of cocaine addiction only if they are maintained for long periods of abstinence that encompass the time-frame during which addicts are most vulnerable to relapse. PMID:22634364

The Short-Term Effects of Lying, Sitting and Standing on Energy Expenditure in Women

PubMed Central

POPP, COLLIN J.; BRIDGES, WILLIAM C.; JESCH, ELLIOT D.

2018-01-01

The deleterious health effects of too much sitting have been associated with an increased risk for overweight and obesity. Replacing sitting with standing is the proposed intervention to increase daily energy expenditure (EE). The purpose of this study was to determine the short-term effects of lying, sitting, and standing postures on EE, and determine the magnitude of the effect each posture has on EE using indirect calorimetry (IC). Twenty-eight healthy females performed three separate positions (lying, sitting, standing) in random order. Inspired and expired gases were collected for 45-minutes (15 minutes for each position) using breath-by-breath indirect calorimetry. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured to estimate EE. Statistical analyses used repeat measures ANOVA to analyze all variables and post hoc t-tests. Based on the ANOVA the individual, time period and order term did not result in a statistically significant difference. Lying EE and sitting EE were not different from each other (P = 0.56). However, standing EE (kcal/min) was 9.0 % greater than lying EE (kcal/min) (P = 0.003), and 7.1% greater than sitting EE (kcal/min) (P = 0.02). The energetic cost of standing was higher compared to lying and sitting. While this is statistically significant, the magnitude of the effect of standing when compared to sitting was small (Cohen’s d = 0.31). Short-term standing does not offer an energetic advantage when compared to sitting.

Environmental enrichment enhances cognitive flexibility in C57BL/6 mice on a touchscreen reversal learning task.

PubMed

Zeleznikow-Johnston, Ariel; Burrows, Emma L; Renoir, Thibault; Hannan, Anthony J

2017-05-01

Environmental enrichment (EE) is any positive modification of the 'standard housing' (SH) conditions in which laboratory animals are typically held, usually involving increased opportunity for cognitive stimulation and physical activity. EE has been reported to enhance baseline performance of wild-type animals on traditional cognitive behavioural tasks. Recently, touchscreen operant testing chambers have emerged as a way of performing rodent cognitive assays, providing greater reproducibility, translatability and automatability. Cognitive tests in touchscreen chambers are performed over numerous trials and thus experimenters have the power to detect subtle enhancements in performance. We used touchscreens to analyse the effects of EE on reversal learning, visual discrimination and hippocampal-dependent spatial pattern separation and working memory. We hypothesized that EE would enhance the performance of mice on cognitive touchscreen tasks. Our hypothesis was partially supported in that EE induced enhancements in cognitive flexibility as observed in visual discrimination and reversal learning improvements. However, no other significant effects of EE on cognitive performance were observed. EE decreased the activity level of mice in the touchscreen chambers, which may influence the enrichment level of the animals. Although we did not see enhancements on all hypothesized parameters, our testing paradigm is capable of detecting EE-induced improved cognitive flexibility in mice, which has implications for both understanding the mechanisms of EE and improving screening of putative cognitive-enhancing therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacological profile of the receptors that mediate external carotid vasoconstriction by 5-HT in vagosympathectomized dogs.

PubMed Central

Villalón, C. M.; Ramírez-San Juan, E.; Castillo, C.; Castillo, E.; López-Muñoz, F. J.; Terrón, J. A.

1995-01-01

1. 5-Hydroxytryptamine (5-HT) can produce vasodilatation or vasoconstriction of the canine external carotid bed depending upon the degree of carotid sympathetic tone. Hence, external carotid vasodilatation to 5-HT in dogs with intact sympathetic tone is primarily mediated by prejunctional 5-HT1-like receptors similar to the 5-HT1D subtype, which inhibit the carotid sympathetic outflow. The present investigation is devoted to the pharmacological analysis of the receptors mediating external carotid vasoconstriction by 5-HT in vagosympathectomized dogs. 2. Intracarotid (i.c.) infusions for 1 min of 5-HT (0.3, 1, 3, 10, 30 and 100 micrograms) resulted in dose-dependent decreases in both external carotid blood flow and the corresponding conductance; both mean arterial blood pressure and heart rate remained unchanged during the infusions of 5-HT. These responses to 5-HT were resistant to blockade by antagonists at 5-HT2 (ritanserin) and 5-HT3/5-HT4 (tropisetron) receptors, but were partly blocked by the 5-HT1-like and 5-HT2 receptor antagonist, methiothepin (0.3 mg kg-1); higher doses of methiothepin (1 and 3 mg kg-1) caused little, if any, further blockade. These methiothepin (3 mg kg-1)-resistant responses to 5-HT were not significantly antagonized by MDL 72222 (0.3 mg kg-1) or tropisetron (3 mg kg-1). 3. The external carotid vasoconstrictor effects of 5-HT were mimicked by the selective 5-HT1-like receptor agonist, sumatriptan (3, 10, 30 and 100 micrograms during 1 min, i.c.), which produced dose-dependent decreases in external carotid blood flow and the corresponding conductance; these effects of sumatriptan were dose-dependently antagonized by methiothepin (0.3, 1 and 3 mg kg-1), but not by 5-HT1D-like receptor blocking doses of metergoline (0.1 mg kg-1). 4. The above vasoconstrictor effects of 5-HT remained unaltered after administration of phentolamine, propranolol, atropine, hexamethonium, brompheniramine, cimetidine and haloperidol, thus excluding the involvement of alpha- and beta-adrenoceptors, muscarinic, nicotinic, histamine and dopamine receptors. Likewise, inhibition of either 5-HT-uptake (with fluoxetine) or cyclo-oxygenase (with indomethacin), depletion of biogenic amines (with reserpine) or blockade of calcium channels (with verapamil) did not modify the effects of 5-HT. 5. Taken together, the above results support our contention that the external carotid vasoconstrictor responses to 5-HT in vagosympathectomized dogs are mainly mediated by activation of sumatriptan-sensitive 5-HT1-like receptors. It must be emphasized, notwithstanding, that other mechanisms of 5-HT, including an interaction with a novel 5-HT receptor (sub)type and/or an indirect action that may lead to the release of a known (or even unknown) neurotransmitter substance cannot be categorically excluded. PMID:8591004

The relaxant 5-HT receptor in the dog coronary artery smooth muscle: pharmacological resemblance to the cloned 5-ht7 receptor subtype.

PubMed Central

Terrón, J. A.

1996-01-01

1. The relaxant effect of 5-hydroxytryptamine (5-HT) in the dog isolated coronary artery deprived of endothelium is mediated by a receptor unrelated to the 5-HT1, 5-HT2, 5-HT3 or 5-HT4 types. Based upon the pharmacological characteristics of this relaxant 5-HT receptor and those reported for the new members of the 5-HT receptor family, the present study explored the possibility that the relaxant 5-HT receptor referred to above, corresponds to the cloned 5-ht7 subtype. Thus, the relaxing and/or blocking effects of several 5-HT receptor drugs as well as some typical and atypical antipsychotic drugs with high affinity for the cloned 5-ht7 receptor in precontracted ring segments were analyzed. 2. 5-HT, 5-carboxamidotryptamine (5-CT) and 5-methoxytryptamine, but not 8-OH-DPAT or sumatriptan, produced concentration-dependent relaxations in endothelium-denuded canine coronary artery rings precontracted with prostaglandin F2a (2 microM). Clozapine (1 microM) produced in some cases a small relaxing effect and antagonized 5-HT- and 5-CT-induced relaxation suggesting a partial agonist effect. In the presence of the 5-HT1D receptor antagonist, GR127935 (100 nM), the rank order of agonist potency was 5-CT > 5-HT > clozapine > or = 5-methoxytryptamine. 8-OH-DPAT and sumatriptan remained inactive as agonists. 3. In GR127935-treated preparations, methiothepin (3 nM) and mianserin (1 microM), as well as the antipsychotics, clozapine (1 microM), pimozide (300 nM), risperidone (3 nM) and spiperone (1 microM), failed to induce a significant relaxation in prostaglandin F2x-precontracted vessels, but produced significant rightward displacements of the concentration-response curves to 5-HT and 5-CT without significantly reducing the Emax. In a final set of experiments with 5-CT, metergoline (100 nM) and mesulergine (300 nM) behaved as competitive antagonists. In contrast, lisuride (3 nM) noncompetitively antagonized 5-CT-induced relaxation. The estimated affinity (apparent pKa values) of the above antagonist drugs for the relaxant 5-HT receptor significantly correlated with their reported affinity at the cloned 5-ht7 receptor. 4. Taken together, the above pharmacological data may suggest that the relaxant 5-HT receptor in the smooth muscle of the canine coronary artery is similar to the cloned 5-ht7 receptor subtype. PMID:8832067

Fluoxetine impairs insulin secretion without modifying extracellular serotonin levels in MIN6 β-cells.

PubMed

Cataldo, L R; Cortés, V A; Mizgier, M L; Aranda, E; Mezzano, D; Olmos, P; Galgani, J E; Suazo, J; Santos, J L

2015-09-01

Pancreatic β-cells synthetize and store Serotonin (5-Hydroxytriptamine, 5HT) which is co-released with insulin. It has been proposed that extracellular 5HT binds to specific cell surface receptors and modulate insulin secretion. On the other hand, Selective Serotonin Reuptake Inhibitor (SSRI) fluoxetine seems to reduce Glucose-Stimulated Insulin Secretion (GSIS). However, it is unknown whether this effect results from changes in extracellular 5HT concentration owed to the blockade of 5HT transporter (SERT) or from non-5HT dependent actions. The aims of this work were: 1) to quantify extracellular 5HT levels and GSIS in β-cell lines, 2) to determine whether extracellular 5HT levels and GSIS are changed by fluoxetine or 5-Hydroxytryptophan (5HTP, the immediate 5HT biosynthetic precursor), and 3) to quantify the expression of Slc6a4 gene (encoding SERT) in β-cell lines in relation to other genes involved in 5HT system. β-cell lines MIN6 and RINm5f were subjected to GSIS protocols, after treatment with fluoxetine, 5HTP or 5HT. Insulin and 5HT were quantified by ELISA and HPLC, respectively. Relative mRNA expression was quantified by RT-qPCR. MIN6 β-cells secretes 5HT in response to glucose, showing a sharp increase in 5HT release when cells were preloaded with 5HTP. Treatment with 5HT or fluoxetine reduces GSIS. Fluoxetine fails to further increases 5HTP-induced elevation of secreted 5HT. MIN6 β-cells express both isoforms of Tryptophan Hydroxylase (Tph1 and Tph2), and have high expression levels of L-Dopa decarboxylase (Ddc), both enzymes involved in 5HT biosynthetic pathway, but do not express the 5HT transporters Slc6a4 or Slc6a3 (the Dopamine-5HT transporter) genes. The inhibitory effect of fluoxetine on β-cell glucose stimulated insulin secretion is not mediated by blockage of 5HT transporter through SERT. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of glial cell line-derived neurotrophic factor on behavior and key members of the brain serotonin system in mouse strains genetically predisposed to behavioral disorders.

PubMed

Naumenko, Vladimir S; Bazovkina, Daria V; Semenova, Alina A; Tsybko, Anton S; Il'chibaeva, Tatyana V; Kondaurova, Elena M; Popova, Nina K

2013-12-01

The effect of glial cell line-derived neurotrophic factor (GDNF) on behavior and on the serotonin (5-HT) system of a mouse strain predisposed to depressive-like behavior, ASC/Icg (Antidepressant Sensitive Cataleptics), in comparison with the parental "nondepressive" CBA/Lac mice was studied. Within 7 days after acute administration, GDNF (800 ng, i.c.v.) decreased cataleptic immobility but increased depressive-like behavioral traits in both investigated mouse strains and produced anxiolytic effects in ASC mice. The expression of the gene encoding the key enzyme for 5-HT biosynthesis in the brain, tryptophan hydroxylase-2 (Tph-2), and 5-HT1A receptor gene in the midbrain as well as 5-HT2A receptor gene in the frontal cortex were increased in GDNF-treated ASC mice. At the same time, GDNF decreased 5-HT1A and 5-HT2A receptor gene expression in the hippocampus of ASC mice. GDNF failed to change Tph2, 5-HT1A , or 5-HT2A receptor mRNA levels in CBA mice as well as 5-HT transporter gene expression and 5-HT1A and 5-HT2A receptor functional activity in both investigated mouse strains. The results show 1) a GDNF-induced increase in the expression of key genes of the brain 5-HT system, Tph2, 5-HT1A , and 5-HT2A receptors, and 2) significant genotype-dependent differences in the 5-HT system response to GDNF treatment. The data suggest that genetically defined cross-talk between neurotrophic factors and the brain 5-HT system underlies the variability in behavioral response to GDNF. Copyright © 2013 Wiley Periodicals, Inc.

5-HT6 receptor blockade regulates primary cilia morphology in striatal neurons.

PubMed

Brodsky, Matthew; Lesiak, Adam J; Croicu, Alex; Cohenca, Nathalie; Sullivan, Jane M; Neumaier, John F

2017-04-01

The 5-HT 6 receptor has been implicated in a variety of cognitive processes including habitual behaviors, learning, and memory. It is found almost exclusively in the brain, is expressed abundantly in striatum, and localizes to neuronal primary cilia. Primary cilia are antenna-like, sensory organelles found on most neurons that receive both chemical and mechanical signals from other cells and the surrounding environment; however, the effect of 5-HT 6 receptor function on cellular morphology has not been examined. We confirmed that 5-HT 6 receptors were localized to primary cilia in wild-type (WT) but not 5-HT 6 knockout (5-HT 6 KO) in both native mouse brain tissue and primary cultured striatal neurons then used primary neurons cultured from WT or 5-HT 6 KO mice to study the function of these receptors. Selective 5-HT 6 antagonists reduced cilia length in neurons cultured from wild-type mice in a concentration and time-dependent manner without altering dendrites, but had no effect on cilia length in 5-HT 6 KO cultured neurons. Varying the expression levels of heterologously expressed 5-HT 6 receptors affected the fidelity of ciliary localization in both WT and 5-HT 6 KO neurons; overexpression lead to increasing amounts of 5-HT 6 localization outside of the cilia but did not alter cilia morphology. Introducing discrete mutations into the third cytoplasmic loop of the 5-HT 6 receptor greatly reduced, but did not entirely eliminate, trafficking of the 5-HT 6 receptor to primary cilia. These data suggest that blocking 5-HT 6 receptor activity reduces the length of primary cilia and that mechanisms that regulate trafficking of 5-HT 6 receptors to cilia are more complex than previously thought. Copyright © 2017 Elsevier B.V. All rights reserved.

Sucrose intake and fasting glucose levels in 5-HT(1A) and 5-HT(1B) receptor mutant mice.

PubMed

Bechtholt, Anita J; Smith, Karen; Gaughan, Stephanie; Lucki, Irwin

2008-03-18

Serotonin (5-HT)(1A) and 5-HT(1B) receptors have been implicated in the incidence and treatment of depression in part through the examination of animals lacking these receptors. Although these receptors have been repeatedly implicated in ingestive behavior there is little information about how 5-HT(1A) and 5-HT(1B) receptor mutant mice react to solutions of varying palatability. In the present experiment male and female 5-HT(1A) and 5-HT(1B) mutant and wild-type mice were presented with increasing concentrations of sucrose using a two-bottle choice procedure. In addition fasting blood glucose levels were assessed. Both male and female 5-HT(1B) mutant mice drank more sucrose than WT mice but also consumed more water. Female, but not male, 5-HT(1A) mutant mice similarly showed increased sucrose consumption, but did not demonstrate increased consumption of water. In addition, the pattern of increased sucrose consumption over genotype and sex was related to fasting blood glucose concentrations such that levels in male 5-HT(1B) mutant mice were reduced relative to wild-type and 5-HT(1A) mutant males, but similar to those of females. The findings in 5-HT(1B) mutant mice emphasize the role of the 5-HT(1B) receptor in regulating ingestive behavior, whereas female sex hormones and 5-HT(1A) receptors may interact to alter sucrose consumption in 5-HT(1A) mutant mice. In addition, these findings may have implications for the role of these receptors in the incidence and treatment of depression since the intake of sucrose has been used as an index of anhedonia in animal models of depression and antidepressant efficacy.

Brain Serotonin Receptors and Transporters: Initiation vs. Termination of Escalated Aggression

PubMed Central

Takahashi, Aki; Quadros, Isabel M.; de Almeida, Rosa M. M.; Miczek, Klaus A.

2013-01-01

Rationale Recent findings have shown a complexly regulated 5-HT system as it is linked to different kinds of aggression. Objective We focus on (1) phasic and tonic changes of 5-HT and (2) state and trait of aggression, and emphasize the different receptor subtypes, their role in specific brain regions, feed-back regulation and modulation by other amines, acids and peptides. Results New pharmacological tools differentiate the first three 5-HT receptor families and their modulation by GABA, glutamate and CRF. Activation of 5-HT1A, 5-HT1B and 5-HT2A/2C receptors in mesocorticolimbic areas, reduce species-typical and other aggressive behaviors. In contrast, agonists at 5-HT1A and 5-HT1B receptors in the medial prefrontal cortex or septal area can increase aggressive behavior under specific conditions. Activation of serotonin transporters reduce mainly pathological aggression. Genetic analyses of aggressive individuals have identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or indirectly (e.g., Neuropeptide Y, αCaMKII, NOS, BDNF). Dysfunction in genes for MAOA escalates pathological aggression in rodents and humans, particularly in interaction with specific experiences. Conclusions Feedback to autoreceptors of the 5-HT1 family and modulation via heteroreceptors are important in the expression of aggressive behavior. Tonic increase of the 5-HT2 family expression may cause escalated aggression, whereas the phasic increase of 5-HT2 receptors inhibits aggressive behaviors. Polymorphisms in the genes of 5-HT transporters or rate-limiting synthetic and metabolic enzymes of 5-HT modulate aggression, often requiring interaction with the rearing environment. PMID:20938650

Serotonin inputs to the dorsal BNST modulate anxiety in a 5-HT1A receptor dependent manner

PubMed Central

Garcia-Garcia, Alvaro L.; Canetta, Sarah; Stujenske, Joseph M.; Burghardt, Nesha S.; Ansorge, Mark S.; Dranovsky, Alex; Leonardo, E. David

2017-01-01

Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in humans and rodents. While the dorsal part of the BNST (dBNST) receives dense 5-HT innervation, whether and how 5-HT in the dBNST normally modulates anxiety remains unclear. Using optogenetics, we demonstrate that activation of 5-HT terminals in the dBNST reduces anxiety in a highly anxiogenic environment. Further analysis revealed that optogenetic inhibition of 5-HT inputs into the dBNST increases anxiety in a less anxiogenic environment. We found that 5-HT predominantly hyperpolarizes dBNST neurons, reducing their activity in a manner that can be blocked by a 5-HT1A antagonist. Finally, we demonstrate that activation of 5-HT1A receptors in the dBNST is necessary for the anxiolytic effect observed following optogenetic stimulation of 5-HT inputs into the dBNST. These data reveal that 5-HT release in the dBNST modulates anxiety-like behavior via 5-HT1A receptors under naturalistic conditions. PMID:28761080

Family of Beyond Line-of-Sight - Terminals (FAB-T)

DTIC Science & Technology

2013-12-01

Inter- operable with the AEHF, APS, Milstar, and UFO -E/EE Inter- operable with the AEHF, APS, Milstar, and UFO -E/EE Inter- operable with the...AEHF, APS, Milstar, and UFO -E/EE Milstar connectivity has been extensively tested; partial AEHF on-orbit testing has been conducted...Program SR-3300. This performance parameter only applies to the CPT configuration. 8. Interoperability with UFO /E and UFO /EE is predicated on

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakamoto, Susumu, E-mail: susumu1029@gmail.com; Kikuchi, Naoshi; Ichikawa, Atsuo

Despite the wide use of everolimus as an antineoplastic coating agent for coronary stents to reduce the rate of restenosis, little is known about the health hazards of everolimus-eluting stents (EES). We describe a case of pneumonitis that developed 2 months after EES implantation for angina. Lung pathology demonstrated an organizing pneumonia pattern that responded to corticosteroid therapy. Although the efficacy of EES for ischemic heart disease is well established, EES carries a risk of pneumonitis.

31 CFR 351.71 - How can I find out what my book-entry Series EE savings bonds are worth?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false How can I find out what my book-entry... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.71 How can I find out what my book-entry Series EE savings bonds are worth? (a) Redemption values. You may access...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mezei, Márk

A global quench is an interesting setting where we can study thermalization of subsystems in a pure state. We investigate entanglement entropy (EE) growth in global quenches in holographic field theories and relate some of its aspects to quantities characterizing chaos. More specifically we obtain four key results: 1. We prove holographic bounds on the entanglement velocity vE and the butterfly effect speed vB that arises in the study of chaos. 2. We obtain the EE as a function of time for large spherical entangling surfaces analytically. We show that the EE is insensitive to the details of the initialmore » state or quench protocol. 3. In a thermofield double state we determine analytically the two-sided mutual information between two large concentric spheres separated in time. 4. We derive a bound on the rate of growth of EE for arbitrary shapes, and develop an expansion for EE at early times. In a companion paper, these results are put in the broader context of EE growth in chaotic systems: we relate EE growth to the chaotic spreading of operators, derive bounds on EE at a given time, and compare the holographic results to spin chain numerics and toy models. In this paper, we perform holographic calculations that provide the basis of arguments presented in that paper.« less

On entanglement spreading from holography

DOE PAGES

Mezei, Márk

2017-05-11

A global quench is an interesting setting where we can study thermalization of subsystems in a pure state. We investigate entanglement entropy (EE) growth in global quenches in holographic field theories and relate some of its aspects to quantities characterizing chaos. More specifically we obtain four key results: 1. We prove holographic bounds on the entanglement velocity vE and the butterfly effect speed vB that arises in the study of chaos. 2. We obtain the EE as a function of time for large spherical entangling surfaces analytically. We show that the EE is insensitive to the details of the initialmore » state or quench protocol. 3. In a thermofield double state we determine analytically the two-sided mutual information between two large concentric spheres separated in time. 4. We derive a bound on the rate of growth of EE for arbitrary shapes, and develop an expansion for EE at early times. In a companion paper, these results are put in the broader context of EE growth in chaotic systems: we relate EE growth to the chaotic spreading of operators, derive bounds on EE at a given time, and compare the holographic results to spin chain numerics and toy models. In this paper, we perform holographic calculations that provide the basis of arguments presented in that paper.« less

Investigation of local anesthetic and antimycobacterial activity of Ottonia martiana Miq. (Piperaceae).

PubMed

Cunico, Miriam M; Trebien, Herbert A; Galetti, Fábio C; Miguel, Obdulio G; Miguel, Marilis D; Auer, Celso G; Silva, Célio L; de Souza, Ana Olívia

2015-01-01

Ottonia martiana is a plant popularly known in Brazil by the use for toothache. Ethanolic extract (EE), hexane fraction (HF), dichloromethane fraction (DF) and piperovatine obtained from O. martiana were assayed in vitro and in vivo. The acute toxicity of EE was determined, and LD50 values of 164.5 and 65.0 mg/kg by the oral and intraperitoneal routes, respectively, indicated a high toxicity for EE in vivo, explaining its popular use by topical administration only. A local anesthetic-like effect of EE and its fractions was observed in experimental models using pain induction, and such effect involved an analgesic action. The antimycobacterial activity of EE, HF, DF and piperovatine was evaluated against Mycobacterium tuberculosis H37Rv ATCC 27924. EE, HF, DF, and piperovatine showed a potential antimycobacterial effect with MICs of 16.0, 62.0, 62.0 and 8.0 μg/mL, respectively. Piperovatine was more effective than the EE or the other fractions. The selectivity index (SI=IC50/MIC) values calculated for EE, HF, DF and piperovatine based on the MICs and the cytotoxicity against J774 macrophages (IC50 by MTT assay) revealed values of 6.43, 2.34, 1.5 and 9.66, respectively.

Efficient SO2 capture by amine functionalized PEG.

PubMed

Yang, Dezhong; Hou, Minqiang; Ning, Hui; Zhang, Jianling; Ma, Jun; Han, Buxing

2013-11-07

Polyethylene glycols (PEGs) are a class of non-toxic, non-volatile, biocompatible, and widely available polymers. In this work, we synthesized N-ethyl-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-2-aminoethanol (EE3AE) that combines the properties of PEG and amines, and N-decyl-N-ethyl-2-aminoethanol (DEAE). Their performances to capture SO2 were studied at different temperatures, pressures, and absorption times. The interaction between the absorbents and SO2 were characterized by NMR and FTIR techniques. It was demonstrated that both EE3AE and DEAE could absorb SO2 efficiently, and there existed chemical and physical interactions between the absorbents and SO2. In particular, the absorption capacity of EE3AE could be as high as 1.09 g SO2 per g EE3AE at 1 atm. The absorption capacity of EE3AE was much larger than that of DEAE because the ether group in the EE3AE interacted with SO2 more strongly than the alkyl group in the DEAE. The SO2 absorbed by EE3AE could be stripped out by bubbling N2 or by applying a vacuum and the EE3AE could be reused. Moreover, both absorbents exhibited a high SO2-CO2 selectivity.

Spatially restricted G protein-coupled receptor activity via divergent endocytic compartments.

PubMed

Jean-Alphonse, Frederic; Bowersox, Shanna; Chen, Stanford; Beard, Gemma; Puthenveedu, Manojkumar A; Hanyaloglu, Aylin C

2014-02-14

Postendocytic sorting of G protein-coupled receptors (GPCRs) is driven by their interactions between highly diverse receptor sequence motifs with their interacting proteins, such as postsynaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), zonula occludens-1 protein (zo-1) (PDZ) domain proteins. However, whether these diverse interactions provide an underlying functional specificity, in addition to driving sorting, is unknown. Here we identify GPCRs that recycle via distinct PDZ ligand/PDZ protein pairs that exploit their recycling machinery primarily for targeted endosomal localization and signaling specificity. The luteinizing hormone receptor (LHR) and β2-adrenergic receptor (B2AR), two GPCRs sorted to the regulated recycling pathway, underwent divergent trafficking to distinct endosomal compartments. Unlike B2AR, which traffics to early endosomes (EE), LHR internalizes to distinct pre-early endosomes (pre-EEs) for its recycling. Pre-EE localization required interactions of the LHR C-terminal tail with the PDZ protein GAIP-interacting protein C terminus, inhibiting its traffic to EEs. Rerouting the LHR to EEs, or EE-localized GPCRs to pre-EEs, spatially reprograms MAPK signaling. Furthermore, LHR-mediated activation of MAPK signaling requires internalization and is maintained upon loss of the EE compartment. We propose that combinatorial specificity between GPCR sorting sequences and interacting proteins dictates an unprecedented spatiotemporal control in GPCR signal activity.

Familial expressed emotion: outcome and course of Israeli patients with schizophrenia.

PubMed

Marom, Sofi; Munitz, Hanan; Jones, Peter B; Weizman, Abraham; Hermesh, Haggai

2002-01-01

We investigated the validity of expressed emotion (EE) in Israel. The study sample consisted of 108 patients with schizophrenia and 15 with schizoaffective disorder, and their key relatives. EE was rated with the Five Minute Speech Sample (FMSS). Patient households were categorized by EE and its two components: criticism and emotional overinvolvement. Patients were rated with the Brief Psychiatric Rating Scale (BPRS) at admission, at discharge, and 6 months after discharge. Readmissions were determined over a 9-month period. High EE and particularly high criticism were significantly associated with poorer outcome (higher rate of and earlier readmissions, and higher BPRS score at followup) and worse illness course (higher annual number of prior psychiatric hospital admissions). Odds ratios between high EE and high criticism and readmission were 2.6 and 3.5, respectively. The strongest predictor of earlier readmission was the interaction of high criticism x poor compliance with medication. The results converge to further confirm the notion that familial EE is a valid crosscultural predictor of the clinical course of schizophrenia. Moreover, EE has predictive power in very chronic samples. Criticism appears to be the crucial EE component linked with short-term outcome. Treatment aimed at reducing high criticism is warranted. The FMSS appears to have predictive validity.

Bleeding pattern with drospirenone 3 mg+ethinyl estradiol 20 mcg 24/4 combined oral contraceptive compared with desogestrel 150 mcg+ethinyl estradiol 20 mcg 21/7 combined oral contraceptive.

PubMed

Anttila, Leena; Kunz, Michael; Marr, Joachim

2009-11-01

The study was conducted to compare cycle control, bleeding pattern and efficacy of two low-dose combined oral contraceptives. Four hundred fifty-three women were randomized to receive a 24/4 regimen of drospirenone 3 mg/ethinyl estradiol 20 mcg (drsp 3 mg/EE 20 mcg; n=230) or a 21/7 regimen of desogestrel 150 mcg/EE 20 mcg (DSG 150 mcg/EE 20 mcg; n=223), and recorded bleeding daily over 7 treatment cycles. The duration [mean 4.7 (SD 1.5)-5.2 (SD 2.2) days in the drsp 3 mg/EE 20 mcg 24/4 group and 5.1 (SD 1.5)-5.4 (SD 2.1) days in the DSG 150 mcg/ EE 20 mcg group] and maximum intensity ("normal bleeding" for >50% of all subjects) of scheduled bleeding in Cycles 1-6 was comparable between treatment groups. The incidence of unscheduled bleeding during Cycles 2-6 was also similar between the two groups (drsp 3 mg/EE 20 mcg, 8.8-17.3%; DSG 150 mcg/ EE 20 mcg, 9.4-16.3%). Drsp 3 mg/EE 20 mcg 24/4 achieved an acceptable bleeding profile with reliable cycle control, comparable with an established formulation.

Development of the 5-HT2CR-Tango System Combined with an EGFP Reporter Gene.

PubMed

Watanabe, Yoshihisa; Tsujimura, Atsushi; Aoki, Miku; Taguchi, Katsutoshi; Tanaka, Masaki

2016-02-01

The serotonin 2C receptor (5-HT2CR) is a G-protein-coupled receptor implicated in emotion, feeding, reward, and cognition. 5-HT2CRs are pharmacological targets for mental disorders and metabolic and reward system abnormalities, as alterations in 5-HT2CR expression, RNA editing, and SNPs are involved in these disturbances. To date, 5-HT2CR activity has mainly been measured by quantifying inositol phosphate production and intracellular Ca(2+) release, but these assays are not suitable for in vivo analysis. Here, we developed a 5-HT2CR-Tango assay system, a novel analysis tool of 5-HT2CR activity based on the G-protein-coupled receptor (GPCR)-arrestin interaction. With desensitization of activated 5-HT2CR by arrestin, this system converts the 5-HT2CR-arrestin interaction into EGFP reporter gene signal via the LexA transcriptional activation system. For validation of our system, we measured activity of two 5-HT2CR RNA-editing isoforms (INI and VGV) in HEK293 cells transfected with EGFP reporter gene. The INI isoform displayed both higher basal- and 5-HT-stimulated activities than the VGV isoform. Moreover, an inhibitory effect of 5-HT2CR antagonist SB242084 was also detected by 5-HT2CR-Tango system. This novel tool is useful for in vitro high-throughput targeted 5-HT2CR drug screening and can be applied to future in vivo brain function studies associated with 5-HT2CRs in transgenic animal models.

Identification, expression, and pharmacology of a Cys{sub 23}-Ser{sub 23} substitution in the human 5-HT{sub 2C} receptor gene (HTR2C)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lappalainen, J.; Ozaki, N.; Goldman, D.

1995-05-20

The function of brain serotonin-2C (5-HT{sub 2C}) receptors, including behavioral and neurochemical responses to 5-HT{sub 2C} agonist challenge, has been suggested to be abnormal in individuals with neuropsychiatric disorders. Thus, it is important to identify polymorphisms and functional variants within this gene. Using SSCP analysis, the authors identified a Cys{sub 23}-Ser{sub 23} substitution (designated 5-HT{sub 2Ccys} and 5-HT{sub 2Cser}) in the first hydrophobic region of the human 5-HT{sub 2C} receptor. Allele frequencies in unrelated Caucasians were 0.13 and 0.87 for 5-HT{sub 2Cser} and 5-HT{sub 2Ccys}, respectively. DNAs from informative CEPH families were typed for this polymorphism and analyzed with respectmore » to 20 linked markers on the X chromosome. Linkage analysis placed the 5-HT{sub 2C} receptor gene (HTR2C) on Xq24. To evaluate whether this amino acid substitution causes a variant function of this receptor, recombinant human 5-HT{sub 2Ccys} and 5-HT{sub 2Cser} receptors were expressed in Xenopus oocytes and tested for responses to 5-HT using electrophysiological techniques. Concentration-response curves for 5-HT were not significantly different in oocytes expressing either form of the receptor, suggesting that the 5-HT{sub 2Ccys} and 5-HT{sub 2Cser} receptor proteins may not differ in their responses to serotonin under baseline physiological conditions. 43 refs., 3 figs., 1 tab.« less

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding.

PubMed

da Cunha-Bang, Sofi; Mc Mahon, Brenda; Fisher, Patrick MacDonald; Jensen, Peter Steen; Svarer, Claus; Knudsen, Gitte Moos

2016-04-01

Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145 for quantification of brain 5-HT4R binding. The Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

The political economy of emergency and essential surgery in global health.

PubMed

Hedges, Jeremy P; Mock, Charles N; Cherian, Meena N

2010-09-01

Emergency and essential surgery (EES) remains a low priority on global health agendas even though a growing body of evidence demonstrates that EES is a cost-effective public health intervention and that it holds the potential to prevent a sizable number of deaths and disabilities. The inferior status of EES should be considered, in part, a political problem and subject to political analysis. This type of political economy examination has been used for other important global health issues but has not been applied to EES. By addressing political concerns and prospects, EES can be better positioned on international agendas, thus improving surgical care delivered to the poor.

Serotonin modulates insect hemocyte phagocytosis via two different serotonin receptors

PubMed Central

Qi, Yi-xiang; Huang, Jia; Li, Meng-qi; Wu, Ya-su; Xia, Ren-ying; Ye, Gong-yin

2016-01-01

Serotonin (5-HT) modulates both neural and immune responses in vertebrates, but its role in insect immunity remains uncertain. We report that hemocytes in the caterpillar, Pieris rapae are able to synthesize 5-HT following activation by lipopolysaccharide. The inhibition of a serotonin-generating enzyme with either pharmacological blockade or RNAi knock-down impaired hemocyte phagocytosis. Biochemical and functional experiments showed that naive hemocytes primarily express 5-HT1B and 5-HT2B receptors. The blockade of 5-HT1B significantly reduced phagocytic ability; however, the blockade of 5-HT2B increased hemocyte phagocytosis. The 5-HT1B-null Drosophila melanogaster mutants showed higher mortality than controls when infected with bacteria, due to their decreased phagocytotic ability. Flies expressing 5-HT1B or 5-HT2B RNAi in hemocytes also showed similar sensitivity to infection. Combined, these data demonstrate that 5-HT mediates hemocyte phagocytosis through 5-HT1B and 5-HT2B receptors and serotonergic signaling performs critical modulatory functions in immune systems of animals separated by 500 million years of evolution. DOI: http://dx.doi.org/10.7554/eLife.12241.001 PMID:26974346

Synthesis of optically active regioregular polythiophenes and their self-organization at the air-water interface.

PubMed

Takeoka, Yuko; Saito, Fumihiko; Rikukawa, Masahiro

2013-07-09

Regioregular polythiophenes containing an optically active substituent in the third position of the thiophene ring, head-to-tail poly(3-[2-((S)-1-methyloctyloxy)ethyl]thiophene)s (HT-P(S)MOETs), were synthesized using highly reactive zinc. For comparison, HT-P(R)MOET and achiral HT-P(±)MOET also were synthesized from R-type monomers and racemic monomers, respectively. The HT-PMOET possessed greater than 95% head-to-tail coupling with a weight-average molecular weight (Mw) between 1.96 × 10(4) and 2.94 × 10(4). The polymers were characterized using (1)H and (13)C NMR, optical rotatory power measurements, circular dichroism (CD), and UV-vis spectroscopy. X-ray diffraction patterns of the cast films demonstrated that regioregular HT-PMOET possessed a strong tendency to self-assemble into highly ordered, crystalline structures. The HT-P(S)MOET and HT-P(R)MOET showed strong Cotton effects, while HT-P(±)MOET showed very weak Cotton effects. The presence of a circular dichroism effect indicated that the side chain chirality induced optical activity in poly(thiophene) main chains. The monolayer formation of HT-PMOET spread on the water surface was characterized using a pressure-area (π-A) isotherm. The molecular areas of HT-P(S)MOET and HT-P(R)MOET molecules on the water surface were 33.5 and 32.9 Å(2), respectively, at 10 °C, which were larger than that of HT-P(±)MOET (27.9 Å(2)), suggesting that optically active HT-PMOET expanded because of the chiral repulsion between side chains. Multilayer films of HT-PMOET were prepared by repeating horizontal deposition of the monolayer on the water surface. The multilayer films of optically active HT-PMOET obtained showed stronger Cotton effects than did the cast films. In addition, electrical conductivities of HT-PMOET multilayer films were superior to those of spin-coated films. Head-to-tail poly(3-[2-((S)-1-methylpropyloxy)ethyl]thiophene) (HT-P(S)MPET), which contained shorter side chain lengths compared to HT-P(S)MOET, also was synthesized. The CD intensities of HT-P(S)MPET multilayer films were smaller than those of HT-P(S)MOET multilayer films, suggesting that the optically active side-chain length is critically important to the optically active self-assembly.

Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization.

PubMed

Thomsen, William J; Grottick, Andrew J; Menzaghi, Frederique; Reyes-Saldana, Hazel; Espitia, Stephen; Yuskin, Diane; Whelan, Kevin; Martin, Michael; Morgan, Michael; Chen, Weichao; Al-Shamma, Hussien; Smith, Brian; Chalmers, Derek; Behan, Dominic

2008-05-01

5-Hydroxytryptamine (5-HT)(2C) receptor agonists hold promise for the treatment of obesity. In this study, we describe the in vitro and in vivo characteristics of lorcaserin [(1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3 benzazepine], a selective, high affinity 5-HT(2C) full agonist. Lorcaserin bound to human and rat 5-HT(2C) receptors with high affinity (K(i) = 15 +/- 1 nM, 29 +/- 7 nM, respectively), and it was a full agonist for the human 5-HT(2C) receptor in a functional inositol phosphate accumulation assay, with 18- and 104-fold selectivity over 5-HT(2A) and 5-HT(2B) receptors, respectively. Lorcaserin was also highly selective for human 5-HT(2C) over other human 5-HT receptors (5-HT(1A), 5-HT(3), 5-HT(4C), 5-HT5(5A), 5-HT(6), and 5-HT(7)), in addition to a panel of 67 other G protein-coupled receptors and ion channels. Lorcaserin did not compete for binding of ligands to serotonin, dopamine, and norepinephrine transporters, and it did not alter their function in vitro. Behavioral observations indicated that unlike the 5-HT(2A) agonist (+/-)-1-(2,5-dimethoxy-4-phenyl)-2-aminopropane, lorcaserin did not induce behavioral changes indicative of functional 5-HT(2A) agonist activity. Acutely, lorcaserin reduced food intake in rats, an effect that was reversed by pretreatment with the 5-HT(2C)-selective antagonist 6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy)pyridin-3-yl-carbamoyl]indoline (SB242,084) but not the 5-HT(2A) antagonist (R)-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (MDL 100,907), demonstrating mediation by the 5-HT(2C) receptor. Chronic daily treatment with lorcaserin to rats maintained on a high fat diet produced dose-dependent reductions in food intake and body weight gain that were maintained during the 4-week study. Upon discontinuation, body weight returned to control levels. These data demonstrate lorcaserin to be a potent, selective, and efficacious agonist of the 5-HT(2C) receptor, with potential for the treatment of obesity.

Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes.

PubMed

Bianchi, M; Moser, C; Lazzarini, C; Vecchiato, E; Crespi, F

2002-03-01

Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the present data show that the initial block of 5-HT reuptake is revealed by the selective increase in 5-HT levels (extracellular content) measured in PRP (not in insulated platelets, IPs) the 1st day of fluoxetine treatment. The initial action of this SSRI upon the 5-HT transporter in brain has also been confirmed by in vivo voltammetric data showing selective increase in the serotonergic signal following local injection of fluoxetine into the brain region studied. Successively, the major effect monitored is a decrease in 5-HT levels, which is more evident in IPs than in PRP. However, it is known that following 2 weeks treatment with an SSRI, 5-HT autoreceptors are desensitized and the serotonin synthesis is restored, together with the intracellular 5-HT levels. The present data showing that the levels of 5-HT in IPs tend to return to control values 12 days after the beginning of chronic fluoxetine treatment suggest that 5-HT levels in IPs (intracellular environment) mirror the influence of SSRI treatment upon the central 5-HT system. On the other hand, at day 12 of the chronic fluoxetine treatment, 5-HT content remains low in PRP. Similarly, low levels of 5-HT have been monitored in brain homogenate of rats chronically treated with fluoxetine. This would support the similarity between PRP preparation and brain homogenate as in both cases cells are disrupted by sample preparation. In conclusion this work supports the literature in proposing platelets as a peripheral model of central functions. In particular, the present data support the idea that peripheral 5-HT platelet levels can reflect the state of the central 5-HT system in conditions of depression. Furthermore, the main outcome of this study is that PRP may mirror central extracellular 5-HT levels, whilst IPs mirror neuronal 5-HT changes.

Interplay Between Electron-Electron, Electron-Impurity and Electron-Boundary Scattering in a Two Dimensional Electron Gas (2DEG)

NASA Astrophysics Data System (ADS)

Abraham, Mathew C.; Ram, Rajeev J.; Gossard, A. C.

2003-03-01

A small group of experiments have been conducted over the past decade that explore the fact that even though electron-electron (e-e) scattering in a 2DEG is momentum conserving, its interplay with electron-impurity (e-i)and electron-boundary (e-b) scattering can change the resistance of bulk and mesoscopic devices respectively. The interplay between e-e and e-i scattering in a bulk sample has been shown to cause a fall in the resistivity as a function of electron temperature in the regime where the scattering length l_ee > l_ei and a rise when l_ee < l_ei. In contrast, the interplay between e-e and e-b scattering has been demonstrated to raise the resistivity of a mesoscopic sized wire as a function of electron temperature in the regime l_ee > lb and a fall when l_ee < l_b. We attempt to present a comprehensive picture of these two apparently competing effects by studying devices that are affected by both phenomena simultaneously.

Expressed emotion is not associated with disorder severity in first-episode mental disorder.

PubMed

Heikkilä, Jyrki; Karlsson, Hasse; Taiminen, Tero; Lauerma, Hannu; Ilonen, Tuula; Leinonen, Kirsi-Marja; Wallenius, Elina; Virtanen, Hilkka; Heinimaa, Markus; Koponen, Salla; Jalo, Päivi; Kaljonen, Anne; Salakangas, Raimo K R

2002-08-30

A family atmosphere characterized by expressed emotion (EE) is a robust predictor of clinical outcome of patients with schizophrenia and mood disorders. However, there is ongoing discussion as to whether EE is more a cause of clinical outcome or a parental reaction to disorder severity. This cross-sectional study examines a sample of 42 consecutive first-episode patients from a defined geographical area with severe mental disorders (schizophrenia-related disorders, psychotic mood disorders, and non-psychotic mood disorders). Their 42 relatives were interviewed, and the relationships between EE variables derived with the five-minute speech sample method (FMSS) and the patients' demographic, premorbid and clinical measures were analyzed. A high EE score was found in 40% of the relatives. High EE was associated with the interviewed relative's not being a spouse and the patient's being young and unmarried. It was not associated with premorbid characteristics, symptom dimensions or the diagnostic group of the patient. These results do not support the hypothesis that EE is a reaction to the clinical features of the patient. Instead, demographic factors may partly mediate the effect of EE on prognosis.

Drospirenone and levonorgestrel in combination with either 30 or 20 mcg ethinylestradiol reduce soluble adhesion molecules in Brazilian women; cross-sectional study.

PubMed

Stocco, Bianca; Fumagalli, Helen Figueiredo; Franceschini, Silvio Antônio; Martinez, Edson Zangiacomi; Marzocchi-Machado, Cleni Mara; Toloi, Maria Regina Torqueti

2012-11-01

The objective of this study was to evaluate the effect of three contraceptive pills containing ethinylestradiol (EE) (20 or 30 mcg) in combination with drospirenone (DRSP) and levonorgestrel (LNG) on plasma concentration of adhesion molecules vascular cell adhesion molecule -1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin. A cross-sectional study was conducted with 72 participants (18-30 years old) distributed into three groups that used oral contraceptives containing EE 20 or 30 mcg combined with DRSP 3 mg or EE 30 mcg/LNG 150 mcg for at least 6 months. The control group was comprised of nonusers of contraceptives. Soluble VCAM-1, soluble ICAM-1 and soluble E-selectin were evaluated by enzyme-linked immunosorbent assay. Compared to the control group, a significant decrease was found in VCAM-1 and ICAM-1 concentrations with use of DRSP/20 EE and LNG/30 EE. DRSP/20 EE and LNG/30 EE induce favorable changes in endothelial function. Copyright © 2012 Elsevier Inc. All rights reserved.

Two-cylinder entanglement entropy under a twist

NASA Astrophysics Data System (ADS)

Chen, Xiao; Witczak-Krempa, William; Faulkner, Thomas; Fradkin, Eduardo

2017-04-01

We study the von Neumann and Rényi entanglement entropy (EE) of the scale-invariant theories defined on the tori in 2  +  1 and 3  +  1 spacetime dimensions. We focus on the spatial bi-partitions of the torus into two cylinders, and allow for twisted boundary conditions along the non-contractible cycles. Various analytical and numerical results are obtained for the universal EE of the relativistic boson and Dirac fermion conformal field theories (CFTs), the fermionic quadratic band touching and the boson with z  =  2 Lifshitz scaling. The shape dependence of the EE clearly distinguishes these theories, although intriguing similarities are found in certain limits. We also study the evolution of the EE when a mass is introduced to detune the system from its scale-invariant point, by employing a renormalized EE that goes beyond a naive subtraction of the area law. In certain cases we find the non-monotonic behavior of the torus EE under RG flow, which distinguishes it from the EE of a disk.

Parental Expressed Emotion During Two Forms of Family-Based Treatment for Adolescent Anorexia Nervosa.

