Effects of diazepam on BOLD activation during the processing of aversive faces

This study aimed to measure, using fMRI, the effect of diazepam on the haemodynamic response to emotional faces. Twelve healthy male volunteers (mean age = 24.83 +/- 3.16 years), were evaluated in a randomized, balanced-order, double-blind, placebo-controlled crossover design. Diazepam (10 mg) or placebo was given 1 h before the neuroimaging acquisition. In a blocked design covert face emotional task, subjects were presented with neutral (A) and aversive (B) (angry or fearful) faces. Participants were also submitted to an explicit emotional face recognition task, and subjective anxiety was evaluated throughout the procedures. Diazepam attenuated the activation of right amygdala and right orbitofrontal cortex and enhanced the activation of right anterior cingulate cortex (ACC) to fearful faces. In contrast, diazepam enhanced the activation of posterior left insula and attenuated the activation of bilateral ACC to angry faces. In the behavioural task, diazepam impaired the recognition of fear in female faces. Under the action of diazepam, volunteers were less anxious at the end of the experimental session. These results suggest that benzodiazepines can differentially modulate brain activation to aversive stimuli, depending on the stimulus features and indicate a role of amygdala and insula in the anxiolytic action of benzodiazepines.

Immediate and long-term effects of polysaccharides-based formulations on human skin

A new trend in cosmetic formulations is the use of biotechnological raw materials as the polysaccharides from Klebsiella pneumoniae, which are supposed to enhance cell renewal, improve skin hydration and micro-relief. Botanical extracts of Myrtus communis leaves contain different sugars, which may provide the same benefits. Thus, the objective of this study was to evaluate through objective and subjective analysis the immediate and long-term effects of cosmetic formulations containing polysaccharides biotechnologically-originated and / or the ones contained in Myrtus communis extracts. Three polysaccharide-based and placebo formulations were applied on the forearm skin of 40 volunteers. Skin hydration, transepidermal water loss (TEWL), viscoelasticity and skin micro-relief measurements were made before and 2 hours after a single application and after 15 and 30 day-periods of daily applications. Answers to a questionnaire about perceptions of formulation cosmetic features constituted the subjective analysis. All polysaccharide-based formulations enhanced skin hydration. Formulations with isolated or combined active substances improved skin barrier function as compared to placebo, in the short and long term studies. Formulations containing Myrtus communis extracts had the highest acceptance. Results suggest that daily use of formulations containing these substances is important for protection of the skin barrier function.

Quantitative analysis of photodynamic therapy effects in rat mammary tumor vascular density using image-pro plus software

Photodynamic therapy (PDT) is a treatment modality that has advanced rapidly in recent years. It causes tissue and vascular damage with the interaction of a photosensitizing agent (PS), light of a proper wavelength, and molecular oxygen. Evaluation of vessel damage usually relies on histopathology evaluation. Results are often qualitative or at best semi-quantitative based on a subjective system. The aim of this study was to evaluate, using CD31 immunohistochem- istry and image analysis software, the vascular damage after PDT in a well-established rodent model of chemically induced mammary tumor. Fourteen Sprague-Dawley rats received a single dose of 7,12-dimethylbenz(a)anthraxcene (80 mg/kg by gavage), treatment efficacy was evaluated by comparing the vascular density of tumors after treatment with Photogem® as a PS, intraperitoneally, followed by interstitial fiber optic lighting, from a diode laser, at 200 mW/cm and light dose of 100 J/cm directed against his tumor (7 animals), with a control group (6 animals, no PDT). The animals were euthanized 30 hours after the lighting and mammary tumors were removed and samples from each lesion were formalin-fixed. Immunostained blood vessels were quantified by Image Pro-Plus version 7.0. The control group had an average of 3368.6 ± 4027.1 pixels per picture and the treated group had an average of 779 ± 1242.6 pixels per area (P < 0.01), indicating that PDT caused a significant decrease in vascular density of mammary tumors. The combined immu- nohistochemistry using CD31, with selection of representative areas by a trained pathology, followed by quantification of staining using Image Pro-Plus version 7.0 system was a practical and robust methodology for vessel damage evalua- tion, which probably could be used to assess other antiangiogenic treatments.

