Neuroendocrine response to a psychosocial stress test is not related to schizotypy but cortisol elevation predicts inflexibility of semantic memory retrieval.

An altered stress response can contribute to the transition from preclinical psychotic symptoms to the clinical manifestation of schizophrenia and other psychotic disorders. The present study was aimed at testing the hypotheses that (i) the autonomic and neuroendocrine responses under psychosocial stress are dysregulated in individuals with high psychosis proneness (schizotypy); (ii) the magnitude of post-stress autonomic activation and cortisol release predicts alterations in semantic memory retrieval. The study was performed in 73 healthy individuals of both sexes with either high or low schizotypal traits preselected out of 609 individuals using the Schizotypal Personality Questionnaire. A psychosocial stress procedure based on public speech was used as a stress model. We found that individuals with high schizotypy engaged in less adaptive emotional stress-coping strategies than low schizotypy individuals. Yet, the neuroendocrine, immune, and sympathetic activation in response to the stress test was not different between the groups. Irrespective of the exposure to the stressor, individuals with high schizotypy were less fluent when retrieving associations from semantic memory. In addition, we demonstrated that acute psychosocial stress reduced the flexibility of semantic memory retrieval. The post-stress mental inflexibility was reliably predicted by the concomitant elevation of cortisol concentrations in saliva. The present study thus brings novel evidence indicating that the acute psychosocial challenge impairs retrieval flexibility in the semantic domain, which may be due to neuroendocrine activation.

Salivary testosterone, testosterone/cortisol ratio and non-verbal behavior in stress.

The relationship between hormone release and non-verbal communication under stress conditions is still not sufficiently explored. The aim of the present study was to test the hypothesis that salivary testosterone concentrations and testosterone/cortisol (T/C) ratios correlate positively with assertive behavior representing a non-aggressive form of dominance during an acute stress situation. As a stress model, a socially evaluated cold pressor test was investigated in healthy men. The non-verbal behavior was analyzed according to the ethological coding system for interviews described by Troisi (1999). Salivary testosterone concentrations did not change throughout the stress test. The T/C ratios decreased significantly over time only in subjects showing high stress perception. The duration of affiliative and the frequency of flight behavior was higher in subjects with high stress perception compared to those with low stress perception. A significant positive correlation between the duration of prosocial behavior and values of T/C ratios was found in the whole sample. The area under the curve values of testosterone positively correlated with the duration of assertive behavior in the group with high stress perception and negatively in the other group. Our findings allow suggesting that the changes in non-verbal behavior during acute psychosocial stress situations may be more pronounced in subjects showing high stress perception. Obtained results motivate further research on a better understanding of the consequences of the lack of sense of full facial expressions, such as wearing face masks, on the balance between hormones and non-verbal behavior under stress conditions.

The administration of the opioid buprenorphine decreases motivational error signals.

While opioid addiction has reached pandemic proportions, we still lack a good understanding of how the administration of opioids interacts with cognitive functions. Error processing - the ability to detect erroneous actions and correct one's behaviour afterwards - is one such cognitive function that might be susceptible to opioidergic influences. Errors are hypothesised to induce aversive negative arousal, while opioids have been suggested to reduce aversive arousal induced by unpleasant and stressful stimuli. Thus, this study investigated whether the acute administration of an opioid would affect error processing. In a double-blind between-subject study, 42 male volunteers were recruited and received either 0.2 mg buprenorphine (a partial µ-opioid receptor agonist and κ-opioid receptor antagonist) or a placebo pill before they performed a stimulus-response task provoking errors. Electroencephalograms (EEG) were recorded while participants performed the task. We observed no group differences in terms of reaction times, error rates, and affective state ratings during the task between buprenorphine and control participants. Additional measures of adaptive control, however, showed interfering effects of buprenorphine administration. On the neural level, decreased Pe (Error Positivity) amplitudes were found in buprenorphine compared to control participants following error commission. Further, frontal delta oscillations were decreased in the buprenorphine group after all responses. Our neural results jointly demonstrate a general reduction in error processing in those participants who received an opioid before task completion, thereby suggesting that opioids might have indeed the potential to dampen motivational error signals. Importantly, the effects of the opioid were evident in more elaborate error processing stages, thereby impacting on processes of conscious error appraisal and evidence accumulation.

Absence of a significant interaction of two common NOS1 and 5-HTT polymorphisms on sensorimotor gating in humans.