PubMed

Allan, Erica; Le Grange, Daniel; Sawyer, Susan M; McLean, Louise A; Hughes, Elizabeth K

2018-01-01

High parental expressed emotion (EE), reflected by criticism or emotional over-involvement, has been related to poorer outcome in family-based treatment (FBT) for adolescent anorexia nervosa. This study assessed EE in 89 mothers and 64 fathers at baseline and end of treatment in a randomised trial comparing conjoint FBT to parent-focused FBT (PFT). Compared with conjoint FBT, PFT was associated with a decrease in maternal criticism, regardless of adolescent remission. Furthermore, an increase in maternal criticism was more likely to be observed in conjoint FBT (80%) than PFT (20%, p = 0.001). Adolescents of mothers who demonstrated an increase in EE, or remained high in EE, were less likely to remit compared with adolescents for whom EE decreased or remained low (33% and 0% vs. 43% and 50%, p = 0.03). There were no significant effects for paternal EE. The results highlight the importance of considering EE when implementing FBT for adolescents with anorexia nervosa. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Change in expressed emotion and treatment outcome in adolescent anorexia nervosa.

PubMed

Moskovich, Ashley A; Timko, C Alix; Honeycutt, Lisa K; Zucker, Nancy L; Merwin, Rhonda M

2017-01-01

Expressed emotion (EE) has been associated with poor outcomes in anorexia nervosa (AN); however, whether changes in EE predict superior treatment outcomes is unknown. The current study examined whether decreases in EE during an open trial of a novel family-based treatment for AN predicted symptoms at end of treatment. Forty-seven adolescents (12-18 years of age) with AN or sub-threshold AN and their parents (mothers: n = 47, fathers: n = 39) participated in 6 months of family treatment. Measures of AN symptomatology (Eating Disorder Examination completed by adolescent and end of treatment recovery status) and parental EE (Family Questionnaire completed by parents which measures two facets of EE: critical communication [CC] and emotional over-involvement [EOI]) were collected at baseline and end of treatment. Parental EOI, but not CC, significantly decreased during the course of treatment. Change in mothers', but not fathers', EE accounted for additional variance in AN symptomatology at end of treatment above baseline EE and baseline AN symptom levels. Findings suggest a greater emphasis on parent support during treatment may improve outcomes.

Hashimoto's thyroiditis with elevated serum IgG4 concentrations is not equivalent to IgG4 Hashimoto's thyroiditis.

PubMed

Yu, Yang; Yu, Nan; Lu, Guizhi; Li, Ting; Zhang, Yang; Zhang, Jing; Gao, Ying; Gao, Yanming; Guo, Xiaohui

2018-06-01

Hashimoto's thyroiditis (HT) with serum IgG4 concentrations greater than 135 mg/dL can be diagnosed as elevated serum IgG4 HT. HT can also be classified into IgG4 HT and non-IgG4 HT based on an immunohistochemistry analysis of IgG4. The aim of our study was to determine the relationship between elevated serum IgG4 HT and IgG4 HT. Both thyroid tissues and serum samples stored before pathological examination from 93 patients with HT were collected. The serum levels of IgG, IgG4, TgAb IgG, TgAb IgG4, TPOAb IgG and TPOAb IgG4 were measured by ELISAs. The expression levels of IgG4, IgG and TGF-β1 in thyroid tissues were detected by immunohistochemistry. Patients with HT were divided into two groups: elevated serum IgG4 HT (n = 12) and nonelevated serum IgG4 HT (n = 81). Hypothyroidism was found in 5 of 12 cases (41.7%) in the elevated serum IgG4 HT group and 10 of 81 cases (12.3%) in the nonelevated serum IgG4 HT group (P = .023). Serologically, there were no significant differences in the levels of TgAb IgG, TPOAb IgG, TgAb IgG4 and TPOAb IgG4 between the two groups, and the expression of TGF-β1 in thyroid tissues was not significantly different between the groups. Most importantly, the frequency of patients who satisfied the criteria for IgG4 HT diagnosis was comparable (25% vs 20.9%, P = .756). The measurement of serum IgG4 allows the identification of patients with HT closely associated with hypothyroidism. However, our study demonstrated that elevated serum IgG4 HT is not equivalent to IgG4 HT. © 2018 John Wiley & Sons Ltd.

Enhancement of cortical extracellular 5-HT by 5-HT1A and 5-HT2C receptor blockade restores the antidepressant-like effect of citalopram in non-responder mice.

PubMed

Calcagno, Eleonora; Guzzetti, Sara; Canetta, Alessandro; Fracasso, Claudia; Caccia, Silvio; Cervo, Luigi; Invernizzi, Roberto W

2009-07-01

We recently found that the response of DBA/2 mice to SSRIs in the forced swim test (FST) was impaired and they also had a smaller basal and citalopram-stimulated increase in brain extracellular serotonin (5-HT) than 'responder' strains. We employed intracerebral microdialysis, FST and selective antagonists of 5-HT1A and 5-HT2C receptors to investigate whether enhancing the increase in extracellular 5-HT reinstated the anti-immobility effect of citalopram in the FST. WAY 100635 (0.3 mg/kg s.c.) or SB 242084 (1 mg/kg s.c.), respectively a selective 5-HT1A and 5-HT2C receptor antagonist, raised the effect of citalopram (5 mg/kg) on extracellular 5-HT in the medial prefrontal cortex of DBA/2N mice (citalopram alone 5.2+/-0.3 fmol/20 microl, WAY 100635+citalopram 9.9+/-2.1 fmol/20 microl, SB 242084+ citalopram 7.6+/-1.0 fmol/20 microl) to the level reached in 'responder' mice given citalopram alone. The 5-HT receptor antagonists had no effect on the citalopram-induced increase in extracellular 5-HT in the dorsal hippocampus. The combination of citalopram with WAY 100635 or SB 242084 significantly reduced immobility time in DBA/2N mice that otherwise did not respond to either drug singly. Brain levels of citalopram in mice given citalopram alone or with 5-HT antagonists did not significantly differ. The results confirm that impaired 5-HT transmission accounts for the lack of effect of citalopram in the FST and suggest that enhancing the effect of SSRIs on extracellular 5-HT, through selective blockade of 5-HT1A and 5-HT2C receptors, could be a useful strategy to restore the response in treatment-resistant depression.

Enhanced Fluorescent Siderophore Biosynthesis and Loss of Phenazine-1-Carboxamide in Phenotypic Variant of Pseudomonas chlororaphis HT66.

PubMed

Liu, Yang; Wang, Zheng; Bilal, Muhammad; Hu, Hongbo; Wang, Wei; Huang, Xianqing; Peng, Huasong; Zhang, Xuehong

2018-01-01

Pseudomonas chlororaphis HT66 is a plant-beneficial bacterium that exhibits wider antagonistic spectrum against a variety of plant pathogenic fungi due to its main secondary metabolite, i.e., phenazine-1-carboxamide (PCN). In the present study, a spontaneous phenotypic variant designated as HT66-FLUO was isolated from the fermentation process of wild-type HT66 strain. The newly isolated phenotypic variant was morphologically distinct from the wild-type strain such as larger cell size, semi-transparent, non-production of PCN (Green or yellow crystals) and enhanced fluorescence under UV light. The whole-genome, RNA-sequencing, and phenotypic assays were performed to identify the reason of phenotypic variation in HT66-FLUO as compared to the HT66. Transcriptomic analysis revealed that 1,418 genes, representing approximately 22% of the 6393 open reading frames (ORFs) had undergone substantial reprogramming of gene expression in the HT66-FLUO. The whole-genome sequence indicated no gene alteration in HT66-FLUO as compared to HT66 according to the known reference sequence. The levels of global regulatory factor gacA and gacS expression were not significantly different between HT66 and HT66-FLUO. It was observed that overexpressing gacS rather than gacA in HT66-FLUO can recover switching of the variant to HT66. The β-galactosidase ( LacZ ) activity and qRT-PCR results indicate the downregulated expression of rsmX, rsmY , and rsmZ in HT66-FLUO as compared to HT66. Overexpressing three small RNAs in HT66-FLUO can revert switching of colony phenotype toward wild-type HT66 up to a certain degree, restore partial PCN production and reduces the fluorescent siderophores yield. However, the origin of the spontaneous phenotypic variant was difficult to be determined. In conclusion, this study helps to understand the gene regulatory effect in the spontaneous phenotypic variant.

Enhanced Fluorescent Siderophore Biosynthesis and Loss of Phenazine-1-Carboxamide in Phenotypic Variant of Pseudomonas chlororaphis HT66

PubMed Central

Liu, Yang; Wang, Zheng; Bilal, Muhammad; Hu, Hongbo; Wang, Wei; Huang, Xianqing; Peng, Huasong; Zhang, Xuehong

2018-01-01

Pseudomonas chlororaphis HT66 is a plant-beneficial bacterium that exhibits wider antagonistic spectrum against a variety of plant pathogenic fungi due to its main secondary metabolite, i.e., phenazine-1-carboxamide (PCN). In the present study, a spontaneous phenotypic variant designated as HT66-FLUO was isolated from the fermentation process of wild-type HT66 strain. The newly isolated phenotypic variant was morphologically distinct from the wild-type strain such as larger cell size, semi-transparent, non-production of PCN (Green or yellow crystals) and enhanced fluorescence under UV light. The whole-genome, RNA-sequencing, and phenotypic assays were performed to identify the reason of phenotypic variation in HT66-FLUO as compared to the HT66. Transcriptomic analysis revealed that 1,418 genes, representing approximately 22% of the 6393 open reading frames (ORFs) had undergone substantial reprogramming of gene expression in the HT66-FLUO. The whole-genome sequence indicated no gene alteration in HT66-FLUO as compared to HT66 according to the known reference sequence. The levels of global regulatory factor gacA and gacS expression were not significantly different between HT66 and HT66-FLUO. It was observed that overexpressing gacS rather than gacA in HT66-FLUO can recover switching of the variant to HT66. The β-galactosidase (LacZ) activity and qRT-PCR results indicate the downregulated expression of rsmX, rsmY, and rsmZ in HT66-FLUO as compared to HT66. Overexpressing three small RNAs in HT66-FLUO can revert switching of colony phenotype toward wild-type HT66 up to a certain degree, restore partial PCN production and reduces the fluorescent siderophores yield. However, the origin of the spontaneous phenotypic variant was difficult to be determined. In conclusion, this study helps to understand the gene regulatory effect in the spontaneous phenotypic variant. PMID:29740409

Serotonin and stress: protective or malevolent actions in the biobehavioral response to repeated trauma?

PubMed

Harvey, Brian H; Naciti, Carla; Brand, Linda; Stein, Dan J

2004-12-01

Structural hippocampus and prefrontal cortex changes occur in patients with posttraumatic stress disorder (PTSD) that appears correlated with cognitive dysfunction. In these brain regions, serotonin (5HT) plays a prominent role in symptom presentation and treatment of PTSD. However, 5HT is both anxiogenic and anxiolytic, and while 5HT reuptake inhibitors are effective in treatment, the role of 5HT in the development of PTSD remains uncertain. Using a model of repeated trauma in rats, we observed significant spatial memory impairment together with significantly increased 5HT(1A) receptor density (B(max)), decreased 5HT(1A) receptor affinity (K(d)), and significantly increased 5HT(2A) receptor affinity on day 7 poststress. The serotonergic agent fluoxetine (FLX; 10 mg/kg/d ip) administered 1 week before stress and continuing throughout the stress procedure, but not the 5HT depleter p-chloro-phenylalanine (PCPA; 300/100/50 mg/kg/d ip), prevented stress-induced cognitive dysfunction. PCPA, however, reversed stress-induced hippocampal 5HT(1A) receptor affinity changes, with FLX narrowly missing significance. Neither drug reversed stress effects on 5HT(2A) receptor affinity. Thus, 5HT plays an important part in the cognitive-behavioral changes evoked by repeated trauma. That raised 5HT activity may mediate hippocampal 5HT(1A) receptor changes evoked by stress suggests a bidirectional role for 5HT in the development of PTSD.

Use of compounded hormone therapy in the United States: report of The North American Menopause Society Survey.

PubMed

Gass, Margery L S; Stuenkel, Cynthia A; Utian, Wulf H; LaCroix, Andrea; Liu, James H; Shifren, Jan L

2015-12-01

A national survey was conducted to determine the extent of use of compounded hormone therapy (C-HT) and to characterize the differences between C-HT users and users of hormone therapy approved by the US Food and Drug Administration (FDA-HT users). This Internet survey enrolled 3,725 women aged 40 to 84 years who were postmenopausal or experiencing the menopause transition. The sample was weighted slightly by age, region, education, and race to reflect population attributes based on US Census data. Overall, 9% of women were current users of HT, and 28% of all respondents were ever-users of HT. C-HT users represented 31% of ever-users of HT, 35% of current users of HT, and 41% of ever-users aged 40 to 49 years. Approximately 13% of ever-users indicated current or past use of testosterone. The most cited reason for using HT was vasomotor symptoms (∼70%). Nonapproved indications for using HT were selected more often by C-HT users. There were four reports of endometrial cancer among the 326 C-HT users compared with none reported among the 738 FDA-HT users. Significance was not determined because of small numbers. This survey indicates substantial use of C-HT across the country and the possibility of higher rates of endometrial side effects with such products. There is a need for standardized data collection on the extent of use of compounded hormones and their potential risks.

Arrhythmogenic Substrates in Sleep-Disordered Breathing with Arterial Hypertension.

PubMed

Amino, Mari; Yoshioka, Koichiro; Aoki, Takuya; Yamamoto, Manabu; Iga, Tomiei; Kanda, Shigetaka; Abe, Tadashi; Inokuchi, Sadaki; Tanabe, Teruhisa; Ikari, Yuji

2016-04-01

Sleep-disordered breathing (SDB) is highly associated with arterial hypertension (HT). Sympathetic hypertonia increases the risk of sudden cardiac death in patients with sleep apnea. This study aims to noninvasively investigate the electrophysiological features in SDB patients with and without arterial HT. Fifty-three patients with SDB were classified into two groups: SDB group and SDB + HT group. Twenty subjects with arterial HT were enrolled as controls (HT group). To assess arrhythmogenic vulnerability, high-resolution 24-hour ambulatory electrocardiograms were obtained for analyzing continuous late potential (LP), T-wave amplitude variability (TAV), and heart rate variability (HRV). A higher incidence of positive LP was observed in the SDB + HT (85%) group than that observed in the SDB (50%) and HT (20%) groups (P < 0.01). TAV was highest in the SDB + HT group (78 μV) compared with the SDB (61 μV) and HT groups (42 μV; P < 0.01). Positive LP and TAV values were observed at night in the SDB + HT and SDB groups. The low-frequency/high-frequency of the HRV analysis was highest in the SDB + HT (4.7) group compared with that in the SDB (2.9) and HT (2.9) groups (P = 0.01). Nocturnal LP, TAV, and HRV examinations were useful to investigate arrhythmogenesis. SDB patients with arterial HT showed a high prevalence of depolarization and repolarization abnormalities and relative sympathetic hyperactivity. This suggests that an electrophysiological instability is more prevalent in SDB patients with arterial HT. © 2015 Wiley Periodicals, Inc.

Robust presynaptic serotonin 5-HT1B receptor inhibition of the striatonigral output and its sensitization by chronic fluoxetine treatment

PubMed Central

Ding, Shengyuan; Li, Li

2015-01-01

The striatonigral projection is a striatal output pathway critical to motor control, cognition, and emotion regulation. Its axon terminals in the substantia nigra pars reticulata (SNr) express a high level of serotonin (5-HT) type 1B receptors (5-HT1BRs), whereas the SNr also receives an intense 5-HT innervation that expresses 5-HT transporters, providing an anatomic substrate for 5-HT and selective 5-HT reuptake inhibitor (SSRI)-based antidepressant treatment to regulate the striatonigral output. In this article we show that 5-HT, by activating presynaptic 5-HT1BRs on the striatonigral axon terminals, potently inhibited the striatonigral GABA output, as reflected in the reduction of the striatonigral inhibitory postsynaptic currents in SNr GABA neurons. Functionally, 5-HT1BR agonism reduced the striatonigral GABA output-induced pause of the spontaneous high-frequency firing in SNr GABA neurons. Equally important, chronic SSRI treatment with fluoxetine enhanced this presynaptic 5-HT1BR-mediated pause reduction in SNr GABA neurons. Taken together, these results indicate that activation of the 5-HT1BRs on the striatonigral axon terminals can limit the motor-promoting GABA output. Furthermore, in contrast to the desensitization of 5-HT1 autoreceptors, chronic SSRI-based antidepressant treatment sensitizes this presynaptic 5-HT1BR-mediated effect in the SNr, a novel cellular mechanism that alters the striatonigral information transfer, potentially contributing to the behavioral effects of chronic SSRI treatment. PMID:25787955

Energy expenditure prediction via a footwear-based physical activity monitor: Accuracy and comparison to other devices

NASA Astrophysics Data System (ADS)

Dannecker, Kathryn

2011-12-01

Accurately estimating free-living energy expenditure (EE) is important for monitoring or altering energy balance and quantifying levels of physical activity. The use of accelerometers to monitor physical activity and estimate physical activity EE is common in both research and consumer settings. Recent advances in physical activity monitors include the ability to identify specific activities (e.g. stand vs. walk) which has resulted in improved EE estimation accuracy. Recently, a multi-sensor footwear-based physical activity monitor that is capable of achieving 98% activity identification accuracy has been developed. However, no study has compared the EE estimation accuracy for this monitor and compared this accuracy to other similar devices. Purpose . To determine the accuracy of physical activity EE estimation of a footwear-based physical activity monitor that uses an embedded accelerometer and insole pressure sensors and to compare this accuracy against a variety of research and consumer physical activity monitors. Methods. Nineteen adults (10 male, 9 female), mass: 75.14 (17.1) kg, BMI: 25.07(4.6) kg/m2 (mean (SD)), completed a four hour stay in a room calorimeter. Participants wore a footwear-based physical activity monitor, as well as three physical activity monitoring devices used in research: hip-mounted Actical and Actigraph accelerometers and a multi-accelerometer IDEEA device with sensors secured to the limb and chest. In addition, participants wore two consumer devices: Philips DirectLife and Fitbit. Each individual performed a series of randomly assigned and ordered postures/activities including lying, sitting (quietly and using a computer), standing, walking, stepping, cycling, sweeping, as well as a period of self-selected activities. We developed branched (i.e. activity specific) linear regression models to estimate EE from the footwear-based device, and we used the manufacturer's software to estimate EE for all other devices. Results. The shoe-based device was not significantly different than the mean measured EE (476(20) vs. 478(18) kcal) (Mean(SE)), respectively, and had the lowest root mean square error (RMSE) by two-fold (29.6 kcal (6.19%)). The IDEEA (445(23) kcal) and DirecLlife (449(13) kcal) estimates of EE were also not different than the measured EE. The Actigraph, Fitbit and Actical devices significantly underestimated EE (339 (19) kcal, 363(18) kcal and 383(17) kcal, respectively (p<.05)). Root mean square errors were 62.1 kcal (14%), 88.2 kcal(18%), 122.2 kcal (27%), 130.1 kcal (26%), and 143.2 kcal (28%) for DirectLife, IDEEA, Actigraph, Actical and Fitbit respectively. Conclusions. The shoe based physical activity monitor was able to accurately estimate EE. The research and consumer physical activity monitors tested have a wide range of accuracy when estimating EE. Given the similar hardware of these devices, these results suggest that the algorithms used to estimate EE are primarily responsible for their accuracy, particularly the ability of the shoe-based device to estimate EE based on activity classifications.

Examination of the Use of Healing Touch by Registered Nurses in the Acute Care Setting.

PubMed

Anderson, Joel G; Friesen, Mary Ann; Swengros, Diane; Herbst, Anna; Mangione, Lucrezia

2017-03-01

Acute care nursing is currently undergoing unprecedented change, with health systems becoming more open to nonpharmacological approaches to patient care. Healing Touch (HT) may be a valuable intervention for acute care patients. Research has shown that HT helps both the patient and the caregiver; however, no study to date has examined the impact that the education of nurses in and their use of HT have on daily care delivery in the acute care setting. The purpose of the current qualitative study was to examine the use of HT by registered nurses in the acute care setting during their delivery of patient care, as well as the impact of education in and use of HT on the nurses themselves. Five themes were identified: (1) use of HT techniques, processes, and sequence; (2) outcomes related to HT; (3) integration of HT into acute care nursing practice; (4) perceptions of HT, from skepticism to openness; and (5) transformation through HT. Education in HT and delivery of this modality by nurses in the acute care setting provide nurses with a transformative tool to improve patient outcomes.

[Hometreatment- an effective alternative to inpatient treatment in child and adolescent psychiatry?].

PubMed

Boege, Isabel; Schepker, Renate; Herpertz-Dahlmann, Beate; Vloet, Timo D

2015-11-01

In many countries hometreatment (HT) offers a cost-effective alternative to hospitalization for children and adolescents with mental health problems requiring intensive mental healthcare. However, the database on HT varies as HT may refer to different models and settings of intensive outpatient treatment. In Germany HT is not used routinely in mental healthcare in child and adolescent psychiatry, therefore the data on HT in Germany, especially in child and adolescent psychiatry, are scarce although funding for studies investigating the effectiveness of HT is available. This review represents a comprehensive search in electronic databases (1980-2014) of literature on HT. It provides as well an overview of the underlying concepts of and the present evidence for HT. In addition, the evidence base on HT for specific child and adolescent mental health disorders is reviewed. Future prospects for the development of HT in Germany facing the upcoming change in health service commissioning (PEPP = «pauschalierendes Entgeltsystem in Psychiatric und Psychosomatik>) are discussed, as HT in child and adolescent psychiatry, when accurately indicated, can be a valid alternative to inpatient treatment.

Sparse Representation of Multimodality Sensing Databases for Data Mining and Retrieval

DTIC Science & Technology

2015-04-09

Savarese. Estimating the Aspect Layout of Object Categories, EEE Conference on Computer Vision and Pattern Recognition (CVPR). 19-JUN-12...Time Equivalent (FTE) support provided by this agreement, and total for each category): (a) Graduate Students Liang Mei, 50% FTE, EE : systems...PhD candidate Min Sun, 50% FTE, EE : systems, PhD candidate Yu Xiang, 50% FTE, EE : systems, PhD candidate Dae Yon Jung, 50% FTE, EE : systems, PhD

Pilot Fullerton in ejection escape suit (EES) on aft flight deck

NASA Image and Video Library

1982-03-30

STS003-31-290 (30 March 1982) --- Astronaut Gordon Fullerton, STS-3 pilot, wearing communications kit assembly (ASSY) mini-headset (HDST) and ejection escape suit (EES), holds flexible hose attached to his EES vent hose fitting and second hose for commander's EES while behind pilots ejection seat (S2) seat back on the aft flight deck. Forward flight deck control panels are visible in the background. Photo credit: NASA

Highly enantioselective production of (R)-halohydrins with whole cells of Rhodotorula rubra KCh 82 culture.

PubMed

Janeczko, Tomasz; Dymarska, Monika; Kostrzewa-Susłow, Edyta

2014-12-04

Biotransformation of ten α-haloacetophenones in the growing culture of the strain Rhodotorula rubra KCh 82 has been carried out. Nine of the substrates underwent an effective enantioselective reduction to the respective (R)-alcohols according to Prelog's rule, with the exception of 2-chloro-1,2-diphenylethan-1-one that was not transformed by this strain. The expected reduction proceeded without dehalogenation, leading to the respective (R)-halohydrins in high yields. The use of this biocatalyst yielded (R)-2-bromo-1-phenyl-ethan-1-ol (enantiomeric excess (ee) = 97%) and its derivatives: 4'-Bromo- (ee = 99%); 4'-Chloro- (ee > 99%); 4'-Methoxy- (ee = 96%); 3'-Methoxy- (ee = 93%); 2'-Methoxy- (ee = 98%). There were also obtained and characterized 2,4'-dichloro-, 2,2',4'-trichloro- and 2-chloro-4'-fluoro-phenyetan-1-ol with >99% of enantiomeric excesses.

Highly Enantioselective Production of (R)-Halohydrins with Whole Cells of Rhodotorula rubra KCh 82 Culture

PubMed Central

Janeczko, Tomasz; Dymarska, Monika; Kostrzewa-Susłow, Edyta

2014-01-01

Biotransformation of ten α-haloacetophenones in the growing culture of the strain Rhodotorula rubra KCh 82 has been carried out. Nine of the substrates underwent an effective enantioselective reduction to the respective (R)-alcohols according to Prelog’s rule, with the exception of 2-chloro-1,2-diphenylethan-1-one that was not transformed by this strain. The expected reduction proceeded without dehalogenation, leading to the respective (R)-halohydrins in high yields. The use of this biocatalyst yielded (R)-2-bromo-1-phenyl-ethan-1-ol (enantiomeric excess (ee) = 97%) and its derivatives: 4'-Bromo- (ee = 99%); 4'-Chloro- (ee > 99%); 4'-Methoxy- (ee = 96%); 3'-Methoxy- (ee = 93%); 2'-Methoxy- (ee = 98%). There were also obtained and characterized 2,4'-dichloro-, 2,2',4'-trichloro- and 2-chloro-4'-fluoro-phenyetan-1-ol with >99% of enantiomeric excesses. PMID:25486054

Serotonin gating of cortical and thalamic glutamate inputs onto principal neurons of the basolateral amygdala.

PubMed

Guo, Ji-Dong; O'Flaherty, Brendan M; Rainnie, Donald G

2017-11-01

The basolateral amygdala (BLA) is a key site for crossmodal association of sensory stimuli and an important relay in the neural circuitry of emotion. Indeed, the BLA receives substantial glutamatergic inputs from multiple brain regions including the prefrontal cortex and thalamic nuclei. Modulation of glutamatergic transmission in the BLA regulates stress- and anxiety-related behaviors. Serotonin (5-HT) also plays an important role in regulating stress-related behavior through activation of both pre- and postsynaptic 5-HT receptors. Multiple 5-HT receptors are expressed in the BLA, where 5-HT has been reported to modulate glutamatergic transmission. However, the 5-HT receptor subtype mediating this effect is not yet clear. The aim of this study was to use patch-clamp recordings from BLA neurons in an ex vivo slice preparation to examine 1) the effect of 5-HT on extrinsic sensory inputs, and 2) to determine if any pathway specificity exists in 5-HT regulation of glutamatergic transmission. Two independent input pathways into the BLA were stimulated: the external capsule to mimic cortical input, and the internal capsule to mimic thalamic input. Bath application of 5-HT reversibly reduced the amplitude of evoked excitatory postsynaptic currents (eEPSCs) induced by stimulation of both pathways. The decrease was associated with an increase in the paired-pulse ratio and coefficient of variation of eEPSC amplitude, suggesting 5-HT acts presynaptically. Moreover, the effect of 5-HT in both pathways was mimicked by the selective 5-HT 1B receptor agonist CP93129, but not by the 5-HT 1A receptor agonist 8-OH DPAT. Similarly the effect of exogenous 5-HT was blocked by the 5-HT 1B receptor antagonist GR55562, but not affected by the 5-HT 1A receptor antagonist WAY 100635 or the 5-HT 2 receptor antagonists pirenperone and MDL 100907. Together these data suggest 5-HT gates cortical and thalamic glutamatergic inputs into the BLA by activating presynaptic 5-HT 1B receptors. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of 5-HT(1A) receptors in learning and memory.

PubMed

Ogren, Sven Ove; Eriksson, Therese M; Elvander-Tottie, Elin; D'Addario, Claudio; Ekström, Joanna C; Svenningsson, Per; Meister, Björn; Kehr, Jan; Stiedl, Oliver

2008-12-16

The ascending serotonin (5-HT) neurons innervate the cerebral cortex, hippocampus, septum and amygdala, all representing brain regions associated with various domains of cognition. The 5-HT innervation is diffuse and extensively arborized with few synaptic contacts, which indicates that 5-HT can affect a large number of neurons in a paracrine mode. Serotonin signaling is mediated by 14 receptor subtypes with different functional and transductional properties. The 5-HT(1A) subtype is of particular interest, since it is one of the main mediators of the action of 5-HT. Moreover, the 5-HT(1A) receptor regulates the activity of 5-HT neurons via autoreceptors, and it regulates the function of several neurotransmitter systems via postsynaptic receptors (heteroreceptors). This review assesses the pharmacological and genetic evidence that implicates the 5-HT(1A) receptor in learning and memory. The 5-HT(1A) receptors are in the position to influence the activity of glutamatergic, cholinergic and possibly GABAergic neurons in the cerebral cortex, hippocampus and in the septohippocampal projection, thereby affecting declarative and non-declarative memory functions. Moreover, the 5-HT(1A) receptor regulates several transduction mechanisms such as kinases and immediate early genes implicated in memory formation. Based on studies in rodents the stimulation of 5-HT(1A) receptors generally produces learning impairments by interfering with memory-encoding mechanisms. In contrast, antagonists of 5-HT(1A) receptors facilitate certain types of memory by enhancing hippocampal/cortical cholinergic and/or glutamatergic neurotransmission. Some data also support a potential role for the 5-HT(1A) receptor in memory consolidation. Available results also implicate the 5-HT(1A) receptor in the retrieval of aversive or emotional memories, supporting an involvement in reconsolidation. The contribution of 5-HT(1A) receptors in cognitive impairments in various psychiatric disorders is still unclear. However, there is evidence that 5-HT(1A) receptors may play differential roles in normal brain function and in psychopathological states. Taken together, the evidence indicates that the 5-HT(1A) receptor is a target for novel therapeutic advances in several neuropsychiatric disorders characterized by various cognitive deficits.

5-HT2C Receptor Desensitization Moderates Anxiety in 5-HTT Deficient Mice: From Behavioral to Cellular Evidence

PubMed Central

Martin, Cédric BP; Martin, Vincent S.; Trigo, José M.; Chevarin, Caroline; Maldonado, Rafael; Fink, Latham H.; Cunningham, Kathryn A.; Hamon, Michel; Lanfumey, Laurence

2015-01-01

Background: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas. Methods: Mice lacking the 5-HT reuptake carrier (5-HTT-/-) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR–induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos–induced expression) levels. Results: Although 5-HTT-/- mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR–mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR–mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT-/- mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT-/- mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR–like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT-/- mutants. Conclusions: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT-/- mice. PMID:25522398

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment.

PubMed

Palacios, Jose M; Pazos, Angel; Hoyer, Daniel

2017-05-01

This paper is a personal account on the discovery and characterization of the 5-HT 2C receptor (first known as the 5-HT 1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT 2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT 1C R, the 5-HT 2C R was discovered while studying the pharmacological features and the distribution of [ 3 H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [ 3 H]mesulergine-labelling to the rat choroid plexus. [ 3 H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT 2 binding, the new binding site was called 5-HT 1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT 1C R (later named 5-HT 2C ) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT 2C R is a GPCR, with a very complex gene structure. It constitutes a rarity in the GPCR family: many 5-HT 2C R variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT 2C R splice variants. Intense research led to therapeutically active 5-HT 2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5-HT 2C R antagonists/inverse agonists. Agomelatine, a 5-HT 2C R antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT 2C R is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT 2C R antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT 2C R may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT 2C R agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT 2C R ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT 2C R is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain.

Modulatory Action by the Serotonergic System: Behavior and Neurophysiology in Drosophila melanogaster

PubMed Central

Majeed, Zana R.; Abdeljaber, Esraa; Soveland, Robin; Cornwell, Kristin; Bankemper, Aubrey; Koch, Felicitas; Cooper, Robin L.

2016-01-01

Serotonin modulates various physiological processes and behaviors. This study investigates the role of 5-HT in locomotion and feeding behaviors as well as in modulation of sensory-motor circuits. The 5-HT biosynthesis was dysregulated by feeding Drosophila larvae 5-HT, a 5-HT precursor, or an inhibitor of tryptophan hydroxylase during early stages of development. The effects of feeding fluoxetine, a selective serotonin reuptake inhibitor, during early second instars were also examined. 5-HT receptor subtypes were manipulated using RNA interference mediated knockdown and 5-HT receptor insertional mutations. Moreover, synaptic transmission at 5-HT neurons was blocked or enhanced in both larvae and adult flies. The results demonstrate that disruption of components within the 5-HT system significantly impairs locomotion and feeding behaviors in larvae. Acute activation of 5-HT neurons disrupts normal locomotion activity in adult flies. To determine which 5-HT receptor subtype modulates the evoked sensory-motor activity, pharmacological agents were used. In addition, the activity of 5-HT neurons was enhanced by expressing and activating TrpA1 channels or channelrhodopsin-2 while recording the evoked excitatory postsynaptic potentials (EPSPs) in muscle fibers. 5-HT2 receptor activation mediates a modulatory role in a sensory-motor circuit, and the activation of 5-HT neurons can suppress the neural circuit activity, while fluoxetine can significantly decrease the sensory-motor activity. PMID:26989517

Serotonin inputs to the dorsal BNST modulate anxiety in a 5-HT1A receptor-dependent manner.

PubMed

Garcia-Garcia, A L; Canetta, S; Stujenske, J M; Burghardt, N S; Ansorge, M S; Dranovsky, A; Leonardo, E D

2017-08-01

Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in humans and rodents. While the dorsal part of the BNST (dBNST) receives dense 5-HT innervation, whether and how 5-HT in the dBNST normally modulates anxiety remains unclear. Using optogenetics, we demonstrate that activation of 5-HT terminals in the dBNST reduces anxiety in a highly anxiogenic environment. Further analysis revealed that optogenetic inhibition of 5-HT inputs into the dBNST increases anxiety in a less anxiogenic environment. We found that 5-HT predominantly hyperpolarizes dBNST neurons, reducing their activity in a manner that can be blocked by a 5-HT 1A antagonist. Finally, we demonstrate that activation of 5-HT 1A receptors in the dBNST is necessary for the anxiolytic effect observed following optogenetic stimulation of 5-HT inputs into the dBNST. These data reveal that 5-HT release in the dBNST modulates anxiety-like behavior via 5-HT 1A receptors under naturalistic conditions.Molecular Psychiatry advance online publication, 1 August 2017; doi:10.1038/mp.2017.165.

Histological alternation and vitellogenin induction in adult rare minnow (Gobiocypris rarus) after exposure to ethynylestradiol and nonylphenol

USGS Publications Warehouse

Zha, J.; Wang, Z.; Wang, N.; Ingersoll, C.

2007-01-01

Adult rare minnow (Gobiocypris rarus) were exposed to 0, 1, 5, and 25 ng/l (nominal concentrations) of 17α-ethynylestradiol (EE2) and 3, 10, and 30 μg/l (nominal concentrations) of 4-nonylphenol (NP) under flow-through conditions for a period of 28 d. Low mortality was observed at 5 and 25 ng/l EE2 and the growth of fish reduced significantly at 25 ng/l EE2 compared to controls. However, the gonadosomatic indices (GSI) of male fish were significantly higher in 1 ng/l EE2 treatments and in 10 and 30 μg/l NP treatments (p < 0.05). Renal somatic indices (RSI) of male fish in EE2 treatments were significantly higher than those in controls (p < 0.05). In contrast, significantly decreased GSI and RSI of female fish could only be observed in 5 and 25 ng/l EE2treatments (p < 0.05). Hepatosomatic indices (HSI) of male fish were significantly higher in 25 ng/l EE2 treatments. However, significantly increased of HSI of female fish could only be observed in 1 ng/l EE2 treatments. Plasma vitellogenin (VTG) induction could be observed in males after exposed to different concentrations of EE2 and NP, and plasma VTG concentrations in females exposed to 5 and 25 ng/l EE2 were also significantly higher than in controls (p < 0.05). At level higher than 5 ng/l EE2 or 30 μg/l NP, hepatic tissue and renal tissue impairment of males could be observed. The pathological male liver was associated with a hypertrophy of hepatocytes and damages to cellar structure and accumulated eosinophilic material. Renal tissue showed different pathological effects which was reflected by accumulated eosinophilic material, hemorrhages within the kidney tubules and hypertrophy of the tubular epithelia. Also at these levels of exposure, feminization of male fish could be noticed and parts of males manifested the testis-ova phenomenon. Ovaries of female rare minnow in 25 ng/l EE2 treatment group were degenerated. Therefore when exposed to EE2 and NP even at environmental observed concentrations, adverse effects could occur in the reproductive system of adult fishes. The observed hepatic tissue and renal tissue impairment should be due to the induction and accumulation of VTG in organs, especially in males.

Extensibility effect of poly(3-hexylthiophene) on the glucose sensing performance of mixed poly(3-hexylthiophene)/octadecylamine/glucose oxidase Langmuir-Blodgett films.

PubMed

Wang, Ke-Hsuan; Hsu, Wen-Ping; Chen, Liang-Huei; Lin, Wei-Don; Lee, Yuh-Lang

2017-07-01

Poly(3-hexylthiophene) (P3HT) is utilized as a material to enhance the glucose sensing performance of glucose oxidase (GOx) Langmuir-Blodgett (LB) films. To enhance the extensibility and homogeneity of the P3HT in the LB films, octadecylamine (ODA) is introduced. The characteristics of the mixed P3HT/ODA Langmuir monolayers are investigated first and then, utilized as template layers to adsorb GOx from the subphase, preparing P3HT/ODA/GOx Langmuir-Blodgett films for glucose sensing. The results show that P3HT molecules tend to aggregate at the air/liquid interface and, furthermore, the P3HT monolayer has a weak ability to adsorb GOx from the subphase. By using mixed P3HT/ODA monolayer, the presence of ODA not only inhibits the aggregation of P3HT, but also increases the adsorption ability of the monolayer to GOx. The extensibility of P3HT and the homogeneity of the P3HT/ODA monolayers are closely related to the concentration of P3HT/ODA stock solutions. On the glucose sensing experiments, the performance of the P3HT/ODA/GOx LB film is greatly improved due to the presence of P3HT and, furthermore, the sensibility increases with increasing extensibility of P3HT molecules. The best sensitivity achieved for the P3HT/ODA/GOx film is 5.4μAmM -1 cm -2 which is over two times the value obtained by the ODA/GOx film (2.3μAmM -1 cm -2 ). Copyright © 2017 Elsevier B.V. All rights reserved.

Serotonergic regulation of distention-induced ATP release from the urothelium.

PubMed

Matsumoto-Miyai, Kazumasa; Yamada, Erika; Shinzawa, Eriko; Koyama, Yoshihisa; Shimada, Shoichi; Yoshizumi, Masaru; Kawatani, Masahito

2016-04-01

Serotonin [5-hydroxytryptamine (5-HT)] is involved in both motor and sensory functions in hollow organs, especially in the gastrointestinal tract. However, the involvement of 5-HT in visceral sensation of the urinary bladder remains unknown. Because distention-induced ATP release from the urothelium plays an essential role in visceral sensation of the urinary bladder, we investigated the regulation of urothelial ATP release by the 5-HT signaling system. RT-PCR and immunohistochemical analyses of the urothelium revealed specific expression of 5-HT 1D and 5-HT 4 receptors. The addition of 5-HT did not affect urothelial ATP release without bladder distention, but it significantly reduced distention-induced ATP release by physiological pressure during urine storage (5 cmH 2 O). The inhibitory effect of 5-HT on distention-elicited ATP release was blocked by preincubation with the 5-HT 1B/1D antagonist GR-127935 but not by the 5-HT 4 antagonist SB-204070. mRNA encoding tryptophan hydroxylase 1 was detected in the urinary bladder by nested RT-PCR amplification, and l-tryptophan or the selective serotonin reuptake inhibitor citalopram also inhibited ATP release, indicating that 5-HT is endogenously synthesized and released in the urinary bladder. The addition of GR-127935 significantly enhanced the distention-elicited ATP release 40 min after distention, whereas SB-204070 reduced the amount of ATP release 20 min after distention. These data suggest that 5-HT 4 facilitates the distention-induced ATP release at an earlier stage, whereas 5-HT 1D inhibits ATP release at a later stage. The net inhibitory effect of 5-HT indicates that the action of 5-HT on the urothelium is mediated predominantly by 5-HT 1D . Copyright © 2016 the American Physiological Society.

5-HT1D receptor inhibits renal sympathetic neurotransmission by nitric oxide pathway in anesthetized rats.

PubMed

García-Pedraza, José-Ángel; García, Mónica; Martín, María-Luisa; Morán, Asunción

2015-09-01

Although serotonin has been shown to inhibit peripheral sympathetic outflow, serotonin regulation on renal sympathetic outflow has not yet been elucidated. This study investigated which 5-HT receptor subtypes are involved. Wistar rats were anesthetized (sodium pentobarbital; 60mg/kg, i.p.), and prepared for in situ autoperfused rat kidney, which allows continuous measurement of systemic blood pressure (SBP), heart rate (HR) and renal perfusion pressure (PP). Electrical stimulation of renal sympathetic nerves resulted in frequency-dependent increases in PP (18.3±1.0, 43.7±2.7 and 66.7±4.0 for 2, 4 and 6Hz, respectively), without altering SBP or HR. 5-HT, 5-carboxamidotryptamine (5-HT1/7 agonist) (0.00000125-0.1μg/kg each) or l-694,247 (5-HT1D agonist; 0.0125μg/kg) i.a. bolus inhibited vasopressor responses by renal nerve electrical stimulation, unlike i.a. bolus of agonists α-methyl-5-HT (5-HT2), 1-PBG (5-HT3), cisapride (5-HT4), AS-19 (5-HT7), CGS-12066B (5-HT1B) or 8-OH-DPAT (5-HT1A) (0.0125μg/kg each). The effect of l-694,247 did not affect the exogenous norepinephrine-induced vasoconstrictions, whereas was abolished by antagonist LY310762 (5-HT1D; 1mg/kg) or l-NAME (nitric oxide; 10mg/kg), but not by indomethacin (COX1/2; 2mg/kg) or glibenclamide (ATP-dependent K(+) channel; 20mg/kg). These results suggest that 5-HT mechanism-induced inhibition of rat vasopressor renal sympathetic outflow is mainly mediated by prejunctional 5-HT1D receptors via nitric oxide release. Copyright © 2015 Elsevier Inc. All rights reserved.

Freewheel running prevents learned helplessness/behavioral depression: role of dorsal raphe serotonergic neurons.

PubMed

Greenwood, Benjamin N; Foley, Teresa E; Day, Heidi E W; Campisi, Jay; Hammack, Sayamwong H; Campeau, Serge; Maier, Steven F; Fleshner, Monika

2003-04-01

Serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) are implicated in mediating learned helplessness (LH) behaviors, such as poor escape responding and expression of exaggerated conditioned fear, induced by acute exposure to uncontrollable stress. DRN 5-HT neurons are hyperactive during uncontrollable stress, resulting in desensitization of 5-HT type 1A (5-HT1A) inhibitory autoreceptors in the DRN. 5-HT1A autoreceptor downregulation is thought to induce transient sensitization of DRN 5-HT neurons, resulting in excessive 5-HT activity in brain areas that control the expression of learned helplessness behaviors. Habitual physical activity has antidepressant/anxiolytic properties and results in dramatic alterations in physiological stress responses, but the neurochemical mediators of these effects are unknown. The current study determined the effects of 6 weeks of voluntary freewheel running on LH behaviors, uncontrollable stress-induced activity of DRN 5-HT neurons, and basal expression of DRN 5-HT1A autoreceptor mRNA. Freewheel running prevented the shuttle box escape deficit and the exaggerated conditioned fear that is induced by uncontrollable tail shock in sedentary rats. Furthermore, double c-Fos/5-HT immunohistochemistry revealed that physical activity attenuated tail shock-induced activity of 5-HT neurons in the rostral-mid DRN. Six weeks of freewheel running also resulted in a basal increase in 5-HT1A inhibitory autoreceptor mRNA in the rostral-mid DRN. Results suggest that freewheel running prevents behavioral depression/LH and attenuates DRN 5-HT neural activity during uncontrollable stress. An increase in 5-HT1A inhibitory autoreceptor expression may contribute to the attenuation of DRN 5-HT activity and the prevention of LH in physically active rats.

ENHANCED 5-HT1A RECEPTOR-DEPENDENT FEEDBACK CONTROL OVER DORSAL RAPHE SEROTONIN NEURONS IN THE SERT KNOCKOUT MOUSE

PubMed Central

Soiza-Reilly, Mariano; Goodfellow, Nathalie M.; Lambe, Evelyn K.; Commons, Kathryn G.

2014-01-01

5-HT1A receptors are widely expressed in the brain and play a critical role in feedback inhibition of serotonin (5-HT) neurons through multiple mechanisms. Yet, it remains poorly understood how these feedback mechanisms, particularly those involving long-range projections, adapt in mood disorders. Here, we examined several aspects of 5-HT1A receptor function in the 5-HT transporter knockout mouse (SERT-KO), a model of vulnerability to stress and mood disorders. We found that in comparison to wild-type (WT) mice, SERT-KO mice had more passive coping in response to acute swim stress and this was accompanied by hypo-activation of medial prefrontal cortex (mPFC) Fos expression. Both of these effects were reversed by systemically blocking 5-HT1A receptors. Ex-vivo electrophysiological experiments showed that 5-HT exerted greater 5-HT1A-mediated inhibitory effects in the mPFC of SERT-KO mice compared to WT. Since 5-HT1A receptors in the mPFC provide a key feedback regulation of the dorsal raphe nucleus (DRN), we used a disinhibition strategy to examined endogenous feedback control of 5-HT neurons. Blocking 5-HT1A receptors disinhibited several fold more 5-HT neurons in the DRN of SERT-KO than in WT mice, revealing the presence of enhanced feedback inhibition of 5-HT neurons in the SERT-KO. Taken together our results indicate that increased stress sensitivity in the SERT-KO is associated with the enhanced capacity of 5-HT1A receptors to inhibit neurons in the mPFC as well as to exert feedback inhibition of DRN 5-HT neurons. PMID:25261781

Single and Competitive Adsorption of 17α-Ethinylestradiol and Bisphenol A with Estrone, β-Estradiol, and Estriol onto Sediment

PubMed Central

Li, Yu; Zhang, Chen; Li, Shanshan; Zhou, Changzhi; Li, Xiaopeng

2014-01-01

The competitive adsorption of bisphenol A (BPA) and17α-ethinylestradiol (EE2) with different endocrine disrupting compounds (EDCs), such as estrone (E1), β-estradiol (E2), and estriol (E3) was investigated in the water-sediment system. The primary and interaction effects of coexisted EDCs on the adsorption of BPA and EE2 were studied in binary and multiple systems. The adsorption selectivity of sediment at different initial concentrations of EDCs was also considered, based on the distribution coefficient (β). In binary systems, coexisted EDCs exhibited a positive effect on the adsorption of BPA, while E3 showed a negative effect on the adsorption of EE2. In ternary systems, the interaction of E1*E3 and E2*BPA showed a synergistic effect on the sorption of BPA and EE2, respectively. In quaternary systems, the interaction of E1*E2*E3 showed a synergistic effect on the adsorption of both BPA and EE2. In the quinary system, coexisted EDCs all showed an antagonistic effect on the adsorption of BPA and EE2, which indicated that the coexisted EDCs competed for adsorption with BPA and EE2. EDCs in the E2-EE2-BPA system presented a superior selectivity of sediment with β values of 43.48–87.86. The order of sediment selectivity (E1 > EE2 > E2 > E3 > BPA) in binary systems was in agreement with EDCs’ adsorption capacity, which suggested that the adsorption was dominated by partition adsorption. PMID:24608971

Emotional exhaustion in primary care during early implementation of the VA's medical home transformation: Patient-aligned Care Team (PACT).