Emotional engagement and orienting: the effects of picture size on affective response

For their survival, humans and animals can rely on motivational systems which are specialized in assessing the valence and imminence of dangers and appetitive cues. The Orienting Response (OR) is a fundamental response pattern that an organism executes whenever a novel or significant stimulus is detected, and has been shown to be consistently modulated by the affective value of a stimulus. However, detecting threatening stimuli and appetitive affordances while they are far away compared to when they are within reach constitutes an obvious evolutionary advantage. Building on the linear relationship between stimulus distance and retinal size, the present research was aimed at investigating the extent to which emotional modulation of distinct processes (action preparation, attentional capture, and subjective emotional state) is affected when reducing the retinal size of a picture. Studies 1-3 examined the effects of picture size on emotional response. Subjective feeling of engagement, as well as sympathetic activation, were modulated by picture size, suggesting that action preparation and subjective experience reflect the combined effects of detecting an arousing stimulus and assessing its imminence. On the other hand, physiological responses which are thought to reflect the amount of attentional resources invested in stimulus processing did not vary with picture size. Studies 4-6 were conducted to substantiate and extend the results of studies 1-3. In particular, it was noted that a decrease in picture size is associated with a loss in the low spatial frequencies of a picture, which might confound the interpretation of the results of studies 1-3. Therefore, emotional and neutral images which were either low-pass filtered or reduced in size were presented, and affective responses were measured. Most effects which were observed when manipulating image size were replicated by blurring pictures. However, pictures depicting highly arousing unpleasant contents were associated with a more pronounced decrease in affective modulation when pictures were reduced in size compared to when they were blurred. The present results provide important information for the study of processes involved in picture perception and in the genesis and expression of an emotional response. In particular, the availability of high spatial frequencies might affect the degree of activation of an internal representation of an affectively charged scene, and might modulate subjective emotional state and preparation for action. Moreover, the manipulation of stimulus imminence revealed important effects of stimulus engagement on specific components of the emotional response, and the implications of the present data for some models of emotions have been discussed. In particular, within the framework of a staged model of emotional response, the tactic and strategic role of response preparation and attention allocation to stimuli varying in engaging power has been discussed, considering the adaptive advantages that each might represent in an evolutionary view. Finally, the identification of perceptual parameters that allow affective processing to be carried out has important methodological applications in future studies examining emotional response in basic research or clinical contexts.

Rhythms of anorexigenic neuropeptides in senegalese sole: Effects of light, feeding regimes and developmental stage.

Increasing knowledge on the endocrine mechanisms that regulate feeding and growth in cultured fish can contribute to make improvement in fish holding conditions and feeding strategies, supporting the development of new techniques that could ameliorate feeding, food conversion efficiency and growth in aquaculture practice. The main objective of this study was to investigate how daily mRNA expression of three specific anorexigenic hormones, i.e. the corticotropin-releasing hormone (CRH) and the paralogues α- and β- proopiomelanocortin (POMC), is modulated by different photoperiods, light spectra and feeding regimes, in both adult and larvae of Solea senegalensis. In addition, as Senegalese sole exhibits a shift from diurnal to nocturnal in locomotor activity and feeding habits during metamorphic process, we tried to elucidate if this shift is accompanied by relevant daily variations in the expression of these anorexigenic hormones before, during and after the completion of metamorphosis. In order to reach this main objective, three main experiments were developed. In a first experiment, adults were reared under LD (12 h light: 12h dark) cycle and fed at mid-light (ML), mid-dark (MD) and at random (RND). In a second experiment, adult specimens were reared in constant darkness (DD) and fed at subjective mid-light (sML) or at RND. Larvae of Senegalese sole were reared under LD cycle with white, blue or red light for 40 days. Our results show an independence of crh mRNA expression from the feeding time and suggest an endogenous control of crh expression in sole. Both pomc paralogues showed significant daily rhythms under LD conditions. The rhythms were maintained or were even more robust under DD conditions for pomc_a, but were completely abolished for pomc_b. Our results indicate an endogenous control of pomc_a expression by the molecular clock in telencephalon and diencephalon, but not in the pituitary gland. Our findings confirm for the first time the significant influence that ambient lighting has on larval growth and development in Senegalese sole, revealing an important effect of light spectra upon functional elements of this species. Our results also emphasize the importance of maintaining cycling light-dark conditions of the adequate wavelengths in aquaculture practices during early development of sole.

Effects of thoracic epidural analgesia on lower urinary tract function in women

The need for an indwelling transurethral catheter in patients with postoperative thoracic epidural analgesia (TEA) is a matter of controversy. Subjective observations are ambivalent and the literature addressing this issue is scarce. As segmental blockade can be achieved with epidural analgesia, we hypothesized that analgesia within segments T4-T11 has no or minimal influence on lower urinary tract function. Thus, we evaluated the effect of TEA on lower urinary tract function by urodynamic studies.

