Paradoxical Effect of Quercetin Antioxidant on Goat Sperm Parameters After Cryopreservation.

BACKGROUND: Some antioxidants have been used in semen extenders to reduce adverse effects caused by excessive reactive oxygen species (ROS) production. The study was carried out to assess the effect of quercetin (QC) antioxidant therapy on goat semen submitted to cryopreservation. OBJECTIVE: To evaluate the effect of quercetin incorporation in different phases of the cryopreservation process of goat spermatozoa. MATERIALS AND METHODS: Five ejaculates from each of four goats (n= 20) were collected and split into four groups: Control (G1), without QC; G2, 15 µM of QC added to semen before centrifugation; G3, 15 µM QC added to semen after centrifugation; G4, 15 µM QC added to semen before centrifugation and 15 µM of QC added to semen after centrifugation (total of 30 µM of QC); and cryopreserved. All semen samples were evaluated after thawing for sperm kinetics, plasma membrane integrity, and ROS levels. RESULTS: Although lower concentrations of ROS were associated with groups that received antioxidant supplementation (P=0.0213), linear and dose dependent (P<0.05) reductions of the total and progressive sperm motility, velocity and percentage of fast cells were related to the QC groups. Likewise, plasma membrane integrity was better preserved (P=0.0154) in the control group (35.5%) than in groups that received QC (G2=32.6%, G3=32.4% and G4=26.7%). CONCLUSION: Although quercetin was efficient at reducing the oxidative stress related to sperm cryopreservation, it exerted a deleterious dose-dependent effect on the kinetics and integrity of the frozen goat semen, contradicating its use in the tested concentrations.

[Which psychiatric symptoms must raise suspicion about a possible brain tumor ?] / Quels symptômes psychiatriques doivent alerter sur la possible présence d'une tumeur cérébrale ?

Many case studies reported psychiatric symptoms during the months before a brain tumor (BT) is diagnosed. Unfortunately, these symptoms are rarely considered as a warning of an organic problem and patients are regularly misoriented towards psychiatric care. Knowing better what psychiatric symptoms look like in patients with a BT would help to diagnose it sooner, which would obviously benefit the patient. The present study aims to quantify the prevalence and further describe psychiatric symptoms occurring before a BT diagnosis. The presence of psychiatric manifestations was systematically investigated in 100 patients with a first diagnosis of BT. Overall, 85 % of the patients reported at least one psychiatric symptom present before the BT diagnosis, most often depressive ones. Somatic manifestations of depression (loss of energy, changes in appetite...) were more often reported than affective or cognitive ones (no negative thought content: no pessimism, no guilty feelings, no worthlessness…). The present research stresses the high prevalence of psychiatric symptoms, especially depressive-like ones, occurring before a BT is diagnosed and provides a first description of these symptoms, as a basis of practical recommendations.

De nombreuses études de cas ont rapporté la présence de symptômes psychiatriques dans les mois qui précèdent le diagnostic d'une tumeur cérébrale (TC). Malheureusement, ces symptômes restent rarement considérés comme renseignant un possible problème organique et les patients sont régulièrement orientés vers une prise en charge psychiatrique. Une meilleure connaissance de la présentation psychiatrique des TC favoriserait un diagnostic précoce, évidemment profitable au patient. L'objectif de cette étude est de quantifier la fréquence des symptômes psychiatriques présents avant le diagnostic de TC et de les décrire. Chez 100 patients adultes avec un premier diagnostic de TC, la présence de manifestations psychiatriques a été évaluée de façon systématique. 85 % des patients ont souffert d'au moins un symptôme psychiatrique avant que la TC ne soit diagnostiquée, avec, à l'avant-plan des éléments dépressifs. Parmi les symptômes dépressifs, les expressions somatiques sont le plus souvent rapportées (perte d'énergie, changement de l'appétit…), au contraire des manifestations cognitives et affectives (pas de contenu de pensées négatives : pessimisme, culpabilité, dévalorisation...). Cette recherche souligne la prévalence élevée de symptômes psychiatriques évoquant le plus souvent un état dépressif avant le diagnostic de TC et apporte une première description de ces symptômes, permettant l'ébauche de certaines recommandations pratiques.

Oxytocin's inhibitory effect on food intake is stronger in obese than normal-weight men.