PubMed

Meredith, Lisa S; Schmidt Hackbarth, Nicole; Darling, Jill; Rodriguez, Hector P; Stockdale, Susan E; Cordasco, Kristina M; Yano, Elizabeth M; Rubenstein, Lisa V

2015-03-01

Transformation of primary care to new patient-centered models requires major changes in healthcare organizations, including interprofessional expectations and organizational policies. Emotional exhaustion (EE) among workers can accompany major organizational change, threatening its success. Yet little guidance exists about the magnitude of associations with EE during primary care transformation. We assessed EE during the initial phase of national primary care transformation in the Veterans Health Administration. Cross-sectional online surveys of primary care clinicians (PCCs) and staff in 23 primary care clinics within 5 healthcare systems in 1 veterans administration administrative region. We used descriptive, bivariate, and multivariable analyses adjusted for clinic membership and weighted for nonresponse. 515 veterans administration employees (191 PCCs and 324 other primary care staff). Outcome is the EE subscale of the Maslach Burnout Inventory. Predictors include clinic characteristics (from administrative data) and self-reported efficacy for change, experiences with transformation, and perspectives about the organization. The overall response rate was 64% (515/811). In total, 53% of PCCs and 43% of staff had high EE. PCCs (vs. other primary care staff), female (vs. male), and non-Latino (vs. Latino) respondents reported higher EE. Respondents reporting higher efficacy for change and participatory decision making had lower EE scores, adjusting for sex and race. Recognition by healthcare organizations of the potential for clinician and staff EE during primary care transformation is critical. Methods for reducing EE by increasing clinician and staff change efficacy and opportunities to participate in decision making should be considered, with attention to PCCs, and women.

Environmental enrichment for a mixed-species nocturnal mammal exhibit.

PubMed

Clark, Fay E; Melfi, Vicky A

2012-01-01

Environmental enrichment (EE) is an integral aspect of modern zoo animal management but, empirical evaluation of it is biased toward species housed in single-species groups. Nocturnal houses, where several nocturnal species are housed together, are particularly overlooked. This study investigated whether three species (nine-banded armadillos, Dasypus novemcinctus; Senegal bush babies, Galago senegalensis; two-toed sloths, Choloepus didactylus) in the nocturnal house at Paignton Zoo Environmental Park, UK could be enriched using food-based and sensory EE. Subjects were an adult male and female of each species. EE was deemed effective if it promoted target species-typical behaviors, behavioral diversity, and increased use of enriched exhibit zones. Results from generalized linear mixed models demonstrated that food-based EE elicited the most positive behavioral effects across species. One set of food-based EEs (Kong®, termite mound and hanging food) presented together was associated with a significant increase in species-typical behaviors, increased behavioral diversity, and increased use of enriched exhibit zones in armadillos and bush babies. Although one type of sensory EE (scented pine cones) increased overall exhibit use in all species, the other (rainforest sounds) was linked to a significant decrease in species-typical behavior in bush babies and sloths. There were no intra or interspecies conflicts over EE, and commensalism occurred between armadillos and bush babies. Our data demonstrate that simple food-based and sensory EE can promote positive behavioral changes in a mixed-species nocturnal mammal exhibit. We suggest that both food and sensory EE presented concurrently will maximize opportunities for naturalistic activity in all species. © 2011 Wiley Periodicals, Inc.

Prenatal and Early Postnatal Environmental Enrichment Reduce Acute Cell Death and Prevent Neurodevelopment and Memory Impairments in Rats Submitted to Neonatal Hypoxia Ischemia.

PubMed

Durán-Carabali, L E; Arcego, D M; Odorcyk, F K; Reichert, L; Cordeiro, J L; Sanches, E F; Freitas, L D; Dalmaz, C; Pagnussat, A; Netto, C A

2018-05-01

Environmental enrichment (EE) is an experimental strategy to attenuate the negative effects of different neurological conditions including neonatal hypoxia ischemia encephalopathy (HIE). The aim of the present study was to investigate the influence of prenatal and early postnatal EE in animals submitted to neonatal HIE model at postnatal day (PND) 3. Wistar rats were housed in EE or standard conditions (SC) during pregnancy and lactation periods. Pups of both sexes were assigned to one of four experimental groups, considering the early environmental conditions and the injury: SC-Sham, SC-HIE, EE-sham, and EE-HIE. The offspring were euthanized at two different time points: 48 h after HIE for biochemical analyses or at PND 67 for histological analyses. Behavioral tests were performed at PND 7, 14, 21, and 60. Offspring from EE mothers had better performance in neurodevelopmental and spatial memory tests when compared to the SC groups. HIE animals showed a reduction of IGF-1 and VEGF in the parietal cortex, but no differences in BDNF and TrkB levels were found. EE-HIE animals showed reduction in cell death, lower astrocyte reactivity, and an increase in AKTp levels in the hippocampus and parietal cortex. In addition, the EE was also able to prevent the hippocampus tissue loss. Altogether, present findings point to the protective potential of the prenatal and early postnatal EE in attenuating molecular and histological damage, as well as the neurodevelopmental impairments and the cognitive deficit, caused by HIE insult at PND 3.

Research across the disciplines: a road map for quality criteria in empirical ethics research.

PubMed

Mertz, Marcel; Inthorn, Julia; Renz, Günter; Rothenberger, Lillian Geza; Salloch, Sabine; Schildmann, Jan; Wöhlke, Sabine; Schicktanz, Silke

2014-03-01

Research in the field of Empirical Ethics (EE) uses a broad variety of empirical methodologies, such as surveys, interviews and observation, developed in disciplines such as sociology, anthropology, and psychology. Whereas these empirical disciplines see themselves as purely descriptive, EE also aims at normative reflection. Currently there is literature about the quality of empirical research in ethics, but little or no reflection on specific methodological aspects that must be considered when conducting interdisciplinary empirical ethics. Furthermore, poor methodology in an EE study results in misleading ethical analyses, evaluations or recommendations. This not only deprives the study of scientific and social value, but also risks ethical misjudgement. While empirical and normative-ethical research projects have quality criteria in their own right, we focus on the specific quality criteria for EE research. We develop a tentative list of quality criteria--a "road map"--tailored to interdisciplinary research in EE, to guide assessments of research quality. These quality criteria fall into the categories of primary research question, theoretical framework and methods, relevance, interdisciplinary research practice and research ethics and scientific ethos. EE research is an important and innovative development in bioethics. However, a lack of standards has led to concerns about and even rejection of EE by various scholars. Our suggested orientation list of criteria, presented in the form of reflective questions, cannot be considered definitive, but serves as a tool to provoke systematic reflection during the planning and composition of an EE research study. These criteria need to be tested in different EE research settings and further refined.

Vascular Endothelial Growth Factor-dependent Spinogenesis Underlies Antidepressant-like Effects of Enriched Environment*

PubMed Central

Huang, Yu-Fei; Yang, Chih-Hao; Huang, Chiung-Chun; Hsu, Kuei-Sen

2012-01-01

Current antidepressant treatments remain limited by poor efficacy and a slow onset of action. Increasing evidence demonstrates that enriched environment (EE) treatment can promote structural and behavioral plasticity in the brain and dampen stress-induced alterations of neuroplasticity. Here, we have examined whether short term exposure to EE is able to produce antidepressant-like effects. Our results show that housing adult mice in an EE cage for 7 days led to antidepressant-like behavioral profiles and a significant increase in the number of dendritic spines in hippocampal CA1 pyramidal neurons. These EE-induced antidepressant-like effects are primarily attributed to increased vascular endothelial growth factor (VEGF) expression through a hypoxia-inducible factor-1α (HIF-1α)-mediated transcriptional mechanism. Blockade of HIF-1α synthesis by lentiviral infection with HIF-1α small hairpin RNAs completely blocked the increase in expression of VEGF and the antidepressant-like effects induced by EE. Moreover, no significant antidepressant-like effects were observed with EE treatment in VEGF receptor 2 (Flk-1) knock-out mice. The increase in HIF-1α expression in the hippocampus induced by EE was associated with a decrease in endogenous levels of microRNA-107 (miR-107). Overexpression of miR-107 in the hippocampus completely blocked EE-induced HIF-1α expression and the antidepressant-like effects. These results support a model in which the down-regulation of miR-107, acting through HIF-1α, mediates VEGF-dependent spinogenesis to underlie the EE-induced antidepressant-like effects. PMID:23074224

Energy expenditure estimate by heart-rate monitor and a portable electromagnetic coils system.

PubMed

Gastinger, Steven; Nicolas, Guillaume; Sorel, Anthony; Sefati, Hamid; Prioux, Jacques

2012-04-01

The aim of this article was to compare 2 portable devices (a heart-rate monitor and an electromagnetic-coil system) that evaluate 2 different physiological parameters--heart rate (HR) and ventilation (VE)--with the objective of estimating energy expenditure (EE). The authors set out to prove that VE is a more pertinent setting than HR to estimate EE during light to moderate activities (sitting and standing at rest and walking at 4, 5, and 6 km/hr). Eleven healthy men were recruited to take part in this study (27.6 ± 5.4 yr, 73.7 ± 9.7 kg). The authors determined the relationships between HR and EE and between VE and EE during light to moderate activities. They compared EE measured by indirect calorimetry (EEREF) with EE estimated by HR monitor (EEHR) and EE estimated by electromagnetic coils (EEMAG) in upright sitting and standing positions and during walking exercises. They compared EEREF with EEHR and EEMAG. The results showed no significant difference between the values of EEREF and EEMAG. However, they showed several significant differences between the values of EEREF and EEHR (for standing at rest and walking at 5 and 6 km/hr). These results showed that the electromagnetic-coil system seems to be more accurate than the HR monitor to estimate EE at rest and during exercise. Taking into consideration these results, it would be interesting to associate the parameters VE and HR to estimate EE. Furthermore, a new version of the electromagnetic-coil device was recently developed and provides the possibility to perform measurement under daily life conditions.

Sorption of carbamazepine, 17α-ethinylestradiol, iopromide and trimethoprim to biomass involves interactions with exocellular polymeric substances.

PubMed

Khunjar, Wendell O; Love, Nancy G

2011-02-01

The sorption of carbamazepine (CBZ), iopromide (IOP), trimethoprim (TMP) and 17α-ethinylestradiol (EE2) was evaluated using four biomass types (pure ammonia oxidizing bacterial culture, two heterotrophic enrichment cultures with varying levels of oxygenase activity, and a full-scale nitrifying activated sludge (NAS) culture). CBZ and IOP did not sorb to the four biomass types. EE2 did not sorb to the pure culture but sorbed significantly to the heterotrophic cultures and NAS. TMP sorbed to the heterotrophic cultures and NAS, and was not evaluated for the pure culture. Three floc characteristics (hydrophobicity, median particle size, organic matter content) correlated moderately well with the EE2 organic matter sorption coefficient (KOM,EE2). Zeta potential did not correlate well with KOM,EE2 but did with KOM,TMP, indicating that TMP sorption is more influenced by electrostatic factors than EE2. Once divalent cation-linked exocellular polymeric substances (EPS) were removed from flocs, EE2 and TMP sorption to the non-EPS (cellular) fraction decreased by approximately 50%. The correlation between KOM,EE2 for the non-EPS cellular fraction deteriorated while the correlation between KOM,TMP improved. EE2 seemed to sorb more strongly to EPS protein whereas TMP sorbed equally to polysaccharide and protein EPS. Attempts to develop predictive models were not successful. Pharmaceuticals that sorbed to biomass samples underwent biodegradation whereas those that did not sorb were not biodegraded, suggesting a relationship between sorption and pharmaceutical biotransformation. Copyright © 2010 Elsevier Ltd. All rights reserved.

Modeling energy expenditure in children and adolescents using quantile regression

PubMed Central

Yang, Yunwen; Adolph, Anne L.; Puyau, Maurice R.; Vohra, Firoz A.; Zakeri, Issa F.

2013-01-01

Advanced mathematical models have the potential to capture the complex metabolic and physiological processes that result in energy expenditure (EE). Study objective is to apply quantile regression (QR) to predict EE and determine quantile-dependent variation in covariate effects in nonobese and obese children. First, QR models will be developed to predict minute-by-minute awake EE at different quantile levels based on heart rate (HR) and physical activity (PA) accelerometry counts, and child characteristics of age, sex, weight, and height. Second, the QR models will be used to evaluate the covariate effects of weight, PA, and HR across the conditional EE distribution. QR and ordinary least squares (OLS) regressions are estimated in 109 children, aged 5–18 yr. QR modeling of EE outperformed OLS regression for both nonobese and obese populations. Average prediction errors for QR compared with OLS were not only smaller at the median τ = 0.5 (18.6 vs. 21.4%), but also substantially smaller at the tails of the distribution (10.2 vs. 39.2% at τ = 0.1 and 8.7 vs. 19.8% at τ = 0.9). Covariate effects of weight, PA, and HR on EE for the nonobese and obese children differed across quantiles (P < 0.05). The associations (linear and quadratic) between PA and HR with EE were stronger for the obese than nonobese population (P < 0.05). In conclusion, QR provided more accurate predictions of EE compared with conventional OLS regression, especially at the tails of the distribution, and revealed substantially different covariate effects of weight, PA, and HR on EE in nonobese and obese children. PMID:23640591

Research across the disciplines: a road map for quality criteria in empirical ethics research

PubMed Central

2014-01-01

Background Research in the field of Empirical Ethics (EE) uses a broad variety of empirical methodologies, such as surveys, interviews and observation, developed in disciplines such as sociology, anthropology, and psychology. Whereas these empirical disciplines see themselves as purely descriptive, EE also aims at normative reflection. Currently there is literature about the quality of empirical research in ethics, but little or no reflection on specific methodological aspects that must be considered when conducting interdisciplinary empirical ethics. Furthermore, poor methodology in an EE study results in misleading ethical analyses, evaluations or recommendations. This not only deprives the study of scientific and social value, but also risks ethical misjudgement. Discussion While empirical and normative-ethical research projects have quality criteria in their own right, we focus on the specific quality criteria for EE research. We develop a tentative list of quality criteria – a “road map” – tailored to interdisciplinary research in EE, to guide assessments of research quality. These quality criteria fall into the categories of primary research question, theoretical framework and methods, relevance, interdisciplinary research practice and research ethics and scientific ethos. Summary EE research is an important and innovative development in bioethics. However, a lack of standards has led to concerns about and even rejection of EE by various scholars. Our suggested orientation list of criteria, presented in the form of reflective questions, cannot be considered definitive, but serves as a tool to provoke systematic reflection during the planning and composition of an EE research study. These criteria need to be tested in different EE research settings and further refined. PMID:24580847

Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice.

PubMed

Spoida, Katharina; Masseck, Olivia A; Deneris, Evan S; Herlitze, Stefan

2014-04-29

Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders, including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circuit specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in the dorsal raphe nucleus (DRN); however, the function of 5-HT2c-Rs and their influence on the serotonergic signals mediating mood disorders remain unclear. To investigate the role of 5-HT2c-Rs in the DRN in mice, we developed a melanopsin-based optogenetic probe for activation of Gq signals in cellular domains, where 5-HT2c-Rs are localized. Our results demonstrate that precise temporal control of Gq signals in 5-HT2c-R domains in GABAergic neurons upstream of 5-HT neurons provides negative feedback regulation of serotonergic firing to modulate anxiety-like behavior in mice.

Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice

PubMed Central

Spoida, Katharina; Masseck, Olivia A.; Deneris, Evan S.; Herlitze, Stefan

2014-01-01

Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders, including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circuit specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in the dorsal raphe nucleus (DRN); however, the function of 5-HT2c-Rs and their influence on the serotonergic signals mediating mood disorders remain unclear. To investigate the role of 5-HT2c-Rs in the DRN in mice, we developed a melanopsin-based optogenetic probe for activation of Gq signals in cellular domains, where 5-HT2c-Rs are localized. Our results demonstrate that precise temporal control of Gq signals in 5-HT2c-R domains in GABAergic neurons upstream of 5-HT neurons provides negative feedback regulation of serotonergic firing to modulate anxiety-like behavior in mice. PMID:24733892

5-HT receptor subtypes as key targets in mediating pigment dispersion within melanophores of teleost, Oreochromis mossambicus.

PubMed

Salim, Saima; Ali, Ayesha S; Ali, Sharique A

2013-02-01

The presence of distinct class of 5-HT receptors in the melanophores of tilapia (Oreochromis mossambicus) is reported. The cellular responses to 5-HT (5-hydroxytryptamine), 5-HT(1), and 5-HT(2), agonists on isolated scale melanophores were observed with regard to pigment translocation within the cells. It was found that 5-HT exerted rapid and strong concentration dependent pigment granule dispersion within the melanophores. The threshold pharmacological dose of 5-HT that could elicit a measurable response was as low as 4.7×10(-12) M/L. Selective 5-HT(1) and 5-HT(2) agonists, sumatriptan and myristicin were investigated and resulted in dose-dependent pigment dispersion. The dispersing effects were effectively antagonized by receptor specific antagonists. It is suggested that 5-HT-induced physiological effects are mediated via distinct classes of receptors that possibly participate in modulation of pigmentary responses of the fish. Copyright © 2012 Elsevier Inc. All rights reserved.

Job Prospects for E/E Engineers.

ERIC Educational Resources Information Center

Basta, Nicholas

1986-01-01

Reviews job prospects for electrical/electronic E/E engineers, indicating that 1985 was not a banner year due to problems in the semiconductor manufacturing industries and in telecommunications. Also indicates that an upturn is expected for 1986 E/E graduates. (JN)

Pilot Fullerton dons EES anti-gravity suit lower torso on middeck

NASA Technical Reports Server (NTRS)

1982-01-01

Pilot Fullerton dons ejection escape suit (EES) anti-gravity (anti-g) suit lower torso on forward port side middeck above potable water tank. Anti-g suit is an olive drab inner garment that complements EES.

31 CFR 351.4 - In what form are Series EE savings bonds issued?

Code of Federal Regulations, 2010 CFR

2010-07-01

... (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE General Information § 351.4 In what form are Series EE savings bonds issued...

Understanding the cognitive impact of the contraceptive estrogen Ethinyl Estradiol: tonic and cyclic administration impairs memory, and performance correlates with basal forebrain cholinergic system integrity.

PubMed

Mennenga, Sarah E; Gerson, Julia E; Koebele, Stephanie V; Kingston, Melissa L; Tsang, Candy W S; Engler-Chiurazzi, Elizabeth B; Baxter, Leslie C; Bimonte-Nelson, Heather A

2015-04-01

Ethinyl Estradiol (EE), a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives, and is found in at least 30 different contraceptive formulations currently prescribed to women as well as hormone therapies prescribed to menopausal women. Thus, EE is prescribed clinically to women at ages ranging from puberty to reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection, modeling the daily rise and fall of serum EE levels with oral regimens. Study II also investigated the impact of low, medium and high doses of EE on the basal forebrain cholinergic system. The low and medium doses utilized here correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. We evaluate cognition using a battery of maze tasks tapping several domains of spatial learning and memory as well as basal forebrain cholinergic integrity using immunohistochemistry and unbiased stereology to estimate the number of choline acetyltransferase (ChAT)-producing cells in the medial septum and vertical/diagonal bands. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory; tonic delivery of low EE, a dose that corresponds to the most popular doses used in the clinic today, did not impact cognition on any measure. Both medium and high injection doses of EE reduced the number of ChAt-immunoreactive cells in the basal forebrain, and cell population estimates in the vertical/diagonal bands negatively correlated with working memory errors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Drospirenone and non-fatal venous thromboembolism: is there a risk difference by dosage of ethinyl-estradiol?

PubMed

Bird, S T; Delaney, J A C; Etminan, M; Brophy, J M; Hartzema, A G

2013-06-01

Previous studies concluded that there was an increased risk of non-fatal venous thromboembolism (VTE) with drospirenone. It is unknown whether the risk is differential by ethinyl-estradiol dosage. To assess the risk of VTE with drospirenone and to determine whether drospirenone and ethinyl-estradiol 20 μg (DRSP/EE20) has a lower VTE risk than drospirenone and ethinyl-estradiol 30 μg (DRSP/EE30). Our cohort included women aged 18-46 years taking drospirenone or levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in the IMS claims database between 2001 and 2009. VTE was defined using ICD-9-CM coding and anticoagulation. The hazard ratio (HR) from Cox proportional hazards models was used to assess the VTE relative risk (RR) with drospirenone compared with levonorgestrel, adjusted by a propensity score used to control for baseline co-morbidity and stratified by EE dosage and user-type (new/current). The study included 238 683 drospirenone and 193,495 levonorgestrel users. Among new and current users, a 1.90-fold (95% CI, 1.51-2.39) increased VTE relative risk was observed for drospirenone (18.0 VTE/10,000 women-years) vs. levonorgestrel (8.9 VTE/10,000 women-years). In analysis of new users, DRSP/EE20 had a 2.35-fold (95% CI, 1.44-3.82) VTE RR versus LNG/EE20. New users of DRSP/EE30 observed an increased RR versus LNG/EE30 among women starting to use COCs between 2001 and 2006 (2.51, 95% CI, 1.12-5.64) but not between 2007 and 2009 (0.76, 95% CI, 0.42-1.39), attributable to an increased incidence rate with LNG/EE30 from 2007 to 2009. In direct comparison, DRSP/EE20 had an elevated risk of VTE compared with DRSP/EE30 (RR, 1.55; 95% CI, 0.99-2.41). We observed a modestly elevated risk of VTE with drospirenone, compared with levonorgestrel. The larger VTE incidence rate observed in DRSP/EE20 than in DRSP/EE30 and the increasing VTE incidence rate with levonorgestrel between 2007 and 2009 were unexpected. Copyright © 2013 International Society on Thrombosis and Haemostasis.

A prospective, randomized evaluation of a novel everolimus-eluting coronary stent: the PLATINUM (a Prospective, Randomized, Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System [PROMUS Element] for the Treatment of Up to Two de Novo Coronary Artery Lesions) trial.

PubMed

Stone, Gregg W; Teirstein, Paul S; Meredith, Ian T; Farah, Bruno; Dubois, Christophe L; Feldman, Robert L; Dens, Joseph; Hagiwara, Nobuhisa; Allocco, Dominic J; Dawkins, Keith D

2011-04-19

We sought to evaluate the clinical outcomes with a novel platinum chromium everolimus-eluting stent (PtCr-EES) compared with a predicate cobalt chromium everolimus-eluting stent (CoCr-EES) in patients undergoing percutaneous coronary intervention (PCI). Randomized trials have demonstrated an excellent safety and efficacy profile for the CoCr-EES. The PtCr-EES uses the identical antiproliferative agent and polymer but with a novel platinum chromium scaffold designed for enhanced deliverability, vessel conformability, side-branch access, radiopacity, radial strength, and fracture resistance. A total of 1,530 patients undergoing PCI of 1 or 2 de novo native lesions were randomized at 132 worldwide sites to CoCr-EES (n = 762) or PtCr-EES (n = 768). The primary endpoint was the 12-month rate of target lesion failure (TLF), the composite of target vessel-related cardiac death, target vessel-related myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR) in the per-protocol population (patients who received ≥1 assigned study stent), powered for noninferiority. The 12-month rate of TLF in the per-protocol population occurred in 2.9% versus 3.4% of patients assigned to CoCr-EES versus PtCr-EES, respectively (difference: 0.5%, 95% confidence interval: -1.3% to 2.3%, p(noninferiority) = 0.001, p(superiority) = 0.60). By intention-to-treat, there were no significant differences between CoCr-EES and PtCr-EES in the 12-month rates of TLF (3.2% vs. 3.5%, p = 0.72), cardiac death or MI (2.5% vs. 2.0%, p = 0.56), TLR (1.9% vs. 1.9%, p = 0.96), or Academic Research Consortium definite or probable stent thrombosis (0.4% vs. 0.4%, p = 1.00). In this large-scale, prospective, single-blind randomized trial, a novel PtCr-EES was noninferior to the predicate CoCr-EES for TLF, with nonsignificant differences in measures of safety and efficacy through 12-month follow-up after PCI. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Toll-like receptors 2 and 4 exert opposite effects on the contractile response induced by serotonin in mouse colon: role of serotonin receptors.

PubMed

Forcén, R; Latorre, E; Pardo, J; Alcalde, A I; Murillo, M D; Grasa, L

2016-08-01

What is the central question of this study? The action of Toll-like receptors (TLRs) 2 and 4 on the motor response to serotonin in mouse colon has not previously been reported. What is the main finding and its importance? Toll-like receptors 2 and 4 modulate the serotonin-induced contractile response in mouse colon by modifying the expression of serotonin (5-HT) receptors. Alterations in 5-HT2A and 5-HT2C receptors explain the increase of the response to serotonin in TLR2(-/-) mice. Alterations in 5-HT2C and 5-HT4 receptors explain the suppression of the response to serotonin in TLR4(-/-) mice. The microbiota, through Toll-like receptors (TLRs), may regulate gastrointestinal motility by activating neuroendocrine mechanisms. We evaluated the influence of TLR2 and TLR4 in spontaneous contractions and in the serotonin (5-HT)-induced motor response in mouse colon, and assessed the 5-HT receptors involved. Muscle contractility studies to evaluate the intestinal spontaneous motility and the response to 5-HT were performed in the colon from wild-type (WT), TLR2(-/-) , TLR4(-/-) and TLR2/4 double knockout (DKO) mice. The 5-HT receptor mRNA expression was determined by real-time PCR. The amplitude and frequency of the spontaneous contractions of the colon were smaller in TLR4(-/-) and TLR2/4 DKO mice with respect to WT mice. In WT, TLR2(-/-) and TLR2/4 DKO mice, 100 μm 5-HT evoked a contractile response. The contractile response induced by 5-HT was significantly higher in TLR2(-/-) than in WT mice. In TLR4(-/-) mice, 5-HT did not evoke any contractile response. The mRNA expression of 5-HT2A was increased in TLR2(-/-) and TLR2/4 DKO mice. The 5-HT2C and 5-HT4 mRNA expressions were increased in TLR4(-/-) and TLR2/4 DKO mice. The 5-HT2C mRNA expression was diminished in TLR2(-/-) mice. The 5-HT3 mRNA expression was increased in TLR2(-/-) , TLR4(-/-) and TLR2/4 DKO mice. The 5-HT7 mRNA expression was diminished in TLR2/4 DKO mice. In WT, TLR2(-/-) and TLR2/4 DKO mice, 5-HT2 , 5-HT3 , 5-HT4 and 5-HT7 receptor antagonists reduced or blocked the contractile response evoked by 5-HT. We postulate that TLR2 and TLR4 modulate the serotonin contractile motor response in mouse colon in an opposing manner by modifying the expression of several serotonin receptors. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder.

PubMed

Bang-Andersen, Benny; Ruhland, Thomas; Jørgensen, Morten; Smith, Garrick; Frederiksen, Kristen; Jensen, Klaus Gjervig; Zhong, Huailing; Nielsen, Søren Møller; Hogg, Sandra; Mørk, Arne; Stensbøl, Tine Bryan

2011-05-12

The synthesis and structure-activity relationship of a novel series of compounds with combined effects on 5-HT(3A) and 5-HT(1A) receptors and on the serotonin (5-HT) transporter (SERT) are described. Compound 5m (Lu AA21004) was the lead compound, displaying high affinity for recombinant human 5-HT(1A) (K(i) = 15 nM), 5-HT(1B) (K(i) = 33 nM), 5-HT(3A) (K(i) = 3.7 nM), 5-HT(7) (K(i) = 19 nM), and noradrenergic β(1) (K(i) = 46 nM) receptors, and SERT (K(i) = 1.6 nM). Compound 5m displayed antagonistic properties at 5-HT(3A) and 5-HT(7) receptors, partial agonist properties at 5-HT(1B) receptors, agonistic properties at 5-HT(1A) receptors, and potent inhibition of SERT. In conscious rats, 5m significantly increased extracellular 5-HT levels in the brain after acute and 3 days of treatment. Following the 3-day treatment (5 or 10 (mg/kg)/day) SERT occupancies were only 43% and 57%, respectively. These characteristics indicate that 5m is a novel multimodal serotonergic compound, and 5m is currently in clinical development for major depressive disorder.

5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

PubMed Central

Ciranna, Lucia; Catania, Maria Vincenza

2014-01-01

Serotonin type 7 receptors (5-HT7) are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD), including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD. PMID:25221471

The 5-HT1-like receptor mediating the increase in canine external carotid blood flow: close resemblance to the 5-HT1D subtype.

PubMed Central

Villalón, C M; Terrón, J A

1994-01-01

1. It has recently been shown that the increase in external carotid blood flow induced by 5-hydroxy-tryptamine (5-HT) in the anaesthetized dog, being mimicked by 5-carboxamidotryptamine (5-CT), inhibited by methiothepin, vagosympathectomy and sympatho-inhibitory drugs, and resistant to blockade by ritanserin and MDL 72222, is mediated by stimulation of prejunctional 5-HT1-like receptors leading to an inhibitory action on carotid sympathetic nerves; these 5-HT1-like receptors are unrelated to either the 5-HT1A, 5-HT1B or 5-HT1C (now 5-HT2C) receptor subtypes. Inasmuch as 5-CT, 5-methoxytryptamine, sumatriptan and metergoline display high affinity, amongst other 5-HT binding sites, for the 5-HT1D subtype, in the present study we have used these drugs in an attempt to determine whether the above inhibitory prejunctional 5-HT1-like receptors correlate with the 5-HT1D subtype. 2. One-minute intracarotid (i.c.) infusions of 5-HT (0.3, 1, 3 and 10 micrograms), 5-CT (0.01, 0.03, 0.1 and 0.3 micrograms), 5-methoxytryptamine (1, 3, 10 and 30 micrograms) and sumatriptan (1, 3, 10, 30 and 100 micrograms) resulted in dose-dependent increases in external carotid blood flow (without changes in mean arterial blood pressure or heart rate) with the following rank order of agonist potency: 5-CT >> 5-HT > 5-methoxytryptamine > or = sumatriptan. Interestingly, sumatriptan-induced vasodilatation was followed by a more pronounced vasoconstriction. 3. The external carotid vasodilator effects of 5-HT, 5-CT, 5-methoxytryptamine and sumatriptan were dose-dependently and specifically antagonized by metergoline (10, 30 and/or 100 micrograms kg-1, i.v.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7812603

Serotonergic mechanisms in addiction-related memories.

PubMed

Nic Dhonnchadha, Bríd A; Cunningham, Kathryn A

2008-12-16

Drug-associated memories are a hallmark of addiction and a contributing factor in the continued use and relapse to drugs of abuse. Repeated association of drugs of abuse with conditioned stimuli leads to long-lasting behavioral responses that reflect reward-controlled learning and participate in the establishment of addiction. A greater understanding of the mechanisms underlying the formation and retrieval of drug-associated memories may shed light on potential therapeutic approaches to effectively intervene with drug use-associated memory. There is evidence to support the involvement of serotonin (5-HT) neurotransmission in learning and memory formation through the families of the 5-HT(1) receptor (5-HT(1)R) and 5-HT(2)R which have also been shown to play a modulatory role in the behavioral effects induced by many psychostimulants. While there is a paucity of studies examining the effects of selective 5-HT(1A)R ligands, the available dataset suggests that 5-HT(1B)R agonists may inhibit retrieval of cocaine-associated memories. The 5-HT(2A)R and 5-HT(2C)R appear to be integral in the strong conditioned associations made between cocaine and environmental cues with 5-HT(2A)R antagonists and 5-HT(2C)R agonists possessing potency in blocking retrieval of cocaine-associated memories following cocaine self-administration procedures. The complex anatomical connectivity between 5-HT neurons and other neuronal phenotypes in limbic-corticostriatal brain structures, the heterogeneity of 5-HT receptors (5-HT(X)R) and the conflicting results of behavioral experiments which employ non-specific 5-HT(X)R ligands contribute to the complexity of interpreting the involvement of 5-HT systems in addictive-related memory processes. This review briefly traces the history of 5-HT involvement in retrieval of drug-cue associations and future targets of serotonergic manipulation that may reduce the impact that drug cues have on addictive behavior and relapse.

The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves.

PubMed

Larson, Eric D; Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C; Finger, Thomas E

2015-12-02

Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT(3A) promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT(3A) mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μM 5-HT and this response is blocked by 1 μM ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μM m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response. Copyright © 2015 the authors 0270-6474/15/3515984-12$15.00/0.

BEopt-CA (Ex): A Tool for Optimal Integration of EE, DR and PV in Existing California Homes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christensen, Craig; Horowitz, Scott; Maguire, Jeff

2014-04-01

This project targeted the development of a software tool, BEopt-CA (Ex) (Building Energy Optimization Tool for California Existing Homes), that aims to facilitate balanced integration of energy efficiency (EE), demand response (DR), and photovoltaics (PV) in the residential retrofit1 market. The intent is to provide utility program managers and contractors in the EE/DR/PV marketplace with a means of balancing the integration of EE, DR, and PV

Photodegradation of 17α-ethynylestradiol in dissolved humic substances solution: Kinetics, mechanism and estrogenicity variation.

PubMed

Ren, Dong; Huang, Bin; Xiong, Dan; He, Huan; Meng, Xiangqi; Pan, Xuejun

2017-04-01

17α-Ethynylestradiol (EE2) in natural waters may cause adverse effects on organisms due to its high estrogenic potency. Laboratory studies were performed to study the effects of a local humic acid (LHA), fulvic acid (LFA) and Aldrich humic acid (AHA) on the photochemical behavior and estrogenic potency of EE2. Here photolytic experiments demonstrated that pure aqueous EE2 could undergo direct and self-sensitized photodegradation at a global rate of 0.0068hr -1 . Photodegradation rate of EE2 in 5.0mg/L dissolved humic substances (DHS) was determined to be 0.0274, 0.0296 and 0.0254hr -1 for LHA, LFA and AHA, respectively. Reactive oxygen species (ROS) and triplet dissolved humic substances ( 3 DHS*) scavenging experiments indicated that the promotion effect of DHS on EE2 photodegradation was mainly aroused by the reactions of HO (35%-50%), 1 O 2 (<10%) and 3 DHS* (22%-34%). However, the photodegradation of EE2 could also be inhibited when DHS exceeded the threshold of 10mg/L. Three hydroxylation products of EE2 were identified using GC-MS and their formation pathways were also proposed. In vitro estrogenicity tests showed that EE2 was transformed into chemicals without estrogenic potency. These findings could extend our knowledge on the photochemical behaviors of steroid estrogens in sunlit natural waters. Copyright © 2016. Published by Elsevier B.V.

On the nature of the solvated electron in ice Ih.

PubMed

de Koning, Maurice; Fazzio, Adalberto; da Silva, Antônio José Roque; Antonelli, Alex

2016-02-14

The water-solvated excess electron (EE) is a key chemical agent whose hallmark signature, its asymmetric optical absorption spectrum, continues to be a topic of debate. While nearly all investigation has focused on the liquid-water solvent, the fact that the crystalline-water solvated EE shows a very similar visible absorption pattern has remained largely unexplored. Here, we present spin-polarized density-functional theory calculations subject to periodic boundary conditions of the interplay between an EE and a number of intrinsic lattice defects in ice Ih. Our results show that the optical absorption signatures in the presence of three unsaturated hydrogen bonds (HB) are very similar to those observed experimentally. Its low-energy side can be attributed to transitions between the EE ground state and a single localized excited level, in a picture that is different from that for the liquid solvent, where this portion has been associated with hydrogen-like s → p excitations. The blue tail, on the other hand, relates to transitions between the EE ground state and delocalized excited states, which is in line with the bound-to-continuum transition interpretations for the EE in liquid water. Finally, we find that, depending on the number of dangling HBs participating in the EE trap, its charge density may spontaneously break the spin degeneracy through exchange interactions with the surrounding electrons, displaying the many-electron quantum nature of the EE problem in ice Ih.

Photocatalytic degradation of 17α-ethinylestradiol (EE2) in the presence of TiO2-doped zeolite.

PubMed

Pan, Zhong; Stemmler, Elizabeth A; Cho, Hong Je; Fan, Wei; LeBlanc, Lawrence A; Patterson, Howard H; Amirbahman, Aria

2014-08-30

Current design limitations and ineffective remediation techniques in wastewater treatment plants have led to concerns about the prevalence of pharmaceutical and personal care products (PPCPs) in receiving waters. A novel photocatalyst, TiO2-doped low-silica X zeolite (TiO2-LSX), was used to study the degradation of the pharmaceutical compound, 17α-ethinylestradiol (EE2). The catalyst was synthesized and characterized using XRD, BET surface analysis, SEM-EDAX, and ICP-OES. The effects of different UV light intensities, initial EE2 concentrations, and catalyst dosages on the EE2 removal efficiency were studied. A higher EE2 removal efficiency was attained with UV-TiO2-LSX when compared with UV-TiO2 or UV alone. The EE2 degradation process followed pseudo-first-order kinetics. A comprehensive empirical model was developed to describe the EE2 degradation kinetics under different conditions using multiple linear regression analysis. The EE2 degradation mechanism was proposed based on molecular calculations, identification of photoproducts using HPLC-MS/MS, and reactive species quenching experiments; the results showed that oxidative degradation pathways initiated by hydroxyl radicals were predominant. This novel TiO2-doped zeolite system provides a promising application for the UV disinfection process in wastewater treatment plants. Copyright © 2014 Elsevier B.V. All rights reserved.

The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves

PubMed Central

Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C.; Finger, Thomas E.

2015-01-01

Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT3A promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT3A mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μm 5-HT and this response is blocked by 1 μm ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μm m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response. SIGNIFICANCE STATEMENT Historically, serotonin (5-hydroxytryptamine; 5-HT) has been described as a candidate neurotransmitter in the gustatory system and recent studies show that type III taste receptor cells release 5-HT in response to various taste stimuli. In the present study, we demonstrate that a subset of gustatory sensory neurons express functional 5-HT3 receptors that play a significant role in the neurotransmission of taste information from taste buds to nerves. In addition, we show that the anesthetic pentobarbital, widely used in taste nerve recordings, blocks 5-HT3 signaling. Therefore, many conclusions drawn from those data need to be reexamined in light of this anesthetic effect. PMID:26631478

Prevalence, clinical profile, iron status, and subject-specific traits for excessive erythrocytosis in andean adults living permanently at 3,825 meters above sea level.

PubMed

De Ferrari, Aldo; Miranda, J Jaime; Gilman, Robert H; Dávila-Román, Victor G; León-Velarde, Fabiola; Rivera-Ch, Maria; Huicho, Luis; Bernabé-Ortiz, Antonio; Wise, Robert A; Checkley, William

2014-11-01

Excessive erythrocytosis (EE) is a prevalent condition in populations living at high altitudes (> 2,500 m above sea level). Few large population-based studies have explored the association between EE and multiple subject-specific traits including oxygen saturation, iron status indicators, and pulmonary function. We enrolled a sex-stratified and age-stratified sample of 1,065 high-altitude residents aged ≥ 35 years from Puno, Peru (3,825 m above sea level) and conducted a standardized questionnaire and physical examination that included spirometry, pulse oximetry, and a blood sample for multiple clinical markers. Our primary objectives were to estimate the prevalence of EE, characterize the clinical profile and iron status indicators of subjects with EE, and describe subject-specific traits associated with EE. Overall prevalence of EE was 4.5% (95% CI, 3.3%-6.0%). Oxygen saturation was significantly lower among EE than non-EE group subjects (85.3% vs 90.1%, P < .001) but no difference was found in iron status indicators between both groups (P > .09 for all values). In multivariable logistic regression, we found that age ≥ 65 years (OR = 2.45, 95% CI, 1.16-5.09), male sex (3.86, 1.78-9.08), having metabolic syndrome (2.66, 1.27-5.75) or being overweight (5.20, 1.95-16.77), pulse oximetry < 85% (14.90, 6.43-34.90), and % predicted FVC < 80% (13.62, 4.40-41.80) were strongly associated with EE. Attributable fractions for EE were greatest for being overweight (26.7%), followed by male sex (21.5%), pulse oximetry < 85% (16.4%), having metabolic syndrome (14.4%), and % predicted FVC < 80% (9.3%). We found a lower prevalence of EE than in previous reports in the Peruvian Andes. Although the presence of hypoxemia and decreased vital capacity were strongly associated with excessive erythrocytosis, being overweight or having metabolic syndrome were associated with an important fraction of cases in our study population.

Prevalence, Clinical Profile, Iron Status, and Subject-Specific Traits for Excessive Erythrocytosis in Andean Adults Living Permanently at 3,825 Meters Above Sea Level

PubMed Central

De Ferrari, Aldo; Miranda, J. Jaime; Gilman, Robert H.; Dávila-Román, Victor G.; León-Velarde, Fabiola; Rivera-Ch, Maria; Huicho, Luis; Bernabé-Ortiz, Antonio; Wise, Robert A.

2014-01-01

BACKGROUND: Excessive erythrocytosis (EE) is a prevalent condition in populations living at high altitudes (> 2,500 m above sea level). Few large population-based studies have explored the association between EE and multiple subject-specific traits including oxygen saturation, iron status indicators, and pulmonary function. METHODS: We enrolled a sex-stratified and age-stratified sample of 1,065 high-altitude residents aged ≥ 35 years from Puno, Peru (3,825 m above sea level) and conducted a standardized questionnaire and physical examination that included spirometry, pulse oximetry, and a blood sample for multiple clinical markers. Our primary objectives were to estimate the prevalence of EE, characterize the clinical profile and iron status indicators of subjects with EE, and describe subject-specific traits associated with EE. RESULTS: Overall prevalence of EE was 4.5% (95% CI, 3.3%-6.0%). Oxygen saturation was significantly lower among EE than non-EE group subjects (85.3% vs 90.1%, P < .001) but no difference was found in iron status indicators between both groups (P > .09 for all values). In multivariable logistic regression, we found that age ≥ 65 years (OR = 2.45, 95% CI, 1.16-5.09), male sex (3.86, 1.78-9.08), having metabolic syndrome (2.66, 1.27-5.75) or being overweight (5.20, 1.95-16.77), pulse oximetry < 85% (14.90, 6.43-34.90), and % predicted FVC < 80% (13.62, 4.40-41.80) were strongly associated with EE. Attributable fractions for EE were greatest for being overweight (26.7%), followed by male sex (21.5%), pulse oximetry < 85% (16.4%), having metabolic syndrome (14.4%), and % predicted FVC < 80% (9.3%). CONCLUSIONS: We found a lower prevalence of EE than in previous reports in the Peruvian Andes. Although the presence of hypoxemia and decreased vital capacity were strongly associated with excessive erythrocytosis, being overweight or having metabolic syndrome were associated with an important fraction of cases in our study population. PMID:24874587

Characterisation of the pharmacokinetics of ethinylestradiol and drospirenone in extended-cycle regimens: population pharmacokinetic analysis from a randomised Phase III study

PubMed Central

Reif, Stefanie; Snelder, Nelleke; Blode, Hartmut

2013-01-01

Objectives The primary objective of this analysis was to characterise the steady-state pharmacokinetics (PK) of ethinylestradiol (EE) and drospirenone (DRSP) in a randomised Phase III study that investigated the contraceptive efficacy and safety of three different regimens of EE 20 µg/DRSP 3 mg. Methods Non-linear mixed-effects modelling was used to develop population PK models for EE and DRSP. EE and DRSP serum concentrations were determined in blood samples obtained from approximately 1100 healthy young women on two occasions during the first cycle (Week 3) and after 6 months (Week 27) of EE 20 µg/DRSP 3 mg use. EE 20 µg/DRSP 3 mg was administered as a flexible extended regimen [24–120 days’ active hormonal intake followed by 4 days with no tablet intake (tablet-free interval)], a conventional 28-day cyclic regimen (24 days’ active hormonal intake followed by 4 days of placebo tablets) or a fixed extended regimen (120 days’ uninterrupted active hormonal intake followed by a 4-day tablet-free interval) over 1 year. Results The population PK of EE and DRSP in this population were successfully described using the developed population models. All three regimens led to similar steady-state drug exposure during long-term treatment. Only minor changes (≤8%) in the steady-state PK of EE and DRSP were observed between Week 3 and Week 27 of an extended regimen. Body weight (BW) and age had a small, statistically significant impact on the PK of EE and DRSP (BW only) in a covariate analysis, however, these changes were not considered to be clinically relevant. Conclusions Extending the established 24/4-day regimen of EE 20 µg/DRSP 3 mg does not change the known steady-state PK of EE and DRSP, suggesting that the clinical efficacy is also similar. This is in line with the published clinical results from this study. PMID:23493606

Characterisation of the pharmacokinetics of ethinylestradiol and drospirenone in extended-cycle regimens: population pharmacokinetic analysis from a randomised Phase III study.

PubMed

Reif, Stefanie; Snelder, Nelleke; Blode, Hartmut

2013-04-01

The primary objective of this analysis was to characterise the steady-state pharmacokinetics (PK) of ethinylestradiol (EE) and drospirenone (DRSP) in a randomised Phase III study that investigated the contraceptive efficacy and safety of three different regimens of EE 20 µg/DRSP 3 mg. Non-linear mixed-effects modelling was used to develop population PK models for EE and DRSP. EE and DRSP serum concentrations were determined in blood samples obtained from approximately 1100 healthy young women on two occasions during the first cycle (Week 3) and after 6 months (Week 27) of EE 20 µg/DRSP 3 mg use. EE 20 µg/DRSP 3 mg was administered as a flexible extended regimen [24-120 days' active hormonal intake followed by 4 days with no tablet intake (tablet-free interval)], a conventional 28-day cyclic regimen (24 days' active hormonal intake followed by 4 days of placebo tablets) or a fixed extended regimen (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) over 1 year. The population PK of EE and DRSP in this population were successfully described using the developed population models. All three regimens led to similar steady-state drug exposure during long-term treatment. Only minor changes (≤ 8%) in the steady-state PK of EE and DRSP were observed between Week 3 and Week 27 of an extended regimen. Body weight (BW) and age had a small, statistically significant impact on the PK of EE and DRSP (BW only) in a covariate analysis, however, these changes were not considered to be clinically relevant. Extending the established 24/4-day regimen of EE 20 µg/DRSP 3 mg does not change the known steady-state PK of EE and DRSP, suggesting that the clinical efficacy is also similar. This is in line with the published clinical results from this study.

A concise review of Hashimoto thyroiditis (HT) and the importance of iodine, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients.Points that need more investigation.

PubMed

Liontiris, Michael I; Mazokopakis, Elias E

2017-01-01

Hashimoto's thyroiditis (HT) is a chronic autoimmune thyroid disease caused by an interaction between genetic factors and environmental conditions, both of which are yet to be fully understood. The management of HT depends on its clinical manifestations, commonly including diffuse or nodular goiter with euthyroidism, subclinical hypothyroidism and permanent hypothyroidism. However, in most cases of patients with HT, lifelong levothyroxine substitution is required. The additional role of diet for the management of HT is usually overlooked. A literature search regarding the importance and the influence of iodine, selenium, vitamin D and gluten on HT was conducted. In HT careful supplementation of possible deficiencies is recommended for the dietary management of these patients. The use of a diet low in gluten among HT patients with or without celiac disease (CD) is discussed.