Subjective stress in female elite athletes and non-athletes: Evidence from cortisol analyses

Stress response can be considered a consequence of psychological or physiological threats to the human organism. Elevated cortisol secretion represents a biological indicator of subjective stress. The extent of subjectively experienced stress depends on individual coping strategies or self-regulation skills. Because of their experience with competitive pressure, athletes might show less pronounced biological stress responses during stressful events compared to non-athletes. In the present study, the short version of the Berlin Intelligence Structure Test, a paper-pencil intelligence test, was used as an experimental stressor. Cortisol responses of 26 female Swiss elite athletes and 26 female non-athlete controls were compared. Salivary free cortisol responses were measured 15 minutes prior to, as well as immediately before and after psychometric testing. In both groups, a significant effect of time was found: High cortisol levels prior to testing decreased significantly during the testing session. Furthermore, athletes exhibited reliably lower cortisol levels than non-athlete controls. No significant interaction effects could be observed. The overall pattern of results supports the idea that elite athletes show a less pronounced cortisol-related stress response due to more efficient coping strategies.

The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA ("ecstasy") in humans

This study assessed the pharmacodynamic and pharmacokinetic effects of the interaction between the selective norepinephrine (NE) transporter inhibitor reboxetine and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in 16 healthy subjects. The study used a double-blind, placebo-controlled crossover design. Reboxetine reduced the effects of MDMA including elevations in plasma levels of NE, increases in blood pressure and heart rate, subjective drug high, stimulation, and emotional excitation. These effects were evident despite an increase in the concentrations of MDMA and its active metabolite 3,4-methylenedioxyamphetamine (MDA) in plasma. The results demonstrate that transporter-mediated NE release has a critical role in the cardiovascular and stimulant-like effects of MDMA in humans.

Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study

This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence.

Effects of high-dose heroin versus morphine in intravenous drug users: a randomised double-blind crossover study

The purpose of this study is to evaluate the effects of high doses of injected opiates as prescribed maintenance in intravenous drugs users. This was accomplished via a randomised double-blind study with crossover at an outpatient clinic in Bern, Switzerland. The subjects were 39 patients with a long history of intravenous opioid use and persistent abuse despite treatment; they were randomly allocated to two groups. Group A was started on controlled injection of graduated doses of morphine up to a satisfying individual dose and was then switched as a double blind to heroin at a randomly determined day between week three and four. Subsequently this group was given heroin for the remaining two to three weeks of the study. Group B was started on heroin and was then switched to morphine in the same manner. Equipotent solutions of 3% morphine and 2% heroin were administered. The main outcome measures were clinical observations, structural interviews and self report of subjective experiences to assess the effects of the drugs. In 16 cases, the study had to be discontinued owing to severe morphine-induced histamine reactions. Thirteen participants in Group B presented these adverse reactions on the day of the switch-over. Full data were thus only obtainable for 17 participants. Average daily doses were 491 mg for heroin and 597 mg for morphine. The findings indicate that heroin significantly produced a lower grade of itching, flushing, urticaria and pain/nausea. A negative correlation between dose and euphoria was observed for both heroin and morphine. The authors concluded that as heroin produces fewer side effects it is the preferred high-dose maintenance prescription to morphine. The perceived euphoric effects are limited in both substances.

Effects of expectation and caffeine on arousal, well-being, and reaction time

The objective of this study is to determine the impact of expectation associated with placebo and caffeine ingestion. We used a three-armed, randomized, double-blind design. Two three-armed experiments varying instruction (true, false, control) investigated the role of expectations of changes in arousal (blood pressure, heart rate), subjective well-being, and reaction time (RT). In Experiment 1 (N = 45), decaffeinated coffee was administered, and expectations were produced in one group by making them believe they had ingested caffeinated coffee. In Experiment 2 (N = 45), caffeinated orange juice was given in both experimental groups, but only one was informed about the true content. In Experiment 1, a significant effect for subjective alertness was found in the placebo treatment compared to the control group. However, for RT and well-being no significant effects were found. In Experiment 2, no significant expectancy effects were found. Caffeine produced large effects for blood pressure in both treatments compared to the control group, but the effects were larger for the false information group. For subjective well-being (alertness, calmness), considerable but nonsignificant changes were found for correctly informed participants, indicating possible additivity of pharmacologic effect and expectations. The results tentatively indicate that placebo and expectancy effects primarily show through introspection.