BACKGROUND/OBJECTIVES: Animal studies and pilot experiments in men indicate that the hypothalamic neuropeptide oxytocin limits food intake, and raise the question of its potential to improve metabolic control in obesity. SUBJECTS/METHODS: We compared the effect of central nervous oxytocin administration (24 IU) via the intranasal route on ingestive behaviour and metabolic function in 18 young obese men with the results in a group of 20 normal-weight men. In double-blind, placebo-controlled experiments, ad libitum food intake from a test buffet was examined in fasted subjects 45 min after oxytocin administration, followed by the assessment of postprandial, reward-driven snack intake. Energy expenditure was repeatedly assessed by indirect calorimetry and blood was sampled to determine concentrations of blood glucose and hormones. RESULTS: Oxytocin markedly reduced hunger-driven food intake in the fasted state in obese but not in normal-weight men, and led to a reduction in snack consumption in both groups, whereas energy expenditure remained generally unaffected. Hypothalamic-pituitary-adrenal axis secretion and the postprandial rise in plasma glucose were blunted by oxytocin in both groups. CONCLUSIONS: Oxytocin exerts an acutely inhibitory impact on food intake that is enhanced rather than decreased in obese compared with normal-weight men. This pattern puts it in contrast to other metabolically active neuropeptides and bodes well for clinical applications of oxytocin in the treatment of metabolic disorders.

[A rare case of lacunar skull deformity associated with craniosynostosis]. / LE CAS CLINIQUE DU MOIS. Une présentation rare de craniosténose associée à un crâne lacunaire.

The lacunar skull is a radiologic description characterised by the presence of lacunae in the cranial vault. Its physiopathology remains up to now poorly understood; it is mostly associated with neural tube defects. The association of a lacunar skull with a craniosynostosis has rarely been described in the literature. The case of a 9-month-old patient presenting a multisutural craniosynostosis with a lacunar skull is reported in this article. The surgical treatment allowed to remodel the skull and to hope for a spontaneous regression of the lacunae.

Dissociating the contributions of slow-wave sleep and rapid eye movement sleep to emotional item and source memory.

Sleep benefits the consolidation of emotional memories, and this influence is commonly attributed to the rapid eye movement (REM) stage of sleep. However, the contributions of sleep stages to memory for an emotional episode may differ for the event per se (i.e., item memory), and the context in which it occurred (source memory). Here, we examined the effects of slow wave sleep (SWS) and REM sleep on the consolidation of emotionally negative and neutral item (picture recognition) and source memory (recall of picture-location and picture-frame color association) in humans. In Study 1, the participants (n=18) learned 48 negative and 48 neutral pictures which were presented at specific locations and preceded by colored frames that had to be associated with the picture. In a within-subject design, learning was either followed by a 3-h early-night SWS-rich or by a late-night REM sleep-rich retention interval, then retrieval was tested. Only after REM-rich sleep, and not after SWS-rich sleep, was there a significant emotional enhancement, i.e., a significantly superior retention of emotional over neutral pictures. On the other hand, after SWS-rich sleep the retention of picture-frame color associations was better than after REM-rich sleep. However, this benefit was observed only for neutral pictures; and it was completely absent for the emotional pictures. To examine whether this absent benefit reflected a suppressive effect of emotionality on associations of minor task relevance, in Study 2 we manipulated the relevance of the picture-frame color association by combining it with information about monetary reward, following otherwise comparable procedures. Here, rewarded picture-frame color associations were equally well retained over SWS-rich early sleep no matter if the frames were associated with emotional or neutral pictures. Results are consistent with the view that REM sleep favors the emotional enhancement of item memory whereas SWS appears to contribute primarily to the consolidation of context-color information associated with the item.

Hepatic syndecan-1 changes associate with dyslipidemia after renal transplantation.