Aromatic interactions impact ligand binding and function at serotonin 5-HT2C G protein-coupled receptors: receptor homology modelling, ligand docking, and molecular dynamics results validated by experimental studies

NASA Astrophysics Data System (ADS)

Córdova-Sintjago, Tania; Villa, Nancy; Fang, Lijuan; Booth, Raymond G.

2014-02-01

The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2 G protein-coupled receptor (GPCR) family consists of types 2A, 2B, and 2C that share ∼75% transmembrane (TM) sequence identity. Agonists for 5-HT2C receptors are under development for psychoses; whereas, at 5-HT2A receptors, antipsychotic effects are associated with antagonists - in fact, 5-HT2A agonists can cause hallucinations and 5-HT2B agonists cause cardiotoxicity. It is known that 5-HT2A TM6 residues W6.48, F6.51, and F6.52 impact ligand binding and function; however, ligand interactions with these residues at the 5-HT2C receptor have not been reported. To predict and validate molecular determinants for 5-HT2C-specific activation, results from receptor homology modelling, ligand docking, and molecular dynamics simulation studies were compared with experimental results for ligand binding and function at wild type and W6.48A, F6.51A, and F6.52A point-mutated 5-HT2C receptors.

Trajectories of total depression and depressive symptoms in prostate cancer patients receiving six months of hormone therapy.

PubMed

Sharpley, Christopher F; Christie, David R H; Bitsika, Vicki; Miller, Bradley J

2017-01-01

The aim of this study was to investigate the effects of hormone therapy (HT) on depression and depressive symptoms in prostate cancer patients undergoing 6 months of HT. One hundred two prostate cancer patients who had been prescribed HT completed the Zung Self-rating Depression Scale (SDS) and two questions about their sexual enjoyment and performance, plus a background questionnaire before HT, after 8 to 10 weeks of HT and again after 16 to 20 weeks of HT. There was a significant increase in SDS scores from before to during HT. High depression score before HT was a significant predictor of later increases in depression during HT. Increases in depressive symptoms were restricted to 8 of the 20 SDS symptoms, the most powerful change being in sexual anhedonia, which was a result of decreased ability to perform during sexual activity. The association between HT and elevated depression is confirmed, but the relative influence of sexual anhedonia over other depressive symptoms expands the understanding of this association. The effects of decreased ability to perform during sex appear to dominate the increase in depression during HT. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The role of serotonin 5-HT2A receptors in memory and cognition

PubMed Central

Zhang, Gongliang; Stackman, Robert W.

2015-01-01

Serotonin 5-HT2A receptors (5-HT2ARs) are widely distributed in the central nervous system, especially in brain region essential for learning and cognition. In addition to endogenous 5-HT, several hallucinogens, antipsychotics, and antidepressants function by targeting 5-HT2ARs. Preclinical studies show that 5-HT2AR antagonists have antipsychotic and antidepressant properties, whereas agonist ligands possess cognition-enhancing and hallucinogenic properties. Abnormal 5-HT2AR activity is associated with a number of psychiatric disorders and conditions, including depression, schizophrenia, and drug addiction. In addition to its traditional activity as a G protein-coupled receptor (GPCR), recent studies have defined novel operations of 5-HT2ARs. Here we review progress in the (1) receptor anatomy and biology: distribution, signaling, polymerization and allosteric modulation; and (2) receptor functions: learning and memory, hallucination and spatial cognition, and mental disorders. Based on the recent progress in basic research on the 5-HT2AR, it appears that post-training 5-HT2AR activation enhances non-spatial memory consolidation, while pre-training 5-HT2AR activation facilitates fear extinction. Further, the potential influence that 5-HT2AR-elicited visual hallucinations may have on visual cue (i.e., landmark) guided spatial cognition is discussed. We conclude that the development of selective 5-HT2AR modulators to target distinct signaling pathways and neural circuits represents a new possibility for treating emotional, neuropsychiatric, and neurodegenerative disorders. PMID:26500553

Conservation of structure, signaling and pharmacology between two serotonin receptor subtypes from decapod crustaceans, Panulirus interruptus and Procambarus clarkii.

PubMed

Spitzer, Nadja; Edwards, Donald H; Baro, Deborah J

2008-01-01

Serotonin (5-HT) plays important roles in the maintenance and modulation of neural systems throughout the animal kingdom. The actions of 5-HT have been well characterized for several crustacean model circuits; however, a dissection of the serotonergic transduction cascades operating in these models has been hampered by the lack of pharmacological tools for invertebrate receptors. Here we provide pharmacological profiles for two 5-HT receptors from the swamp crayfish, Procambarus clarkii: 5-HT(2beta) and 5-HT(1alpha). In so doing, we also report the first functional expression of a crustacean 5-HT(1) receptor, and show that it inhibits accumulation of cAMP. The drugs mCPP and quipazine are 5-HT(1alpha) agonists and are ineffective at 5-HT(2beta). Conversely, methiothepin and cinanserin are antagonists of 5-HT(2beta) but do not block 5-HT(1alpha). A comparison of these two receptors with their orthologs from the California spiny lobster, Panulirus interruptus, indicates conservation of protein structure, signaling and pharmacology. This conservation extends beyond crustacean infraorders. The signature residues that form the ligand-binding pocket in mammalian 5-HT receptors are found in the crustacean receptors. Similarly, the protein domains involved in G protein coupling are conserved between the two crustacean receptors and other characterized arthropod and mammalian 5-HT receptors. Considering the apparent conservation of pharmacological properties between crustacean 5-HT receptors, these tools could be applicable to related crustacean physiological preparations.

The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?

PubMed Central

Ferreri, Florian; Drapier, Dominique; Baloche, Emmanuelle; Ouzid, Mehemed; Zimmer, Luc; Llorca, Pierre-Michel

2018-01-01

Abstract Background The denomination of typical antipsychotic for loxapine has poor relation to current knowledge of the molecule’s relevant modes of action. Materials and Methods Competition binding experiments were performed on expressed human recombinant receptors in CHO cells and HEK-293 cells for D1 to D5, 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro autoradiographies using [11C]-Raclopride [18F]-Altanserin [18F]-MPPF [11C]-SB207145, and [18F]-2FNQ1P were measured in brain tissue of a male primate followed by addition of increasing doses of loxapine succinate. Results In cell cultures, the measured Kb confirmed high affinity of loxapine for the D2; intermediate affinity for the D1, D4, D5, 5-HT2C receptorsl and a lack of affinity toward D3, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors. In brain tissue, PET autoradiographies showed a radiopharmaceutical displacement at low concentrations of loxapine on D2 and 5-HT2A receptors. Conclusion This preclinical study reveals that loxapine receptorial spectrum is close to an “atypical” profile (D2/5HT2A ratio, 1.14). Loxapine is rightly classified as a DS-RAn agent in the Neuroscience Based Nomenclature classification. PMID:29106549

Role of 5-HT1-7 receptors in short- and long-term memory for an autoshaping task: intrahippocampal manipulations.

PubMed

Liy-Salmeron, Gustavo; Meneses, Alfredo

2007-05-25

It was previously reported that brain areas containing serotonin (5-hydroxytryptamine, 5-HT) receptors mediate memory consolidation as well as short (STM)- and long-term memory (LTM). Here the effects of systemic and intrahippocampal administration of 5-HT agonists and antagonists on an autoshaping learning task were explored, which requires hippocampal translation and transduction as well as 5-HT receptors expression. As previously reported ketamine (glutamatergic antagonist) and two well-known amnesic drugs, scopolamine (cholinergic antagonist) and dizocilpine (NMDA antagonist) impaired STM but not LTM; dizocilpine even improved the latter. Since ketamine produces hallucinations and impairs memory in humans, we address the question if well-known antipsychotic haloperidol and clozapine might affect STM deficit. Indeed, systemic administration of clozapine

Metabolites of hirsuteine and hirsutine, the major indole alkaloids of Uncaria rhynchophylla, in rats.

PubMed

Nakazawa, Takahiro; Banba, Koh-ichi; Hata, Kazumasa; Nihei, Yutaka; Hoshikawa, Ayumi; Ohsawa, Keisuke

2006-08-01

The metabolic fate of hirsuteine (HT) and hirsutine (HS), the major indole alkaloids of Uncaria rhynchophylla, was investigated using rats. On HPLC analysis, urine from rats orally administered HT were found to contain two metabolites (HT1 and HT2) together with unchanged HT. Similarly HS also was metabolized to two compounds (HS1 and HS2). Metabolite structures were determined to be 11-hydroxyhirsuteine-11-O-beta-D-glucuronide (HT1), 11-hydroxyhirsuteine (HT2), 11-hydroxyhirsutine-11-O-beta-D-glucuronide (HS1) and 11-hydroxyhirsutine (HS2), based on spectroscopic and chemical data. HT1 and HS1 were also detected in bile from rats administered HT and HS, respectively. Total cumulative urinary excretion within 72 h of oral administration was approximately 14% and 26% of the HT and HS doses, respectively, while total cumulative biliary excretion was 35% and 46%, respectively. HT and HS 11-hydroxylation were catalyzed by rat liver microsomes. This 11-hydroxylation activity was inhibited by addition of SKF-525A (a nonselective CYP inhibitor) or cimetidine (a CYP2C inhibitor). These results indicate that orally administered HT and HS are converted to 11-hydroxy metabolites in rats, and that the metabolites are predominantly excreted in bile rather than urine following glucuronidation. Furthermore, the results suggest that CYP2C enzymes are involved, at least in part, in the specific 11-hydroxylation of HT and HS.

Impact of Heart Transplantation on the Functional Status of US Children With End-Stage Heart Failure.

PubMed

Peng, David M; Zhang, Yulin; Rosenthal, David N; Palmon, Michal; Chen, Sharon; Kaufman, Beth D; Maeda, Katsuhide; Hollander, Seth A; McDonald, Nancy; Smoot, Leslie B; Bernstein, Daniel; Almond, Christopher S

2017-03-07

There are limited data describing the functional status (FS) of children after heart transplant (HT). We sought to describe the FS of children surviving at least 1 year after HT, to evaluate the impact of HT on FS, and to identify factors associated with abnormal FS post-HT. Organ Procurement and Transplantation Network data were used to identify all US children <21 years of age surviving ≥1 year post-HT from 2005 to 2014 with a functional status score (FSS) available at 3 time points (listing, transplant, ≥1 year post-HT). Logistic regression and generalized estimating equations were used to identify factors associated with abnormal FS (FSS≤8) post-HT. A total of 1633 children met study criteria. At the 1-year assessment, 64% were "fully active/no limitations" (FSS=10), 21% had "minor limitations with strenuous activity" (FSS=9); and 15% scored ≤8. In comparison with listing FS, FS at 1 year post-HT increased in 91% and declined/remained unchanged in 9%. A stepwise regression procedure selected the following variables for association with abnormal FS at 1 year post-HT: ≥18 years of age (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.7), black race (OR, 1.5; 95% CI, 1.1-2.0), support with ≥inotropes at HT (OR, 1.7; 95% CI, 1.2-2.5), hospitalization status at HT (OR, 1.5; 95% CI, 1.0-2.19), chronic steroid use at HT (OR, 1.5; 95% CI, 1.0-2.2), and treatment for early rejection (OR, 2.0; 95% CI, 1.5-2.7). Among US children who survive at least 1 year after HT, FS is excellent for the majority of patients. HT is associated with substantial improvement in FS for most children. Early rejection, older age, black race, chronic steroid use, hemodynamic support at HT, and being hospitalized at HT are associated with abnormal FS post-HT. © 2017 American Heart Association, Inc.

A multicentric study regarding the use of hormone therapy during female mid-age (REDLINC VI).

PubMed

Blümel, J E; Chedraui, P; Barón, G; Benítez, Z; Flores, D; Espinoza, M T; Gomez, G; González, E; Hernández, L; Lima, S; Martino, M; Montaño, A; Monterrosa, A; Mostajo, D; Ojeda, E; Onatra, W; Robles, C; Saavedra, J; Sánchez, H; Tserotas, K; Vallejo, M S; Vallejo, C

2014-08-01

Menopausal hormone therapy (HT) has shown benefits for women; however, associated drawbacks (i.e. risks, costs, fears) have currently determined its low use. To determine the prevalence of current HT use among mid-aged women and describe the characteristics of those who have never used, have abandoned or are currently using HT. In addition, reasons for not using HT were analyzed. This was a cross-sectional study that analyzed a total of 6731 otherwise healthy women (45-59 years old) of 15 cities in 11 Latin American countries. Participants were requested to fill out the Menopause Rating Scale (MRS) and a questionnaire containing sociodemographic data and items regarding the menopause and HT use. The prevalence of current HT use was 12.5%. Oral HT (43.7%) was the most frequently used type of HT, followed by transdermal types (17.7%). The main factors related to the current use of HT included: positive perceptions regarding HT (odds ratio (OR) 11.53, 95% confidence interval (CI) 9.41-14.13), being postmenopausal (OR 3.47, 95% CI 2.75-4.36) and having a better socioeconomic level. A total of 48.8% of surveyed women had used HT in the past, but abandoned it due to symptom improvement or being unconcerned; fear of cancer or any other secondary effects were also reported but in less than 10%. Among women who had never used HT, 28% reported the lack of medical prescription as the main reason, followed by the absence of symptoms (27.8%). Among those reporting lack of prescription as the main reason for not using HT, 30.6% currently had severe menopausal symptoms (total MRS score > 16); 19.5% of women were using alternative 'natural' therapies, with 35.1% of them displaying severe menopausal symptoms as compared to a 22.5% observed among current HT users. The use of HT has not regained the rates observed a decade ago. Positive perceptions regarding HT were related to a higher use. Lack of medical prescription was the main reason for not using HT among non-users, many of whom were currently displaying severe menopausal symptoms.

Agonist properties of N,N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors.

PubMed

Smith, R L; Canton, H; Barrett, R J; Sanders-Bush, E

1998-11-01

Extensive behavioral and biochemical evidence suggests an agonist role at the 5-HT2A receptor, and perhaps the 5-HT2C receptor, in the mechanism of action of hallucinogenic drugs. However the published in vitro pharmacological properties of N,N-dimethyltryptamine (DMT), an hallucinogenic tryptamine analog, are not consistent with this hypothesis. We, therefore, undertook an extensive investigation into the properties of DMT at 5-HT2A and 5-HT2C receptors. In fibroblasts transfected with the 5-HT2A receptor or the 5-HT2C receptor, DMT activated the major intracellular signaling pathway (phosphoinositide hydrolysis) to an extent comparable to that produced by serotonin. Because drug efficacy changes with receptor density and cellular microenvironment, we also examined the properties of DMT in native preparations using a behavioral and biochemical approach. Rats were trained to discriminate an antagonist ketanserin from an agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in a two-lever choice paradigm. Pharmacological studies showed that responding on the DOI and ketanserin lever reflected agonist and antagonist activity at 5-HT2A receptors, and hence, was a suitable model for evaluating the in vivo functional properties of DMT. Like other 5-HT2A receptor agonists, DMT substituted fully for DOI. Intact choroid plexus was used to evaluate the agonist properties at endogenous 5-HT2C receptors; DMT was a partial agonist at 5-HT2C receptors in this native preparation. Thus, we conclude that DMT behaves as an agonist at both 5-HT2A and 5-HT2A receptors. One difference was evident in that the 5-HT2C, but not the 5-HT2A, receptor showed a profound desensitization to DMT over time. This difference is interesting in light of the recent report that the hallucinogenic activity of DMT does not tolerate in humans and suggests the 5-HT2C receptor plays a less prominent role in the action of DMT.

Investigation of 5-HT3 receptor-triggered serotonin release from guinea-pig isolated colonic mucosa: a role of PYY-containing endocrine cell.

PubMed

Kojima, Shu-Ichi; Kojima, Ken; Fujita, Tomoe

2017-03-15

The effect of a 5-HT 3 receptor-selective agonist SR57227A was investigated on the outflow of 5-hydroxytryptamine (5-HT) from isolated muscle layer-free mucosal preparations of guinea-pig colon. The mucosal preparations were incubated in vitro and the outflow of 5-HT from these preparations was determined by high-performance liquid chromatography with electrochemical detection. SR57227A (100μM) produced a tetrodotoxin-resistant and sustained increase in the outflow of 5-HT from the mucosal preparations. The SR57227A-evoked sustained 5-HT outflow was completely inhibited by the 5-HT 3 receptor antagonist ramosetron (1μM). The neuropeptide Y 1 receptor antagonist BIBO3304 (100nM) partially inhibited the SR57227A-evoked sustained 5-HT outflow, but the Y 2 receptor antagonist BIIE0246 (1μM) or the glucagon-like peptide-1 (GLP-1) receptor antagonist exendin-(9-39) (1μM), showed a minimal effect on the SR57227A-evoked sustained 5-HT outflow. In the presence of BIBO3304 (100nM) and exendin-(9-39) (1μM), SR57227A (100μM) failed to produce a sustained increase in the outflow of 5-HT. The Y 1 receptor agonist [Leu 31 , Pro 34 ]-neuropeptide Y (10nM), but not GLP-1-(7-36) amide (100nM), produced a sustained increase in the outflow of 5-HT. We found that 5-HT 3 receptor-triggered 5-HT release from guinea-pig colonic mucosa is mediated by the activation of 5-HT 3 receptors located at endocrine cells (enterochromaffin cells and peptide YY (PYY)-containing endocrine cells). The activation of both Y 1 and GLP-1 receptors appears to be required for the maintenance of 5-HT 3 receptor-triggered 5-HT release. It is therefore considered that 5-HT 3 receptors located at colonic mucosa play a crucial role in paracrine signaling between enterochromaffin cells and PYY-containing endocrine cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Environmental, Institutional, and Demographic Predictors of Environmental Literacy among Middle School Children

PubMed Central

Stevenson, Kathryn T.; Peterson, M. Nils; Bondell, Howard D.; Mertig, Angela G.; Moore, Susan E.

2013-01-01

Building environmental literacy (EL) in children and adolescents is critical to meeting current and emerging environmental challenges worldwide. Although environmental education (EE) efforts have begun to address this need, empirical research holistically evaluating drivers of EL is critical. This study begins to fill this gap with an examination of school-wide EE programs among middle schools in North Carolina, including the use of published EE curricula and time outdoors while controlling for teacher education level and experience, student attributes (age, gender, and ethnicity), and school attributes (socio-economic status, student-teacher ratio, and locale). Our sample included an EE group selected from schools with registered school-wide EE programs, and a control group randomly selected from NC middle schools that were not registered as EE schools. Students were given an EL survey at the beginning and end of the spring 2012 semester. Use of published EE curricula, time outdoors, and having teachers with advanced degrees and mid-level teaching experience (between 3 and 5 years) were positively related with EL whereas minority status (Hispanic and black) was negatively related with EL. Results suggest that school-wide EE programs were not associated with improved EL, but the use of published EE curricula paired with time outdoors represents a strategy that may improve all key components of student EL. Further, investments in teacher development and efforts to maintain enthusiasm for EE among teachers with more than 5 years of experience may help to boost student EL levels. Middle school represents a pivotal time for influencing EL, as improvement was slower among older students. Differences in EL levels based on gender suggest boys and girls may possess complementary skills sets when approaching environmental issues. Our findings suggest ethnicity related disparities in EL levels may be mitigated by time spent in nature, especially among black and Hispanic students. PMID:23533631

Synthesis, structures, and photophysical properties of π-expanded oligothiophene 8-mers and their Saturn-like C₆₀ complexes.

PubMed

Shimizu, Hideyuki; Cojal González, José D; Hasegawa, Masashi; Nishinaga, Tohru; Haque, Tahmina; Takase, Masayoshi; Otani, Hiroyuki; Rabe, Jürgen P; Iyoda, Masahiko

2015-03-25

Two isomers of a multifunctional π-expanded macrocyclic oligothiophene 8-mer, E,E-1 and Z,Z-1, were synthesized using a McMurry coupling of a dialdehyde composed of four 2,5-thienylene and three ethynylene units under high dilution conditions. On the other hand, cyclo[8](2,5-thienylene-ethynylene) 2 was synthesized by intramolecular Sonogashira cyclization of ethynyl bromide 5. From STM measurements, both E,E-1 and Z,Z-1 formed self-assembled monolayers at the solid-liquid interface to produce porous networks, and from X-ray analyses of E,E-1 and 2, both compounds had a round shape with a honeycomb stacked structure. E,E-1 formed various fibrous polymorphs due to nanophase separation of the macrorings. E,E-1 and Z,Z-1 in solution exhibited photochromism upon irradiation with visible and UV light, respectively, and this photoisomerization was confirmed by using STM. Furthermore, amorphous films of Z,Z-1 and E,E-1 showed photoisomerization, although single crystals, fibers, and square tubes of E,E-1 remained unchanged under similar conditions. E,E-1 with a 12.5-14.7 Å inner cavity incorporated fullerene C60 in the cavity in solution and the solid state to produce a Saturn-like complex, whose structure was determined by X-ray analysis. 2 also formed a Saturn-like complex with C60 in the solid state. These Saturn-like complexes are stabilized by van der Waals interactions between the sulfur atoms of 8-mer and C60. The complexes exhibited charge-transfer interactions in the solid state. Like E,E-1, Saturn-like complex E,E-1⊃C60 formed small cube and fiber structures depending on the solvent used, whereas those of Saturn-like complex 2⊃C60 were limited due to the rigidity of the macroring of 2.

A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microg ethinyl estradiol combined with 100 microg levonorgestrel.

PubMed

Skouby, Sven O; Endrikat, Jan; Düsterberg, Bernd; Schmidt, Werner; Gerlinger, Christoph; Wessel, Jens; Goldstein, Henri; Jespersen, Joergen

2005-02-01

To evaluate the impact on lipid and carbohydrate variables of a combined one-third ethinyl estradiol (EE)/levonorgestrel (LNG) dose reduction in oral contraceptives. In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg EE and 100 microg LNG (20 EE/100 LNG) was compared with a reference preparation containing 30 microg EE and 150 microg LNG (30 EE/150 LNG). One-year data from 48 volunteers were obtained. We found a decrease of HDL2 cholesterol and increases of low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and total triglycerides in both treatment groups from baseline to the 13th treatment cycle. Although for four of six variables, the changes in the 20 EE group were lower compared with the 30 EE group, none of the differences between the two treatments were statistically significant. The median values for the fasting levels of insulin, C-peptide and free fatty acids slightly increased or remained unchanged while the fasting glucose levels slightly decreased after 13 treatment cycles. While the glucose area under the curve (AUC) (0-3 h) was similar in both groups during the OGTT, the insulin AUC(0-3 h) was less increased in the 20 EE/100 LNG group compared with the 30 EE/150 LNG group. None of the differences between the treatment groups for any of the carbohydrate metabolism variables were statistically significant at any time point. Both study treatments were safe and well tolerated by the volunteers. Similar effects on the lipid and carbohydrate profiles were found for both preparations. The balanced one-third EE dose reduction in this new oral contraceptive caused slightly lower, but insignificant, changes in the lipid and carbohydrate variables compared with the reference treatment.

Predicting free-living energy expenditure using a miniaturized ear-worn sensor: an evaluation against doubly labeled water.

PubMed

Bouarfa, Loubna; Atallah, Louis; Kwasnicki, Richard Mark; Pettitt, Claire; Frost, Gary; Yang, Guang-Zhong

2014-02-01

Accurate estimation of daily total energy expenditure (EE)is a prerequisite for assisted weight management and assessing certain health conditions. The use of wearable sensors for predicting free-living EE is challenged by consistent sensor placement, user compliance, and estimation methods used. This paper examines whether a single ear-worn accelerometer can be used for EE estimation under free-living conditions.An EE prediction model as first derived and validated in a controlled setting using healthy subjects involving different physical activities. Ten different activities were assessed showing a tenfold cross validation error of 0.24. Furthermore, the EE prediction model shows a mean absolute deviation(MAD) below 1.2 metabolic equivalent of tasks. The same model was applied to a free-living setting with a different population for further validation. The results were compared against those derived from doubly labeled water. In free-living settings, the predicted daily EE has a correlation of 0.74, p 0.008, and a MAD of 272 kcal day. These results demonstrate that laboratory-derived prediction models can be used to predict EE under free-living conditions [corrected].

Study on Thermal Decomposition Characteristics of Ammonium Nitrate Emulsion Explosive in Different Scales

NASA Astrophysics Data System (ADS)

Wu, Qiujie; Tan, Liu; Xu, Sen; Liu, Dabin; Min, Li

2018-04-01

Numerous accidents of emulsion explosive (EE) are attributed to uncontrolled thermal decomposition of ammonium nitrate emulsion (ANE, the intermediate of EE) and EE in large scale. In order to study the thermal decomposition characteristics of ANE and EE in different scales, a large-scale test of modified vented pipe test (MVPT), and two laboratory-scale tests of differential scanning calorimeter (DSC) and accelerating rate calorimeter (ARC) were applied in the present study. The scale effect and water effect both play an important role in the thermal stability of ANE and EE. The measured decomposition temperatures of ANE and EE in MVPT are 146°C and 144°C, respectively, much lower than those in DSC and ARC. As the size of the same sample in DSC, ARC, and MVPT successively increases, the onset temperatures decrease. In the same test, the measured onset temperature value of ANE is higher than that of EE. The water composition of the sample stabilizes the sample. The large-scale test of MVPT can provide information for the real-life operations. The large-scale operations have more risks, and continuous overheating should be avoided.

Current maternal depression moderates the relation between critical expressed emotion in mothers and depressive symptoms in their adolescent daughters.

PubMed

Mellick, William; Kalpakci, Allison; Sharp, Carla

2015-06-30

Prior studies have examined critical expressed emotion (EE-Crit) in mothers in the intergenerational transmission of depression. However, the potential moderating effect of maternal depression diagnostic status in relation to EE-Crit and youth depressive symptoms has yet to be determined. A total of N=121 biological mother/daughter dyads that differed in maternal depression diagnostic status were recruited for the present study: (1) currently depressed mothers (current depression, n=29); (2) formerly depressed mothers (past depression, n=39); and (3) mothers free from any psychiatric history (healthy controls, n=53). Mothers were administered structured clinical interviews and completed self-report measures of EE-Crit and psychopathology, and daughters self-reported depressive symptoms. Results indicated no significant group differences in EE-Crit; however, current maternal depression status moderated EE-Crit such that the magnitude of the relation between EE-Crit and adolescent depressive symptoms was significantly greater in daughters of currently depressed mothers. These findings highlight the importance of considering current maternal depression, rather than a history of maternal depression, in relation to EE-Crit and adolescent depressive symptoms, providing impetus for future investigations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment

PubMed Central

Muller, Christopher L; Anacker, Allison MJ; Rogers, Tiffany D; Goeden, Nick; Keller, Elizabeth H; Forsberg, C Gunnar; Kerr, Travis M; Wender, Carly LA; Anderson, George M; Stanwood, Gregg D; Blakely, Randy D; Bonnin, Alexandre; Veenstra-VanderWeele, Jeremy

2017-01-01

Biomarker, neuroimaging, and genetic findings implicate the serotonin transporter (SERT) in autism spectrum disorder (ASD). Previously, we found that adult male mice expressing the autism-associated SERT Ala56 variant have altered central serotonin (5-HT) system function, as well as elevated peripheral blood 5-HT levels. Early in gestation, before midbrain 5-HT projections have reached the cortex, peripheral sources supply 5-HT to the forebrain, suggesting that altered maternal or placenta 5-HT system function could impact the developing embryo. We therefore used different combinations of maternal and embryo SERT Ala56 genotypes to examine effects on blood, placenta and embryo serotonin levels and neurodevelopment at embryonic day E14.5, when peripheral sources of 5-HT predominate, and E18.5, when midbrain 5-HT projections have reached the forebrain. Maternal SERT Ala56 genotype was associated with decreased placenta and embryonic forebrain 5-HT levels at E14.5. Low 5-HT in the placenta persisted, but forebrain levels normalized by E18.5. Maternal SERT Ala56 genotype effects on forebrain 5-HT levels were accompanied by a broadening of 5-HT-sensitive thalamocortical axon projections. In contrast, no effect of embryo genotype was seen in concepti from heterozygous dams. Blood 5-HT levels were dynamic across pregnancy and were increased in SERT Ala56 dams at E14.5. Placenta RNA sequencing data at E14.5 indicated substantial impact of maternal SERT Ala56 genotype, with alterations in immune and metabolic-related pathways. Collectively, these findings indicate that maternal SERT function impacts offspring placental 5-HT levels, forebrain 5-HT levels, and neurodevelopment. PMID:27550733

Gaddum and LSD: the birth and growth of experimental and clinical neuropharmacology research on 5-HT in the UK

PubMed Central

Green, A R

2008-01-01

The vasoconstrictor substance named serotonin was identified as 5-hydroxytryptamine (5-HT) by Maurice Rapport in 1949. In 1951, Rapport gave Gaddum samples of 5-HT substance allowing him to develop a bioassay to both detect and measure the amine. Gaddum and colleagues rapidly identified 5-HT in brain and showed that lysergic acid diethylamide (LSD) antagonized its action in peripheral tissues. Gaddum accordingly postulated that 5-HT might have a role in mood regulation. This review examines the role of UK scientists in the first 20 years following these major discoveries, discussing their role in developing assays for 5-HT in the CNS, identifying the enzymes involved in the synthesis and metabolism of 5-HT and investigating the effect of drugs on brain 5-HT. It reviews studies on the effects of LSD in humans, including Gaddum's self-administration experiments. It outlines investigations on the role of 5-HT in psychiatric disorders, including studies on the effect of antidepressant drugs on the 5-HT concentration in rodent and human brain, and the attempts to examine 5-HT biochemistry in the brains of patients with depressive illness. It is clear that a rather small group of both preclinical scientists and psychiatrists in the UK made major advances in our understanding of the role of 5-HT in the brain, paving the way for much of the knowledge now taken for granted when discussing ways that 5-HT might be involved in the control of mood and the idea that therapeutic drugs used to alleviate psychiatric illness might alter the function of cerebral 5-HT. PMID:18516072

Control of hypertension in treated children and its association with target organ damage.

PubMed

Seeman, Tomáš; Dostálek, Lukáš; Gilík, Jiří

2012-03-01

The aim of our study was to investigate the control of hypertension (HT) in treated children using ambulatory blood pressure (BP) monitoring (ABPM). We retrospectively reviewed all ABPM studies in our center. Controlled HT was defined as systolic and diastolic BP index (patients' BP divided by the 95th percentile) at daytime and nighttime <1.0 or alternatively as BP load (percentage of BP readings above the 95th percentile) <25% in children on antihypertensive therapy. A total of 195 ABPM studies were included. The mean age was 13.6 ± 4.0 years. One hundred and thirty two children had renoparenchymal HT, 10 renovascular (RVH), 10 endocrine, 4 cardiovascular, 29 primary (PH) and 5 children other forms of HT. 53% of all children had controlled HT. There was no difference in the prevalence of controlled HT between primary and secondary HT (52% and 53%) using the BP index criterion. Children with renoparenchymal HT had significantly better control of HT than children with RVH (58% vs. 20% P = 0.02). The use of angiotensin-converting enzyme inhibitors (ACEI) monotherapy was significantly more effective in controlling HT than the use of calcium-channel blockers (CCB, P = 0.02). The prevalence of left ventricular hypertrophy in children with uncontrolled HT (assessed in 58 patients) was significantly higher than in children with controlled HT (46% vs. 13%, P < 0.01). This is the first pediatric study, to our knowledge, on BP control in hypertensive children using ABPM. It indicates that control of HT is inadequate in ~50% of treated children. Inadequate control of HT is associated with target organ damage in this population. © 2012 American Journal of Hypertension, Ltd.

Aggressive Encounters Alter the Activation of Serotonergic Neurons and the Expression of 5-HT1A mRNA in the Hamster Dorsal Raphe Nucleus

PubMed Central

Cooper, Matthew A.; Grober, Matthew S.; Nicholas, Christopher; Huhman, Kim L.

2009-01-01

Serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN) have been implicated in stress-induced changes in behavior. Previous research indicates that stressful stimuli activate 5-HT neurons in select subregions of the DRN. Uncontrollable stress is thought to sensitize 5-HT neurons in the DRN and allow for an exaggerated 5-HT response to future stimuli. In the current study, we tested the hypothesis that following aggressive encounters, losing male Syrian hamsters would exhibit increased c-Fos immunoreactivity in 5-HT DRN neurons compared to winners or controls. In addition, we tested the hypothesis that losers would have decreased 5-HT1A mRNA levels in the DRN compared to winners or controls. We found that a single 15-min aggressive encounter increased c-Fos expression in 5-HT and non-5-HT neurons in losers compared to winners and controls. The increased c-Fos expression in losers was restricted to ventral regions of the rostral DRN. We also found that four 5-min aggressive encounters reduced total 5-HT1A mRNA levels in the DRN in losers compared to winners and controls, and that differences in mRNA levels were not restricted to specific DRN subregions. These results suggest that social defeat activates neurons in select subregions of the DRN and reduces message for DRN 5-HT1A autoreceptors. Our results support the hypothesis that social stress can activate 5-HT neurons in the DRN, reduce 5-HT1A autoreceptor-mediated inhibition, and lead to hyperactivity of 5-HT neurons. PMID:19362123

Relationship of ROS accumulation and superoxide dismutase isozymes in developing anther with floret fertility of rice under heat stress.

PubMed

Zhao, Qian; Zhou, Lujian; Liu, Jianchao; Du, Xiaoxia; Asad, Muhammad-Asad-Ullah; Huang, Fudeng; Pan, Gang; Cheng, Fangmin

2018-01-01

High temperature (HT) at meiosis stage is one of most important environment constraint affecting spikelet fertility and rice yield. In this paper, the effects of HT exposure at meiosis stage on the ROS (reactive oxygen species) accumulation, various superoxide dismutase (SOD, EC1.15.1.11) isozymes in developing anther, and its relationship with HT-induced decline in pollen viability and floret fertility were investigated by using four rice cultivars differing in heat tolerance under well-controlled climatic condition. Results showed that HT exposure significantly increased ROS level and malondialdehyde (MDA) content in rice anther, and this occurrence was strongly responsible for the HT-induced decline in pollen viability and harmful effect of HT adversity on floret fertility. However, the increased extent of ROS concentration in rice anther under HT exposure was greatly variable, depending on both the intensity and duration of HT exposure and different rice cultivars used. The SOD and CAT activities of HT-sensitive cultivars decreased more profoundly than those of HT-tolerant cultivars under the same HT regimes. Among various types of SOD enzymes, Cu/Zn-SODa expressed highly in rice anther and responded sensitively to HT exposure, while Cu/Zn-SODb expressed weakly in rice anther and preferentially in rice leaves. HT exposure suppressed the expression of Cu/Zn-SODa in developing anther, which was closely associated with the down-regulated transcripts of cCu/Zn-SOD1 gene. Hence, Cu/Zn-SODa may play a central role in the regulation of total SOD activity and ROS detoxification in rice anther as affected by HT exposure at meiosis stage. Copyright © 2017. Published by Elsevier Masson SAS.

Gaddum and LSD: the birth and growth of experimental and clinical neuropharmacology research on 5-HT in the UK.

PubMed

Green, A R

2008-08-01

The vasoconstrictor substance named serotonin was identified as 5-hydroxytryptamine (5-HT) by Maurice Rapport in 1949. In 1951, Rapport gave Gaddum samples of 5-HT substance allowing him to develop a bioassay to both detect and measure the amine. Gaddum and colleagues rapidly identified 5-HT in brain and showed that lysergic acid diethylamide (LSD) antagonized its action in peripheral tissues. Gaddum accordingly postulated that 5-HT might have a role in mood regulation. This review examines the role of UK scientists in the first 20 years following these major discoveries, discussing their role in developing assays for 5-HT in the CNS, identifying the enzymes involved in the synthesis and metabolism of 5-HT and investigating the effect of drugs on brain 5-HT. It reviews studies on the effects of LSD in humans, including Gaddum's self-administration experiments. It outlines investigations on the role of 5-HT in psychiatric disorders, including studies on the effect of antidepressant drugs on the 5-HT concentration in rodent and human brain, and the attempts to examine 5-HT biochemistry in the brains of patients with depressive illness. It is clear that a rather small group of both preclinical scientists and psychiatrists in the UK made major advances in our understanding of the role of 5-HT in the brain, paving the way for much of the knowledge now taken for granted when discussing ways that 5-HT might be involved in the control of mood and the idea that therapeutic drugs used to alleviate psychiatric illness might alter the function of cerebral 5-HT.

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

PubMed

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; De Maeyer, J H; Stanghellini, V

2012-04-01

The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. © 2012 Blackwell Publishing Ltd.

Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

PubMed Central

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

2012-01-01

Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5-HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5-HT4 agonists for GI disorders differ in chemical structure and selectivity for 5-HT4 receptors. Selectivity for 5-HT4 over non-5-HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT4 agonists may offer improved safety to treat patients with impaired GI motility. PMID:22356640

Adult AMPA GLUA1 receptor subunit loss in 5-HT neurons results in a specific anxiety-phenotype with evidence for dysregulation of 5-HT neuronal activity.

PubMed

Weber, Tillmann; Vogt, Miriam A; Gartside, Sarah E; Berger, Stefan M; Lujan, Rafael; Lau, Thorsten; Herrmann, Elke; Sprengel, Rolf; Bartsch, Dusan; Gass, Peter

2015-05-01

Both the glutamatergic and serotonergic (5-HT) systems are implicated in the modulation of mood and anxiety. Descending cortical glutamatergic neurons regulate 5-HT neuronal activity in the midbrain raphe nuclei through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors. To analyze the functional role of GLUA1-containing AMPA receptors in serotonergic neurons, we used the Cre-ERT2/loxP-system for the conditional inactivation of the GLUA1-encoding Gria1 gene selectively in 5-HT neurons of adult mice. These Gria1(5-HT-/-) mice exhibited a distinct anxiety phenotype but showed no alterations in locomotion, depression-like behavior, or learning and memory. Increased anxiety-related behavior was associated with significant decreases in tryptophan hydroxylase 2 (TPH2) expression and activity, and subsequent reductions in tissue levels of 5-HT, its metabolite 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine in the raphe nuclei. However, TPH2 expression and activity as well as monoamine levels were unchanged in the projection areas of 5-HT neurons. Extracellular electrophysiological recordings of 5-HT neurons revealed that, while α1-adrenoceptor-mediated excitation was unchanged, excitatory responses to AMPA were enhanced and the 5-HT1A autoreceptor-mediated inhibitory response to 5-HT was attenuated in Gria1(5-HT-/-) mice. Our data show that a loss of GLUA1 protein in 5-HT neurons enhances AMPA receptor function and leads to multiple local molecular and neurochemical changes in the raphe nuclei that dysregulate 5-HT neuronal activity and induce anxiety-like behavior.

Vortioxetine restores reversal learning impaired by 5-HT depletion or chronic intermittent cold stress in rats.

PubMed

Wallace, Ashley; Pehrson, Alan L; Sánchez, Connie; Morilak, David A

2014-10-01

Current treatments for depression, including serotonin-specific reuptake inhibitors (SSRIs), are only partially effective, with a high incidence of residual symptoms, relapse, and treatment resistance. Loss of cognitive flexibility, a component of depression, is associated with dysregulation of the prefrontal cortex. Reversal learning, a form of cognitive flexibility, is impaired by chronic stress, a risk factor for depression, and the stress-induced impairment in reversal learning is sensitive to chronic SSRI treatment, and is mimicked by serotonin (5-HT) depletion. Vortioxetine, a novel, multimodal-acting antidepressant, is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist, and inhibits the 5-HT transporter. Using adult male rats, we first investigated the direct effects of vortioxetine, acting at post-synaptic 5-HT receptors, on reversal learning that was compromised by 5-HT depletion using 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), effectively eliminating any contribution of 5-HT reuptake blockade. PCPA induced a reversal learning impairment that was alleviated by acute or sub-chronic vortioxetine administration, suggesting that post-synaptic 5-HT receptor activation contributes to the effects of vortioxetine. We then investigated the effects of chronic dietary administration of vortioxetine on reversal learning that had been compromised in intact animals exposed to chronic intermittent cold (CIC) stress, to assess vortioxetine's total pharmacological effect. CIC stress impaired reversal learning, and chronic vortioxetine administration prevented the reversal-learning deficit. Together, these results suggest that the direct effect of vortioxetine at 5-HT receptors may contribute to positive effects on cognitive flexibility deficits, and may enhance the effect of 5-HT reuptake blockade.

5-HT2C receptor involvement in the control of persistence in the reinforced spatial alternation animal model of obsessive-compulsive disorder.

PubMed

Papakosta, Vassiliki-Maria; Kalogerakou, Stamatina; Kontis, Dimitris; Anyfandi, Eleni; Theochari, Eirini; Boulougouris, Vasileios; Papadopoulos, Sokrates; Panagis, George; Tsaltas, Eleftheria

2013-04-15

The serotonergic system is implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, the distinct role of serotonin (5-HT) receptor subtypes remains unclear. This study investigates the contribution of 5-HT2A and 5-HT2C receptors in the modulation of persistence in the reinforced spatial alternation model of OCD. Male Wistar rats were assessed for spontaneous and pharmacologically induced (by m-chlorophenylpiperazine: mCPP) directional persistence in the reinforced alternation OCD model. Systemic administration of mCPP (non-specific 5-HT agonist, 2.5mg/kg), M100907 (selective 5-HT2A receptor antagonist, 0.08 mg/kg), SB242084 (selective 5-HT2C receptor antagonist, 0.5 mg/kg) and vehicle was used. Experiment 1 investigated M100907 and SB242084 effects in animals spontaneously exhibiting high and low persistence during the early stages of alternation training. Experiment 2 investigated M100900 and SB242084 effects on mCPP-induced persistence. Under the regime used in Experiment 1, 5-HT2A or 5-HT2C receptor antagonism did not affect spontaneous directional persistence in either high or low persistence groups. In Experiment 2, 5-HT2C but not 5-HT2A receptor antagonism significantly reduced, but did not abolish, mCPP-induced directional persistence. These findings suggest that 5-HT2C but not 5-HT2A receptors contribute to the modulation of mCPP-induced persistent behaviour, raising the possibility that the use of 5-HT2C antagonists may have a therapeutic value in OCD. Copyright © 2013 Elsevier B.V. All rights reserved.

Ontogeny of brain and blood serotonin levels in 5-HT receptor knockout mice: potential relevance to the neurobiology of autism.

PubMed

Janusonis, Skirmantas; Anderson, George M; Shifrovich, Ilya; Rakic, Pasko

2006-11-01

The most consistent neurochemical finding in autism has been elevated group mean levels of blood platelet 5-hydroxytryptamine (5-HT, serotonin). The origin and significance of this platelet hyperserotonemia remain poorly understood. The 5-HT(1A) receptor plays important roles in the developing brain and is also expressed in the gut, the main source of platelet 5-HT. Post-natal tissue levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan were examined in the brain, duodenum and blood of 5-HT(1A) receptor-knockout and wild-type mice. At 3 days after birth, the knockout mice had lower mean brain 5-HT levels and normal mean platelet 5-HT levels. Also, at 3 days after birth, the mean tryptophan levels in the brain, duodenum and blood of the knockout mice were around 30% lower than those of the wild-type mice. By 2 weeks after birth, the mean brain 5-HT levels of the knockout mice normalized, but their mean platelet 5-HT levels became 24% higher than normal. The possible causes of these dynamic shifts were explored by examining correlations between central and peripheral levels of 5-HT, 5-HIAA and tryptophan. The results are discussed in relation to the possible role of 5-HT in the ontogeny of autism.

Identification of spinal 5-HT sub 3 receptors and their role in the modulation of nociceptive responses in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glaum, S.R.

1988-01-01

The project consisted of two related studies: (1) the characterization of serotonin binding sites in crude and purified synaptic membranes prepared from the rat spinal cord, and (2) the association of serotonin binding sites with functional 5-HT receptor responses in the modulation of nociceptive information at the level of the spinal cord. The first series of experiments involved the preparation of membranes from the dorsal and ventral halves of the rat spinal cord and the demonstration of specific ({sup 3}H)serotonin binding to these membranes. High affinity binding sites which conformed to the 5-HT{sub 3} subtype were identified in dorsal, butmore » not ventral spinal cord synaptic membranes. These experiments also confirmed the presence of high affinity ({sup 3}H)5-HT binding sites in dorsal spinal cord synaptic membranes of the 5-HT{sub 1} subtype. The second group of studies demonstrated the ability of selective 5-HT{sub 3} antagonists to inhibit the antinociceptive response to intrathecally administered 5-HT, as measured by a change in tail flick and hot plate latencies. Intrathecal pretreatment with the selective 5-HT{sub 3} antagonists ICS 205-930 or MDL 72222 abolished the antinociceptive effects of 5-HT. Furthermore, the selective 5-HT{sub 3} agonist 2-methyl-5-HT mimicked the antinociceptive effects of 5-HT.« less

Translating 5-HT receptor pharmacology.

PubMed

Sanger, G J

2009-12-01

Since metoclopramide was first described (in 1964) there have been several attempts to develop compounds which retained gastrointestinal prokinetic activity (via 5-HT(4) receptor activation) but without the limiting side effects associated with dopamine D(2) receptor antagonism. Early compounds (mosapride, cisapride, renzapride, tegaserod) were identified before several of the 5-HT receptors were even described (including 5-HT(4) and 5-HT(2B)), whereas prucalopride came later. Several compounds were hampered by non-selectivity, introducing cardiac liability (cisapride: activity at human Ether-a-go-go Related Gene) or potentially, a reduced intestinal prokinetic activity caused by activity at a second 5-HT receptor (renzapride: antagonism at the 5-HT(3) receptor; tegaserod: antagonism at the 5-HT(2B) receptor). Poor intrinsic activity at gastrointestinal 5-HT(4) receptors has also been an issue (mosapride, tegaserod). Perhaps prucalopride has now achieved the profile of good selectivity of action and high intrinsic activity at intestinal 5-HT(4) receptors, without clinically-meaningful actions on 5-HT(4) receptors in the heart. The progress of this compound for treatment of chronic constipation, as well as competitor molecules such as ATI-7505 and TD-5108, will now be followed with interest as each attempts to differentiate themselves from each other. Perhaps at last, 5-HT(4) receptor agonists are being given the chance to show what they can do.