Source of funding and results of studies of health effects of mobile phone use: systematic review of experimental studies

OBJECTIVES: There is concern regarding the possible health effects of cellular telephone use. We examined whether the source of funding of studies of the effects of low-level radiofrequency radiation is associated with the results of studies. We conducted a systematic review of studies of controlled exposure to radiofrequency radiation with health-related outcomes (electroencephalogram, cognitive or cardiovascular function, hormone levels, symptoms, and subjective well-being). DATA SOURCES: We searched EMBASE, Medline, and a specialist database in February 2005 and scrutinized reference lists from relevant publications. DATA EXTRACTION: Data on the source of funding, study design, methodologic quality, and other study characteristics were extracted. The primary outcome was the reporting of at least one statistically significant association between the exposure and a health-related outcome. Data were analyzed using logistic regression models. DATA SYNTHESIS: Of 59 studies, 12 (20%) were funded exclusively by the telecommunications industry, 11 (19%) were funded by public agencies or charities, 14 (24%) had mixed funding (including industry), and in 22 (37%) the source of funding was not reported. Studies funded exclusively by industry reported the largest number of outcomes, but were least likely to report a statistically significant result: The odds ratio was 0.11 (95% confidence interval, 0.02-0.78), compared with studies funded by public agencies or charities. This finding was not materially altered in analyses adjusted for the number of outcomes reported, study quality, and other factors. CONCLUSIONS: The interpretation of results from studies of health effects of radiofrequency radiation should take sponsorship into account.

Does subjective burden of early breast cancer and its treatment affect immune measures during adjuvant therapy?

Psychosocial factors have been described as affecting cellular immune measures in healthy subjects. In patients with early breast cancer we explored bi-directional psycho-immune effects to determine whether subjective burden has an impact on immune measures, and vice versa. Patients (n = 239) operated for early breast cancer and randomized into International Breast Cancer Study Group (IBCSG) adjuvant clinical trials were assessed immediately before the beginning of adjuvant treatment (baseline) and 3 and 6 months thereafter, at the beginning of the corresponding treatment cycle. Cellular immune measures (leukocytes, lymphocytes, lymphocyte subset counts), markers of activation of the cellular immune system (beta2-microglobulin, soluble interleukin-2 receptor serum levels), and self-report subjective burden (global indicators of physical well-being, mood, coping effort) were assessed concurrently. The relationship between subjective burden and gradients of immune measures was investigated with regression analyses controlling for adjuvant treatment. There was a pattern of small negative associations between all variables assessing subjective burden before the beginning of adjuvant therapy with the gradients of the markers of activation of the cellular immune system and NK cell counts. In particular, better mood predicted a decline in the course of beta2-microglobulin and IL-2r at months 3 and 6. The gradient of beta2-microglobulin was associated with mood and coping effort at month 3. However, the effect sizes were very small. In conclusion, in this explorative investigation, there was an indication for subjective burden affecting and being affected by markers of activation of the cellular immune system during the first 3 and 6 months of adjuvant therapy. The question of clinical significance remains unanswered. These associations have to be investigated with refined assessment tools and schedules.

Reading on LCD vs e-Ink displays: effects on fatigue and visual strain

Purpose:  Most recently light and mobile reading devices with high display resolutions have become popular and they may open new possibilities for reading applications in education, business and the private sector. The ability to adapt font size may also open new reading opportunities for people with impaired or low vision. Based on their display technology two major groups of reading devices can be distinguished. One type, predominantly found in dedicated e-book readers, uses electronic paper also known as e-Ink. Other devices, mostly multifunction tablet-PCs, are equipped with backlit LCD displays. While it has long been accepted that reading on electronic displays is slow and associated with visual fatigue, this new generation is explicitly promoted for reading. Since research has shown that, compared to reading on electronic displays, reading on paper is faster and requires fewer fixations per line, one would expect differential effects when comparing reading behaviour on e-Ink and LCD. In the present study we therefore compared experimentally how these two display types are suited for reading over an extended period of time. Methods:  Participants read for several hours on either e-Ink or LCD, and different measures of reading behaviour and visual strain were regularly recorded. These dependent measures included subjective (visual) fatigue, a letter search task, reading speed, oculomotor behaviour and the pupillary light reflex. Results:  Results suggested that reading on the two display types is very similar in terms of both subjective and objective measures. Conclusions:  It is not the technology itself, but rather the image quality that seems crucial for reading. Compared to the visual display units used in the previous few decades, these more recent electronic displays allow for good and comfortable reading, even for extended periods of time.

Listening to your heart and feeling yourself: effects of exposure to interoceptive signals during the ultimatum game

The ultimatum game (UG) is commonly used to study the tension between financial self-interest and social equity motives. Here, we investigated whether experimental exposure to interoceptive signals influences participants' behavior in the UG. Participants were presented with various bodily sounds--i.e., their own heart, another person's heart, or the sound of footsteps--while acting both in the role of responder and proposer. We found that listening to one's own heart sound, compared to the other bodily sounds: (1) increased subjective feelings of unfairness, but not rejection behavior, in response to unfair offers and (2) increased the unfair offers while playing in the proposer role. These findings suggest that heightened feedback of one's own visceral processes may increase a self-centered perspective and drive socioeconomic exchanges accordingly. In addition, this study introduces a valuable procedure to manipulate online the access to interoceptive signals and for exploring the interplay between viscero-sensory information and cognition.