Syndecan-1 is a transmembrane heparan sulfate (HS) proteoglycan present on hepatocytes and involved in uptake of triglyceride-rich lipoproteins via its HS polysaccharide side chains. We hypothesized that altered hepatic syndecan-1 metabolism could be involved in dyslipidemia related to renal transplantation. In a rat renal transplantation model elevated plasma triglycerides were associated with fivefold increased expression of hepatic syndecan-1 mRNA (p < 0.01), but not protein. Expression of syndecan-1 sheddases (ADAM17, MMP9) and heparanase was significantly up-regulated after renal transplantation (all p < 0.05). Profiling of HS side chains revealed loss of hepatic HS upon renal transplantation accompanied by significant decreased functional capacity for VLDL binding (p = 0.02). In a human renal transplantation cohort (n = 510), plasma levels of shed syndecan-1 were measured. Multivariate analysis showed plasma syndecan-1 to be independently associated with triglycerides (p < 0.0001) and inversely with HDL cholesterol (p < 0.0001). Last, we show a physical association of syndecan-1 to HDL from renal transplant recipients (RTRs), but not to HDL from healthy controls. Our data suggest that after renal transplantation loss of hepatic HS together with increased syndecan-1 shedding hampers lipoprotein binding and uptake by the liver contributing to dyslipidemia. Our data open perspectives toward improvement of lipid profiles by targeted inhibition of syndecan-1 catabolism in renal transplantation.

Role of γ-aminobutyric acid signalling in the attenuation of counter-regulatory hormonal responses after antecedent hypoglycaemia in healthy men.

The attenuated counter-regulatory response to hypoglycaemia after antecedent hypoglycaemic episodes has been observed in animals to be associated with an increase in γ-aminobutyric acid (GABA) signalling. We therefore tested the hypothesis that the pharmacological suppression of GABAergic activity during a repeated hypoglycaemic episode enhances counter-regulatory responses. Fourteen healthy men participated in two experimental sessions each comprising three insulin-induced hypoglycaemic episodes. Before the third hypoglycaemic episode, participants received the GABA-antagonistic drug modafinil (200 mg orally) and placebo, respectively. In the placebo condition, the secretion of norepinephrine, adrenocorticotropic hormone, cortisol and growth hormone, and the perception of neuroglycopenic symptoms were attenuated during the third as compared with the first hypoglycaemic episode (each p < 0.05). Modafinil reversed this effect for the noradrenergic response (p < 0.05), while not significantly altering the attenuation of other hormonal responses and symptom perception (p > 0.3). Our findings indicate that increased GABAergic transmission could contribute to aspects of the attenuated counter-regulatory response after recurrent hypoglycaemia in humans.

The role of sleep and sleep deprivation in consolidating fear memories.

Sleep, in particular REM sleep, has been shown to improve the consolidation of emotional memories. Here, we investigated the role of sleep and sleep deprivation on the consolidation of fear memories and underlying neuronal mechanisms. We employed a Pavlovian fear conditioning paradigm either followed by a night of polysomnographically monitored sleep, or wakefulness in forty healthy participants. Recall of learned fear was better after sleep, as indicated by stronger explicitly perceived anxiety and autonomous nervous responses. These effects were positively correlated with the preceding time spent in REM sleep and paralleled by activation of the basolateral amygdala. These findings suggest REM sleep-associated consolidation of fear memory in the human amygdala. In view of the critical participation of fear learning mechanisms in the etiology of anxiety and post-traumatic stress disorder, deprivation of REM sleep after exposure to distressing events is an interesting target for further investigation.

The role of REM sleep in the processing of emotional memories: evidence from behavior and event-related potentials.

Emotional memories are vividly remembered for the long-term. Rapid eye movement (REM) sleep has been repeatedly proposed to support the superior retention of emotional memories. However, its exact contribution and, specifically, whether its effect is mainly on the consolidation of the contents or the processing of the affective component of emotional memories is not clear. Here, we investigated the effects of sleep rich in slow wave sleep (SWS) or REM sleep on the consolidation of emotional pictures and the accompanying changes in affective tone, using event-related potentials (ERPs) together with subjective ratings of valence and arousal. Sixteen healthy, young men learned 50 negative and 50 neutral pictures before 3-h retention sleep intervals that were filled with either SWS-rich early or REM sleep-rich late nocturnal sleep. In accordance with our hypothesis, recognition was better for emotional pictures than neutral pictures after REM compared to SWS-rich sleep. This emotional enhancement after REM-rich sleep expressed itself in an increased late positive potential of the ERP over the frontal cortex 300-500 ms after stimulus onset for correctly classified old emotional pictures compared with new emotional and neutral pictures. Valence and arousal ratings of emotional pictures were not differentially affected by REM or SWS-rich sleep after learning. Our results corroborate that REM sleep contributes to the consolidation of emotional contents in memory, but suggest that the affective tone is preserved rather than reduced by the processing of emotional memories during REM sleep.