A Subpopulation of Serotonergic Neurons That Do Not Express the 5-HT1A Autoreceptor

PubMed Central

2012-01-01

5-HT neurons are topographically organized in the hindbrain, and have been implicated in the etiology and treatment of psychiatric diseases such as depression and anxiety. Early studies suggested that the raphe 5-HT neurons were a homogeneous population showing similar electrical properties, and feedback inhibition mediated by 5-HT1A autoreceptors. We utilized histochemistry techniques in ePet1-eGFP and 5-HT1A-iCre/R26R mice to show that a subpopulation of 5-HT neurons do not express the somatodendritic 5-HT1A autoreceptor mRNA. In addition, we performed patch-clamp recordings followed by single-cell PCR in ePet1-eGFP mice. From 134 recorded 5-HT neurons located in the dorsal, lateral, and median raphe, we found lack of 5-HT1A mRNA expression in 22 cells, evenly distributed across raphe subfields. We compared the cellular characteristics of these neuronal types and found no difference in passive membrane properties and general excitability. However, when injected with large depolarizing current, 5-HT1A-negative neurons fired more action potentials, suggesting a lack of autoinhibitory action of local 5-HT release. Our results support the hypothesis that the 5-HT system is composed of subpopulations of serotonergic neurons with different capacity for adaptation. PMID:23336048

The Type 7 Serotonin Receptor, 5-HT7, Is Essential in the Mammary Gland for Regulation of Mammary Epithelial Structure and Function

PubMed Central

Pai, Vaibhav P.; Hernandez, Laura L.; Stull, Malinda A.; Horseman, Nelson D.

2015-01-01

Autocrine-paracrine activity of serotonin (5-hydroxytryptamine, 5-HT) is a crucial homeostatic parameter in mammary gland development during lactation and involution. Published studies suggested that the 5-HT7 receptor type was important for mediating several effects of 5-HT in the mammary epithelium. Here, using 5-HT7 receptor-null (HT7KO) mice we attempt to understand the role of this receptor in mediating 5-HT actions within the mammary gland. We demonstrate for the first time that HT7KO dams are inefficient at sustaining their pups. Histologically, the HT7KO mammary epithelium shows a significant deviation from the normal secretory epithelium in morphological architecture, reduced secretory vesicles, and numerous multinucleated epithelial cells with atypically displaced nuclei, during lactation. Mammary epithelial cells in HT7KO dams also display an inability to transition from lactation to involution as normally seen by transition from a columnar to a squamous cell configuration, along with alveolar cell apoptosis and cell shedding. Our results show that 5-HT7 is required for multiple actions of 5-HT in the mammary glands including core functions that contribute to changes in cell shape and cell turnover, as well as specialized secretory functions. Understanding these actions may provide new interventions to improve lactation performance and treat diseases such as mastitis and breast cancer. PMID:25664318

Serotonin hyperinnervation and upregulated 5-HT2A receptor expression and motor-stimulating function in nigrostriatal dopamine-deficient Pitx3 mutant mice.

PubMed

Li, Li; Qiu, Guozhen; Ding, Shengyuan; Zhou, Fu-Ming

2013-01-23

The striatum receives serotonin (5-hydroxytryptamine, 5-HT) innervation and expresses 5-HT2A receptors (5-HT2ARs) and other 5-HT receptors, raising the possibility that the striatal 5-HT system may undergo adaptive changes after chronic severe dopamine (DA) loss and contribute to the function and dysfunction of the striatum. Here we show that in transcription factor Pitx3 gene mutant mice with a selective, severe DA loss in the dorsal striatum mimicking the DA denervation in late Parkinson's disease (PD), both the 5-HT innervation and the 5-HT2AR mRNA expression were increased in the dorsal striatum. Functionally, while having no detectable motor effect in wild type mice, the 5-HT2R agonist 2,5-dimethoxy-4-iodoamphetamine increased both the baseline and l-dopa-induced normal ambulatory and dyskinetic movements in Pitx3 mutant mice, whereas the selective 5-HT2AR blocker volinanserin had the opposite effects. These results demonstrate that Pitx3 mutant mice are a convenient and valid mouse model to study the compensatory 5-HT upregulation following the loss of the nigrostriatal DA projection and that the upregulated 5-HT2AR function in the DA deficient dorsal striatum may enhance both normal and dyskinetic movements. Copyright © 2012 Elsevier B.V. All rights reserved.

Oxidative damage and brain concentrations of free amino acid in chicks exposed to high ambient temperature.

PubMed

Chowdhury, Vishwajit S; Tomonaga, Shozo; Ikegami, Taro; Erwan, Edi; Ito, Kentaro; Cockrem, John F; Furuse, Mitsuhiro

2014-03-01

High ambient temperatures (HT) reduce food intake and body weight in young chickens, and HT can cause increased expression of hypothalamic neuropeptides. The mechanisms by which HT act, and the effects of HT on cellular homeostasis in the brain, are however not well understood. In the current study lipid peroxidation and amino acid metabolism were measured in the brains of 14 d old chicks exposed to HT (35 °C for 24- or 48-h) or to control thermoneutral temperature (CT; 30 °C). Malondialdehyde (MDA) was measured in the brain to determine the degree of oxidative damage. HT increased body temperature and reduced food intake and body weight gain. HT also increased diencephalic oxidative damage after 48 h, and altered some free amino acid concentrations in the diencephalon. Diencephalic MDA concentrations were increased by HT and time, with the effect of HT more prominent with increasing time. HT altered cystathionine, serine, tyrosine and isoleucine concentrations. Cystathionine was lower in HT birds compared with CT birds at 24h, whilst serine, tyrosine and isoleucine were higher at 48 h in HT birds. An increase in oxidative damage and alterations in amino acid concentrations in the diencephalon may contribute to the physiological, behavioral and thermoregulatory responses of heat-exposed chicks. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task.

PubMed

Meneses, Alfredo

2004-12-06

There is an important debate regarding the functional role of the 5-HT(1A) and 5-HT(7) receptor in memory systems. Hence, the objective of this paper is to investigate the function of serotonin (5-hydroxytryptamine, 5-HT) in memory consolidation, utilising an autoshaping Pavlovian/instrumental learning test. Specific antagonists at 5-HT(1A) (WAY 100635) and 5-HT(7) (SB-269970 or DR 4004) receptors administered i.p. or s.c.) after training, significantly decreased the improvement of performance produced by the 5-HT(1A/7) agonist 8-OH-DPAT to levels lower than controls'. These same antagonists attenuated the decreased level of performance produced by mCPP, although they decrease the performance levels after p-chloroamphetamine (PCA) lesion of the 5-HT system, which has no effect on its own on the conditioned response. Moreover, SB-269970 or DR 4004 reversed amnesia induced by scopolamine and dizocilpine. These data confirm a role for 5-HT(1A) and 5-HT(7) receptors in memory formation and support the hypothesis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals. These findings support a potential role for both 5-HT(1A) and 5-HT(7) receptors in the pathophysiology and/or treatment of schizophrenia, cognitive deficits and the mechanism of action of atypical antipsychotic drugs.

Effect of serotonin on platelet function in cocaine exposed blood

PubMed Central

Ziu, Endrit; Hadden, Coedy; Li, Yicong; Lowery, Curtis Lee; Singh, Preeti; Ucer, Serra S.; Mercado, Charles P.; Gu, Howard H.; Kilic, Fusun

2014-01-01

5-hydroxytryptamine (5-HT) reuptake inhibitors counteract the pro-thrombotic effect of elevated plasma 5-HT by down-regulating the 5-HT uptake rates of platelets. Cocaine also down-regulates the platelet 5-HT uptake rates but in contrast, the platelets of cocaine-injected mice show a much higher aggregation rate than the platelets of control mice. To examine the involvement of plasma 5-HT in cocaine-mediated platelet aggregation, we studied the function of platelets isolated from wild-type and transgenic, peripheral 5-HT knock-out (TPH1-KO) mice, and cocaine-insensitive dopamine transporter knock in (DAT-KI) mice. In cocaine-injected mice compared to the control mice, the plasma 5-HT level as well as the surface level of P-selectin was elevated; in vitro platelet aggregation in the presence of type I fibrillar collagen was enhanced. However, cocaine injection lowered the 5-HT uptake rates of platelets and increased the plasma 5-HT levels of the DAT-KI mice but did not change their platelets aggregation rates further which are already hyper-reactive. Furthermore, the in vitro studies supporting these in vivo findings suggest that cocaine mimics the effect of elevated plasma 5-HT level on platelets and in 5-HT receptor- and transporter-dependent pathways in a two-step process propagates platelet aggregation by an additive effect of 5-HT and nonserotonergic catecholamine. PMID:25091505

Extent and Determinants of Thermogenic Responses to 24 Hours of Fasting, Energy Balance, and Five Different Overfeeding Diets in Humans

PubMed Central

Pannacciulli, Nicola; Bonfiglio, Susan; Pacak, Karel; Krakoff, Jonathan

2013-01-01

Context: Individual variation in the ability to convert excess calories to heat and the effects of dietary macronutrient composition are unclear. Objective: Stability and determinants of the energy expenditure (EE) response to overconsumption were assessed. Design, Setting, and Participants: Twenty subjects (75% male) with normal glucose regulation were evaluated during 24 hours each of energy balance, fasting, and 5 different diets with 200% energy requirements in a clinical research unit. Interventions: Five 1-day overfeeding diets were given in random order: high carbohydrate (75%) and low protein (3%); high carbohydrate and normal protein (20%); high fat (46%) and low protein; high fat (60%) and normal protein; and balanced (50% carbohydrates, 20% protein). Main Outcome Measures: The 24-hour EE, sleeping EE, and thermic effect of food (TEF) during each diet were measured with a metabolic chamber. Appetitive hormones were measured before and after the diets. Results: The EE response to overfeeding exhibited good intraindividual reproducibility. Similar increases above eucaloric feeding in 24-hour EE (mean 10.7 ± 5.7%, P < .001; range 2.9–18.8%) and sleeping EE (14.4 ± 11.3%, P < .001; range 1.0–45.1%) occurred when overfeeding diets containing 20% protein, despite differences in fat and carbohydrate content, but the EE response during overfeeding diets containing 3% protein was attenuated. The percent body fat negatively correlated with TEF during normal protein overfeeding (r = −0.53, P < .01). Fasting peptide YY negatively correlated with TEF (r = −0.56, P < .01) and the increase in sleeping EE (r = −0.54, P < .01) during overfeeding. Conclusions: There is an intrinsic EE response to overfeeding that negatively associates with adiposity, although it represents a small percentage of consumed calories. PMID:23666976

Systematic Review and Quality Appraisal of Economic Evaluation Publications in Dentistry.

PubMed

Tonmukayakul, U; Calache, H; Clark, R; Wasiak, J; Faggion, C M

2015-10-01

Economic evaluation (EE) studies have been undertaken in dentistry since the late 20th century because economic data provide additional information to policy makers to develop guidelines and set future direction for oral health services. The objectives of this study were to assess the methodological quality of EEs in oral health. Electronic searching of Ovid MEDLINE, the Cochrane Library, and the NHS Economic Evaluation Database from 1975 to 2013 were undertaken to identify publications that include costs and outcomes in dentistry. Relevant reference lists were also searched for additional studies. Studies were retrieved and reviewed independently for inclusion by 3 authors. Furthermore, to appraise the EE methods, 1 author applied the Drummond 10-item (13-criteria) checklist tool to each study. Of the 114 publications identified, 79 studies were considered full EE and 35 partial. Twenty-eight studies (30%) were published between the years 2011 and 2013. Sixty-four (53%) studies focused on dental caries prevention or treatment. Median appraisal scores calculated for full and partial EE studies were 11 and 9 out of 13, respectively. Quality assessment scores showed that the quality of partial EE studies published after 2000 significantly improved (P = 0.02) compared to those published before 2000. Significant quality improvement was not found in full EE studies. Common methodological limitations were identified: absence of sensitivity analysis, discounting, and insufficient information on how costs and outcomes were measured and valued. EE studies in dentistry increased over the last 40 y in both quantity and quality, but a number of publications failed to satisfy some components of standard EE research methods, such as sensitivity analysis and discounting. © International & American Associations for Dental Research 2015.

Magnetoliposomes Loaded with Poly-Unsaturated Fatty Acids as Novel Theranostic Anti-Inflammatory Formulations

PubMed Central

Calle, Daniel; Negri, Viviana; Ballesteros, Paloma; Cerdán, Sebastián

2015-01-01

We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning 1H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved 1H resonances from highly mobile ω-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ω-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ω-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ω-3 PUFA-EE may become useful anti-inflammatory agents for image guided drug delivery. PMID:25767616

Media communication strategies for climate-friendly lifestyles - Addressing middle and lower class consumers for social-cultural change via Entertainment-Education

NASA Astrophysics Data System (ADS)

Lubjuhn, S.; Pratt, N.

2009-11-01

This paper argues that Entertainment-Education (E-E) is a striking communication strategy for reaching middle and lower socio-economic classes with climate-friendly lifestyle messages. On the international level (e.g. in the US and the Netherlands) E-E approaches are being theoretically grounded, whereas in Germany they are not yet. Therefore further theoretical discussion and mapping of E-E approaches is central for future research. As a first step towards providing further theoretical foundations for E-E in the field of sustainability, the authors suggest a threefold mapping of E-E approaches. The threefold mapping of E-E approaches for communicating climate-friendly lifestyles to middle and lower class consumers is based on recent results from academic research and practical developments on the media market. The commonalities among the three is that they all promote pro-sustainability messages in an affective-orientated rather than cognitive-orientated, factual manner. Differences can be found in: the sender of the sustainability message, the targeted consumer groups and the media approach in use. Based on this, the paper draws the conclusion that two new paths for further research activities in the field of Entertainment-Education can be proposed: (1) Improving the existing approaches in practice by using theoretical foundation from the E-E field. This comprises at its core (A) to do formative, process and summative effect research on the messages and (B) to use E-E theory from the field of social psychology, sociology and communication science for further improvement and (2) Generating new E-E theories by analyzing the existing practical approaches in the media to communicate climate change.

Environmental enrichment synergistically improves functional recovery by transplanted adipose stem cells in chronic hypoxic-ischemic brain injury.

PubMed

Seo, Jung Hwa; Kim, Hyongbum; Park, Eun Sook; Lee, Jong Eun; Kim, Dong Wook; Kim, Hyun Ok; Im, Sang Hee; Yu, Ji Hea; Kim, Ji Yeon; Lee, Min-Young; Kim, Chul Hoon; Cho, Sung-Rae

2013-01-01

We investigated the effects of environmental enrichment (EE) on the function of transplanted adipose stem cells (ASCs) and the combined effect of EE and ASC transplantation on neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in 7-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At 6 weeks of age, the mice were randomly injected with either ASCs or PBS into the striatum and were randomly assigned to either EE or standard cages (SC), comprising ASC-EE (n=18), ASC-SC (n=19), PBS-EE (n=12), PBS-SC (n=17), and untreated controls (n=23). Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. The fate of transplanted cells and the levels of endogenous neurogenesis, astrocyte activation, and paracrine factors were also measured. As a result, EE and ASC transplantation synergistically improved rotarod latency, forelimb-use asymmetry, and grip strength compared to those of the other groups. The number of engrafted ASCs and βIII-tubulin(+) neurons derived from the transplanted ASCs was significantly higher in mice in EE than those in SC. EE and ASC transplantation also synergistically increased BrdU(+)βIII-tubulin(+) neurons, GFAP(+) astrocytic density, and fibroblast growth factor 2 (FGF2) level but not the level of CS-56(+) glial scarring in the striatum. In conclusion, EE and ASC transplantation synergistically improved neurobehavioral functions. The underlying mechanisms of this synergism included enhanced repair processes such as higher engraftment of the transplanted ASCs, increased endogenous neurogenesis and astrocytic activation coupled with upregulation of FGF2.

Post-weaning Environmental Enrichment, But Not Chronic Maternal Isolation, Enhanced Ethanol Intake during Periadolescence and Early Adulthood

PubMed Central

Berardo, Luciana R.; Fabio, María C.; Pautassi, Ricardo M.

2016-01-01

This study analyzed ethanol intake in male and female Wistar rats exposed to maternal separation (MS) during infancy (postnatal days 1–21, PD1–21) and environmental enrichment (EE) during adolescence (PD 21–42). Previous work revealed that MS enhances ethanol consumption during adulthood. It is still unknown if a similar effect is found during adolescence. Several studies, in turn, have revealed that EE reverses stress experiences, and reduces ethanol consumption and reinforcement; although others reported greater ethanol intake after EE. The interactive effects between these treatments upon ethanol’s effects and intake have yet to be explored. We assessed chronic ethanol intake and preference (12 two-bottle daily sessions, spread across 30 days, 1st session on PD46) in rats exposed to MS and EE. The main finding was that male – but not female – rats that had been exposed to EE consumed more ethanol than controls given standard housing, an effect that was not affected by MS. Subsequent experiments assessed several factors associated with heightened ethanol consumption in males exposed to MS and EE; namely taste aversive conditioning and hypnotic-sedative consequences of ethanol. We also measured anxiety response in the light-dark box and in the elevated plus maze tests; and exploratory patterns of novel stimuli and behaviors indicative of risk assessment and risk-taking, via a modified version of the concentric square field (CSF) test. Aversive conditioning, hypnosis and sleep time were similar in males exposed or not to EE. EE males, however, exhibited heightened exploration of novel stimuli and greater risk taking behaviors in the CSF test. It is likely that the promoting effect of EE upon ethanol intake was due to these effects upon exploratory and risk-taking behaviors. PMID:27790100

Neural network versus activity-specific prediction equations for energy expenditure estimation in children.

PubMed

Ruch, Nicole; Joss, Franziska; Jimmy, Gerda; Melzer, Katarina; Hänggi, Johanna; Mäder, Urs

2013-11-01

The aim of this study was to compare the energy expenditure (EE) estimations of activity-specific prediction equations (ASPE) and of an artificial neural network (ANNEE) based on accelerometry with measured EE. Forty-three children (age: 9.8 ± 2.4 yr) performed eight different activities. They were equipped with one tri-axial accelerometer that collected data in 1-s epochs and a portable gas analyzer. The ASPE and the ANNEE were trained to estimate the EE by including accelerometry, age, gender, and weight of the participants. To provide the activity-specific information, a decision tree was trained to recognize the type of activity through accelerometer data. The ASPE were applied to the activity-type-specific data recognized by the tree (Tree-ASPE). The Tree-ASPE precisely estimated the EE of all activities except cycling [bias: -1.13 ± 1.33 metabolic equivalent (MET)] and walking (bias: 0.29 ± 0.64 MET; P < 0.05). The ANNEE overestimated the EE of stationary activities (bias: 0.31 ± 0.47 MET) and walking (bias: 0.61 ± 0.72 MET) and underestimated the EE of cycling (bias: -0.90 ± 1.18 MET; P < 0.05). Biases of EE in stationary activities (ANNEE: 0.31 ± 0.47 MET, Tree-ASPE: 0.08 ± 0.21 MET) and walking (ANNEE 0.61 ± 0.72 MET, Tree-ASPE: 0.29 ± 0.64 MET) were significantly smaller in the Tree-ASPE than in the ANNEE (P < 0.05). The Tree-ASPE was more precise in estimating the EE than the ANNEE. The use of activity-type-specific information for subsequent EE prediction equations might be a promising approach for future studies.

Interrelations of Maternal Expressed Emotion, Maltreatment, and Separation/Divorce and Links to Family Conflict and Children’s Externalizing Behavior

PubMed Central

Narayan, Angela; Cicchetti, Dante; Rogosch, Fred A.; Toth, Sheree L.

2014-01-01

Research has documented that maternal expressed emotion-criticism (EE-Crit) from the Five-Minute Speech Sample (FMSS) predicts family conflict and children’s externalizing behavior in clinical and community samples. However, studies have not examined EE-Crit in maltreating or separated/divorced families, or whether these family risks exacerbate the links between EE-Crit and family conflict and externalizing behavior. The current study examined the associations between maternal EE-Crit, maltreatment, and separation/divorce, and whether maltreatment and separation/divorce moderated associations between EE-Crit and children’s externalizing problems, and EE-Crit and family conflict. Participants included 123 children (M = 8.01 years, SD = 1.58; 64.2% males) from maltreating (n = 83) or low-income, comparison (n = 40) families, and 123 mothers (n = 48 separated/divorced). Mothers completed the FMSS for EE-Crit and the Family Environment Scale for family conflict. Maltreatment was coded with the Maltreatment Classification System using information from official Child Protection Services (CPS) reports from the Department of Human Services (DHS). Trained summer camp counselors rated children’s externalizing behavior. Maltreatment was directly associated with higher externalizing problems, and separation/divorce, but not maltreatment, moderated the association between EE-Crit and externalizing behavior. Analyses pertaining to family conflict were not significant. Findings indicate that maltreatment is a direct risk factor for children’s externalizing behavior and separation/divorce is a vulnerability factor for externalizing behavior in family contexts with high maternal EE-Crit. Intervention, prevention, and policy efforts to promote resilience in high-risk families may be effective in targeting maltreating and critical parents, especially those with co-occurring separation/divorce. PMID:25037461

Multigenerational effects of bisphenol A or ethinyl estradiol exposure on F2 California mice (Peromyscus californicus) pup vocalizations

PubMed Central

Johnson, Sarah A.; Farrington, Michelle J.; Murphy, Claire R.; McAllister, Leif A.; Kaur, Sarabjit; Chun, Catherine; Ortega, Madison T.; Marshall, Brittney L.; Hoffmann, Frauke; Ellersieck, Mark R.; Schenk, A. Katrin

2018-01-01

Rodent pups use vocalizations to communicate with one or both parents in biparental species, such as California mice (Peromyscus californicus). Previous studies have shown California mice developmentally exposed to endocrine disrupting chemicals, bisphenol A (BPA) or ethinyl estradiol (EE), demonstrate later compromised parental behaviors. Reductions in F1 parental behaviors might also be due to decreased emissions of F2 pup vocalizations. Thus, vocalizations of F2 male and female California mice pups born to F1 parents developmentally exposed to BPA, EE, or controls were examined. Postnatal days (PND) 2–4 were considered early postnatal period, PND 7 and 14 were defined as mid-postnatal period, and PND 21 and 28 were classified as late postnatal period. EE pups showed increased latency to emit the first syllable compared to controls. BPA female pups had decreased syllable duration compared to control and EE female pups during the early postnatal period but enhanced responses compared to controls at late postnatal period; whereas, male BPA and EE pups showed greater syllable duration compared to controls during early postnatal period. In mid-postnatal period, F2 BPA and EE pups emitted greater number of phrases than F2 control pups. Results indicate aspects of vocalizations were disrupted in F2 pups born to F1 parents developmentally exposed to BPA or EE, but their responses were not always identical, suggesting BPA might not activate estrogen receptors to the same extent as EE. Changes in vocalization patterns by F2 pups may be due to multigenerational exposure to BPA or EE and/or reduced parental care received. PMID:29912934

Predicting energy expenditure through hand rim propulsion power output in individuals who use wheelchairs.

PubMed

Conger, Scott A; Scott, Stacy N; Bassett, David R

2014-07-01

To examine the relationship between hand rim propulsion power and energy expenditure (EE) during wheelchair wheeling and to investigate whether adding other variables to the model could improve on the prediction of EE. Individuals who use manual wheelchairs (n=14) performed five different wheeling activities in a wheelchair with a PowerTap power meter hub built into the right rear wheel. Activities included wheeling on a smooth, level surface at three different speeds (4.5, 5.5 and 6.5 km/h), wheeling on a rubberised track at one speed (5.5 km/h) and wheeling on a sidewalk course that included uphill and downhill segments at a self-selected speed. EE was measured using a portable indirect calorimetry system. Stepwise linear regression was performed to predict EE from power output variables. A repeated-measures analysis of variance was used to compare the measured EE to the estimates from the power models. Bland-Altman plots were used to assess the agreement between the criterion values and the predicted values. EE and power were significantly correlated (r=0.694, p<0.001). Regression analysis yielded three significant prediction models utilising measured power; measured power and speed; and measured power, speed and heart rate. No significant differences were found between measured EE and any of the prediction models. EE can be accurately and precisely estimated based on hand rim propulsion power. These results indicate that power could be used as a method to assess EE in individuals who use wheelchairs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Body Segment Kinematics and Energy Expenditure in Active Videogames.

PubMed

Böhm, Birgit; Hartmann, Michael; Böhm, Harald

2016-06-01

Energy expenditure (EE) in active videogames (AVGs) is a component for assessing its benefit for cardiovascular health. Existing evidence suggests that AVGs are able to increase EE above rest and when compared with playing passive videogames. However, the association between body movement and EE remains unclear. Furthermore, for goal-directed game design, it is important to know the contribution of body segments to EE. This knowledge will help to acquire a certain level of exercise intensity during active gaming. Therefore, the purpose of this study was to determine the best predictors of EE from body segment energies, acceleration, and heart rate during different game situations. EE and body segment movement of 17 subjects, aged 22.1 ± 2.5 years, were measured in two different AVGs. In randomized order, the subjects played a handheld-controlled Nintendo(®) Wii™ tennis (NWT) game and a whole body-controlled Sony EyeToy(®) waterfall (ETW) game. Body segment movement was analyzed using a three-dimensional motion capture system. From the video data, mean values of mechanical energy change and acceleration of 10 body segments were analyzed. Measured EE was significantly higher in ETW (7.8 ± 1.4 metabolic equivalents [METs]) than in NWT (3.4 ± 1.0 METs). The best prediction parameter for the more intense ETW game was the energy change of the right thigh and for the less intense hand-controlled NWT game was the energy change of the upper torso. Segment acceleration was less accurate in predicting EE. The best predictors of metabolic EE were the thighs and the upper torso in whole body and handheld-controlled games, respectively. Increasing movement of these body segments would lead to higher physical activity intensity during gaming, reducing sedentary behavior.

Serotonin and decision making processes.

PubMed

Homberg, Judith R

2012-01-01

Serotonin (5-HT) is an important player in decision making. Serotonergic antidepressant, anxiolytic and antipsychotic drugs are extensively used in the treatment of neuropsychiatric disorders characterized by impaired decision making, and exert both beneficial and harmful effects in patients. Detailed insight into the serotonergic mechanisms underlying decision making is needed to strengthen the first and weaken the latter. Although much remains to be done to achieve this, accumulating studies begin to deliver a coherent view. Thus, high central 5-HT levels are generally associated with improved reversal learning, improved attentional set shifting, decreased delay discounting, and increased response inhibition, but a failure to use outcome representations. Based on 5-HT's evolutionary role, I hypothesize that 5-HT integrates expected, or changes in, relevant sensory and emotional internal/external information, leading to vigilance behaviour affecting various decision making processes. 5-HT receptor subtypes play distinctive roles in decision making. 5-HT(2A) agonists and 5-HT2c antagonists decrease compulsivity, whereas 5-HT(2A) antagonists and 5-HT(2C) agonists decrease impulsivity. 5-HT(6) antagonists univocally affect decision making processes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Serotonin 5-HT3 and 5-HT4 ligands: an update of medicinal chemistry research in the last few years.

PubMed

Modica, M N; Pittalà, V; Romeo, G; Salerno, L; Siracusa, M A

2010-01-01

The biogenic amine serotonin (5-hydroxytryptamine, 5-HT) is one of the most studied neurotransmitters in the central nervous system. It acts through the activation of at least fourteen 5-HT receptor subtypes. Over the last two decades, high attention was devoted to the 5-HT(3) and 5-HT(4) receptors due to their colocalization in the gastrointestinal tract and because their ligands are useful in the treatment of intestinal serotonergic system dysfunctions. The focus of this review is to discuss the literature concerning recent advances on 5-HT(3)R and 5-HT(4)R ligands and their structure-activity relationships from a medicinal chemistry perspective. During the last few years, new and significant progresses have been made in the field of novel potent and selective ligands, mixed ligands, agonists, partial agonists, and antagonists, and a number of patents have been filed. Furthermore several ligands targeting the 5-HT(3)R and 5-HT(4)R have been proposed for novel therapeutic indications such as the treatment of various psychiatric disorders.

Distinct circuits underlie the effects of 5-HT1B receptors on aggression and impulsivity

PubMed Central

Nautiyal, Katherine M.; Tanaka, Kenji F.; Barr, Mary M.; Tritschler, Laurent; Le Dantec, Yannick; David, Denis J.; Gardier, Alain M.; Blanco, Carlos; Hen, René; Ahmari, Susanne E.

2015-01-01

Summary Impulsive and aggressive behaviors are both modulated by serotonergic signaling, specifically through the serotonin 1B receptor (5-HT1BR). 5-HT1BR knockout mice show increased aggression and impulsivity, and 5-HT1BR polymorphisms are associated with aggression and drug addiction in humans. To dissect the mechanisms by which the 5-HT1BR affects these phenotypes, we developed a mouse model to spatially and temporally regulate 5-HT1BR expression. Our results demonstrate that forebrain 5-HT1B heteroreceptors expressed during an early postnatal period contribute to the development of the neural systems underlying adult aggression. However, distinct heteroreceptors acting during adulthood are involved in mediating impulsivity. Correlating with the impulsivity, dopamine in the nucleus accumbens is elevated in the absence of 5-HT1BRs, and normalized following adult rescue of the receptor. Overall, these data show that while adolescent expression of 5-HT1BRs influences aggressive behavior, a distinct set of 5-HT1B receptors modulate impulsive behavior during adulthood. PMID:25892302

Activation of serotonin 2C receptors in dopamine neurons inhibits binge-like eating in mice

PubMed Central

Xu, Pingwen; He, Yanlin; Cao, Xuehong; Valencia-Torres, Lourdes; Yan, Xiaofeng; Saito, Kenji; Wang, Chunmei; Yang, Yongjie; Hinton, Antentor; Zhu, Liangru; Shu, Gang; Myers, Martin G.; Wu, Qi; Tong, Qingchun; Heisler, Lora K.; Xu, Yong

2016-01-01

Background Neural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited. Methods We combined neuroanatomical, pharmacological, electrophysiological, Cre-lox, and chemogenetic approaches to investigate the functions of 5-HT 2C receptor (5-HT2CR) expressed by dopamine (DA) neurons in the regulation of binge-like eating behavior in mice. Results We showed that 5-HT stimulates DA neural activity through a 5-HT2CR-mediated mechansim, and activation of this midbrain 5-HT-DA neural circuit effectively inhibits binge-like eating behavior in mice. Notably, 5-HT medications, including fluoxetine, d-Fenfluramine, and lorcaserin (a selective 5-HT2CR agonist), act upon 5-HT2CRs expressed by DA neurons to inhibit binge-like eating in mice. Conclusions We identified the 5-HT2CR population in DA neurons as one potential target for anti-binge therapies, and provided pre-clinical evidence that 5-HT2CR agonists could be used to treat binge eating. PMID:27516377

Selective increases in serotonin 5-HT1B/1D and 5-HT2A/2C binding sites in adult rat basal ganglia following lesions of serotonergic neurons.

PubMed

Compan, V; Segu, L; Buhot, M C; Daszuta, A

1998-05-18

Quantitative autoradiography was used to examine possible adaptive changes in serotonin 5-HT1B/1D and 5-HT2A/2C receptor binding sites in adult rat basal ganglia, after partial or severe lesions of serotonergic neurons produced by intraraphe injections of variable amounts of 5,7-dihydroxytryptamine. In controls, the 5-HT1B/1D sites labeled with S-CM-G[125I]TNH2 were evenly distributed in the core and the shell of the nucleus accumbens. The density of 5-HT1B/1D sites was higher in the ventral than dorsal part of the striatum and no regional differences were detected along the rostrocaudal axis of the structure. The 5-HT2A/2C sites labeled with [125I]DOI were preferentially distributed in the mediodorsal striatum and higher densities were detected in the shell than core of the nucleus accumbens. Following 5,7-dihydroxytryptamine injections, there were no changes in binding of either receptor subtype after partial lesions entailing 80-90% 5-HT depletions. After severe 5-HT depletions (over 95%), large increases in 5-HT1B/1D binding were observed in the substantia nigra (78%), but no changes took place in the globus pallidus. Increases in 5-HT1B/1D binding were also detected in the shell of the nucleus accumbens (27%). Similar sized increases in 5-HT2A/2C binding (22%) were restricted to the medial striatum. The present results suggest a preferential association between 5-HT1B/1D receptors and the striatonigral neurons containing substance P, as indicated by the striatal distribution of these receptors and their selective increases in the substantia nigra after severe 5-HT deprivation. We recently proposed a similar relationship between the 5-HT4 receptors and the striatopallidal neurons containing met-enkephalin. Moreover, the increases in 5-HT1B/1D binding in the substantia nigra and in the shell of the nucleus accumbens reinforce the view of an implication of this receptor subtype in motor functions. In contrast, the prominent increases in 5-HT2A/2C binding after severe 5-HT deprivation as restricted to the medial region of the striatum and suggest up-regulation of most probably 5-HT2C receptors in a region implicated in cognitive functions. Copyright 1998 Elsevier Science B. V.

Apamin increases 5-HT cell firing in raphe dorsalis and extracellular 5-HT levels in amygdala: a concomitant in vivo study in anesthetized rats.

PubMed

Crespi, F

2009-07-24

The family of calcium-activated slow-potassium (SK) channels comprises 3 members, the SK1, SK2 and SK3 channels, all expressed in neurons, known to mediate the slow-afterhyperpolarization occurring after action potentials. In rats, the SK2 and SK3 channels are expressed in the ascending monoaminergic systems, in particular in the serotonin (5-HT) neurons of the raphe dorsalis nucleus (RDN). In mammals the amygdala, a limbic structure involved in the control of emotion and mood, receives 5-HT-containing projections originating in the RDN. The aim of the present study was to investigate the role of SK channels in mediating the release of 5-HT in the amygdala. Apamin, a polypeptiditic compound with SK2-SK3 channel selectivity, was used to block the channels. A dual probing methodology with Nafion coated carbon-fiber micro-electrode (Nafion-mCFE) was implemented to measure concomitantly the extracellular levels of 5-HT in the amygdala and the firing rate of 5-HT neurons in the RDN of anesthetized rats. Subcutaneous administration of apamin increased both the extracellular 5-HT levels in the amygdala and the firing rate of RDN neurons at doses as low as 12.5 microg. The recorded RDN neurons were of 5-HT phenotype, according to electrophysiologic signature and to the effects observed with peripheral administration of 8-hydroxy-2-(d-n-propyl-amino) tetralin (8-OH-DPAT) a 5-HT(1A) agonist known to selectively reduce the firing of 5-HT neurons in RDN. Increases of extracellular 5-HT levels in the amygdala were also seen when apamin was microinjected into the RDN, suggesting a role for 5-HT neurons of the RDN as target for subcutaneously administered apamin. The confirmation of the involvement of 5-HT neurons projecting from RDN to the amygdala in mediating the effects of apamin was obtained by micro-infusion of tetradotoxine into the bundle of 5-HT ascending fibers located in the region of the posterior amygdala. Attenuation of 5-HT release in the amygdala was observed in presence of increased firing of 5-HT neurons of the RDN. In conclusion, the dual CFE micro-sensor probing approach was used to show that apamin increases 5-HT release in the amygdala by increasing the firing rate of 5-HT neurons in RDN.

Environmental education: A blueprint for achievement?

DOE Office of Scientific and Technical Information (OSTI.GOV)

McErlean, A.J.; Williams, E.; Wittwer, F.

1995-09-01

The present national effort devoted to environmental education (EE), particularly as it relates to K-12 education, is examined and indexed to other current events and their support levels. For the most part, EE efforts are embedded in science, mathematics, and engineering programs (SME), and the relationships to these other areas are discussed. In the present context, many aspects such as social, ethical, and religious consideration of EE are not addressed. The relationships between EE and the expectation for scientific literacy (SL) and improved environmental decision-making in both short- and long-term contexts are also examined. Under existing programs, the prognosis formore » serious, effective accomplishment, or credible impact on universal EE literacy or enhanced decision-making, is doubtful.« less

5-hydroxytryptamine level and 5-HT2A receptor mRNA expression in the guinea pigs eyes with spectacle lens-induced myopia

PubMed Central

Yang, Ji-Wen; Xu, Yan-Chun; Sun, Lin; Tian, Xiao-Dan

2010-01-01

AIM To investigate 5-hydroxytryptamine (5-HT) function and 5-HT receptor 2A (5-HT2A) mRNA expression in the formation of lens-induced myopia (LIM). METHODS Lens-induced myopia construction method was applied to generate myopia on guinea pig right eye (LIM eye). RESULTS LIM eyes formed significant myopia with longer axial length. 5-HT level in retina, choroids and sclera from LIM eyes was significantly higher than that in control group. 5-HT2A mRNA expression was also significantly up-regulated. CONCLUSION Refraction lens could induce myopia in guinea pig and 5-HT may play an important role in the formation of myopia by binding with 5-HT2A receptor. PMID:22553578

Effect of 5-hydroxytryptamine on duodenal mucosal bicarbonate secretion in mice.

PubMed

Tuo, Bi-Guang; Isenberg, Jon I

2003-09-01

5-hydroxytryptamine (5-HT) is an important neurotransmitter and intercellular messenger that modulates many gastrointestinal functions. Because little is known about the role of 5-HT in the regulation of duodenal bicarbonate secretion, we examined the role of 5-HT on duodenal bicarbonate secretion and define neural pathways involved in the actions of 5-HT. Duodenal mucosa from National Institutes of Health Swiss mice was stripped of seromuscular layers and mounted in Ussing chambers. The effect of 5-HT on duodenal bicarbonate secretion was determined by the pH stat technique. Acetylcholine (ACh) release from duodenal mucosa was assessed by preincubating the tissue with [(3)H] choline and measuring 5-HT-evoked release of tritium. 5-HT added to the serosal bath markedly stimulated duodenal bicarbonate secretion and short circuit current (Isc) in a dose-dependent manner (10(-7) mol/L to 10(-3) mol/L; P < 0.0001), whereas mucosally added 5-HT was without effect. 5-HT-stimulated bicarbonate secretion was independent of luminal Cl(-). Pretreatment with tetrodotoxin (TTX) (10(-6) mol/L) or atropine (10(-5) mol/L) markedly reduced 5-HT-stimulated duodenal bicarbonate secretion (by 60% and 65%, respectively; P < 0.001) and Isc (by 45% and 27%, respectively; P < 0.001 and P < 0.05). Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME) (10(-3) mol/L), propranolol (10(-5) mol/L), or phentolamine (10(-5) mol/L) did not significantly alter 5-HT-stimulated duodenal mucosal bicarbonate secretion or Isc. 5-HT concentration-dependently evoked ACh release from duodenal mucosal preparations (P < 0.0001). TTX markedly inhibited 5-HT-evoked ACh release (P < 0.001). 5-HT is a potent activator of duodenal mucosal bicarbonate secretion in mice. Duodenal bicarbonate secretion induced by 5-HT in vitro occurs principally via a cholinergic neural pathway.

Serotonin- and two putative serotonin receptors-like immunohistochemical reactivities in the ground crickets Dianemobius nigrofasciatus and Allonemobius allardi.

PubMed

Shao, Qi-Miao; Fouda, Maged Mohamed Ali; Takeda, Makio

2010-11-01

Serotonin (5-hydroxytryptamine; 5-HT)- and two putative serotonin receptors, 5-HT1A- and 5-HT1B-like, immunohistochemical reactivities were investigated in the cephalic ganglia of two ground crickets, Dianemobius nigrofasciatus and Allonemobius allardi. 5-HT-ir was strongly expressed in the central body, accessory medulla region of the optic lobe, frontal ganglion, posterior cortex of the protocerebrum, dorsolateral region of the protocerebrum, and the suboesphageal ganglion (SOG) in both crickets. However, 5-HT1A-ir and 5-HT1B-ir showed quite mutually distinct patterns that were also distinct from 5-HT-ir. 5-HT1A-ir was located in the pars intercerebralis, dorsolateral region of the protocerebrum, optic tract, optic lobe, and the midline of the SOG in both crickets. 5-HT1B-ir was located in the pars intercerebralis and dorsolateral region of the protocerebrum, and detected weakly in the optic lobe, tritocerebrum, and the midline of the SOG in both crickets. Interspecific differences were observed with 5-HT1A-ir. 5-HT1A-ir was expressed weakly in two neurons in the mandibular neuromere of the SOG in D. nigrofasciatus, while it was expressed strongly in the tritocerebrum, mandibular neuromere, and maxillary neuromere of the SOG in A. allardi and co-localized with CLOCK-ir (CLK-ir). 5HT-1B-ir was co-localized with CLK-ir in the tritocerebrum, mandibular neuromere, and maxillary neuromere of the SOG when double-labeling was conducted in both crickets. These results indicated that 5-HT and both types of 5-HT receptors may regulate circadian photo-entrainment or photoperiodism in A. allardi, while only 5-HT1B may be involved in circadian photo-entrainment or photoperiodism in D. nigrofasciatus. Copyright 2010 Elsevier Ltd. All rights reserved.

Transglutaminase-dependent RhoA activation and depletion by serotonin in vascular smooth muscle cells.

PubMed

Guilluy, Christophe; Rolli-Derkinderen, Malvyne; Tharaux, Pierre-Louis; Melino, Gerry; Pacaud, Pierre; Loirand, Gervaise

2007-02-02

The small G protein RhoA plays a major role in several vascular processes and cardiovascular disorders. Here we analyze the mechanisms of RhoA regulation by serotonin (5-HT) in arterial smooth muscle. 5-HT (0.1-10 microM) induced activation of RhoA followed by RhoA depletion at 24-72 h. Inhibition of 5-HT1 receptors reduced the early phase of RhoA activation but had no effect on 5-HT-induced delayed RhoA activation and depletion, which were suppressed by the 5-HT transporter inhibitor fluoxetine and the transglutaminase inhibitor monodansylcadaverin and in type 2 transglutaminase-deficient smooth muscle cells. Coimmunoprecipitations demonstrated that 5-HT associated with RhoA both in vitro and in vivo. This association was calcium-dependent and inhibited by fluoxetine and monodansylcadaverin. 5-HT promotes the association of RhoA with the E3 ubiquitin ligase Smurf1, and 5-HT-induced RhoA depletion was inhibited by the proteasome inhibitor MG132 and the RhoA inhibitor Tat-C3. Simvastatin, the Rho kinase inhibitor Y-27632, small interfering RNA-mediated RhoA gene silencing, and long-term 5-HT stimulation induced Akt activation. In contrast, inhibition of 5-HT-mediated RhoA degradation by MG132 prevented 5-HT-induced Akt activation. Long-term 5-HT stimulation also led to the inhibition of the RhoA/Rho kinase component of arterial contraction. Our data provide evidence that 5-HT, internalized through the 5-HT transporter, is transamidated to RhoA by transglutaminase. Transamidation of RhoA leads to RhoA activation and enhanced proteasomal degradation, which in turn is responsible for Akt activation and contraction inhibition. The observation of transamidation of 5-HT to RhoA in pulmonary artery of hypoxic rats suggests that this process could participate in pulmonary artery remodeling and hypertension.

Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone.

PubMed

Shortall, Sinead E; Spicer, Clare H; Ebling, Francis J P; Green, A Richard; Fone, Kevin C F; King, Madeleine V

2016-11-01

The psychoactive effects of mephedrone are commonly compared with those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action, users often employ repeated administration to maintain its psychoactive effects. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1 ml/kg, i.p.) or mephedrone HCl (10 mg/kg) at 2 h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (150 µg) or 6-hydroxydopamine (300 µg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30 min) with the 5-HT 1A receptor antagonist WAY-100635 (0.5 mg/kg), 5-HT 1B receptor antagonist GR 127935 (3 mg/kg) or the 5-HT 7 receptor antagonist SB-258719 (10 mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing) and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT 1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT 1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT 1B and 5-HT 1A receptors. © 2015 Society for the Study of Addiction.

5-HT3 and 5-HT4 antagonists inhibit peristaltic contractions in guinea-pig distal colon by mechanisms independent of endogenous 5-HT.

PubMed

Sia, Tiong C; Whiting, Malcolm; Kyloh, Melinda; Nicholas, Sarah J; Oliver, John; Brookes, Simon J; Dinning, Phil G; Wattchow, David A; Spencer, Nick J

2013-01-01

Recent studies have shown that endogenous serotonin is not required for colonic peristalsis in vitro, nor gastrointestinal (GI) transit in vivo. However, antagonists of 5-Hydroxytryptamine (5-HT) receptors can inhibit peristalsis and GI-transit in mammals, including humans. This raises the question of how these antagonists inhibit GI-motility and transit, if depletion of endogenous 5-HT does not cause any significant inhibitory changes to either GI-motility or transit? We investigated the mechanism by which 5-HT3 and 5-HT4 antagonists inhibit distension-evoked peristaltic contractions in guinea-pig distal colon. In control animals, repetitive peristaltic contractions of the circular muscle were evoked in response to fixed fecal pellet distension. Distension-evoked peristaltic contractions were unaffected in animals with mucosa and submucosal plexus removed, that were also treated with reserpine (to deplete neuronal 5-HT). In control animals, peristaltic contractions were blocked temporarily by ondansetron (1-10 μM) and SDZ-205-557 (1-10 μM) in many animals. Interestingly, after this temporary blockade, and whilst in the continued presence of these antagonists, peristaltic contractions recovered, with characteristics no different from controls. Surprisingly, similar effects were seen in mucosa-free preparations, which had no detectable 5-HT, as detected by mass spectrometry. In summary, distension-evoked peristaltic reflex contractions of the circular muscle layer of the guinea-pig colon can be inhibited temporarily, or permanently, in the same preparation by selective 5-HT3 and 5-HT4 antagonists, depending on the concentration of the antagonists applied. These effects also occur in preparations that lack any detectable 5-HT. We suggest caution should be exercised when interpreting the effects of 5-HT3 and 5-HT4 antagonists; and the role of endogenous 5-HT, in the generation of distension-evoked colonic peristalsis.

Entrepreneurship Education and Academic Performance

ERIC Educational Resources Information Center

Johansen, Vegard

2014-01-01

The significant increase of entrepreneurship education (EE) is a trend in Europe. Entrepreneurship education is supposed to promote general and specific entrepreneurial abilities and improve academic performance. This paper evaluates whether EE influences academic performance, measured by Grade Point Average. The main indicator used for EE is the…

Executive functions in men and postmenopausal women.

PubMed

Castonguay, Nathalie; Lussier, Maxime; Bugaiska, Aurélia; Lord, Catherine; Bherer, Louis

2015-01-01

This study was designed to assess sex differences in older adults (55-65 years old) in executive functions and to examine the influence of hormone therapy (HT) in postmenopausal women. We have assessed task performance in memory, visuospatial, and executive functions in 29 women using HT, 29 women who never used HT, and 30 men. Men outperformed never users in task switching and updating. HT users outperformed never users in updating. HT users outperformed never users and men in visual divided attention. The present study support previous findings that sex and HT impact cognition and bring new insights on sex and HT-related differences in executive functions.

Separation of non-racemic mixtures of enantiomers: an essential part of optical resolution.