NMDA receptor blockade by memantine does not prevent adaptation to recurrent hypoglycaemia in healthy men.

AIMS: Recurrent hypoglycaemia leads to an attenuation of hypoglycaemic symptoms and hormonal counterregulatory responses. This phenomenon poses a severe problem in the treatment of patients with diabetes mellitus, but the underlying neuroendocrine mechanisms are unclear. On the basis of animal experimental findings, we hypothesized that counterregulatory attenuation represents a basic adaptive learning process relying on synaptic long-term potentiation or depression. If so, attenuation should be prevented by blocking glutamatergic N-methyl-D-aspartate (NMDA) receptors. METHODS: Sixteen healthy young men participated in two conditions, separated by 4 weeks. Participants received the NMDA antagonist memantine over 5 days (15 mg/day) in one condition and placebo in the other one. After 3 days of drug administration, participants underwent two hypoglycaemic clamps on day 4 and another one on day 5. We assessed blood concentrations of counterregulatory hormones (cortisol, ACTH, epinephrine, norepinephrine, growth hormone and glucagon) as well as subjective symptoms of hypoglycaemia and word-list recall as an indicator of short-term memory. RESULTS: Counterregulatory responses of all hormones as well as neuroglycopenic and autonomic symptom ratings showed robust attenuation following the third as compared to the first hypoglycaemia (p < 0.05). NMDA receptor antagonization by memantine impaired memory function but did not alter any neuroendocrine measure of counterregulatory attenuation (p > 0.17). CONCLUSIONS: Attenuation of the endocrine as well as symptomatic counterregulatory response to recurrent hypoglycaemia is not prevented by the NMDA receptor blocker memantine. Our results do not support the view that adaptation to repeated hypoglycaemia relies on NMDA receptor-mediated plastic processes involving long-term potentiation or depression.

[Availability of patient information in the emergency department : Wish and reality]. / Verfügbarkeit von Patienteninformationen in der Notaufnahme : Wunsch und Wirklichkeit.

BACKGROUND: Fast access to information from other healthcare service providers is particularly important in emergency medicine, as the patients are often unknown and treatment decisions have to be made promptly. OBJECTIVES: The study aims to identify the challenges that emergency departments face in obtaining information on patient history, the expected benefits of easier access to information and which information is most urgently needed. MATERIALS AND METHODS: An online survey throughout Germany was carried out among medical staff working in emergency departments. In all, 181 questionnaires were fully completed and could be included in the data analysis. RESULTS: Of the respondents, 77.9% said it was difficult or very difficult to receive external data at the point of patient care. The survey participants estimate that they need an average of around 47 min to obtain information about one patient. 99.4% believe that patient care would benefit from an easier and faster information exchange. Medication lists, discharge letters, information on previous illnesses and allergies were classified as the most important data elements. CONCLUSIONS: There is an urgent need for action with regard to the considerable effort involved in obtaining information on emergency patients. Digital solutions such as the recently introduced emergency data set can offer additional value for clinical emergency care if they are widely used.

Local medial microenvironment directs phenotypic modulation of smooth muscle cells after experimental renal transplantation.

Smooth muscle cells (SMCs) play a key role in the pathogenesis of occlusive vascular diseases, including transplant vasculopathy. Neointimal SMCs in experimental renal transplant vasculopathy are graft-derived. We propose that neointimal SMCs in renal allografts are derived from the vascular media resulting from a transplantation-induced phenotypic switch. We examined the molecular changes in the medial microenvironment that lead to phenotypic modulation of SMCs in rat renal allograft arteries with neointimal lesions. Dark Agouti donor kidneys were transplanted into Wistar Furth recipients and recovered at day 56. Neointimal and medial layers were isolated using laser microdissection. Gene expression was analyzed using low-density arrays and confirmed by immunostaining. In allografts, neointimal SMCs expressed increased levels of Tgf ß1 and Pdgfb. In medial allograft SMCs, gene expression of Ctgf, Tgf ß1 and Pdgfrb was upregulated. Gene expression of Klf4 was upregulated as well, while expression of Sm22α was downregulated. Finally, PDGF-BB-stimulated phenotypically modulated SMCs, as evidenced by reduced contractile function in vitro which was accompanied by increased Klf4 and Col1α1, and reduced α-Sma and Sm22α expression. In transplant vasculopathy, neointimal PDGF-BB induces phenotypic modulation of medial SMCs, through upregulation of KLF4 in the media to contribute to (further) expansion of the neointima.

Association of complement C3 gene variants with renal transplant outcome of deceased cardiac dead donor kidneys.

Local renal complement activation by the donor kidney plays an important role in the pathogenesis of renal injury inherent to kidney transplantation. Contradictory results were reported about the protective effects of the donor C3F allotype on renal allograft outcome. We investigated the influence of the donor C3F allotype on renal transplant outcome, taking all different donor types into account. C3 allotypes of 1265 donor-recipient pairs were determined and divided into four genotypic groups according to the C3F allotype of the donor and the recipient. The four genotypic groups were analyzed for association with primary nonfunction (PNF), delayed graft function, acute rejection, death-censored graft survival and patient survival. Considering all donor types, multivariable analysis found no association of the donor C3F allotype with renal allograft outcome. Also, for living and deceased brain-dead donors, no association with allograft outcome was found. Post hoc subgroup analysis within deceased cardiac dead (DCD) donors revealed an independent protective association of donor C3F allotype with PNF. This study shows that the donor C3F allotype is not associated with renal allograft outcome after kidney transplantation. Subgroup analysis within DCD donors revealed an independent protective association of the donor C3F allotype with PNF, which is preliminary and warrants further validation.

Intranasal administration of insulin to the brain impacts cognitive function and peripheral metabolism.

In recent years, the central nervous system (CNS) has emerged as a principal site of insulin action. This notion is supported by studies in animals relying on intracerebroventricular insulin infusion and by experiments in humans that make use of the intranasal pathway of insulin administration to the brain. Employing neurobehavioural and metabolic measurements as well as functional imaging techniques, these studies have provided insight into a broad range of central and peripheral effects of brain insulin. The present review focuses on CNS effects of insulin administered via the intranasal route on cognition, in particular memory function, and whole-body energy homeostasis including glucose metabolism. Furthermore, evidence is reviewed that suggests a pathophysiological role of impaired brain insulin signaling in obesity and type 2 diabetes, which are hallmarked by peripheral and possibly central nervous insulin resistance, as well as in conditions such as Alzheimer's disease where CNS insulin resistance might contribute to cognitive dysfunction.

Therapeutic potential of vasopressin V2 receptor antagonist in a mouse model for autosomal dominant polycystic kidney disease: optimal timing and dosing of the drug.

BACKGROUND: The renoprotective effect of vasopressin V2 receptor antagonist (V2RA) is currently being tested in a clinical trial in early autosomal dominant polycystic kidney disease (ADPKD). If efficacious, this warrants life-long treatment with V2RA, however, with associated side effects as polydipsia and polyuria. We questioned whether we could reduce the side effects without influencing the renoprotective effect by starting the treatment later in the disease or by lowering drug dosage. METHODS: To investigate this, we administered V2RA OPC-31260 at a high (0.1%) and low (0.05%) dose to a tamoxifen-inducible kidney epithelium-specific Pkd1-deletion mouse model starting treatment at Day 21 (early) or 42 (advanced). After 3 and 6 weeks of treatment, we monitored physiologic and potential renoprotective effects. RESULTS: Initiation of V2RA treatment at advanced stage of the disease lacked renoprotective effects and had less pronounced physiologic effects than early initiation. After 3 weeks on a high dose, cyst ratio and kidney weight were reduced versus untreated controls (18 versus 25%, P = 0.05, and 0.33 versus 0.45 g, P = 0.03, respectively). After 6 weeks of treatment, however, this did not reach significance anymore, even at a high dose (cyst ratio 24 versus 27%, P = 0.12, and kidney weight 0.55 versus 0.66 g, P = 0.38). CONCLUSIONS: Our results suggest that intervention with V2RA should be instituted early in ADPKD and that it might be necessary to further increase the dosage of this drug later in the disease to decrease cyst growth.