PubMed

Faigl, Ferenc; Fogassy, Elemér; Nógrádi, Mihály; Pálovics, Emese; Schindler, József

2010-03-07

Non-racemic enantiomeric mixtures form homochiral and heterochiral aggregates in melt or suspension, during adsorption or recrystallization, and these diastereomeric associations determine the distribution of the enantiomers between the solid and other (liquid or vapour) phases. That distribution depends on the stability order of the homo- and heterochiral aggregates (conglomerate or racemate formation). Therefore, there is a correlation between the binary melting point phase diagrams and the experimental ee(I)vs. ee(0) curves (ee(I) refers to the crystallized enantiomeric mixtures, ee(0) is the composition of the starting ones). Accordingly, distribution of the enantiomeric mixtures between two phases is characteristic and usually significant enrichment can be achieved. There are two exceptions: no enrichment could be observed under thermodynamically controlled conditions when the starting enantiomer composition corresponded to the eutectic composition, or when the method used was unsuitable for separation. In several cases, when kinetic control governed the crystallization, the character of the ee(0)-ee(I) curve did not correlate with the melting point binary phase diagram.

Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis

PubMed Central

Blanchard, Carine; Wang, Ning; Stringer, Keith F.; Mishra, Anil; Fulkerson, Patricia C.; Abonia, J. Pablo; Jameson, Sean C.; Kirby, Cassie; Konikoff, Michael R.; Collins, Margaret H.; Cohen, Mitchell B.; Akers, Rachel; Hogan, Simon P.; Assa’ad, Amal H.; Putnam, Philip E.; Aronow, Bruce J.; Rothenberg, Marc E.

2006-01-01

Eosinophilic esophagitis (EE) is an emerging disorder with a poorly understood pathogenesis. In order to define disease mechanisms, we took an empirical approach analyzing esophageal tissue by a genome-wide microarray expression analysis. EE patients had a striking transcript signature involving 1% of the human genome that was remarkably conserved across sex, age, and allergic status and was distinct from that associated with non-EE chronic esophagitis. Notably, the gene encoding the eosinophil-specific chemoattractant eotaxin-3 (also known as CCL26) was the most highly induced gene in EE patients compared with its expression level in healthy individuals. Esophageal eotaxin-3 mRNA and protein levels strongly correlated with tissue eosinophilia and mastocytosis. Furthermore, a single-nucleotide polymorphism in the human eotaxin-3 gene was associated with disease susceptibility. Finally, mice deficient in the eotaxin receptor (also known as CCR3) were protected from experimental EE. These results implicate eotaxin-3 as a critical effector molecule for EE and provide insight into disease pathogenesis. PMID:16453027

Expressed emotion and sociocultural moderation in the course of schizophrenia.

PubMed

Aguilera, Adrian; López, Steven R; Breitborde, Nicholas J K; Kopelowicz, Alex; Zarate, Roberto

2010-11-01

This study examined whether the sociocultural context moderates the relationship between families' expressed emotion (EE) and clinical outcomes in schizophrenia. In a sample of 60 Mexican American caregivers and their ill relatives, we first assessed whether EE and its indices (criticism, emotional overinvolvement [EOI], and warmth) related to relapse. Second, we extended the analysis of EE and its indices to a longitudinal assessment of symptomatology. Last, we tested whether bidimensional acculturation moderated the relationship between EE (and its indices) and both relapse and symptom trajectory over time. Results indicated that EOI was associated with increased relapse and that criticism was associated with increased symptomatology. Additionally, as patients' Mexican enculturation (Spanish language and media involvement) decreased, EE was increasingly related to relapse. For symptomatology, as patients' U.S. acculturation (English language and media involvement) increased, EE was associated with increased symptoms longitudinally. Our results replicate and extend past research on how culture might shape the way family factors relate to the course of schizophrenia. PsycINFO Database Record (c) 2010 APA, all rights reserved

Comparative receptor mapping of serotoninergic 5-HT3 and 5-HT4 binding sites*

NASA Astrophysics Data System (ADS)

López-Rodríguez, María L.; Morcillo, María José; Benhamú, Bellinda; Rosado, María Luisa

1997-11-01

The clinical use of currently available drugs acting at the5-HT4 receptor has been hampered by their lack of selectivityover 5-HT3 binding sites. For this reason, there is considerableinterest in the medicinal chemistry of these serotonin receptor subtypes, andsignificant effort has been made towards the discovery of potent and selectiveligands. Computer-aided conformational analysis was used to characterizeserotoninergic 5-HT3 and 5-HT4 receptorrecognition. On the basis of the generally accepted model of the5-HT3 antagonist pharmacophore, we have performed a receptormapping of this receptor binding site, following the active analog approach(AAA) defined by Marshall. The receptor excluded volume was calculated as theunion of the van der Waals density maps of nine active ligands(pKi ≥ 8.9), superimposed in pharmacophoric conformations.Six inactive analogs (pKi < 7.0) were subsequently used todefine the essential volume, which in its turn can be used to define theregions of steric intolerance of the 5-HT3 receptor. Five activeligands (pKi ≥ 9.3) at 5-HT4 receptors wereused to construct an antagonist pharmacophore for this receptor, and todetermine its excluded volume by superimposition of pharmacophoricconformations. The volume defined by the superimposition of five inactive5-HT4 receptor analogs that possess the pharmacophoric elements(pKi ≤ 6.6) did not exceed the excluded volume calculated forthis receptor. In this case, the inactivity may be due to the lack of positiveinteraction of the amino moiety with a hypothetical hydrophobic pocket, whichwould interact with the voluminous substituents of the basic nitrogen ofactive ligands. The difference between the excluded volumes of both receptorshas confirmed that the main difference is indeed in the basic moiety. Thus,the 5-HT3 receptor can only accommodate small substituents inthe position of the nitrogen atom, whereas the 5-HT4 receptorrequires more voluminous groups. Also, the basic nitrogen is located at ca.8.0 Å from the aromatic moiety in the 5-HT4 antagonistpharmacophore, whereas this distance is ca. 7.5 Å in the5-HT3 antagonist model. The comparative mapping of bothserotoninergic receptors has allowed us to confirm the three-componentpharmacophore accepted for the 5-HT3 receptor, as well as topropose a steric model for the 5-HT4 receptor binding site. Thisstudy offers structural insights to aid the design of new selective ligands,and the resulting models have received some support from the synthesis of twonew active and selective ligands: 24 (Ki(5-HT3)= 3.7 nM; Ki(5-HT4) > 1000 nM) and 25(Ki(5-HT4) = 13.7 nM;Ki(5-HT3) > 10 000 nM).

High Affinity Binding of Epibatidine to Serotonin Type 3 Receptors*

PubMed Central

Drisdel, Renaldo C.; Sharp, Douglas; Henderson, Tricia; Hales, Tim G.; Green, William N.

2008-01-01

Epibatidine and mecamylamine are ligands used widely in the study of nicotinic acetylcholine receptors (nAChRs) in the central and peripheral nervous systems. In the present study, we find that nicotine blocks only 75% of 125I-epibatidine binding to rat brain membranes, whereas ligands specific for serotonin type 3 receptors (5-HT3Rs) block the remaining 25%. 125I-Epibatidine binds with a high affinity to native 5-HT3Rs of N1E-115 cells and to receptors composed of only 5-HT3A subunits expressed in HEK cells. In these cells, serotonin, the 5-HT3R-specific antagonist MDL72222, and the 5-HT3R agonist chlorophenylbiguanide readily competed with 125I-epibatidine binding to 5-HT3Rs. Nicotine was a poor competitor for 125I-epibatidine binding to 5-HT3Rs. However, the noncompetitive nAChR antagonist mecamylamine acted as a potent competitive inhibitor of 125I-epibatidine binding to 5-HT3Rs. Epibatidine inhibited serotonin-induced currents mediated by endogenous 5-HT3Rs in neuroblastoma cell lines and 5-HT3ARs expressed in HEK cells in a competitive manner. Our results demonstrate that 5-HT3Rs are previously uncharacterized high affinity epibatidine binding sites in the brain and indicate that epibatidine and mecamylamine act as 5-HT3R antagonists. Previous studies that depended on epibatidine and mecamylamine as nAChR-specific ligands, in particular studies of analgesic properties of epibatidine, may need to be reinterpreted with respect to the potential role of 5-HT3Rs. PMID:17702741

[Effect of (+/-)-pindolol on the central 5-HT1A receptor by the use of in vivo microdialysis and hippocampal slice preparations].

PubMed

Tsuji, Keiichiro

2002-06-01

Although it is suggested that (+/-)-pindolol, a beta-adrenergic/5-HT1A receptor antagonist, may enhance the efficacy of selective serotonin reuptake inhibitors (SSRI), the results of double-blind studies are contradictory and recent animal studies suggest that (+/-)-pindolol may act as a partial agonist to the 5-HT1A receptor. In this study we have investigated the effect of (+/-)-pindolol on both pre- and postsynaptic 5-HT1A receptors using in vivo microdialysis and hippocampal slice preparations. (+/-)-pindolol and flesinoxan, a 5-HT1A receptor full agonist, significantly decreased the extracellular levels of 5-HT in the raphe and prefrontal cortex. The 5-HT and other 5-HT1A receptor agonists, flesinoxan and 8-hydroxy-2- (di-n-propylamino)tetralon (8-OH-DPAT), significantly decreased the population excitatory postsynaptic potential (EPSP) in the CA3-CA1 excitatory synapse in a dose-dependent manner. The effect of 5-HT and other 5-HT1A receptor agonists accompanied the increase in paired-pulse facilitation (ppf) induced by short-interval two stimuli and were reversed by the coadministration of the 5-HT1A receptor agonist, NAN-190, but not by (+/-)-pindolol. (+/-)-pindolol also suppressed the EPSP, but this effect was not reversed by NAN-190. These results suggest that (+/-)-pindolol acts as a partial agonist to the somatodendritic 5-HT1A receptor in the raphe, whereas it may have no action on the postsynaptic 5-HT1A receptor in the hippocampus.

Functional expression of 5-HT{sub 2A} receptor in osteoblastic MC3T3-E1 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirai, Takao; Kaneshige, Kota; Kurosaki, Teruko

2010-05-28

In the previous study, we reported the gene expression for proteins related to the function of 5-hydroxytryptamine (5-HT, serotonin) and elucidated the expression patterns of 5-HT{sub 2} receptor subtypes in mouse osteoblasts. In the present study, we evaluated the possible involvement of 5-HT receptor subtypes and its inactivation system in MC3T3-E1 cells, an osteoblast cell line. DOI, a 5-HT{sub 2A} and 5-HT{sub 2C} receptor selective agonist, as well as 5-HT concentration-dependently increased proliferative activities of MC3T3-E1 cells in their premature period. This effect of 5-HT on cell proliferation were inhibited by ketanserin, a 5-HT{sub 2A} receptor specific antagonist. Moreover, bothmore » DOI-induced cell proliferation and phosphorylation of ERK1 and 2 proteins were inhibited by PD98059 and U0126, selective inhibitors of MEK in a concentration-dependent manner. Furthermore, treatment with fluoxetine, a 5-HT specific re-uptake inhibitor which inactivate the function of extracellular 5-HT, significantly increased the proliferative activities of MC3T3-E1 cells in a concentration-dependent manner. Our data indicate that 5-HT fill the role for proliferation of osteoblast cells in their premature period. Notably, 5-HT{sub 2A} receptor may be functionally expressed to regulate mechanisms underlying osteoblast cell proliferation, at least in part, through activation of ERK/MAPK pathways in MC3T3-E1 cells.« less

Cognitive effects of hormone therapy continuation or discontinuation in a sample of women at risk for Alzheimer’s disease

PubMed Central

Wroolie, Tonita E.; Kenna, Heather A.; Williams, Katherine E.; Rasgon, Natalie L.

2015-01-01

Use of estrogen-based hormone therapy (HT), as a protection from cognitive decline and Alzheimer’s disease, is controversial although cumulative data supports HT use when initiated close to menopause onset with estrogen formulations containing 17β-estradiol (17β-E) being preferable to conjugated equine estrogen formulations. Little is known regarding specific populations of women who may derive benefit from HT. Women with heightened risk for AD (aged 49-69), all of whom were taking HT for at least one year, most of whom initiated HT close to menopause onset, underwent cognitive assessment followed by randomization to continue or discontinue HT. Assessments were repeated at two years after randomization. Women who continued HT performed better on cognitive domains composed of measures of verbal memory, and combined attention, working memory, and processing speed measures. Women who used 17β-E versus conjugated equine estrogen, whether randomized to continue or discontinue HT showed better verbal memory performance at the 2-year follow-up assessment. An interaction was also found with HT randomization and family history of AD in a first degree relative. All women offspring of patients with AD declined in verbal memory however, women who continued HT declined less than women who discontinued HT. Women without a first-degree relative with AD showed verbal memory improvement (likely due to practice effects) with continuance and declined with discontinuance of HT. Continuation of HT use appears to protect cognition in women with heightened risk for AD when initiated close to menopause onset. PMID:26209223

Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for psychopathology

PubMed Central

Booij, Linda; Tremblay, Richard E.; Szyf, Moshe; Benkelfat, Chawki

2015-01-01

Background Despite more than 60 years of research in the role of serotonin (5-HT) in psychopathology, many questions still remain. From a developmental perspective, studies have provided more insight into how 5-HT dysfunctions acquired in utero or early in life may modulate brain development. This paper discusses the relevance of the developmental role of 5-HT for the understanding of psychopathology. We review developmental milestones of the 5-HT system, how genetic and environmental 5-HT disturbances could affect brain development and the potential role of DNA methylation in 5-HT genes for brain development. Methods Studies were identified using common databases (e.g., PubMed, Google Scholar) and reference lists. Results Despite the widely supported view that the 5-HT system matures in early life, different 5-HT receptors, proteins and enzymes have different developmental patterns, and development is brain region–specific. A disruption in 5-HT homeostasis during development may lead to structural and functional changes in brain circuits that modulate emotional stress responses, including subcortical limbic and (pre)frontal areas. This may result in a predisposition to psychopathology. DNA methylation might be one of the underlying physiologic mechanisms. Limitations There is a need for prospective studies. The impact of stressors during adolescence on the 5-HT system is understudied. Questions regarding efficacy of drugs acting on 5-HT still remain. Conclusion A multidisciplinary and longitudinal approach in designing studies on the role of 5-HT in psychopathology might help to bring us closer to the understanding of the role of 5-HT in psychopathology. PMID:25285876

Physiological, Biochemical, and Molecular Mechanisms of Heat Stress Tolerance in Plants

PubMed Central

Hasanuzzaman, Mirza; Nahar, Kamrun; Alam, Md. Mahabub; Roychowdhury, Rajib; Fujita, Masayuki

2013-01-01

High temperature (HT) stress is a major environmental stress that limits plant growth, metabolism, and productivity worldwide. Plant growth and development involve numerous biochemical reactions that are sensitive to temperature. Plant responses to HT vary with the degree and duration of HT and the plant type. HT is now a major concern for crop production and approaches for sustaining high yields of crop plants under HT stress are important agricultural goals. Plants possess a number of adaptive, avoidance, or acclimation mechanisms to cope with HT situations. In addition, major tolerance mechanisms that employ ion transporters, proteins, osmoprotectants, antioxidants, and other factors involved in signaling cascades and transcriptional control are activated to offset stress-induced biochemical and physiological alterations. Plant survival under HT stress depends on the ability to perceive the HT stimulus, generate and transmit the signal, and initiate appropriate physiological and biochemical changes. HT-induced gene expression and metabolite synthesis also substantially improve tolerance. The physiological and biochemical responses to heat stress are active research areas, and the molecular approaches are being adopted for developing HT tolerance in plants. This article reviews the recent findings on responses, adaptation, and tolerance to HT at the cellular, organellar, and whole plant levels and describes various approaches being taken to enhance thermotolerance in plants. PMID:23644891

Serum magnesium but not calcium was associated with hemorrhagic transformation in stroke overall and stroke subtypes: a case-control study in China.

PubMed

Tan, Ge; Yuan, Ruozhen; Wei, ChenChen; Xu, Mangmang; Liu, Ming

2018-05-26

Association between serum calcium and magnesium versus hemorrhagic transformation (HT) remains to be identified. A total of 1212 non-thrombolysis patients with serum calcium and magnesium collected within 24 h from stroke onset were enrolled. Backward stepwise multivariate logistic regression analysis was conducted to investigate association between calcium and magnesium versus HT. Calcium and magnesium were entered into logistic regression analysis in two models, separately: model 1, as continuous variable (per 1-mmol/L increase), and model 2, as four-categorized variable (being collapsed into quartiles). HT occurred in 140 patients (11.6%). Serum calcium was slightly lower in patients with HT than in patient without HT (P = 0.273). But serum magnesium was significantly lower in patients with HT than in patients without HT (P = 0.007). In logistic regression analysis, calcium displayed no association with HT. Magnesium, as either continuous or four-categorized variable, was independently and inversely associated with HT in stroke overall and stroke of large-artery atherosclerosis (LAA). The results demonstrated that serum calcium had no association with HT in patients without thrombolysis after acute ischemic stroke. Serum magnesium in low level was independently associated with increasing HT in stroke overall and particularly in stroke of LAA.

Urinary excretion of 5-hydroxyindoleacetic acid, serotonin and 6-sulphatoxymelatonin in normoserotonemic and hyperserotonemic autistic individuals.

PubMed

Mulder, Erik J; Anderson, George M; Kemperman, Ramses F J; Oosterloo-Duinkerken, Alida; Minderaa, Ruud B; Kema, Ido P

2010-01-01

A substantial proportion of individuals with autism have elevated levels of platelet serotonin (5-HT). We examined whether platelet hyperserotonemia is associated with increased gut 5-HT synthesis, altered 5-HT catabolism or altered melatonin production. Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT was compared in 10 normoserotonemic and 10 hyperserotonemic age-matched autistic individuals. The relationship of urinary 6-sulfatoxymelatonin (6-SM) excretion to platelet 5-HT, and to urinary 5-HT and 5-HIAA excretion, was also examined. In the hyperserotonemic group, significant increases at trend level in urinary excretion of 5-HIAA (p = 0.061) and 5-HT (p = 0.071) and a significant decrease for 6-SM were found (p = 0.027). The urinary 5-HIAA:5-HT ratio was similar in the normo- versus the hyperserotonemic groups. The catabolism of 5-HT does not differ in the groups, but greater exposure of the platelet to 5-HT cannot be ruled out as a cause of the platelet hyperserotonemia of autism. Although only trend level significant, the data point to a need for larger studies to examine more thoroughly the relationships between platelet hyperserotonemia, gut 5-HT synthesis and melatonin production. (c) 2009 S. Karger AG, Basel.

Enrichment rescues contextual discrimination deficit associated with immediate shock.

PubMed

Clemenson, Gregory D; Lee, Star W; Deng, Wei; Barrera, Vanessa R; Iwamoto, Kei S; Fanselow, Michael S; Gage, Fred H

2015-03-01

Adult animals continue to modify their behavior throughout life, a process that is highly influenced by past experiences. To shape behavior, specific mechanisms of neural plasticity to learn, remember, and recall information are required. One of the most robust examples of adult plasticity in the brain occurs in the dentate gyrus (DG) of the hippocampus, through the process of adult neurogenesis. Adult neurogenesis is strongly upregulated by external factors such as voluntary wheel running (RUN) and environmental enrichment (EE); however, the functional differences between these two factors remain unclear. Although both manipulations result in increased neurogenesis, RUN dramatically increases the proliferation of newborn cells and EE promotes their survival. We hypothesize that the method by which these newborn neurons are induced influences their functional role. Furthermore, we examine how EE-induced neurons may be primed to encode and recognize features of novel environments due to their previous enrichment experience. Here, we gave mice a challenging contextual fear-conditioning (FC) procedure to tease out the behavioral differences between RUN-induced neurogenesis and EE-induced neurogenesis. Despite the robust increases in neurogenesis seen in the RUN mice, we found that only EE mice were able to discriminate between similar contexts in this task, indicating that EE mice might use a different cognitive strategy when processing contextual information. Furthermore, we showed that this improvement was dependent on EE-induced neurogenesis, suggesting a fundamental functional difference between RUN-induced neurogenesis and EE-induced neurogenesis. © 2014 Wiley Periodicals, Inc.

Enrichment Rescues Contextual Discrimination Deficit Associated With Immediate Shock

PubMed Central

Clemenson, Gregory D.; Lee, Star W.; Deng, Wei; Barrera, Vanessa R.; Iwamoto, Kei S.; Fanselow, Michael S.; Gage, Fred H.

2015-01-01

Adult animals continue to modify their behavior throughout life, a process that is highly influenced by past experiences. To shape behavior, specific mechanisms of neural plasticity to learn, remember, and recall information are required. One of the most robust examples of adult plasticity in the brain occurs in the dentate gyrus (DG) of the hippocampus, through the process of adult neurogenesis. Adult neurogenesis is strongly upregulated by external factors such as voluntary wheel running (RUN) and environmental enrichment (EE); however, the functional differences between these two factors remain unclear. Although both manipulations result in increased neurogenesis, RUN dramatically increases the proliferation of newborn cells and EE promotes their survival. We hypothesize that the method by which these newborn neurons are induced influences their functional role. Furthermore, we examine how EE-induced neurons may be primed to encode and recognize features of novel environments due to their previous enrichment experience. Here, we gave mice a challenging contextual fear-conditioning (FC) procedure to tease out the behavioral differences between RUN-induced neurogenesis and EE-induced neurogenesis. Despite the robust increases in neurogenesis seen in the RUN mice, we found that only EE mice were able to discriminate between similar contexts in this task, indicating that EE mice might use a different cognitive strategy when processing contextual information. Furthermore, we showed that this improvement was dependent on EE-induced neurogenesis, suggesting a fundamental functional difference between RUN-induced neurogenesis and EE-induced neurogenesis. PMID:25330953

Electrochemically modified dissolved organic matter accelerates the combining photodegradation and biodegradation of 17α-ethinylestradiol in natural aquatic environment.

PubMed

He, Huan; Huang, Bin; Fu, Gen; Xiong, Dan; Xu, Zhixiang; Wu, Xinhao; Pan, Xuejun

2018-06-15

The photochemical conversion and microbial transformation of pollutants mediated by dissolved organic matter (DOM), including 17α-ethinylestradiol (EE2), are often accompanied in natural water. However, there are few studies to explore the connection and mechanism between the two processes. This research aims to investigate the mechanism of DOM after electrochemically modification mediated EE2 combining photodegradation and biodegradation in the environment and it want to explain the natural phenomena of DOM after electrochemical advanced treatment entering the water environment mediated EE2 natural degradation. The results showed that combining photodegradation with biodegradation rates of EE2 mediated by DOM and electrochemically modified DOM (E-DOM) were promoted obviously. The efficiency of EE2 biodegradation was shown to be strongly correlated with electron accepting capacity (EAC) of DOM. Electrochemical modification can increase the EAC of DOM leading to EE2 biodegradation accelerated, and it also can form more triplet-state DOM moieties to promote the EE2 photodegradation in irradiation conditions, due to the increasing of quinone-type structures in DOM. Moreover, cell polymeric secretion (CPS) secreted from the microorganism could be stimulated to an excited state by irradiation, and that also accelerated EE2 degradation. Photolysis combined with biochemical degradation yielded less toxic degradation products. This study shows that the emission of DOM in wastewater after electrochemical treatment could accelerate estrogen degradation and play a positive role on the pollutant transformation in the environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Novel Approach to Identify Potential Bioactive Plant Metabolites: Pharmacological and Metabolomics Analyses of Ethanol and Hot Water Extracts of Several Canadian Medicinal Plants of the Cree of Eeyou Istchee.

PubMed

Shang, Nan; Saleem, Ammar; Musallam, Lina; Walshe-Roussel, Brendan; Badawi, Alaa; Cuerrier, Alain; Arnason, John T; Haddad, Pierre S

2015-01-01

We evaluated and compared the antidiabetic potential and molecular mechanisms of 17 Cree plants' ethanol extracts (EE) and hot water extracts (HWE) on glucose homeostasis in vitro and used metabolomics to seek links with the content of specific phytochemicals. Several EE of medical plants stimulated muscle glucose uptake and inhibited hepatic G6Pase activity. Some HWE partially or completely lost these antidiabetic activities in comparison to EE. Only R. groenlandicum retained similar potential between EE and HWE in both assays. In C2C12 muscle cells, EE of R. groenlandicum, A. incana and S. purpurea stimulated glucose uptake by activating AMP-activated protein kinase (AMPK) pathway and increasing glucose transporter type 4 (GLUT4) expression. In comparison to EE, HWE of R. groenlandicum exhibited similar activities; HWE of A. incana completely lost its effect on all parameters; interestingly, HWE of S. purpurea activated insulin pathway instead of AMPK pathway to increase glucose uptake. In the liver, for a subset of 5 plants, HWE and EE activated AMPK pathway whereas the EE and HWE of S. purpurea and K. angustifolia also activated insulin pathways. Quercetin-3-O-galactoside and quercetin 3-O-α-L-arabinopyranoside, were successfully identified by discriminant analysis as biomarkers of HWE plant extracts that stimulate glucose uptake in vitro. More importantly, the latter compound was not identified by previous bioassay-guided fractionation.

Neurogenesis Inhibition Prevents Enriched Environment to Prolong and Strengthen Social Recognition Memory, But Not to Increase BDNF Expression.

PubMed

Pereira-Caixeta, Ana Raquel; Guarnieri, Leonardo O; Pena, Roberta R; Dias, Thomáz L; Pereira, Grace Schenatto

2017-07-01

Hippocampus-dependent memories, such as social recognition (SRM), are modulated by neurogenesis. However, the precise role of newborn neurons in social memory processing is still unknown. We showed previously that 1 week of enriched environment (EE) is sufficient to increase neurogenesis in the hippocampus (HIP) and the olfactory bulb (OB) of mice. Here, we tested the hypothesis that 1 week of EE would enhance SRM persistence and strength. In addition, as brain-derived neurotrophic factor (BDNF) may mediate some of the neurogenesis effects on memory, we also tested if 1 week of EE would increase BDNF expression in the HIP and OB. We also predicted that neurogenesis inhibition would block the gain of function caused by EE on both SRM and BDNF expression. We found that EE increased BDNF expression in the HIP and OB of mice; at the same time, it allowed SRM to last longer. In addition, mice on EE had their SRM unaffected by memory consolidation interferences. As we predicted, treatment with the anti-mitotic drug AraC blocked EE effects on SRM. Surprisingly, neurogenesis inhibition did not affect the BDNF expression, increased by EE. Together, our results suggest that newborn neurons improve SRM persistence through a BDNF-independent mechanism. Interestingly, this study on social memory uncovered an unexpected dissociation between the effect of adult neurogenesis and BDNF expression on memory persistence, reassuring the idea that not all neurogenesis effects on memory are BDNF-dependent.

Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts.

PubMed

Gergs, Ulrich; Jung, Franziska; Buchwalow, Igor B; Hofmann, Britt; Simm, Andreas; Treede, Hendrik; Neumann, Joachim

2017-12-01

Using transgenic (TG) mice that overexpress the human serotonin (5-HT) 4a receptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor 5-hydroxy-tryptophan (5-HTP) can exert inotropic and chronotropic effects in cardiac preparations from TG mice but not from wild-type (WT) mice; similar results were found in human atrial preparations as well as in intact TG animals using echocardiography. Moreover, by immunohistochemistry we could detect 5-HT metabolizing enzymes and 5-HT transporters in mouse hearts as well as in human atria. Hence, in the presence of an inhibitor of aromatic l-amino acid decarboxylase, the positive inotropic effects of 5-HTP were absent in TG and isolated human atrial preparations, and, moreover, inhibitors of enzymes involved in 5-HT degradation enhanced the efficacy of 5-HT in TG atria. A releaser of neurotransmitters increased inotropy in the isolated TG atrium, and this effect could be blocked by a 5-HT 4a receptor antagonist. Fluoxetine, an inhibitor of 5-HT uptake, elevated the potency of 5-HT to increase contractility in the TG atrium. In addition, inhibitors of organic cation and monoamine transporters apparently reduced the positive inotropic potency of 5-HT in the TG atrium. Hence, we tentatively conclude that a local production and degradation of 5-HT in the mammalian heart and more specifically in mammalian myocytes probably occurs. Conceivably, this formation of 5-HT and possibly impaired degradation may be clinically relevant in cases of unexplained tachycardia and other arrhythmias. NEW & NOTEWORTHY The present work suggests that inotropically active serotonin (5-HT) can be formed in the mouse and human heart and probably by cardiomyocytes themselves. Moreover, active degradation of 5-HT seems to occur in the mammalian heart. These findings may again increase the interest of researchers for cardiac effects of 5-HT. Copyright © 2017 the American Physiological Society.

Regulatory Mechanisms Controlling Maturation of Serotonin Neuron Identity and Function

PubMed Central

Spencer, William C.; Deneris, Evan S.

2017-01-01

The brain serotonin (5-hydroxytryptamine; 5-HT) system has been extensively studied for its role in normal physiology and behavior, as well as, neuropsychiatric disorders. The broad influence of 5-HT on brain function, is in part due to the vast connectivity pattern of 5-HT-producing neurons throughout the CNS. 5-HT neurons are born and terminally specified midway through embryogenesis, then enter a protracted period of maturation, where they functionally integrate into CNS circuitry and then are maintained throughout life. The transcriptional regulatory networks controlling progenitor cell generation and terminal specification of 5-HT neurons are relatively well-understood, yet the factors controlling 5-HT neuron maturation are only recently coming to light. In this review, we first provide an update on the regulatory network controlling 5-HT neuron development, then delve deeper into the properties and regulatory strategies governing 5-HT neuron maturation. In particular, we discuss the role of the 5-HT neuron terminal selector transcription factor (TF) Pet-1 as a key regulator of 5-HT neuron maturation. Pet-1 was originally shown to positively regulate genes needed for 5-HT synthesis, reuptake and vesicular transport, hence 5-HT neuron-type transmitter identity. It has now been shown to regulate, both positively and negatively, many other categories of genes in 5-HT neurons including ion channels, GPCRs, transporters, neuropeptides, and other transcription factors. Its function as a terminal selector results in the maturation of 5-HT neuron excitability, firing characteristics, and synaptic modulation by several neurotransmitters. Furthermore, there is a temporal requirement for Pet-1 in the control of postmitotic gene expression trajectories thus indicating a direct role in 5-HT neuron maturation. Proper regulation of the maturation of cellular identity is critical for normal neuronal functioning and perturbations in the gene regulatory networks controlling these processes may result in long-lasting changes in brain function in adulthood. Further study of 5-HT neuron gene regulatory networks is likely to provide additional insight into how neurons acquire their mature identities and how terminal selector-type TFs function in postmitotic vertebrate neurons. PMID:28769770

Assessment of population coverage of hypertension screening in Thailand based on the effective coverage framework.

PubMed

Charoendee, Kulpimol; Sriratanaban, Jiruth; Aekplakorn, Wichai; Hanvoravongchai, Piya

2018-03-27

Hypertension (HT) is a major risk factor, and accessible and effective HT screening services are necessary. The effective coverage framework is an assessment tool that can be used to assess health service performance by considering target population who need and receive quality service. The aim of this study is to measure effective coverage of hypertension screening services at the provincial level in Thailand. Over 40 million individual health service records in 2013 were acquired. Data on blood pressure measurement, risk assessment, HT diagnosis and follow up were analyzed. The effectiveness of the services was assessed based on a set of quality criteria for pre-HT, suspected HT, and confirmed HT cases. Effective coverage of HT services for all non-HT Thai population aged 15 or over was estimated for each province and for all Thailand. Population coverage of HT screening is 54.6%, varying significantly across provinces. Among those screened, 28.9% were considered pre-HT, and another 6.0% were suspected HT cases. The average provincial effective coverage was at 49.9%. Around four-fifths (82.6%) of the pre-HT group received HT and Cardiovascular diseases (CVD) risk assessment. Among the suspected HT cases, less than half (38.0%) got a follow-up blood pressure measurement within 60 days from the screening date. Around 9.2% of the suspected cases were diagnosed as having HT, and only one-third of them (36.5%) received treatment within 6 months. Within this group, 21.8% obtained CVD risk assessment, and half of them had their blood pressure under control (50.8%) with less than 1 % (0.7%) of them managed to get the CVD risk reduced. Our findings suggest that hypertension screening coverage, post-screening service quality, and effective coverage of HT screening in Thailand were still low and they vary greatly across provinces. It is imperative that service coverage and its effectiveness are assessed, and both need improvement. Despite some limitations, measurement of effective coverage could be done with existing data, and it can serve as a useful tool for performance measurement of public health services.

Regulatory Mechanisms Controlling Maturation of Serotonin Neuron Identity and Function.

PubMed

Spencer, William C; Deneris, Evan S

2017-01-01

The brain serotonin (5-hydroxytryptamine; 5-HT) system has been extensively studied for its role in normal physiology and behavior, as well as, neuropsychiatric disorders. The broad influence of 5-HT on brain function, is in part due to the vast connectivity pattern of 5-HT-producing neurons throughout the CNS. 5-HT neurons are born and terminally specified midway through embryogenesis, then enter a protracted period of maturation, where they functionally integrate into CNS circuitry and then are maintained throughout life. The transcriptional regulatory networks controlling progenitor cell generation and terminal specification of 5-HT neurons are relatively well-understood, yet the factors controlling 5-HT neuron maturation are only recently coming to light. In this review, we first provide an update on the regulatory network controlling 5-HT neuron development, then delve deeper into the properties and regulatory strategies governing 5-HT neuron maturation. In particular, we discuss the role of the 5-HT neuron terminal selector transcription factor (TF) Pet-1 as a key regulator of 5-HT neuron maturation. Pet-1 was originally shown to positively regulate genes needed for 5-HT synthesis, reuptake and vesicular transport, hence 5-HT neuron-type transmitter identity. It has now been shown to regulate, both positively and negatively, many other categories of genes in 5-HT neurons including ion channels, GPCRs, transporters, neuropeptides, and other transcription factors. Its function as a terminal selector results in the maturation of 5-HT neuron excitability, firing characteristics, and synaptic modulation by several neurotransmitters. Furthermore, there is a temporal requirement for Pet-1 in the control of postmitotic gene expression trajectories thus indicating a direct role in 5-HT neuron maturation. Proper regulation of the maturation of cellular identity is critical for normal neuronal functioning and perturbations in the gene regulatory networks controlling these processes may result in long-lasting changes in brain function in adulthood. Further study of 5-HT neuron gene regulatory networks is likely to provide additional insight into how neurons acquire their mature identities and how terminal selector-type TFs function in postmitotic vertebrate neurons.

5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver

USDA-ARS?s Scientific Manuscript database

Mice lacking 5-HT 2C receptors displayed hepatic insulin resistance, a phenotype normalized by re-expression of 5-HT2CRs only in pro-opiomelanocortin (POMC) neurons. 5-HT2CR deficiency also abolished the anti-diabetic effects of meta-chlorophenylpiperazine (a 5-HT2CR agonist); these effects were re...

10 CFR 905.17 - What are the requirements for the energy efficiency and/or renewable energy report (EE/RE report...

Code of Federal Regulations, 2010 CFR

2010-01-01

... include: (1) Customer name, address, phone number, email and Website if applicable, and contact person; (2... of EPAct. Customers must submit, in writing, an EE/RE report every 5 years. (g) Maintaining EE/RE...

Exploring stroke survivor experience of participation in an enriched environment: a qualitative study.

PubMed

White, Jennifer H; Bartley, Emma; Janssen, Heidi; Jordan, Louise-Anne; Spratt, Neil

2015-01-01

Data highlight the importance of undertaking intense and frequent repetition of activities within stroke rehabilitation to maximise recovery. An enriched environment (EE) provides a medium in which these activities can be performed and enhanced recovery achieved. An EE has been shown to promote neuroplasticity in animal models of stroke, facilitating enhanced recovery of motor and cognitive function. However, the benefit of enriching the environment of stroke survivors remains unknown. To qualitatively explore stroke survivors' experience of implementation of exposure to an EE within a typical stroke rehabilitation setting, in order to identify facilitators and barriers to participation. Semi-structured interviews with 10 stroke survivors (7 females and 3 males, mean age of 70.5 years) exposed to an EE for a 2-week period following exposure to routine rehabilitation within a stroke rehabilitation ward. An inductive thematic approach was utilised to collect and analyse data. Qualitative themes emerged concerning the environmental enrichment paradigm including: (1) "It got me moving" - perceived benefits of participation in an EE; (2) "You can be bored or you can be busy." - Attenuating factors influencing participation in an EE; (3) "I don't like to make the staff busier" - limitations to use of the EE. This study provides preliminary support for the implementation of an EE within a typical stroke rehabilitation setting from a patient perspective. Reported benefits included (1) increased motor, cognitive and sensory stimulation, (2) increased social interaction, (3) alleviation of degree of boredom and (4) increased feelings of personal control. However, participants also identified a number of barriers affecting implementation of the EE. We have previously published findings on perceptions of nursing staff working with stroke survivors in this enriched rehabilitation environment who identified that patients benefited from having better access to physical, cognitive and social activities. Together, results contribute to valuable evidence for future implementation of an EE in stroke rehabilitation settings. Implications for Rehabilitation Stroke survivor access to an enriched environment (EE): RESULTS identified that participation in both individual and communal forms of environment enrichment within the stroke rehabilitation ward resulted in increased access to activities providing increased opportunities for enhanced motor, cognitive and sensory stimulation. Increased access to and participation in activities of the environmental enrichment (individual and communal) interrupted the ongoing cycle of boredom and inactivity experienced by many participants. This study provides preliminary support for the implementation of an EE within a typical stroke rehabilitation setting from a patient perspective.

Could the 5-HT1B receptor inverse agonism affect learning consolidation?

PubMed

Meneses, A

2001-03-01

Diverse evidence indicates that, the 5-HT system might play a role in learning and memory, since it occurs in brain areas mediating such processes and 5-HT drugs modulate them. Hence in this work, in order to explore further 5-HT involvement on learning and memory 5-HT1B receptors' role is investigated. Evidence indicates that SB-224289 (a 5-HT1B receptor inverse agonist) post-training injection facilitated learning consolidation in an associative autoshaping learning task, this effect was partially reversed by GR 127935 (a 5-HT1B/1D receptor antagonist), but unaffected by MDL 100907 (a 5-HT2A receptor antagonist) or ketanserin (a 5-HT1D/2A/7 receptor antagonist) at low doses. Moreover, SB-224289 antagonized the learning deficit produced by TFMPP (a 5-HT1A/1B/1D/2A/2C receptor agonist), GR 46611 (a 5-HT1A/1B/1D receptor agonist), mCPP (a 5-HT2A/2C/3/7 receptor agonist/antagonist) or GR 127935 (at low dose). SB-224289 did not alter the 8-OH-DPAT (a 5-HT1A/7 receptor agonist) learning facilitatory effect. SB-224289 eliminated the deficit learning produced by the anticholinergic muscarinic scopolamine or the glutamatergic antagonist dizocilpine. Administration of both, GR 127935 (5mg/kg) plus ketanserin (0.01 mg/kg) did not modify learning consolidation; nevertheless, when ketanserin dose was increased (0.1-1.0mg/kg) and SB-224289 dose was maintained constant, a learning facilitation effect was observed. Notably, SB-224289 at 1.0mg/kg potentiated a subeffective dose of the 5-HT1B/1D receptor agonist/antagonist mixed GR 127935, which facilitated learning consolidation and this effect was abolished by ketanserin at a higher dose. Collectively, the data confirm and extend the earlier findings with GR 127935 and the effects of non-selective 5-HT(1B) receptor agonists. Clearly 5-HT1B agonists induced a learning deficit which can be reversed with SB-224289. Perhaps more importantly, SB-224289 enhances learning consolidation when given alone and can reverse the deficits induced by both cholinergic and glutamatergic antagonist. Hence, 5-HT1B receptor inverse agonists or antagonists could represent drugs for the treatment of learning and memory dysfunctions.

Hashimoto's Thyroiditis Pathology and Risk for Thyroid Cancer

PubMed Central

Paparodis, Rodis; Imam, Shahnawaz; Todorova-Koteva, Kristina; Staii, Anca

2014-01-01

Background: Hashimoto's thyroiditis (HT) has been found to coexist with differentiated thyroid cancer (DTC) in surgical specimens, but an association between the two conditions has been discounted by the medical literature. Therefore, we performed this study to determine any potential relationship between HT and the risk of developing DTC. Methods: We collected data for thyrotropin (TSH), thyroxine (T4), thyroid peroxidase antibody (TPO-Ab) titers, surgical pathology, and weight-based levothyroxine (LT4) replacement dose for patients who were referred for thyroid surgery. Patients with HT at final pathology were studied further. To estimate thyroid function, patients with preoperative hypothyroid HT (Hypo-HT) were divided into three equal groups based on their LT4 replacement: LT4-Low (<0.90 μg/kg), LT4-Mid (0.90–1.43 μg/kg), and LT4-High (>1.43 μg/kg). A group of preoperatively euthyroid (Euth-HT) patients but with HT by pathology was also studied. All subjects were also grouped based on their TPO-Ab titer in TPO-high (titer >1:1000) or TPO-low/negative (titer <1:1000 or undetectable) groups. The relationship of HT and DTC was studied extensively. Results: Of 2811 subjects, 582 had HT on surgical pathology, 365 of whom were Euth-HT preoperatively. DTC was present in 47.9% of the Euth-HT, in 59.7% of LT4-Low, 29.8% of LT4-Mid, and 27.9% of LT4-High groups. The relative risk (RR) for DTC was significantly elevated for the Euth-HT and LT4-Low groups (p<0.001), but not for the LT4-Mid or LT4-High replacement dose groups. TPO-low/negative status conferred an increased RR in the Euth-HT and LT4-Low replacement dose groups (p<0.001 both), while TPO-high status decreased it in Euth-HT group (p<0.05) and made it nonsignificant in the LT4-Low group. Conclusions: HT pathology increases the risk for DTC only in euthyroid subjects and those with partially functional thyroid glands (LT4-Low) but not in fully hypothyroid HT (LT4-Mid and LT4-High). High TPO-Ab titers appear to protect against DTC in patients with HT. PMID:24708347

An immunocapture/scintillation proximity analysis of G alpha q/11 activation by native serotonin (5-HT)2A receptors in rat cortex: blockade by clozapine and mirtazapine.

PubMed

Mannoury La Cour, C; Chaput, C; Touzard, M; Millan, M J

2009-02-01

Though transduction mechanisms recruited by heterologously expressed 5-HT(2A) receptors have been extensively studied, their interaction with specific subtypes of G-protein remains to be directly evaluated in cerebral tissue. Herein, as shown by an immunocapture/scintillation proximity analysis, 5-HT, the prototypical 5-HT(2A) agonist, DOI, and Ro60,0175 all enhanced [(35)S]GTPgammaS binding to G alpha q/11 in rat cortex with pEC(50) values of 6.22, 7.24 and 6.35, respectively. No activation of G o or G s/olf was seen at equivalent concentrations of DOI. Stimulation of G alpha q/11 by 5-HT (30 microM) and DOI (30 microM) was abolished by the selective 5-HT(2A) vs. 5-HT(2C)/5-HT(2B) antagonists, ketanserin (pK(B) values of 9.11 and 8.88, respectively) and MDL100,907 (9.82 and 9.68). By contrast, 5-HT-induced [(35)S]GTPgammaS binding to G alpha q/11 was only weakly inhibited by the preferential 5-HT(2C) receptor antagonists, RS102,221 (6.94) and SB242,084 (7.39), and the preferential 5-HT(2B) receptor antagonist, LY266,097 (6.66). The antipsychotic, clozapine, which had marked affinity for 5-HT(2A) receptors, blocked the recruitment of G alpha q/11 by 5-HT and DOI with pK(B) values of 8.54 and 8.14, respectively. Its actions were mimicked by the "atypical" antidepressant and 5-HT(2A) receptor antagonist, mirtazapine, which likewise blocked 5-HT and DOI-induced G alpha q/11 protein activation with pK(B) values of 7.90 and 7.76, respectively. In conclusion, by use of an immunocapture/scintillation proximity strategy, this study shows that native 5-HT(2A) receptors in rat frontal cortex specifically recruit G alpha q/11 and that this action is blocked by clozapine and mirtazapine. Quantification of 5-HT(2A) receptor-mediated G alpha q/11 activation in frontal cortex should prove instructive in characterizing the actions of diverse classes of psychotropic agent. 2008 Wiley-Liss, Inc.

A Pharmacological Analysis of an Associative Learning Task: 5-HT1 to 5-HT7 Receptor Subtypes Function on a Pavlovian/Instrumental Autoshaped Memory

PubMed Central

Meneses, Alfredo

2003-01-01

Recent studies using both invertebrates and mammals have revealed that endogenous serotonin (5-hydroxytryptamine [5-HT]) modulates plasticity processes, including learning and memory. However, little is currently known about the mechanisms, loci, or time window of the actions of 5-HT. The aim of this review is to discuss some recent results on the effects of systemic administration of selective agonists and antagonists of 5-HT on associative learning in a Pavlovian/instrumental autoshaping (P/I-A) task in rats. The results indicate that pharmacological manipulation of 5-HT1-7 receptors or 5-HT reuptake sites might modulate memory consolidation, which is consistent with the emerging notion that 5-HT plays a key role in memory formation. PMID:14557609

MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction.

PubMed

Dahan, Diana; Hien, Tran Thi; Tannenberg, Philip; Ekman, Mari; Rippe, Catarina; Boettger, Thomas; Braun, Thomas; Tran-Lundmark, Karin; Tran, Phan-Kiet; Swärd, Karl; Albinsson, Sebastian

2017-01-01

Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced. Enhanced 5-HT-induced contraction in Dicer KO pulmonary arteries was associated with increased 5-HT2A receptor mRNA expression whereas 5-HT1B and 5-HT2B receptor mRNAs were unchanged. Contraction by the 5-HT2A agonist TCB-2 was increased in Dicer KO as was the response to the 5-HT2B agonist BW723C86. Effects of Src and protein kinase C inhibition were similar in control and KO arteries, but the effect of inhibition of Rho kinase was reduced. We identified miR-30c as a potential candidate for 5-HT2A receptor regulation as it repressed 5-HT2A mRNA and protein. Our findings show that 5-HT receptor signaling in the arterial wall is subject to regulation by microRNAs and that this entails altered 5-HT2A receptor expression and signaling. © 2017 S. Karger AG, Basel.

Serotonergic modulation of nicotine-induced kinetic tremor in mice.

PubMed

Kunisawa, Naofumi; Iha, Higor A; Nomura, Yuji; Onishi, Misaki; Matsubara, Nami; Shimizu, Saki; Ohno, Yukihiro

2017-06-01

We previously demonstrated that nicotine elicited kinetic tremor by elevating the neural activity of the inferior olive via α7 nicotinic acetylcholine (nACh) receptors. Since α7 nACh receptors reportedly facilitate synaptic monoamine release, we explored the role of 5-HT receptors in induction and/or modulation of nicotine tremor. Treatment of mice with nicotine induced kinetic tremor that normally appeared during movement. The 5-HT 1A agonist, 8-hydroxydipropylaminotetraline (8-OH-DPAT), significantly enhanced nicotine-induced tremor and the action of 8-OH-DPAT was antagonized by WAY-100135 (5-HT 1A antagonist). In addition, the cerebral 5-HT depletion by repeated treatment with p-chlorophenylalanine did not reduce, but rather potentiated the facilitatory effects of 8-OH-DPAT. In contrast, the 5-HT 2 agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), significantly attenuated nicotine tremor, which was antagonized by ritanserin (5-HT 2 antagonist). The 5-HT 3 agonist SR-57227 did not affect nicotine-induced tremor. Furthermore, when testing the direct actions of 5-HT antagonists, nicotine tremor was inhibited by WAY-100135, but was unaffected by ritanserin, ondansetron (5-HT 3 antagonist) or SB-258585 (5-HT 6 antagonist). These results suggest that postsynaptic 5-HT 1A receptors are involved in induction of nicotine tremor mediated by α7 nACh receptors. In addition, 5-HT 2 receptors have an inhibitory modulatory role in induction of nicotine tremor. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Inverse agonist and neutral antagonist actions of synthetic compounds at an insect 5-HT1 receptor.

PubMed

Troppmann, B; Balfanz, S; Baumann, A; Blenau, W

2010-04-01

5-Hydroxytryptamine (5-HT) has been shown to control and modulate many physiological and behavioural functions in insects. In this study, we report the cloning and pharmacological properties of a 5-HT(1) receptor of an insect model for neurobiology, physiology and pharmacology. A cDNA encoding for the Periplaneta americana 5-HT(1) receptor was amplified from brain cDNA. The receptor was stably expressed in HEK 293 cells, and the functional and pharmacological properties were determined in cAMP assays. Receptor distribution was investigated by RT-PCR and by immunocytochemistry using an affinity-purified polyclonal antiserum. The P. americana 5-HT(1) receptor (Pea5-HT(1)) shares pronounced sequence and functional similarity with mammalian 5-HT(1) receptors. Activation with 5-HT reduced adenylyl cyclase activity in a dose-dependent manner. Pea5-HT(1) was expressed as a constitutively active receptor with methiothepin acting as a neutral antagonist, and WAY 100635 as an inverse agonist. Receptor mRNA was present in various tissues including brain, salivary glands and midgut. Receptor-specific antibodies showed that the native protein was expressed in a glycosylated form in membrane samples of brain and salivary glands. This study marks the first pharmacological identification of an inverse agonist and a neutral antagonist at an insect 5-HT(1) receptor. The results presented here should facilitate further analyses of 5-HT(1) receptors in mediating central and peripheral effects of 5-HT in insects.

Heat treatment as postharvest tool for improving quality in extra-early nectarines.

PubMed

Falagán, Natalia; Artés, Francisco; Aguayo, Encarna

2018-03-01

Extra-early nectarine cultivars such as 'VioWhite 5' could present a lack of organoleptic and nutritional quality. Heat treatments (HT) can be applied to improve their primary characteristics. In this experiment, control (non-treated), HT 1 (3 h; 45 °C) and HT 2 (2 h; 50 °C) were studied. Fruit were stored (10 days; 0 ± 0.5 °C; 90-95% RH) followed by a simulated retail sale period (3 days; 15 °C; 70-75% RH). HT fruit showed higher weight loss (2.76 ± 0.06% and 3.32 ± 0.01% for HT 1 and HT 2 , respectively; vs. 2.23 ± 0.14% for control) and lower firmness than control samples (28.88% and 21.67% less for HT 1 and HT 2 , respectively). HT treatments induced an increase in soluble solids content and a decrease in total acidity, which led to a better sensory quality. These changes were positively received by consumers. Total antioxidant capacity was enhanced by HT due to an increase in phenolic compound content. A higher enzymatic activity was found in pectin methylesterase and polygaracturonase in HT nectarines when compared to control. The application of HT on extra-early nectarine cv. demonstrated a strong potential to improve consumption quality in the industry. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Characterization of prejunctional 5-HT receptors mediating inhibition of sympathetic vasopressor responses in the pithed rat.

PubMed Central

Villalón, C. M.; Contreras, J.; Ramírez-San Juan, E.; Castillo, C.; Perusquía, M.; Terrón, J. A.

1995-01-01

1. It has recently been shown that continuous infusions of 5-hydroxytryptamine (5-HT) are able to inhibit, in a dose-dependent manner, the pressor responses induced by preganglionic (T7-T9) sympathetic stimulation in pithed rats pretreated with desipramine (50 micrograms kg-1, i.v.). This inhibitory effect, besides being significantly more pronounced at lower frequencies of stimulation (0.03-I Hz) and devoid of tachyphylaxis, is reversible after interrupting the infusions of 5-HT (up to 5.6 micrograms kg-1 min-1). In the present study we have characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5-HT. 2. The inhibition induced by 5.6 micrograms kg-1 min-1 of 5-HT on sympathetically-induced pressor responses was not blocked after i.v. treatment with physiological saline (1 ml kg-1), ritanserin (0.1 mg kg-1), MDL 72222 (0.15 mg kg-1) or tropisetron (3 mg kg-1), which did not modify the sympathetically-induced pressor responses per se, but was significantly antagonized by the 5-HT1-like and 5-HT2 receptor antagonist, methysergide (0.3 mg kg-1), which also produced a slight attenuation of the pressor responses to 0.03 and 0.1 Hz per se. 3. Unexpectedly and contrasting with methysergide, the 5-HT1-like and 5-HT2 receptor antagonists, methiothepin (0.01, 0.03 and 0.1 mg kg-1) and metergoline (1 and 3 mg kg-1), apparently failed to block the above 5-HT-induced inhibition. Nevertheless, it is noteworthy that these antagonists also blocked the electrically-induced pressor responses per se, presumably by blockade of vascular alpha 1-adrenoceptors and, indeed, this property might have masked their potential antagonism at the inhibitory 5-HT1-like receptors. 4. Consistent with the above findings, 5-carboxamidotryptamine (5-CT, a potent 5-HT1-like receptor agonist), metergoline and methysergide mimicked the inhibitory action of 5-HT with the following rank order of agonist potency: 5CT > > 5-HT > metergoline > or = methysergide. 5. Taken together, the above results suggest that the inhibitory action of 5-HT on the electrically-induced pressor responses is primarily mediated by an action on inhibitory prejunctional 5-HT1-like receptors leading to a decrease in the sympathetic nerve discharge. Interestingly, 5-HT-induced excitatory mechanisms could be made manifest once the inhibitory action of 5-HT had been antagonized. PMID:8719815

Pharmacological characterization of the 5-HT receptor-mediated contraction in the mouse isolated ileum

PubMed Central

Tuladhar, B R; Womack, M D; Naylor, R J

2000-01-01

The pharmacological characterization of a 5-HT receptor-mediated contractile response in the mouse isolated ileum is described. In the presence of methysergide (1 μM), 5-hydroxytryptamine (5-HT, 0.3–100 μM) produced phasic concentration-dependent contractions of segments of the mouse isolated ileum with a pEC50 value of 5.47±0.09. The 5-HT3 receptor selective agonists m-chlorophenylbiguanide (0.3–100 μM, pEC50 5.81±0.04), 1-phenylbiguanide (3–100 μM, pEC50 5.05±0.06) and 2-methyl-5-HT (3–100 μM, pEC50 5.00±0.07) acted as full agonists to induce contractile responses. 5-methoxytryptamine (0.1–100 μM), RS 67506 (0.1–100 μM) and α-methyl-5-HT (0.1–100 μM) failed to mimic the 5-HT responses. The contractile response to 5-HT was not antagonized by either 5-HT2 receptor antagonists ritanserin (0.1 μM) or ketanserin (1 μM) nor the 5-HT4 receptor antagonist SB 204070 (0.1 μM). The 5-HT3 receptor selective antagonists granisetron (0.3–1 nM), tropisetron (1–10 nM), ondansetron (10 nM–1 μM) and MDL 72222 (10 nM–1 μM) caused rightward displacement of the concentration-response curves to 5-HT. The lower concentrations of the antagonists caused approximate parallel rightward shifts of the concentration-response curves to 5-HT with apparent pKB values for granisetron (9.70±0.39), tropisetron (9.18±0.20), ondansetron (8.84±0.24) and MDL 72222 (8.65±0.35). But higher concentrations of antagonists resulted in a progressive reduction in the maximum responses. The contractile response to 5-HT was abolished by tetrodotoxin (0.3 μM); atropine (0.1 and 1 μM) decreased the maximum response of the 5-HT concentration-response curve by approximately 65%. It is concluded that a neuronally located 5-HT3 receptor mediates a contractile response to 5-HT in the mouse ileum. The 5-HT3 receptor in the mouse ileum has a different pharmacological profile to that reported for the guinea-pig ileum. PMID:11139451

Antagonism of lateral saphenous vein serotonin receptors from steers grazing endophyte-free, wild-type, or novel endophyte-infected tall fescue

USDA-ARS?s Scientific Manuscript database

Pharmacologic profiling of 5-hydroxytryptamine (5HT) receptors of bovine lateral saphenous vein has shown that cattle grazing endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have altered responses to ergovaline (ERV), 5HT, 5HT2A and 5HT7 agonists. To determine if 5HT...

Antagonism of 5-hydroxytryptamine2A Receptor Results in Decreased Contractile Response of Bovine Lateral Saphenous Vein to Tall Fescue Alkaloids

USDA-ARS?s Scientific Manuscript database

Pharmacologic profiling of 5-hydroxytryptamine (5HT) receptors of bovine lateral saphenous vein has shown that cattle grazing endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have altered responses to ergovaline (ERV), 5HT, 5HT2A and 5HT7 agonists. To determine if 5HT...

Moving beyond the EE and ESD Disciplinary Debate in Formal Education

ERIC Educational Resources Information Center

McKeown, Rosalyn; Hopkins, Charles

2007-01-01

Many educators think of Education for Sustainable Development (ESD) on a disciplinary level--what is Environmental Education's (EE) contribution to a more sustainable future? Briefly, we describe differences and similarities between EE and ESD. Next, we examine four levels of activity--disciplinary, whole school, educational system, and…

Job Prospects for E/E Engineers.

ERIC Educational Resources Information Center

Basta, Nicholas

1987-01-01

Discusses the trends in employment in the electrical/electronics (E/E) engineering industry. States that although the number of E/E graduates grew at a rate of over 11 percent from 1985 to 1986, the economy continues to be the major determinant in the job outlook in the field. (TW)

31 CFR 353.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT REGULATIONS GOVERNING DEFINITIVE UNITED STATES SAVINGS BONDS, SERIES EE AND HH General Information § 353.2 Definitions. (a) Bond, or Series EE or HH savings bond, as used in this part, means a definitive United States Savings Bond of Series EE or HH. (b...

Increased hypothalamic 5-HT2A receptor gene expression and effects of pharmacologic 5-HT2A receptor inactivation in obese A{sup y} mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nonogaki, Katsunori; Nozue, Kana; Oka, Yoshitomo

2006-12-29

Serotonin (5-hydroxytryptamine; 5-HT) 2A receptors contribute to the effects of 5-HT on platelet aggregation and vascular smooth muscle cell proliferation, and are reportedly involved in decreases in plasma levels of adiponectin, an adipokine, in diabetic subjects. Here, we report that systemic administration of sarpogrelate, a 5-HT2A receptor antagonist, suppressed appetite and increased hypothalamic pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript, corticotropin releasing hormone, 5-HT2C, and 5-HT1B receptor gene expression. A{sup y} mice, which have ectopic expression of the agouti protein, significantly increased hypothalamic 5-HT2A receptor gene expression in association with obesity compared with wild-type mice matched for age. Systemic administration ofmore » sarpogrelate suppressed overfeeding, body weight gain, and hyperglycemia in obese A{sup y} mice, whereas it did not increase plasma adiponectin levels. These results suggest that obesity increases hypothalamic 5-HT2A receptor gene expression, and pharmacologic inactivation of 5-HT2A receptors inhibits overfeeding and obesity in A{sup y} mice, but did not increase plasma adiponectin levels.« less

Functionalized Poly(3-hexylthiophene)s via Lithium–Bromine Exchange

PubMed Central

2015-01-01

Poly(3-hexylthiophene) (P3HT) is one of the most extensively investigated conjugated polymers and has been employed as the active material in many devices including field-effect transistors, organic photovoltaics and sensors. As a result, methods to further tune the properties of P3HT are desirable for specific applications. Herein, we report a facile postpolymerization modification strategy to functionalize the 4-position of commercially available P3HT in two simple steps–bromination of the 4-position of P3HT (Br–P3HT) followed by lithium−bromine exchange and quenching with an electrophile. We achieved near quantitative lithium–bromine exchange with Br–P3HT, which requires over 100 thienyl lithiates to be present on a single polymer chain. The lithiated-P3HT is readily combined with functional electrophiles, resulting in P3HT derivatives with ketones, secondary alcohols, trimethylsilyl (TMS) group, fluorine, or an azide at the 4-position. We demonstrated that the azide-modified P3HT could undergo Cu-catalyzed or Cu-free click chemistry, significantly expanding the complexity of the structures that can be appended to P3HT using this method. PMID:25620811

Effects of histamine and 5-hydroxytryptamine on the growth rate of xenografted human bronchogenic carcinomas.

PubMed

Sheehan, P F; Baker, T; Tutton, P J; Barkla, D H

1996-01-01

1. The influence of histamine and 5-hydroxytryptamine (5-HT) antagonists and agonists on the volume doubling times (Td) of human bronchogenic carcinomas propagated as s.c. xenografts in immunosuppressed mice was examined. 2. The H2-receptor antagonists, cimetidine and ranitidine, increased Td. 3. Treatment with the H2-receptor agonist, 4-methyl histamine, had no effect on Td. 4. Co-administration of 4-methyl histamine and cimetidine abolished the effects of cimetidine. 5. The 5-HT2-receptor antagonists, cinanserin and ketanserin, both increased Td. 6. Treatment with the 5-HT1/2-receptor agonist quipazine (0.1 mg/kg, reflecting 5-HT2 agonist activity) decreased Td, while a higher dose (10.0 mg/kg) had no effect. 7. The 5-HT1/2-receptor antagonist, methiothepin, decreased Td. 8. The 5-HT uptake inhibitor, fluoxetine, increased Td in one tumour line but not in another, while the 5-HT releaser/depletor, fenfluramine, increased Td. 9. Histamine may stimulate tumour growth through the histamine H2-receptor, while the dominant effect of 5-HT is 5-HT1-receptor inhibition. 10. Tumour growth in some bronchogenic carcinomas may involve 5-HT uptake mechanisms.

Frameworking memory and serotonergic markers.

PubMed

Meneses, Alfredo

2017-07-26

The evidence for neural markers and memory is continuously being revised, and as evidence continues to accumulate, herein, we frame earlier and new evidence. Hence, in this work, the aim is to provide an appropriate conceptual framework of serotonergic markers associated with neural activity and memory. Serotonin (5-hydroxytryptamine [5-HT]) has multiple pharmacological tools, well-characterized downstream signaling in mammals' species, and established 5-HT neural markers showing new insights about memory functions and dysfunctions, including receptors (5-HT1A/1B/1D, 5-HT2A/2B/2C, and 5-HT3-7), transporter (serotonin transporter [SERT]) and volume transmission present in brain areas involved in memory. Bidirectional influence occurs between 5-HT markers and memory/amnesia. A growing number of researchers report that memory, amnesia, or forgetting modifies neural markers. Diverse approaches support the translatability of using neural markers and cerebral functions/dysfunctions, including memory formation and amnesia. At least, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors and SERT seem to be useful neural markers and therapeutic targets. Hence, several mechanisms cooperate to achieve synaptic plasticity or memory, including changes in the expression of neurotransmitter receptors and transporters.

Energy expenditure while playing active and inactive video games.

PubMed

Leatherdale, Scott T; Woodruff, Sarah J; Manske, Stephen R

2010-01-01

To examine energy expenditure (EE) when playing active and inactive videogames (VG). Predicted EE was measured among 51 undergraduate students while playing active and inactive VG (Ontario, Canada). Predicted EE was significantly higher playing the active VG compared to the inactive VG according to heart rate monitor (97.4 kcal vs 64.7 kcal) and SenseWear armband (192.4 kcal vs 42.3 kcal) estimates. Active VG may be a viable intervention tool for increasing EE among students who would otherwise be spending time in sedentary screen-based behaviors.

Measurement of the ϕ → π0e+e- transition form factor with the KLOE detector

NASA Astrophysics Data System (ADS)

Anastasi, A.; Babusci, D.; Bencivenni, G.; Berlowski, M.; Bloise, C.; Bossi, F.; Branchini, P.; Budano, A.; Caldeira Balkeståhl, L.; Cao, B.; Ceradini, F.; Ciambrone, P.; Curciarello, F.; Czerwiński, E.; D'Agostini, G.; Danè, E.; De Leo, V.; De Lucia, E.; De Santis, A.; De Simone, P.; Di Cicco, A.; Di Domenico, A.; Di Salvo, R.; Domenici, D.; D'Uffizi, A.; Fantini, A.; Felici, G.; Fiore, S.; Gajos, A.; Gauzzi, P.; Giardina, G.; Giovannella, S.; Graziani, E.; Happacher, F.; Heijkenskjöld, L.; Ikegami Andersson, W.; Johansson, T.; Kamińska, D.; Krzemien, W.; Kupsc, A.; Loffredo, S.; Mandaglio, G.; Martini, M.; Mascolo, M.; Messi, R.; Miscetti, S.; Morello, G.; Moricciani, D.; Moskal, P.; Papenbrock, M.; Passeri, A.; Patera, V.; Perez del Rio, E.; Ranieri, A.; Salabura, P.; Santangelo, P.; Sarra, I.; Schioppa, M.; Silarski, M.; Sirghi, F.; Tortora, L.; Venanzoni, G.; Wiślicki, W.; Wolke, M.

2016-06-01

A measurement of the vector to pseudoscalar conversion decay ϕ →π0e+e- with the KLOE experiment is presented. A sample of ˜9500 signal events was selected from a data set of 1.7 fb-1 of e+e- collisions at √{ s} ˜mϕ collected at the DAΦNE e+e- collider. These events were used to perform the first measurement of the transition form factor |Fϕπ0 (q2) | and a new measurement of the branching ratio of the decay: BR (ϕ →π0e+e-) = (1.35 ±0.05-0.10+0.05) ×10-5. The result improves significantly on previous measurements and is in agreement with theoretical predictions.

ISR corrections to associated HZ production at future Higgs factories

NASA Astrophysics Data System (ADS)

Greco, Mario; Montagna, Guido; Nicrosini, Oreste; Piccinini, Fulvio; Volpi, Gabriele

2018-02-01

We evaluate the QED corrections due to initial state radiation (ISR) to associated Higgs boson production in electron-positron (e+e-) annihilation at typical energies of interest for the measurement of the Higgs properties at future e+e- colliders, such as CEPC and FCC-ee. We apply the QED Structure Function approach to the four-fermion production process e+e- →μ+μ- b b bar , including both signal and background contributions. We emphasize the relevance of the ISR corrections particularly near threshold and show that finite third order collinear contributions are mandatory to meet the expected experimental accuracy. We analyze in turn the rôle played by a full four-fermion calculation and beam energy spread in precision calculations for Higgs physics at future e+e- colliders.

Fractional reactive extraction for symmetrical separation of 4-nitro-D,L-phenylalanine in centrifugal contactor separators: experiments and modeling.

PubMed

Tang, Kewen; Wen, Ping; Zhang, Panliang; Huang, Yan

2015-01-01

The enantioselective liquid-liquid extraction of 4-nitro-D,L-phenylalanine (D,L-Nphy) using PdCl2 {(s)-BINAP} as extractant in dichloroethane was studied experimentally in a countercurrent cascade of 10 centrifugal contactor separators (CCSs) at 5°C, involving flow ratio, extractant concentration, and Cl(-) concentration. The steady-state enantiomeric excess (ee) in both stream exits was 90.86% at a 93.29% yield. The predicted value was modeled using an equilibrium stage approach. The correlation between model and experiment was satisfactory. The model was applied to optimize the production of both enantiomers in >97% ee and >99% ee. 14 stages and 16 stages are required for 97% ee and 99% ee for both enantiomers, respectively. © 2014 Wiley Periodicals, Inc.

Student perceptions of the education environment in a Spanish medical podiatry school.

PubMed

Palomo-López, Patricia; Becerro-de-Bengoa-Vallejo, Ricardo; Calvo-Lobo, César; Tovaruela-Carrión, Natalia; Rodríguez-Sanz, David; Elena Losa-Iglesias, Marta; López-López, Daniel

2018-01-01

The aim of this study was to explore students' perceptions of the educational environment (EE) in a Spanish school of podiatry. Various aspects of EE were compared by academic year in the program. This was a cross-sectional study using a questionnaire to collect perceptions using data from a 2015 survey. Podiatric medical students from Extremadura University participated in this study. EE was assessed with the Dundee Ready Education Environment Measure (DREEM) tool.The DREEM questionnaire covers five domains of student perceptions, including learning, teachers, academic self-perceptions, atmosphere, and social self-perceptions. Two hundred thirty-five students participated, resulting in a 90.73% response rate. Participants included similar numbers of students from different years in the program, and most were women. The global EE score was 2.58 out of 4, indicating that students' perceptions were more positive than negative. Although some weaknesses were detected in this school, students viewed the EE positively in all five DREEM domains. Academic year in the program were generally not related to perceptions of EE. Podiatric medical students declared, in general, that the EE was more positive than negative in our school, according to the DREEM questionnaire. However, although the results are on the whole good, some areas need to be revised to make improvements.

British American Tobacco's partnership with Earthwatch Europe and its implications for public health.

PubMed

McDaniel, Patricia A; Malone, Ruth E

2012-01-01

This paper explores a partnership between British American Tobacco (BAT) and the environmental organisation Earthwatch Europe (EE) and considers its implications for countries implementing Article 5.3 of the World Health Organization Framework Convention on Tobacco Control. We reviewed approximately 100 internal BAT documents, interviewed EE's former executive director and examined media accounts and BAT and EE websites. We analysed materials by reviewing them iteratively, identifying themes, constructing a timeline of events and assembling a case study. BAT sought a partnership with EE to gain a global ally that could provide entrée into the larger non-governmental organisation (NGO) community. EE debated the ethics of working with BAT, resolving them in BAT's favour and taking a narrow view of its own overall organisational mission. To protect its reputation, EE delayed public disclosure of the partnership. Instead, EE promoted it to policy-makers and other NGOs, extending BAT's reputation and reach into influential circles. The potential for normalising the tobacco industry presence within government through NGO partnerships and the benefits that accrued to BAT even when the partnership was not being publicised show why governments seeking to protect effective tobacco control policies from industry influence need to consider ways to identify and discourage 'hidden' NGO partnerships.

Emotional exhaustion and cognitive performance in apparently healthy teachers: a longitudinal multi-source study.

PubMed

Feuerhahn, Nicolas; Stamov-Roßnagel, Christian; Wolfram, Maren; Bellingrath, Silja; Kudielka, Brigitte M

2013-10-01

We investigate how emotional exhaustion (EE), the core component of burnout, relates to cognitive performance, job performance and health. Cognitive performance was assessed by self-rated cognitive stress symptoms, self-rated and peer-rated cognitive impairments in everyday tasks and a neuropsychological test of learning and memory (LGT-3); job performance and physical health were gauged by self-reports. Cross-sectional linear regression analyses in a sample of 100 teachers confirm that EE is negatively related to cognitive performance as assessed by self-rating and peer-rating as well as neuropsychological testing (all p < .05). Longitudinal linear regression analyses confirm similar trends (p < .10) for self-rated and peer-rated cognitive performance. Executive control deficits might explain impaired cognitive performance in EE. In longitudinal analyses, EE also significantly predicts physical health. Contrary to our expectations, EE does not affect job performance. When reversed causation is tested, none of the outcome variables at Time 1 predict EE at Time 2. This speaks against cognitive dysfunctioning serving as a vulnerability factor for exhaustion. In sum, results underpin the negative consequences of EE for cognitive performance and health, which are relevant for individuals and organizations alike. In this way, findings might contribute to the understanding of the burnout syndrome. Copyright © 2012 John Wiley & Sons, Ltd.

Experiences and factors influencing a sample of teachers in New York state public elementary and middle schools to focus on environmental education in their teaching

NASA Astrophysics Data System (ADS)

Tooker, Gail Patricia

This study focuses on how fourteen elementary and middle level teachers in New York chose to teach environmental topics as part of their science curricula. Prior research suggested that factors influencing teachers to make curricular decisions are different from those that motivated them to become teachers in the first place (Espinet, et.al. 1992). This was supported by the results of this study, which found that most of these teachers made the decision to begin teaching environmental education (EE) well after deciding to become teachers and that the decision to teach EE was influenced by a variety of factors including participation in EE-oriented in-service programs, media coverage of environmental issues, encouragement from colleagues and school administrators to undertake EE, and personal experiences in childhood or early adulthood with the environment and/or with EE. Studies examining experiences that influence people to practice "environmentally responsible" behaviors (Chawla, 1995; McGarry, 1994; Tanner, 1994) suggested that positive childhood contacts with nature were important predictors for such behavior in adulthood. Findings of this study were largely consistent with these results, however, this sample of teachers viewed their childhood nature experiences as being mostly responsible for the development of their appreciation of the environment, while their actual decision to begin teaching EE was primarily influenced by other experiences, as discussed above. This study also examined how these teachers prepared themselves for teaching EE. The findings indicate that these teachers used a wide variety of preparation strategies. A minority reported becoming prepared for teaching EE through their pre-service teacher education programs. These results were in agreement with prior findings that most teacher education programs in this country do not include a focus on EE. Even where preparation for EE is included, it has been rated by the participants as inadequate (Disinger, 1990; McKeown-Ice, 1995). The sample was established via nomination by EE experts in New York and written invitation. Seven males and seven females representing grades K through 8th volunteered to participate. Data on potentially influential experiences and demographic factors were gathered via written questionnaire and structured interviews and were analyzed using conventional qualitative analysis techniques.

Rikkunshito and isoliquiritigenin counteract 5-HT-induced 2C receptor-mediated activation of pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus.

PubMed

Arai, Takeshi; Maejima, Yuko; Muroya, Shinji; Yada, Toshihiko

2013-08-01

Anorexia deteriorates the quality of life in patients with anorexia nervosa, stress disorders, gastrointestinal disorders, and cancer. Pro-opiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC), serotonin (5-HT) and its 2C receptor (5-HT2CR) are implicated in anorexia. Rikkunshito, a traditional Japanese medicine, has been used to treat anorexia and gastrointestinal disorders. The present study aimed to clarify whether rikkunshito influences the 5-HT action on ARC POMC neurons. We isolated single neurons from the ARC of adult rats and measured cytosolic Ca²⁺ concentration ([Ca²⁺](i)) by fura-2 microfluorometry combined with immunocytochemical identification of POMC neurons. Administration of 5-HT increased [Ca²⁺](i) in ARC neurons, and 80% of the 5-HT-responsive neurons were immunoreactive to POMC. Rikkunshito concentration-dependently and 5-HT2CR antagonist SB242084 significantly suppressed 5-HT-induced [Ca²⁺](i) increases. The rikkunshito-suppressed neurons highly overlapped SB242084-suppressed neurons. Isoliquiritigenin, an ingredient of rikkunshito, suppressed 5-HT-induced [Ca²⁺](i) increases to a lesser extent than rikkunshito. These results demonstrate that rikkunshito counteracts 5-HT-induced 5-HT2CR-mediated Ca²⁺ signaling in ARC POMC neurons, and that isoliquiritigenin may serve as an active component of rikkunshito. The ability of rikkunshito to antagonize 5-HT action in ARC POMC neurons could underlie the rikkunshito's action to attenuate anorexia induced by excessive 5-HT release and/or action associated with psychiatric diseases, gastrointestinal disorders, cancer, and anti-cancer medicines. Copyright © 2013 Elsevier Ltd. All rights reserved.

Involvement of CAT in the detoxification of HT-induced ROS burst in rice anther and its relation to pollen fertility.

PubMed

Zhao, Qian; Zhou, Lujian; Liu, Jianchao; Cao, Zhenzhen; Du, Xiaoxia; Huang, Fudeng; Pan, Gang; Cheng, Fangmin

2018-05-01

HT-induced ROS burst in developing anther is closely related to the lowered CAT activity as the result of the markedly suppressed OsCATB transcript, thereby causing severe fertility injury for rice plants exposed to HT at meiosis stage. The reproductive stage of rice plants is highly sensitive to heat stress. In this paper, different rice cultivars were used to investigate the relationship of HT-induced floret sterility with reactive oxygen species (ROS) detoxification in rice anthers under well-controlled climatic conditions. Results showed that high temperature (HT) exposure significantly enhanced the ROS level and malondialdehyde (MDA) content in developing anther, and the increase in ROS amount in rice anther under HT exposure was closely associated with HT-induced decline in the activities of several antioxidant enzymes. For various antioxidant enzymes, SOD and CAT were more susceptible to the ROS burst in rice anther induced by HT exposure than APX and POD, in which SOD and CAT activity in developing anther decreased significantly by HT exposure, whereas APX activity was relatively stable among different temperature regimes. HT-induced decrease in CAT activity was attributable to the suppressed transcript of OsCATB. This occurrence was strongly responsible for HT-induced increase in ROS level and oxidative-damage in rice anther, thereby it finally caused significant reduction in pollen viability and floret fertility for the rice plants exposed to HT during meiosis. Exogenous application of 1000 µM salicylic acid (SA) may alleviate HT-induced reduction in pollen viability and floret fertility, concomitantly with the increased CAT activity and reduced ROS level in rice anther.

Cognitive Effects of Hormone Therapy Continuation or Discontinuation in a Sample of Women at Risk for Alzheimer Disease.

PubMed

Wroolie, Tonita E; Kenna, Heather A; Williams, Katherine E; Rasgon, Natalie L

2015-11-01

Use of estrogen-based hormone therapy (HT) as a protection from cognitive decline and Alzheimer disease (AD) is controversial, although cumulative data support HT use when initiated close to menopause onset with estrogen formulations containing 17β-estradiol preferable to conjugated equine estrogen formulations. Little is known regarding specific populations of women who may derive benefit from HT. Women with heightened risk for AD (aged 49-69), all of whom were taking HT for at least 1 year and most of whom initiated HT close to menopause onset, underwent cognitive assessment followed by randomization to continue or discontinue HT. Assessments were repeated at 2 years after randomization. Women who continued HT performed better on cognitive domains composed of measures of verbal memory and combined attention, working memory, and processing speed measures. Women who used 17β-estradiol versus conjugated equine estrogen, whether randomized to continue or discontinue HT, showed better verbal memory performance at the 2-year follow-up assessment. An interaction was also found with HT randomization and family history of AD in a first-degree relative. All female offspring of patients with AD declined in verbal memory; however, women who continued HT declined less than women who discontinued HT. Women without a first-degree relative with AD showed verbal memory improvement (likely because of practice effects) with continuance and declined with discontinuance of HT. Continuation of HT use appears to protect cognition in women with heightened risk for AD when initiated close to menopause onset. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Effects of chronic sumatriptan and zolmitriptan treatment on 5-HT receptor expression and function in rats.

PubMed

Reuter, U; Salomone, S; Ickenstein, G W; Waeber, C

2004-05-01

Triptans are commonly used anti-migraine drugs and show agonist action mainly at serotonin 5-HT(1B/1D/1F) receptors. It is not known whether frequent or long-term treatment with these drugs would alter 5-HT receptor function. We investigated the effects of protracted (14-18 days) sumatriptan and zolmitriptan treatment in rats on 5-HT(1) receptor mRNA expression and function in tissues related to migraine pathophysiology. RT-PCR analysis revealed that 5-HT(1B/1D/1F) receptor mRNA was reduced in the trigeminal ganglion after treatment with either triptan (reduction by: sumatriptan 39% and zolmitriptan 61% for 5-HT(1B); 60%vs 41% for 5-HT(1D); 32%vs 68% for 5-HT(1F)). Sumatriptan attenuated 5-HT(1D) receptor mRNA by 49% in the basilar artery, whereas zolmitriptan reduced 5-HT(1B) mRNA in this tissue by 70%. No change in 5-HT(1) receptor mRNA expression was observed in coronary artery and dura mater. Chronic triptan treatment had no effect in two functional assays [sumatriptan mediated inhibition (50 mg/kg, i.p.) of electrically induced plasma protein extravasation in dura mater and 5-nonyloxytryptamine-stimulated [(35)S]guanosine-5'-O-(3-thio)triphosphate binding in substantia nigra]. Furthermore, vasoconstriction to 5-HT in isolated basilar artery was not affected by chronic triptan treatment, while it was slightly reduced in coronary artery. We conclude that, although our treatment protocol altered mRNA receptor expression in several tissues relevant to migraine pathophysiology, it did not attenuate 5-HT(1) receptor-dependent functions in rats.

The 5-HT{sub 2A} serotoninergic receptor is expressed in the MCF-7 human breast cancer cell line and reveals a mitogenic effect of serotonin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sonier, Brigitte; Arseneault, Madeleine; Institut National de la Recherche Scientifique-Institut Armand-Frappier, Montreal, Que.

2006-05-19

Serotonin (5-hydroxytryptamine, 5-HT) has been described as a mitogen in a variety of cell types and carcinomas. It exerts its mitogenic effect by interacting with a wide range of 5-HT receptor types. Certain studies suggest that some selective serotonin re-uptake inhibitors promote breast cancer in animals and humans. This study attempts to clarify the role of serotonin in promoting the growth of neoplastic mammary cells. Expression of the 5-HT{sub 2A} serotoninergic receptor subtype in MCF-7 cells was determined by RT-PCR, Western blotting, and immunofluorescence analysis. The mitogenic effect of 5-HT on MCF-7 cells was determined by means of the MTTmore » proliferation assay. We have demonstrated that the 5-HT{sub 2A} receptor subtype is fully expressed in the MCF-7 human breast cancer cell line, in terms of encoding mRNA and receptor protein. Automated sequencing has confirmed that the 5-HT{sub 2A} receptor present in this cell line is identical to the 5-HT{sub 2A} receptor found in human platelets and in human cerebral cortex. Furthermore, this receptor was found by immunofluorescence to be on the plasma membrane. MTT proliferation assays revealed that 5-HT and DOI, a selective 5-HT{sub 2A} receptor subtype agonist, stimulated MCF-7 cell. These results indicate that 5-HT plays a mitogenic role in neoplastic mammary cells. Our data also indicate that 5-HT exerts this positive growth effect on MCF-7 cells through, in part, the 5-HT{sub 2A} receptor subtype, which is fully expressed in this cell line.« less

Chromatographic analysis of age-related changes in mucosal serotonin transmission in the murine distal ileum

PubMed Central

2012-01-01

Background In the upper bowel, alterations in motility and absorption of key nutrients have been observed as part of the normal ageing process. Serotonin (5-HT) is a key signalling molecule in the gastrointestinal tract and is known to influence motility, however little is known of how the ageing process alters 5-HT signalling processes in the bowel. Results An isocratic chromatographic method was able to detect all 5-HT precursors and metabolites. Using extracellular and intracellular sampling approaches, we were able to monitor all key parameters associated with the transmission process. There was no alteration in the levels of tryptophan and 5-HTP between 3 and 18 month old animals. There was a significant increase in the ratio of 5-HT:5-HTP and an increase in intracellular 5-HT between 3 and 18 month old animals suggesting an increase in 5-HT synthesis. There was also a significant increase in extracellular 5-HT with age, suggesting increased 5-HT release. There was an age-related decrease in the ratio of intracellular 5-HIAA:extracellular 5-HT, whilst the amount of 5-HIAA did not change with age. In the presence of an increase in extracellular 5-HT, the lack of an age-related change in 5-HIAA is suggestive of a decrease in re-uptake via the serotonin transporter (SERT). Conclusions We have used intracellular and extracellular sampling to provide more insight into alterations in the neurotransmission process of 5-HT during normal ageing. We observed elevated 5-HT synthesis and release and a possible decrease in the activity of SERT. Taken together these changes lead to increased 5-HT availability and may alter motility function and could lead to the changes in adsorption observed in the elderly. PMID:22494644

Spinal 5-HT2 and 5-HT3 receptors mediate low, but not high, frequency TENS-induced antihyperalgesia in rats

PubMed Central

Radhakrishnan, Rajan; King, Ellen W.; Dickman, Janelle K.; Herold, Carli A.; Johnston, Natalie F.; Spurgin, Megan L.; Sluka, Kathleen A.

2009-01-01

Transcutaneous electrical nerve stimulation (TENS) is a form of non-pharmacological treatment for pain. Involvement of descending inhibitory systems is implicated in TENS-induced analgesia. In the present study, the roles of spinal 5-HT and α2-adrenoceptors in TENS analgesia were investigated in rats. Hyperalgesia was induced by inflaming the knee joint with 3% kaolin—carrageenan mixture and assessed by measuring paw withdrawal latency (PWL) to heat before and 4 h after injection. The (1) α2-adrenergic antagonist yohimbine (30 μg), (2) 5-HT antagonist methysergide (5-HT1 and 5-HT2,30 μg), one of the 5-HT receptor subtype antagonists, (3) NAN-190 (5-HT1A, 15 μg), (4) ketanserin (5-HT2A, 30 μg), (5) MDL-72222 (5-HT3, 12 μg), or (6) vehicle was administered intrathecally prior to TENS treatment. Low (4 Hz) or high (100 Hz) frequency TENS at sensory intensity was then applied to the inflamed knee for 20 min and PWL was determined. Selectivity of the antagonists used was confirmed using respective agonists administered intrathecally. Yohimbine had no effect on the antihyperalgesia produced by low or high frequency TENS. Methysergide and MDL-72222 prevented the antihyperalgesia produced by low, but not high, frequency TENS. Ketanserin attenuated the antihyperalgesic effects of low frequency TENS whereas NAN-190 had no effect. The results from the present study show that spinal 5-HT receptors mediate low, but not high, frequency TENS-induced antihyperalgesia through activation of 5-HT2A and 5-HT3 receptors in rats. Furthermore, spinal noradrenergic receptors are not involved in either low or high frequency TENS antihyperalgesia. PMID:14499437

BAG3 protects against hyperthermic stress by modulating NF-κB and ERK activities in human retinoblastoma cells.

PubMed

Yunoki, Tatsuya; Tabuchi, Yoshiaki; Hayashi, Atsushi; Kondo, Takashi

2015-03-01

BCL2-associated athanogene 3 (BAG3), a co-chaperone of HSP70, is a cytoprotective and anti-apoptotic protein that acts against various stresses, including heat stress. Here, we examined the effect of BAG3 on the sensitivity of human retinoblastoma cells to hyperthermia (HT). We examined the effects of BAG3 knockdown on the sensitivity of Y79 and WERI-Rb-1cells to HT (44 °C, 1 h) by evaluating apoptosis and cell proliferation using western blotting, real-time quantitative PCR (qPCR), flow cytometry, and a WST-8 assay kit. Furthermore, we examined the effects of activating nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK) using western blotting and real time qPCR. HT induced considerable apoptosis along with the activation of caspase-3 and chromatin condensation. The sensitivity of Y79 and WERI-Rb-1 cells to HT was significantly enhanced by BAG3 knockdown. Compared to HT alone, the combination of BAG3 knockdown and HT reduced phosphorylation of the inhibitors of kappa B α (IκBα) and p65, a subunit of NF-κB, and degraded IκB kinase γ (IKKγ) during the recovery period after HT. Furthermore, BAG3 knockdown increased the HT-induced phosphorylation of ERK after HT treatment, and the ERK inhibitor U0126 significantly improved the viability of the cells treated with a combination of BAG3 knockdown and HT. The silencing of BAG3 seems to enhance the effects of HT, at least in part, by maintaining HT-induced inactivity of NF-κB and the phosphorylation of ERK. These findings indicate that BAG3 may be a potential molecular target for modifying the outcomes of HT in retinoblastoma.

Effects of OPC-14523, a combined sigma and 5-HT1a ligand, on pre- and post-synaptic 5-HT1a receptors.

PubMed

Bermack, Jordanna E; Debonnel, Guy

2007-01-01

OPC-14523 (OPC) is a novel compound with high affinity for sigma and 5-HT1A receptors that shows 'antidepressant-like' effects in animal models of depression. We have previously demonstrated that OPC produces an increase in 5-HT neurotransmission and a decreased response of 5-HT neurons to the acute administration of paroxetine in the DRN, an effect that appears to be mediated by OPC's 5-HT1A receptor affinity. The current study sets out to investigate more specifically the effects of OPC on 5-HT1A pre- and post-synaptic receptors, to assess whether it acts as an agonist or antagonist. Using an electrophysiological model of in vivo extracellular recordings in anaesthetized rats, the effects of OPC was assessed on pre-synaptic DRN 5-HT1A autoreceptors and post-synaptically on hippocampal 5-HT1A receptors of CA3 pyramidal neurons. OPC applied by microiontophoresis, produced a significant decrease in the firing activity of 5-HT neurons of the DRN and of quisqualate-activated CA3 pyramidal neurons of the dorsal hippocampus. The effects of OPC on 5-HT1A receptors were significantly reduced by the co-application of the 5-HT1A antagonist WAY-100635. In addition, the effects of OPC were not blocked by the injection of the sigma antagonists NE-100 or haloperidol. Therefore, OPC is acting as an agonist on both pre- and post-synaptic 5-HT1A receptors. The current findings combined with previous data on OPC suggest a pharmacological profile that warrants further investigation.

Serotonin (1A) receptor involvement in acute 3,4-methylenedioxymethamphetamine (MDMA) facilitation of social interaction in the rat.

PubMed

Morley, Kirsten C; Arnold, Jonathon C; McGregor, Iain S

2005-06-01

The current study assessed whether various co-administered serotonin (5-HT) receptor antagonists could prevent some of the acute behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in rats. In the social interaction test, MDMA (5 mg/kg) significantly increased the duration of total social interaction between two conspecifics meeting for the first time. Microanalysis showed that MDMA increased adjacent lying and approach behaviours while reducing anogenital sniffing. MDMA (5 mg/kg) also caused elements of the serotonin syndrome including low body posture and piloerection. In the emergence test, MDMA significantly increased hide time and emergence latency indicating increased anxiety-like behavior. Pretreatment with the 5HT 1A receptor antagonist, WAY 100635 (1 mg/kg), prevented MDMA-induced increases in social interaction and markers of the serotonin syndrome while the 5-HT 1B receptor antagonist GR 55562 (1 mg/kg) and 5-HT 2A receptor antagonist ketanserin (1 mg/kg) were ineffective. The 5-HT 2B/2C receptor antagonist, SB 206553 (2 mg/kg), prevented MDMA-induced prosocial effects but caused pronounced thigmotaxis (hyperactivity at the periphery of the testing chamber). The anxiogenic effect of MDMA on the emergence test was not prevented by pretreatment with any of the 5-HT receptor antagonists tested. These results indicate that prosocial effect of MDMA may involve 5-HT 1A and possibly 5-HT 2B/2C receptors. In contrast, MDMA-induced generalised anxiety, as measured by the emergence test, seems unlikely to involve the 5-HT 1A, 5-HT 1B or 5-HT 2A, 5-HT 2B or 5-HT 2C receptors.

Alterations in melatonin and 5-HT signalling in the colonic mucosa of mice with dextran-sodium sulfate-induced colitis.

PubMed

MacEachern, Sarah J; Keenan, Catherine M; Papakonstantinou, Evangelia; Sharkey, Keith A; Patel, Bhavik Anil

2018-05-01

Inflammatory bowel disease (IBD) is characterized by pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in mucosal 5-HT (serotonin) signalling occur in animal models of colitis and in humans suffering from IBD. Melatonin is co-released with 5-HT from the mucosa and has a wide variety of actions in the GI tract. Here, we examined how melatonin signalling is affected by colitis and determined how this relates to 5-HT signalling. Using electroanalytical approaches, we investigated how 5-HT release, reuptake and availability as well as melatonin availability are altered in dextran sodium sulfate (DSS)-induced colitis in mice. Studies were conducted to explore if melatonin treatment during active colitis could reduce the severity of colitis. We observed an increase in 5-HT and a decrease in melatonin availability in DSS-induced colitis. A significant reduction in 5-HT reuptake was observed in DSS-induced colitis animals. A reduction in the content of 5-HT was observed, but no difference in tryptophan levels were observed. A reduction in deoxycholic acid-stimulated 5-HT availability and a significant reduction in mechanically-stimulated 5-HT and melatonin availability were observed in DSS-induced colitis. Orally or rectally administered melatonin once colitis was established did not significantly suppress inflammation. Our data suggest that DSS-induced colitis results in a reduction in melatonin availability and an increase in 5-HT availability, due to a reduction/loss of tryptophan hydroxylase 1 enzyme, 5-HT content and 5-HT transporters. Mechanosensory release was more susceptible to inflammation when compared with chemosensory release. © 2018 The British Pharmacological Society.

Inhibition of excitatory non-adrenergic non-cholinergic bronchoconstriction in guinea-pig airways in vitro by activation of an atypical 5-HT receptor.