Deficient recognition of emotional prosody in primary focal dystonia.

BACKGROUND: Primary dystonia is a movement disorder attributed mainly to basal ganglia dysfunction. Besides motor control, striatopallidal structures are known to implement also non-motor functions including processing of cognitive and emotional information. Previous research has already demonstrated deficient recognition of emotional faces in patients with primary focal dystonia. However, it remains elusive if emotional prosody processing in dystonia is also affected. METHODS: In this study, 30 patients with primary cervical dystonia (CD) and 30 healthy control subjects (HC) had to classify auditory presented words according to their emotional prosody (angry, happy, relaxed, sad). RESULTS: Analysis of hit rates and reaction times revealed a significantly poorer performance of patients with CD in judging angrily intonated words. Additional psychological assessment (SCL-90 R) demonstrated a higher level of psychological distress in patients with CD who displayed symptoms of somatization, anxiety and depression. CONCLUSIONS: Together these findings bring further insight into the basal ganglia involvement in processing of emotional prosody and emphasize the importance to identify the psychopathological symptoms in patients with CD as complementary to the motor deficit.

Comparison of the surgical Pleth Index™ with haemodynamic variables to assess nociception-anti-nociception balance during general anaesthesia.

BACKGROUND: The Surgical Pleth Index (SPI) is proposed as a means to assess the balance between noxious stimulation and the anti-nociceptive effects of anaesthesia. In this study, we compared SPI, mean arterial pressure (MAP), and heart rate (HR) as a means of assessing this balance. METHODS: We studied a standard stimulus [head-holder insertion (HHI)] and varying remifentanil concentrations (CeREMI) in a group of patients undergoing neurosurgery. Patients receiving target-controlled infusions were randomly assigned to one of the three CeREMI (2, 4, or 6 ng m⁻¹), whereas propofol target was fixed at 3 µg ml⁻¹. Steady state for both targets was achieved before HHI. Intravascular volume status (IVS) was evaluated using respiratory variations in arterial pressure. Prediction probability (Pk) and ordinal regression were used to assess SPI, MAP, and HR performance at indicating CeREMI, and the influence of IVS and chronic treatment for high arterial pressure, as possible confounding factors. RESULTS: The maximum SPI, MAP, or HR observed after HHI correctly indicated CeREMI in one of the two patients [accurate prediction rate (APR)=0.5]. When IVS and chronic treatment for high arterial pressure were taken into account, the APR was 0.6 for each individual variable and 0.8 when all of them predicted the same CeREMI. That increase in APR paralleled an increase in Pk from 0.63 to 0.89. CONCLUSIONS: SPI, HR, and MAP are of comparable value at gauging noxious stimulation-CeREMI balance. Their interpretation is improved by taking account of IVS, treatment for chronic high arterial pressure, and concordance between their predictions.

Unexpected entropy response to saline spraying at the end of posterior fossa surgery: a few cases report.

The Spectral Entropy proposed to monitor the depth of anesthesia includes the State Entropy (SE) computed from the EEG (0.8-32 Hz frequency band), and the Response Entropy (RE) computed from EEG and facial muscles activity (0.5-47 Hz frequency band). We report an unexpected Entropy response to saline spraying at the end of posterior fossa surgery. Six patients undergoing scheduled functional surgery of the posterior fossa were included in this report. They were anesthetized with propofol and remifentanil using TCI and received an intubation dose of rocuronium. At the end of surgery, saline spraying, performed for hemostatic purpose and wreckage elimination, resulted in a sustained increase in RE and SE without hemodynamic modification in four patients, while no change was observed in the two other ones. In one of the responding patients, 0.1 mg kg(-1) rocuronium attenuated the Entropy response. In the two non responders, repetition of spraying or rocuronium administration did not change Entropy value. Recovery from anesthesia was comparable in all patients and none of them complained from awareness. We conclude that Entropy can increase during posterior fossa surgery in non-paralyzed patients. This response probably reflects an increase in facial muscle activity rather than a change in depth of anesthesia, as far as it can be attenuated by a small dose of rocuronium. While this hypothesis requires further investigation, these observations suggest that saline spraying may confound interpretation of Entropy during posterior fossa surgery.

Acute stress and food-related reward activation in the brain during food choice during eating in the absence of hunger.

BACKGROUND: Stress results in eating in the absence of hunger, possibly related to food reward perception. HYPOTHESIS: Stress decreases food reward perception. AIM: Determine the effect of acute stress on food choice and food choice reward-related brain activity. SUBJECTS: Nine females (BMI = 21.5 + or - 2.2 kg/m(2), age = 24.3 + or - 3.5 years). PROCEDURE: Fasted subjects came twice to randomly complete either a rest or stress condition. Per session, two functional MRI scans were made, wherein the subjects chose the subsequent meal (food images). The rewarding value of the food was measured as liking and wanting. Food characteristics (for example, crispiness, fullness of taste and so on), energy intake, amount of each macronutrient chosen, plasma cortisol and Visual Analog Scale (VAS) hunger and satiety were measured. RESULTS: Fasted state was confirmed by high hunger (80 + or - 5 mm VAS). Breakfast energy intake (3 + or - 1 MJ) and liking were similar in all conditions. Wanting was lower postprandially (Delta = -0.3 items/category, P<0.01). Breakfast decreased hunger (-42 mm VAS, P<0.01). Postprandially, energy intake (-1.1 MJ), protein intake (-14.7 g) and carbohydrate intake (-32.7 g all P<0.05) were lower. Fat intake was not different (-7.3, P = 0.4). Putamen activity was not lower postprandially. Cortisol levels were increased in the stress condition (Area under the curve of cortisol: DeltaAUC = +2.2 x 10(4) nmol min(-1) l(-1), P<0.05). Satiety was lower after breakfast (-8 mm VAS, P<0.01). Postprandial energy intake, protein intake and carbohydrate intake were relatively higher compared with the rest condition, resulting from more choice for crispiness and fullness of taste (P<0.05). Brain activation was reduced in reward areas: amygdala, hippocampus and cingulate cortex (AUC = -13.33, -1.34, -2.56% blood oxygen level dependent (BOLD) s for choosing breakfast and AUC = -9.31, -1.25, -2.34%BOLD s<0.05 for choosing the second meal). Putamen activation was decreased postprandially (AUC = -1.2%BOLD s, P<0.05). CONCLUSION: Reward signaling and reward sensitivity were significantly lower under stress, coinciding with increased energy intake from food choice for more crispiness and fullness of taste. The changes in putamen activation may reflect specifically decreased reward prediction sensitivity.

Blocking AMPA receptor signalling by caroverine infusion does not affect counter-regulation of hypoglycaemia in healthy men.

AIMS/HYPOTHESIS: Glutamatergic pathways are assumed to play a critical role in the hormonal stress response to hypoglycaemia. In rats, glutamate signalling at the amino-3-hydroxy-5-methyl-4-isoxazol propionate (AMPA) receptor contributes to hormone release induced by behavioural stressors. We hypothesised that blocking the AMPA receptor by caroverine in healthy men would impair their perception of neuroglycopenia and thereby diminish hormonal counter-regulation as well as symptoms of hypoglycaemia, as a model of stress. METHODS: In a balanced double-blind study, two hypoglycaemic clamp sessions (mean blood glucose 2.4 mmol/l for 50 min) were performed in ten healthy men during intravenous administration of 80 mg caroverine or placebo. We assessed concentrations of counter-regulatory hormones as well as subjective symptoms related to hypoglycaemia. RESULTS: AMPA receptor antagonisation by caroverine did not influence the perception of neuroglycopenic and autonomic hypoglycaemia-associated symptoms (p > 0.39 for all). Notwithstanding, caroverine did increase basal and counter-regulatory glucagon secretion (p < 0.002) and slightly enhanced counter-regulatory growth hormone concentrations (p = 0.07). Counter-regulatory release of ACTH, cortisol, adrenaline (epinephrine) and noradrenaline (norepinephrine) did not differ between conditions (p > 0.11 for all). CONCLUSIONS/INTERPRETATION: Antagonising AMPA receptor signalling by caroverine infusion failed to diminish and even slightly amplified counter-regulatory hormone release during hypoglycaemia in healthy men. The discrepancy with previous findings in rats may be due to different dosages or administration routes and calls for further investigations on the role of AMPA receptor signalling in hypoglycaemia counter-regulation in humans.