PubMed

Ward, J K; Fox, A J; Barnes, P J; Belvisi, M G

1994-04-01

1. The effect of 5-hydroxytryptamine (5-HT) was studied on excitatory neurally mediated non-adrenergic non-cholinergic (NANC) contractions evoked by electrical field stimulation (EFS) in guinea-pig isolated bronchi. 2. 5-HT (0.1-100 microM) produced a concentration-dependent inhibition of the excitatory NANC response with 50.9 +/- 5.0% (n = 5, P < 0.01) inhibition at 100 microM. This inhibition was not significantly affected by the 5-HT2 antagonist, ketanserin (1 microM) when inhibitions (+/- ketanserin) at each concentration of 5-HT were compared by unpaired t tests; however, this concentration appeared to produce a leftward shift (approximately 10 fold) of the 5-HT concentration-inhibition curve. Ketanserin (1 microM) was effective in blocking bronchoconstriction evoked by activation of 5-HT2A receptors on airway smooth muscle. In the presence of ketanserin (1 microM) 5-HT (100 microM) evoked an inhibition of 57.4 +/- 5.9% (n = 5, P < 0.01) with an EC50 of 0.57 microM. 3. Inhibition evoked by 5-HT (0.1-100 microM) was unaffected by the alpha-adrenoceptor antagonist phentolamine (1 microM), the beta 2-adrenoceptor antagonist, ICI 118551 (0.1 microM), the 5-HT1A/B antagonist, cyanopindolol (1 microM) or the 5-HT3/4 antagonist, ICS 205-930 (1 microM). 4. Methiothepin (0.1 microM) produced an insurmountable inhibition of the effect of 5-HT (0.1-100 microM), reducing the maximum inhibition produced by 5-HT (100 microM) to 30.2 +/- 5.0% (n = 5, P < 0.001) and suggesting a non-competitive antagonism. Methiothepin inhibited the effect of 5-HT (10 microM) in a concentration-dependent manner with an IC50 of 81 nM. 5. Selective 5-HT receptor agonists were also tested on excitatory NANC responses. 5-Carboxamidotryptamine (5-CT, 0.1-100 MicroM) was the most potent, producing a concentration-dependent inhibition with an EC50 of 0.13 MicroM. Calculation of approximate IC25 values (concentration of the agonist required to give a 25% inhibition of the excitatory NANC response) gave a rank order of potency 5-CT > 5-HT> > 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) >alpha-methyl-5-hydroxytryptamine (alpha-Me-5HT). Sumatriptan, 5-methoxytryptamine (5-MeOT) and 2-methyl-5-hydroxytryptamine (2-Me-5HT) were essentially inactive with IC25> 100 MicroM.6. 5-HT (10 microM) did not significantly affect contractile responses to exogenously applied substance P(1 nM-10 Microm).7. The effect of 5-HT was unchanged after incubation with the nitric oxide (NO) synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 100 Microm). However, pretreatment with charybdotoxin (ChTX,0.1-30 nM), a blocker of the large conductance Ca2+-activated K+channel (K+ca), produced a concentration-dependent inhibition of the effect of 5-HT (10 MicroM).8. 5-HT evokes a concentration-dependent inhibition of e-NANC bronchoconstriction in guinea-pig isolated bronchi but does not affect cumulative concentration-dependent contractile responses to substance P, suggesting that inhibition is via a prejunctional receptor. Effects of selective antagonists and agonists suggest that an atypical 5-HT receptor mediates this inhibition. The inhibitory effect of 5-HT does not involve the production of NO, but may involve the opening a ChTX-sensitive K+ca channel.These data suggest that an atypical 5-HT receptor inhibits the release of neuropeptides from sensory C fibres and may act as other inhibitory neuromodulators via the opening of a common K'channel.

Sequential Prediction for Information Fusion and Control

DTIC Science & Technology

2013-10-14

the notation simple, we drop the subscript x in the following. In particular, we use ht for hx,t , cWt for cWx,t , ∫t for Pt (·|x), etc. The...admissibility condition to be proved is sup ht2Hx © EUª∫t [ht (U )]+ cWt (ht ) ™ ∑ cWt °1(ht°1). Note that ø ∫t ,exp µ ° 1 Ω ht ∂¿ = X u2U ∫1(u)exp ≥ ° 1Ω Pt°1 s

Identification of a cys-ser substitution in the 5-HT{sub 2C} (HTR2C) receptor gene and allelic association to violent behavior and alcoholism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lappalainen, J.; Ozaki, N.; Goldman, D.

1994-09-01

Several lines of evidence suggest that brain serotonergic functions, including behavioral and neurochemical responses to 5-HT{sub 2C} agonist, are abnormal in some individuals with alcoholism and aggressive behaviors. The aim of the present study was to identify coding sequence variants in the human 5-HT{sub 2C} receptor gene which may cause abnormal or variant function of this receptor. Using SSCP analysis, a non-conservative cys-ser substitution was found in the 5-HT{sub 2C} receptor (designated 5-HT{sub 2Ccys} and 5-HT{sub 2Cser}). The polymorphism was typed in CEPH families to genetically map the gene. To test for association of the variant to alcoholism, violent behaviormore » and serotonin function, the 5-HT{sub 2C} genotypes of 151 non-related Finnish male alcoholic violent offenders and impulsive fire setters and 127 Finnish psychiatrically interviewed healthy male volunteers were determined. CSF 5-HIAA concentrations were available for 74 alcoholic violent offenders and 25 healthy volunteers. Linkage analysis placed the 5-HT{sub 2C} gene on Xq21, a region that has been previously shown to contain genes for several mental retardation syndromes. The 5-HT{sub 2Ccys}/5-HT{sub 2Cser} genotype frequencies in alcoholic violent offenders and controls differed significantly (0.90/0.10 and 0.82/0.18, respectively, P=0.048). The association was found to be strongest in the violent offenders who did not fulfill the criteria for antisocial personality disorder (5-HT{sub 2Ccys}/5-HT{sub 2Cser} 0.93/0.07, p=0.021). No association was found between CSF 5-HIAA concentrations and 5-HT{sub 2C} genotype. These results implicate a 5-HT{sub 2C} receptor amino acid substitution in predisposition to alcohol abuse and violent behavior in a subgroup of alcoholics.« less

Serotonin neuron development: shaping molecular and structural identities.

PubMed

Deneris, Evan; Gaspar, Patricia

2018-01-01

The continuing fascination with serotonin (5-hydroxytryptamine, 5-HT) as a nervous system chemical messenger began with its discovery in the brains of mammals in 1953. Among the many reasons for this decades-long interest is that the small numbers of neurons that make 5-HT influence the excitability of neural circuits in nearly every region of the brain and spinal cord. A further reason is that 5-HT dysfunction has been linked to a range of psychiatric and neurological disorders many of which have a neurodevelopmental component. This has led to intense interest in understanding 5-HT neuron development with the aim of determining whether early alterations in their generation lead to brain disease susceptibility. Here, we present an overview of the neuroanatomical organization of vertebrate 5-HT neurons, their neurogenesis, and prodigious axonal architectures, which enables the expansive reach of 5-HT neuromodulation in the central nervous system. We review recent findings that have revealed the molecular basis for the tremendous diversity of 5-HT neuron subtypes, the impact of environmental factors on 5-HT neuron development, and how 5-HT axons are topographically organized through disparate signaling pathways. We summarize studies of the gene regulatory networks that control the differentiation, maturation, and maintenance of 5-HT neurons. These studies show that the regulatory factors controlling acquisition of 5-HT-type transmitter identity continue to play critical roles in the functional maturation and the maintenance of 5-HT neurons. New insights are presented into how continuously expressed 5-HT regulatory factors control 5-HT neurons at different stages of life and how the regulatory networks themselves are maintained. WIREs Dev Biol 2018, 7:e301. doi: 10.1002/wdev.301 This article is categorized under: Nervous System Development > Vertebrates: General Principles Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Nervous System Development > Secondary: Vertebrates: Regional Development. © 2017 Wiley Periodicals, Inc.

Heart transplantation in Fontan patients across Australia and New Zealand.

PubMed

Shi, William Y; Yong, Matthew S; McGiffin, David C; Jain, Pankaj; Ruygrok, Peter N; Marasco, Silvana F; Finucane, Kirsten; Keogh, Anne; d'Udekem, Yves; Weintraub, Robert G; Konstantinov, Igor E

2016-07-15

Patients with Fontan physiology may eventually require heart transplantation (HT). We determined the rates and outcomes of HT in a national, population-based multicentre study. From 1990 to 2015, 1369 patients underwent the Fontan procedure as recorded in the Australia and New Zealand Fontan Registry. We identified those who underwent HT and analysed their outcomes. We compared rates of HT between two catchment areas. In area 1 (n=721), patients were referred to the national paediatric HT programme or its associated adult programme. In area 2 (n=648), patients were referred to the national paediatric HT programme or one of the other adult HT programmes. Mean follow-up time post-Fontan was 11±8 years. Freedom from Fontan failure was 74%±3.9% at 20 years. HT was performed in 34 patients. Patients living in area 1 were more likely to have HT (4.0%, 29/721 vs 0.8%, 5/648, p<0.001) with a cumulative proportion of 3.4% vs 0.7% at 10 years and 6.8% vs 1.2% at 20 years (p=0.002). Area 1 patients were more likely to undergo HT (hazard ratio 4.7, 95% CI 1.7 to 13.5, p=0.003) on multivariable regression. Post-HT survival at 1, 5 and 10 years was 91%, 78% and 71%, respectively. Compared with other patients with congenital heart disease (n=87), Fontan patients had similar in-hospital outcomes and long-term survival. Although HT after the Fontan procedure can be achieved with excellent outcomes, most patients with Fontan failure do not undergo HT. Significant regional differences in rates of HT in Fontan patients exist. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Leptin, adiponectin and serotonin levels in lean and obese dogs.

PubMed

Park, Hyung-Jin; Lee, Sang-Eun; Oh, Jung-Hyun; Seo, Kyoung-Won; Song, Kun-Ho

2014-05-13

Serotonin (5-hydroytryptamine or 5HT) is associated with numerous behavioral and psychological factors and is a biochemical marker of mood. 5HT is involved in the hypothalamic regulation of energy consumption. 5HT controls appetite in the central nerve system (CNS) and stimulates intestinal mobility. There are few studies looking at the role of 5HT and the relationship between peripheral circulating serotonin and obesity. The aim of this study was to find any differences in leptin, adiponectin, and 5HT between lean and obese dogs and to identify correlations among these factors. Leptin, triglyceride (TG) and cholesterol levels were higher in the obese group (all p < 0.01). Adiponectin and 5HT levels were higher in the lean group compared to the obese group (p < 0.01). Leptin (r = 0.628, p < 0.01), TG (r = 0.491, p < 0.01) and cholesterol (r = 0.419, p < 0.01) were positively correlated with body condition score (BCS), and adiponectin (r = -0.446, p < 0.01) and 5HT (r = -0.490, p < 0.01) were negatively correlated with BCS. Leptin was negatively correlated with adiponectin (r = -0.294, p < 0.01) and 5HT (r = -0.343, p < 0.01). 5HT was negatively correlated with leptin (r = -0.343, p < 0.01), TG (r = -0.268, p < 0.05) and cholesterol (r = -0.357, p < 0.05). 5HT is an important appetite control neurotransmitter, but there are limited studies for 5HT levels related to obesity in dogs. To the best of our knowledge, this is the first study to evaluate peripheral 5HT levels in obese dogs. From this research, we can assume that 5HT may be correlated with canine obesity. Further studies will be needed to further elucidate the role of low serum 5HT levels in canine obesity.

Leptin, adiponectin and serotonin levels in lean and obese dogs

PubMed Central

2014-01-01

Background Serotonin (5-hydroytryptamine or 5HT) is associated with numerous behavioral and psychological factors and is a biochemical marker of mood. 5HT is involved in the hypothalamic regulation of energy consumption. 5HT controls appetite in the central nerve system (CNS) and stimulates intestinal mobility. There are few studies looking at the role of 5HT and the relationship between peripheral circulating serotonin and obesity. The aim of this study was to find any differences in leptin, adiponectin, and 5HT between lean and obese dogs and to identify correlations among these factors. Results Leptin, triglyceride (TG) and cholesterol levels were higher in the obese group (all p < 0.01). Adiponectin and 5HT levels were higher in the lean group compared to the obese group (p < 0.01). Leptin (r = 0.628, p < 0.01), TG (r = 0.491, p < 0.01) and cholesterol (r = 0.419, p < 0.01) were positively correlated with body condition score (BCS), and adiponectin (r = -0.446, p < 0.01) and 5HT (r = -0.490, p < 0.01) were negatively correlated with BCS. Leptin was negatively correlated with adiponectin (r = -0.294, p < 0.01) and 5HT (r = -0.343, p < 0.01). 5HT was negatively correlated with leptin (r = -0.343, p < 0.01), TG (r = -0.268, p < 0.05) and cholesterol (r = -0.357, p < 0.05). Conclusions 5HT is an important appetite control neurotransmitter, but there are limited studies for 5HT levels related to obesity in dogs. To the best of our knowledge, this is the first study to evaluate peripheral 5HT levels in obese dogs. From this research, we can assume that 5HT may be correlated with canine obesity. Further studies will be needed to further elucidate the role of low serum 5HT levels in canine obesity. PMID:24886049

Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster.

PubMed

Blenau, Wolfgang; Daniel, Stöppler; Balfanz, Sabine; Thamm, Markus; Baumann, Arnd

2017-01-01

Serotonin (5-hydroxytryptamine, 5-HT) is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects) and deuterostomes (e.g., mammals). In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In Drosophila melanogaster , a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT 1A , Dm5-HT 1B , and Dm5-HT 7 couple to cAMP signaling cascades, the Dm5-HT 2A receptor leads to Ca 2+ signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth D. melanogaster gene was uncovered coding for a Dm5-HT 2B receptor. Knowledge about this receptor's pharmacological properties is very limited. This is quite surprising because Dm5-HT 2B has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT 2B mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT 2B 's pharmacology, we evaluated the receptor's response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT 2B signaling in vitro and in vivo .

Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster

PubMed Central

Blenau, Wolfgang; Daniel, Stöppler; Balfanz, Sabine; Thamm, Markus; Baumann, Arnd

2017-01-01

Serotonin (5-hydroxytryptamine, 5-HT) is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects) and deuterostomes (e.g., mammals). In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In Drosophila melanogaster, a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT1A, Dm5-HT1B, and Dm5-HT7 couple to cAMP signaling cascades, the Dm5-HT2A receptor leads to Ca2+ signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth D. melanogaster gene was uncovered coding for a Dm5-HT2B receptor. Knowledge about this receptor’s pharmacological properties is very limited. This is quite surprising because Dm5-HT2B has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT2B mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT2B’s pharmacology, we evaluated the receptor’s response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT2B signaling in vitro and in vivo. PMID:28553207

Inhibition of excitatory non-adrenergic non-cholinergic bronchoconstriction in guinea-pig airways in vitro by activation of an atypical 5-HT receptor.

PubMed Central

Ward, J. K.; Fox, A. J.; Barnes, P. J.; Belvisi, M. G.

1994-01-01

1. The effect of 5-hydroxytryptamine (5-HT) was studied on excitatory neurally mediated non-adrenergic non-cholinergic (NANC) contractions evoked by electrical field stimulation (EFS) in guinea-pig isolated bronchi. 2. 5-HT (0.1-100 microM) produced a concentration-dependent inhibition of the excitatory NANC response with 50.9 +/- 5.0% (n = 5, P < 0.01) inhibition at 100 microM. This inhibition was not significantly affected by the 5-HT2 antagonist, ketanserin (1 microM) when inhibitions (+/- ketanserin) at each concentration of 5-HT were compared by unpaired t tests; however, this concentration appeared to produce a leftward shift (approximately 10 fold) of the 5-HT concentration-inhibition curve. Ketanserin (1 microM) was effective in blocking bronchoconstriction evoked by activation of 5-HT2A receptors on airway smooth muscle. In the presence of ketanserin (1 microM) 5-HT (100 microM) evoked an inhibition of 57.4 +/- 5.9% (n = 5, P < 0.01) with an EC50 of 0.57 microM. 3. Inhibition evoked by 5-HT (0.1-100 microM) was unaffected by the alpha-adrenoceptor antagonist phentolamine (1 microM), the beta 2-adrenoceptor antagonist, ICI 118551 (0.1 microM), the 5-HT1A/B antagonist, cyanopindolol (1 microM) or the 5-HT3/4 antagonist, ICS 205-930 (1 microM). 4. Methiothepin (0.1 microM) produced an insurmountable inhibition of the effect of 5-HT (0.1-100 microM), reducing the maximum inhibition produced by 5-HT (100 microM) to 30.2 +/- 5.0% (n = 5, P < 0.001) and suggesting a non-competitive antagonism. Methiothepin inhibited the effect of 5-HT (10 microM) in a concentration-dependent manner with an IC50 of 81 nM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7518294

A comparison of the effects on central 5-HT function of sibutramine hydrochloride and other weight-modifying agents

PubMed Central

Heal, D J; Cheetham, S C; Prow, M R; Martin, K F; Buckett, W R

1998-01-01

Effects on 5-HT function of sibutramine and its active metabolites, BTS 54 354 and BTS 54 505, were compared with fluoxetine, (+)-fenfluramine and (+)-amphetamine.In vitro sibutramine weakly inhibited [3H]-5-HT uptake into brain synaptosomes. BTS 54 354, BTS 54 505 and fluoxetine were powerful [3H]-5-HT uptake inhibitors, whereas (+)-fenfluramine and (+)-amphetamine were very much weaker. Conversely, whilst sibutramine, its metabolites and fluoxetine did not release [3H]-5-HT from brain slices at ⩽10−5M, (+)-fenfluramine and (+)-amphetamine concentration-dependently increased [3H]-5-HT release.Sibutramine and fluoxetine had no effect on 5-hydroxytryptophan (5-HTP) accumulation in either frontal cortex or hypothalamus at doses <10 mg kg−1. In contrast, (+)-amphetamine (⩾3 mg kg−1) reduced 5-HTP in hypothalamus, whilst (+)-fenfluramine (⩾1 mg kg−1) decreased 5-HTP in both regions.Sibutramine (10 mg kg−1 i.p.) and fluoxetine (10 mg kg−1 i.p.) produced slow, prolonged increases of extracellular 5-HT in the anterior hypothalamus. In contrast, (+)-fenfluramine (3 mg kg−1 i.p.) and (+)-amphetamine (4 mg kg−1 i.p.) induced rapid, short-lasting increases in extracellular 5-HT.Only (+)-fenfluramine (10 mg kg−1) altered 5-HT2A receptors in rat frontal cortex when given for 14 days, producing a 61% reduction in receptor number and a 18% decrease in radioligand affinity.These results show that sibutramine powerfully enhances central 5-HT function via its secondary and primary amine metabolites; this effect, like that of fluoxetine, is almost certainly mediated through 5-HT uptake inhibition. By contrast, (+)-fenfluramine enhances 5-HT function predominantly by increasing 5-HT release. (+)-Amphetamine, though weaker than (+)-fenfluramine, also enhances 5-HT function by release. PMID:9786502

Serotonergic Mechanisms in Addiction-Related Memories

PubMed Central

Nic Dhonnchadha, Bríd Á; Cunningham, Kathryn A.

2008-01-01

Drug-associated memories are a hallmark of addiction and a contributing factor in the continued use and relapse to drugs of abuse. Repeated association of drugs of abuse with conditioned stimuli leads to long-lasting behavioral responses that reflect reward-controlled learning and participate in the establishment of addiction. A greater understanding of the mechanisms underlying the formation and retrieval of drug-associated memories may shed light on potential therapeutic approaches to effectively intervene with drug use-associated memory. There is evidence to support the involvement of serotonin (5-HT) neurotransmission in learning and memory formation through the families of the 5-HT1 receptor (5-HT1R) and 5-HT2R which have also been shown to play a modulatory role in the behavioral effects induced by many psychostimulants. While there is a paucity of studies examining the effects of selective 5-HT1AR ligands, the available dataset suggests that 5-HT1BR agonists may inhibit retrieval of cocaine-associated memories. The 5-HT2AR and 5-HT2CR appear to be integral in the strong conditioned associations made between cocaine and environmental cues with 5-HT2AR antagonists and 5-HT2CR agonists possessing potency in blocking retrieval of cocaine-associated memories following cocaine self-administration procedures. The complex anatomical connectivity between 5-HT neurons and other neuronal phenotypes in limbic-corticostriatal brain structures, the heterogeneity of 5-HT receptors (5-HTXR) and the conflicting results of behavioral experiments which employ non-specific 5-HTXR ligands contribute to the complexity of interpreting the involvement of 5-HT systems in addictive-related memory processes. This review briefly traces the history of 5-HT involvement in retrieval of drug-cue associations and future targets of serotonergic manipulation that may reduce the impact that drug cues have on addictive behavior and relapse. PMID:18639587

The absence of 5-HT4 receptors modulates depression- and anxiety-like responses and influences the response of fluoxetine in olfactory bulbectomised mice: Adaptive changes in hippocampal neuroplasticity markers and 5-HT1A autoreceptor.

PubMed

Amigó, J; Díaz, A; Pilar-Cuéllar, F; Vidal, R; Martín, A; Compan, V; Pazos, A; Castro, E

2016-12-01

Preclinical studies support a critical role of 5-HT 4 receptors (5-HT 4 Rs) in depression and anxiety, but their influence in depression- and anxiety-like behaviours and the effects of antidepressants remain partly unknown. We evaluated 5-HT 4 R knockout (KO) mice in different anxiety and depression paradigms and mRNA expression of some neuroplasticity markers (BDNF, trkB and Arc) and the functionality of 5-HT 1A R. Moreover, the implication of 5-HT 4 Rs in the behavioural and molecular effects of chronically administered fluoxetine was assessed in naïve and olfactory bulbectomized mice (OBX) of both genotypes. 5-HT 4 R KO mice displayed few specific behavioural impairments including reduced central activity in the open-field (anxiety), and decreased sucrose consumption and nesting behaviour (anhedonia). In these mice, we measured increased levels of BDNF and Arc mRNA and reduced levels of trkB mRNA in the hippocampus, and a desensitization of 5-HT 1A autoreceptors. Chronic administration of fluoxetine elicited similar behavioural effects in WT and 5-HT 4 R KO mice on anxiety-and depression-related tests. Following OBX, locomotor hyperactivity and anxiety were similar in both genotypes. Interestingly, chronic fluoxetine failed to reverse this OBX-induced syndrome in 5-HT 4 R KO mice, a response associated with differential effects in hippocampal neuroplasticity biomarkers. Fluoxetine reduced hippocampal Arc and BDNF mRNA expressions in WT but not 5-HT 4 R KO mice subjected to OBX. These results demonstrate that the absence of 5-HT 4 Rs triggers adaptive changes that could maintain emotional states, and that the behavioural and molecular effects of fluoxetine under pathological depression appear to be critically dependent on 5-HT 4 Rs. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effect of Serotonin-Targeting Antidepressants on Neurogenesis and Neuronal Maturation of the Hippocampus Mediated via 5-HT1A and 5-HT4 Receptors

PubMed Central

Segi-Nishida, Eri

2017-01-01

Antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs) specifically increase serotonin (5-HT) levels in the synaptic cleft and are widely used to treat mood and anxiety disorders. There are 14 established subtypes of 5-HT receptors in rodents, each of which has regionally different expression patterns. Many preclinical studies have suggested that the hippocampus, which contains abundant 5-HT1A and 5-HT4 receptor subtypes in the dentate gyrus (DG), is critically involved in the mechanisms of action of antidepressants. This review article will analyze studies demonstrating regulation of hippocampal functions and hippocampus-dependent behaviors by SSRIs and similar serotonergic agents. Multiple studies indicate that 5-HT1A and 5-HT4 receptor signaling in the DG contributes to SSRI-mediated promotion of neurogenesis and increased neurotrophic factors expression. Chronic SSRI treatment causes functions and phenotypes of mature granule cells (GCs) to revert to immature-like phenotypes defined as a “dematured” state in the DG, and to increase monoamine reactivity at the dentate-to-CA3 synapses, via 5-HT4 receptor signaling. Behavioral studies demonstrate that the 5-HT1A receptors on mature GCs are critical for expression of antidepressant effects in the forced swim test and in novelty suppressed feeding; such studies also note that 5-HT4 receptors mediate neurogenesis-dependent antidepressant activity in, for example, novelty-suppressed feeding. Despite their limitations, the collective results of these studies describe a potential new mechanism of action, in which 5-HT1A and 5-HT4 receptor signaling, either independently or cooperatively, modulates the function of the hippocampal DG at multiple levels, any of which could play a critical role in the antidepressant actions of 5-HT-enhancing drugs. PMID:28559799

Identification of unique release kinetics of serotonin from guinea-pig and human enterochromaffin cells

PubMed Central

Raghupathi, Ravinarayan; Duffield, Michael D; Zelkas, Leah; Meedeniya, Adrian; Brookes, Simon J H; Sia, Tiong Cheng; Wattchow, David A; Spencer, Nick J; Keating, Damien J

2013-01-01

The major source of serotonin (5-HT) in the body is the enterochromaffin (EC) cells lining the intestinal mucosa of the gastrointestinal tract. Despite the fact that EC cells synthesise ∼95% of total body 5-HT, and that this 5-HT has important paracrine and endocrine roles, no studies have investigated the mechanisms of 5-HT release from single primary EC cells. We have developed a rapid primary culture of guinea-pig and human EC cells, allowing analysis of single EC cell function using electrophysiology, electrochemistry, Ca2+ imaging, immunocytochemistry and 3D modelling. Ca2+ enters EC cells upon stimulation and triggers quantal 5-HT release via L-type Ca2+ channels. Real time amperometric techniques reveal that EC cells release 5-HT at rest and this release increases upon stimulation. Surprisingly for an endocrine cell storing 5-HT in large dense core vesicles (LDCVs), EC cells release 70 times less 5-HT per fusion event than catecholamine released from similarly sized LDCVs in endocrine chromaffin cells, and the vesicle release kinetics instead resembles that observed in mammalian synapses. Furthermore, we measured EC cell density along the gastrointestinal tract to create three-dimensional (3D) simulations of 5-HT diffusion using the minimal number of variables required to understand the physiological relevance of single cell 5-HT release in the whole-tissue milieu. These models indicate that local 5-HT levels are likely to be maintained around the activation threshold for mucosal 5-HT receptors and that this is dependent upon stimulation and location within the gastrointestinal tract. This is the first study demonstrating single cell 5-HT release in primary EC cells. The mode of 5-HT release may represent a unique mode of exocytosis amongst endocrine cells and is functionally relevant to gastrointestinal sensory and motor function. PMID:24099799

The clinical effectiveness of healing touch.

PubMed

Wilkinson, Dawn S; Knox, Pamela L; Chatman, James E; Johnson, Terrance L; Barbour, Nilufer; Myles, Yvonne; Reel, Antonio

2002-02-01

(1) to determine the clinical effectiveness of Healing Touch (HT) on variables assumed to be related to health enhancement; (2) to determine whether practitioner training level moderates treatment effectiveness. Mixed-method repeated measures design with quasi-experimental and naturalistic approaches, paired with nomothetic and idiographic analyses. Practitioner's offices or client's home. Twenty-two (22) clients who had never experienced HT. Three treatment conditions: no treatment (NT), HT only (standard HT care), and HT+ (Standard HT care plus music plus guided imagery). Secretory immunoglobulin A (sIgA) concentrations in saliva, self-reports of stress levels, client perceptions of health enhancement, and qualitative questionnaires about individual effects. Clients of practitioners with more training experienced statistically significant positive sIgA change over the HT treatment series, while clients of practitioners with less experience did not. Clients reported a statistically significant reduction of stress level after both HT conditions. Perceived enhancement of health was reported by 13 of 22 clients (59%). Themes of relaxation, connection, and enhanced awareness were identified in the qualitative analysis of the HT experience. Pain relief was reported by 6 of 11 clients (55%) experiencing pain. The data support the clinical effectiveness of HT in health enhancement, specifically for raising sIgA concentrations, lowering stress perceptions and relieving pain. The evidence indicates that positive responses were not exclusively as a result of placebo, that is, client beliefs, expectations, and behaviors regarding HT.

Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks.

PubMed

De Vadder, Filipe; Grasset, Estelle; Mannerås Holm, Louise; Karsenty, Gérard; Macpherson, Andrew J; Olofsson, Louise E; Bäckhed, Fredrik

2018-06-19

The enteric nervous system (ENS) is crucial for essential gastrointestinal physiologic functions such as motility, fluid secretion, and blood flow. The gut is colonized by trillions of bacteria that regulate host production of several signaling molecules including serotonin (5-HT) and other hormones and neurotransmitters. Approximately 90% of 5-HT originates from the intestine, and activation of the 5-HT 4 receptor in the ENS has been linked to adult neurogenesis and neuroprotection. Here, we tested the hypothesis that the gut microbiota could induce maturation of the adult ENS through release of 5-HT and activation of 5-HT 4 receptors. Colonization of germ-free mice with a microbiota from conventionally raised mice modified the neuroanatomy of the ENS and increased intestinal transit rates, which was associated with neuronal and mucosal 5-HT production and the proliferation of enteric neuronal progenitors in the adult intestine. Pharmacological modulation of the 5-HT 4 receptor, as well as depletion of endogenous 5-HT, identified a mechanistic link between the gut microbiota and maturation of the adult ENS through the release of 5-HT and activation of the 5-HT 4 receptor. Taken together, these findings show that the microbiota modulates the anatomy of the adult ENS in a 5-HT-dependent fashion with concomitant changes in intestinal transit. Copyright © 2018 the Author(s). Published by PNAS.

Abrogated Freud-1/CC2D1A repression of 5-HT1A autoreceptors induces fluoxetine-resistant anxiety/depression-like behavior

PubMed Central

Vahid-Ansari, Faranak; Daigle, Mireille; Manzini, M. Chiara; Tanaka, Kenji F.; Hen, René; Geddes, Sean D.; Béïque, Jean-Claude; James, Jonathan; Merali, Zul; Albert, Paul R.

2017-01-01

Freud-1/CC2D1A represses the gene transcription of serotonin-1A (5-HT1A) autoreceptors, which negatively regulate 5-HT tone. To test the role of Freud-1 in vivo, we generated mice with adulthood conditional knockout of Freud-1 in 5-HT neurons (cF1ko). In cF1ko mice, 5-HT1A autoreceptor protein, binding and hypothermia response were increased, with reduced 5-HT content and neuronal activity in the dorsal raphe. The cF1ko mice displayed increased anxiety- and depression-like behavior that was resistant to chronic antidepressant (fluoxetine) treatment. Using conditional Freud-1/5-HT1A double knockout (cF1/1A dko) to disrupt both Freud-1 and 5-HT1A genes in 5-HT neurons, no increase in anxiety- or depression-like behaviour was seen upon knockout of Freud-1 on the 5-HT1A autoreceptor-negative background, rather a reduction in depression-like behaviour emerged. These studies implicate transcriptional dys-regulation of 5-HT1A autoreceptors by the repressor Freud-1 in anxiety and depression and provide a clinically relevant genetic model of antidepressant resistance. Targeting specific transcription factors like Freud-1 to restore transcriptional balance may augment response to antidepressant treatment. PMID:29101244

The platelet-poor plasma 5-HT response to carbohydrate rich meal administration in adult autistic patients compared with normal controls.

PubMed

Vered, Yaffa; Golubchik, Pavel; Mozes, Tamar; Strous, Rael; Nechmad, Allon; Mester, Roberto; Weizman, Abraham; Spivak, Baruch

2003-07-01

There are cumulative data indicating involvement of the 5-HT system in autistic disorder. Most studies examining 5-HT function have focused on whole blood 5-HT content. The carbohydrate-rich meal test (CRMT) is a dietary manipulation that could significantly influence platelet-poor plasma (PPP) 5-HT levels and reflect the responsiveness of the serotonergic system in 'free' plasma. In this study, CRMT was used as an indicator of 5-HT responsivity in drug-free adults with autistic disorder (n = 7), compared with normal controls (n = 10). The PPP 5-HT levels were measured at baseline and during 3 h after administration of the CRMT. A significant elevation in PPP 5-HT levels in adult autistic patients was reached 60 min after meal administration (p < 0.03 vs control and p = 0.05 vs baseline) and a significant decrease was noted after 120 min (p < 0.01 vs baseline). In contrast to the biphasic response of the autistic patients, normal controls exhibited a gradual linear increase of PPP 5-HT levels. Our results indicate that in adult autistic patients, the pattern of PPP 5-HT responsivity to a dietary challenge of CRMT is dysregulated compared with normal controls and provide further support for the role of 5-HT in autism. Copyright 2003 John Wiley & Sons, Ltd.

Risk of Depression, Chronic Morbidities, and l-Thyroxine Treatment in Hashimoto Thyroiditis in Taiwan: A Nationwide Cohort Study.

PubMed

Lin, I-Ching; Chen, Hsin-Hung; Yeh, Su-Yin; Lin, Cheng-Li; Kao, Chia-Hung

2016-02-01

The aim of this study was to evaluate the risk of depression in and effect of L-thyroxine therapy on patients with Hashimoto thyroiditis (HT) in Taiwan.In this retrospective, nationwide cohort study, we retrieved data from the Longitudinal Health Insurance Database 2000. We collected data of 1220 patients with HT and 4880 patients without HT for the period 2000 to 2011. The mean follow-up period for the HT cohort was 5.77 years. Univariate and multivariate Cox proportional hazards regression models were used to estimate the risk of depression in the HT cohort.In the HT cohort, 89.6% of the patients were women. Compared with the non-HT cohort, the HT cohort exhibited a higher prevalence of diabetes mellitus, hyperlipidemia, and coronary artery disease. Furthermore, the HT cohort showed a higher overall incidence of depression compared with the non-HT cohort (8.67 and 5.49 per 1000 person-year; crude hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.18-2.13). The risk of depression decreased after administration of L-thyroxine treatment for more than 1 year (adjusted HR = 1.02; 95% CI = 0.66-1.59).In Taiwan, the overall incidence of depression was greater in the young HT cohort. L-thyroxine treatment reduced the risk of depression.

Risk of Depression, Chronic Morbidities, and l-Thyroxine Treatment in Hashimoto Thyroiditis in Taiwan

PubMed Central

Lin, I-Ching; Chen, Hsin-Hung; Yeh, Su-Yin; Lin, Cheng-Li; Kao, Chia-Hung

2016-01-01

Abstract The aim of this study was to evaluate the risk of depression in and effect of l-thyroxine therapy on patients with Hashimoto thyroiditis (HT) in Taiwan. In this retrospective, nationwide cohort study, we retrieved data from the Longitudinal Health Insurance Database 2000. We collected data of 1220 patients with HT and 4880 patients without HT for the period 2000 to 2011. The mean follow-up period for the HT cohort was 5.77 years. Univariate and multivariate Cox proportional hazards regression models were used to estimate the risk of depression in the HT cohort. In the HT cohort, 89.6% of the patients were women. Compared with the non-HT cohort, the HT cohort exhibited a higher prevalence of diabetes mellitus, hyperlipidemia, and coronary artery disease. Furthermore, the HT cohort showed a higher overall incidence of depression compared with the non-HT cohort (8.67 and 5.49 per 1000 person-year; crude hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.18–2.13). The risk of depression decreased after administration of l-thyroxine treatment for more than 1 year (adjusted HR = 1.02; 95% CI = 0.66–1.59). In Taiwan, the overall incidence of depression was greater in the young HT cohort. l-thyroxine treatment reduced the risk of depression. PMID:26871858

Serotonin Improves High Fat Diet Induced Obesity in Mice.

PubMed

Watanabe, Hitoshi; Nakano, Tatsuya; Saito, Ryo; Akasaka, Daisuke; Saito, Kazuki; Ogasawara, Hideki; Minashima, Takeshi; Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Inoue, Nao; Ikeda, Ikuo; Chen, Xiangning; Miyake, Masato; Kitazawa, Haruki; Shirakawa, Hitoshi; Sato, Kan; Tahara, Kohji; Nagasawa, Yuya; Rose, Michael T; Ohwada, Shyuichi; Watanabe, Kouichi; Aso, Hisashi

2016-01-01

There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLeod, John A., E-mail: jmcleod@suda.edu.cn; Pitman, Amy L.; Moewes, Alexander

The electronic structure of [6,6]-phenyl C{sub 61} butyric acid methyl ester (PCBM), poly(3-hexylthiophene) (P3HT), and P3HT/PCBM blends is studied using soft X-ray emission and absorption spectroscopy and density functional theory calculations. We find that annealing reduces the HOMO-LUMO gap of P3HT and P3HT/PCBM blends, whereas annealing has little effect on the HOMO-LUMO gap of PCBM. We propose a model connecting torsional disorder in a P3HT polymer to the HOMO-LUMO gap, which suggests that annealing helps to decrease the torsional disorder in the P3HT polymers. Our model is used to predict the characteristic length scales of the flat P3TH polymer segmentsmore » in P3HT and P3HT/PCBM blends before and after annealing. Our approach may prove useful in characterizing organic photovoltaic devices in situ or even in operando.« less

Simultaneous determination of estrogens (ethinylestradiol and norgestimate) concentrations in human and bovine serum albumin by use of fluorescence spectroscopy and multivariate regression analysis.

PubMed

Hordge, LaQuana N; McDaniel, Kiara L; Jones, Derick D; Fakayode, Sayo O

2016-05-15

The endocrine disruption property of estrogens necessitates the immediate need for effective monitoring and development of analytical protocols for their analyses in biological and human specimens. This study explores the first combined utility of a steady-state fluorescence spectroscopy and multivariate partial-least-square (PLS) regression analysis for the simultaneous determination of two estrogens (17α-ethinylestradiol (EE) and norgestimate (NOR)) concentrations in bovine serum albumin (BSA) and human serum albumin (HSA) samples. The influence of EE and NOR concentrations and temperature on the emission spectra of EE-HSA EE-BSA, NOR-HSA, and NOR-BSA complexes was also investigated. The binding of EE with HSA and BSA resulted in increase in emission characteristics of HSA and BSA and a significant blue spectra shift. In contrast, the interaction of NOR with HSA and BSA quenched the emission characteristics of HSA and BSA. The observed emission spectral shifts preclude the effective use of traditional univariate regression analysis of fluorescent data for the determination of EE and NOR concentrations in HSA and BSA samples. Multivariate partial-least-squares (PLS) regression analysis was utilized to correlate the changes in emission spectra with EE and NOR concentrations in HSA and BSA samples. The figures-of-merit of the developed PLS regression models were excellent, with limits of detection as low as 1.6×10(-8) M for EE and 2.4×10(-7) M for NOR and good linearity (R(2)>0.994985). The PLS models correctly predicted EE and NOR concentrations in independent validation HSA and BSA samples with a root-mean-square-percent-relative-error (RMS%RE) of less than 6.0% at physiological condition. On the contrary, the use of univariate regression resulted in poor predictions of EE and NOR in HSA and BSA samples, with RMS%RE larger than 40% at physiological conditions. High accuracy, low sensitivity, simplicity, low-cost with no prior analyte extraction or separation required makes this method promising, compelling, and attractive alternative for the rapid determination of estrogen concentrations in biomedical and biological specimens, pharmaceuticals, or environmental samples. Published by Elsevier B.V.

Characterisation of the transcriptome of male and female wild-type guppy brains with RNA-Seq and consequences of exposure to the pharmaceutical pollutant, 17α-ethinyl estradiol.

PubMed

Saaristo, Minna; Wong, Bob B M; Mincarelli, Laura; Craig, Allison; Johnstone, Christopher P; Allinson, Mayumi; Lindström, Kai; Craft, John A

2017-05-01

Waterways are increasingly being contaminated by chemical compounds that can disrupt the endocrinology of organisms. One such compound is 17α-ethinyl estradiol (EE2), a synthetic estrogen used in the contraceptive pill. Despite considerable research interest in the effects of EE2 on reproduction and gene expression, surprisingly, only a few studies have capitalised on technologies, such as next-generation sequencing (NGS), to uncover the molecular pathways related to EE2 exposure. Accordingly, using high-throughput sequencing technologies, the aim of our study was to explore the effects of EE2 on brain transcriptome in wild-type male and female guppy (Poecilia reticulata). We conducted two sets of experiments, where fish were exposed to EE2 (measured concentrations: 8ng/L and 38ng/L) in a flow-through system for 21days. The effects on the brain transcriptome on both males and females were assessed using Illumina sequencing (MiSeq and HiSeq) platform followed by bioinformatics analysis (edgeR, DESeq2). Here, we report that exposure to EE2 caused both up- and downregulation of specific transcript abundances, and affected transcript abundance in a sex-specific manner. Specifically, we found 773 transcripts, of which 60 were male-specific, 61 female-specific and 285 treatment-specific. EE2 affected expression of 165 transcripts in males, with 88 downregulated and 77 upregulated, while in females, 120 transcripts were affected with 62 downregulated and 58 upregulated. Finally, RT-qPCR validation demonstrated that expression of transcripts related to transposable elements, neuroserpin and heat shock protein were significantly affected by EE2-exposure. Our study is the first to report brain transcriptome libraries for guppies exposed to EE2. Not only does our study provide a valuable resource, it offers insights into the mechanisms underlying the feminizing effects on the brains of organisms exposed to environmentally realistic concentrations of EE2. Copyright © 2017 Elsevier B.V. All rights reserved.

High SMAD7 and p-SMAD2,3 expression is associated with environmental enteropathy in children.

PubMed

Syed, Sana; Dinallo, Vincenzo; Iqbal, Najeeha T; Di Iorio, Laura; Di Fusco, Davide; Guleria, Shan; Amadi, Beatrice C; Sadiq, Kamran; Moskaluk, Christopher; Ali, S Asad; Kelly, Paul; Monteleone, Giovanni

2018-02-01

Enteropathies such as Crohn's disease are associated with enteric inflammation characterized by impaired TGF-β signaling, decreased expression of phosphorylated (p)-SMAD2,3 and increased expression of SMAD7 (an inhibitor of SMAD3 phosphorylation). Environmental enteropathy (EE) is an acquired inflammatory disease of the small intestine (SI), which is associated with linear growth disruption, cognitive deficits, and reduced oral vaccine responsiveness in children <5 y in resource-poor countries. We aimed to characterize EE inflammatory pathways by determining SMAD7 and p-SMAD2,3 levels (using Western blotting) in EE duodenal biopsies (N = 19 children, 7 from Pakistan, 12 from Zambia) and comparing these with healthy controls (Ctl) and celiac disease (CD) patients from Italy. Densitometric analysis of immunoblots showed that EE SI biopsies expressed higher levels of both SMAD7 (mean±SD in arbitrary units [a.u.], Ctl = 0.47±0.20 a.u., EE = 1.13±0.25 a.u., p-value = 0.03) and p-SMAD2,3 (mean±SD, Ctl = 0.38±0.14 a.u., EE = 0.60±0.10 a.u., p-value = 0.03). Immunohistochemistry showed that, in EE, SMAD7 is expressed in both the epithelium and in mononuclear cells of the lamina propria (LP). In contrast, p-SMAD3 in EE is expressed much more prominently in epithelial cells than in the LP. The high SMAD7 immunoreactivity and lack of p-SMAD3 expression in the LP suggests defective TGF-β signaling in the LP in EE similar to a previously reported SMAD7-mediated inflammatory pathway in refractory CD and Crohn's disease. However, Western blot densitometry showed elevated p-SMAD2,3 levels in EE, possibly suggesting a different inflammatory pathway than Crohn's disease but more likely reflecting cumulative protein expression from across all compartments of the mucosa as opposed to the LP alone. Further studies are needed to substantiate these preliminary results and to illustrate the relationship between SMAD proteins, TGF-β signaling, and inflammatory cytokine production, all of which may be potential therapeutic targets.

Very Late Scaffold Thrombosis of Bioresorbable Vascular Scaffold: Systematic Review and a Meta-Analysis.

PubMed

Toyota, Toshiaki; Morimoto, Takeshi; Shiomi, Hiroki; Yoshikawa, Yusuke; Yaku, Hidenori; Yamashita, Yugo; Kimura, Takeshi

2017-01-09

This study sought to compare the 2-year outcomes between bioresorbable vascular scaffold (BVS) and everolimus-eluting metallic drug-eluting stent (EES). The occurrence of very late stent/scaffold thrombosis (VLST) of BVS beyond 1 year after implantation is an increasing concern. We conducted a meta-analysis of 24 studies (BVS: n = 2,567 and EES: n = 19,806) reporting the 2-year outcomes of BVS and/or EES to compare the risk of BVS versus EES for stent/scaffold thrombosis (ST) and target lesion failure (TLF) in 7 comparative studies (3 randomized and 4 observational), and to estimate the pooled incidence rates of ST and TLF including additional 17 single-arm studies. In the 7 comparative studies, the risk for VLST between 1 and 2 years was numerically higher in BVS than in EES (odds ratio [OR]: 2.03 [95% confidence interval (CI): 0.62 to 6.71]). The excess risk of BVS relative to EES for ST through 2 years was significant (OR: 2.08 [95% CI: 1.02 to 4.26]). The risk for TLF was neutral between BVS and EES. In the 24 studies, the pooled estimated incidence rates of VLST, and ST through 2 years were higher in BVS than in EES (0.240 [95% CI: 0.022 to 0.608]% vs. 0.003 [95% CI: 0.000 to 0.028]%, and 1.43 [95% CI: 0.67 to 2.41]% vs. 0.56 [95% CI: 0.43 to 0.70]%, respectively). The corresponding rates for TLF were comparable between BVS and EES (1.88 [95% CI: 1.30 to 2.55]% and 1.78 [95% CI: 1.17 to 2.49]% and 7.90 [95% CI: 6.26 to 9.69]% and 7.49 [95% CI: 5.86 to 9.29]%, respectively). In this meta-analysis, BVS as compared with EES was associated with higher risk for VLST between 1 and 2 years and ST through 2 years. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Water 16-mers and hexamers: assessment of the three-body and electrostatically embedded many-body approximations of the correlation energy or the nonlocal energy as ways to include cooperative effects.

PubMed

Qi, Helena W; Leverentz, Hannah R; Truhlar, Donald G

2013-05-30

This work presents a new fragment method, the electrostatically embedded many-body expansion of the nonlocal energy (EE-MB-NE), and shows that it, along with the previously proposed electrostatically embedded many-body expansion of the correlation energy (EE-MB-CE), produces accurate results for large systems at the level of CCSD(T) coupled cluster theory. We primarily study water 16-mers, but we also test the EE-MB-CE method on water hexamers. We analyze the distributions of two-body and three-body terms to show why the many-body expansion of the electrostatically embedded correlation energy converges faster than the many-body expansion of the entire electrostatically embedded interaction potential. The average magnitude of the dimer contributions to the pairwise additive (PA) term of the correlation energy (which neglects cooperative effects) is only one-half of that of the average dimer contribution to the PA term of the expansion of the total energy; this explains why the mean unsigned error (MUE) of the EE-PA-CE approximation is only one-half of that of the EE-PA approximation. Similarly, the average magnitude of the trimer contributions to the three-body (3B) term of the EE-3B-CE approximation is only one-fourth of that of the EE-3B approximation, and the MUE of the EE-3B-CE approximation is one-fourth that of the EE-3B approximation. Finally, we test the efficacy of two- and three-body density functional corrections. One such density functional correction method, the new EE-PA-NE method, with the OLYP or the OHLYP density functional (where the OHLYP functional is the OptX exchange functional combined with the LYP correlation functional multiplied by 0.5), has the best performance-to-price ratio of any method whose computational cost scales as the third power of the number of monomers and is competitive in accuracy in the tests presented here with even the electrostatically embedded three-body approximation.

The 5-HT[subscript 3A] Receptor Is Essential for Fear Extinction

ERIC Educational Resources Information Center

Kondo, Makoto; Nakamura, Yukiko; Ishida, Yusuke; Yamada, Takahiro; Shimada, Shoichi

2014-01-01

The 5-HT [subscript 3] receptor, the only ionotropic 5-HT receptor, is expressed in limbic regions, including the hippocampus, amygdala, and cortex. However, it is not known whether it has a role in fear memory processes. Analysis of 5-HT [subscript 3A] receptor knockout mice in fear conditioning paradigms revealed that the 5-HT [subscript 3A]…