The neurotransmitter serotonin has been critically implicated in the pathogenesis of several mental disorders. The serotonin transporter (5-HTT) is a key regulator of serotonergic neurotransmission and its genetic variability is associated with increased risk of psychopathology. One well known polymorphic locus in the 5-HTT gene affecting its expression is a tandem repeat in the promoter region (5-HTTLPR). It has been reported that 5-HTT is functionally coupled with the neuronal nitric oxide synthase (NOS1 or nNOS), an enzyme catalyzing the production of nitric oxide (NO). We have previously demonstrated that a tandem repeat polymorphism in the promoter of NOS1 exon 1f (Ex1f-VNTR) is associated with sensorimotor gating, a marker of inhibitory processing and a well established endophenotype of several neuropsychiatric disorders. Here we investigated the combined genetic effects of NOS1 Ex1f-VNTR and 5-HTTLPR on sensorimotor gating, measured by prepulse inhibition (PPI) of the acoustic startle reflex, in 164 healthy adults. We found no evidence for the interaction between NOS1 Ex1f-VNTR and 5-HTTLPR on PPI. PPI was associated with NOS1 Ex1f-VNTR, but not 5-HTTLPR. Our data suggest that while NOS1 plays a role in sensorimotor gating, the nitrergic pathway of gating regulation does not involve the action of 5-HTT.

Behavioral alterations induced by post-weaning isolation rearing of rats are accompanied by reduced VGF/BDNF/TrkB signaling in the hippocampus.

Post-weaning social isolation has been shown to be a relevant animal model for studying the mechanisms underlying psychopathological states induced by early-life stressful experiences. Besides extensively studied brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) receptor, increasing attention is being given to a neuropeptide precursor VGF (non-acronymic). Several lines of evidence indicate an interplay between the neurotrophins and nitric oxide signaling. This study investigated the long-term consequences of post-weaning social isolation on behavior, VGF/BDNF/TrkB pathway and two isoforms of nitric oxide synthase (NOS) in the hippocampus and examined whether these effects were sex-specific. Male and female Sprague-Dawley rats were reared either in social isolation or social groups from postnatal day 21 for 9 weeks (n = 12-15/group and sex). Post-weaning social isolation induced impairments in sensorimotor gating and increased anxiety-like behavior in rats of both sexes. These behavioral alterations were accompanied by attenuated gene expression of VGF and TrkB receptor in the hippocampus. Isolation-induced reduction in VGF gene expression was more evident in male isolates. Similar changes were found in neuronal NOS (nNOS) gene expression with reduced mRNA levels in male isolates. Gene expression of BDNF and inducible NOS was not influenced by isolation rearing or sex. In addition, sex-specific patterns of VGF and nNOS gene expression in the hippocampus with higher mRNA levels in males than in females were revealed. The present study demonstrates a relationship between nNOS, VGF, BDNF, and TrkB confirming a link between nitric oxide and neurotrophins signaling pathways. Our findings indicate that long-term post-weaning social isolation alters signaling via VGF/BDNF/TrkB and nNOS that could interfere with neurodevelopmental processes which may contribute to pathological behavioral symptoms in adulthood. Future studies are needed to support this suggestion since the direct mechanistic link has not been approached in this study.

Psychopharmacological modulation of event-related potentials suggests that first-hand pain and empathy for pain rely on similar opioidergic processes.

Accumulating evidence suggests that empathy for pain recruits similar neural processes as the first-hand experience of pain. The pain-related P2, an event-related potential component, has been suggested as a reliable indicator of neural processes associated with first-hand pain. Recent evidence indicates that placebo analgesia modulates this component for both first-hand pain and empathy for pain. Moreover, a psychopharmacological study showed that administration of an opioid antagonist blocked the effects of placebo analgesia on self-report of both first-hand pain and empathy for pain. Together, these findings suggest that the opioid system plays a similar role during first-hand pain and empathy for pain. However, such a conclusion requires evidence showing that neural activity during both experiences is similarly affected by psychopharmacological blockage of opioid receptors. Here, we measured pain-related P2 amplitudes and self-report in a group of participants who first underwent a placebo analgesia induction procedure. Then, they received an opioid receptor antagonist known to block the previously induced analgesic effects. Self-report showed that blocking opioid receptors after the induction of placebo analgesia increased both first-hand pain and empathy for pain, replicating previous findings. Importantly, P2 amplitudes were also increased during both experiences. Thus, the present findings extend models proposing that empathy for pain is partially grounded in first-hand pain by suggesting that this also applies to the underlying opioidergic neurochemical processes.

Competition, testosterone, and adult neurobehavioral plasticity.

Motivation in performance is often measured via competitions. Winning a competition has been found to increase the motivation to perform in subsequent competitions. One potential neurobiological mechanism that regulates the motivation to compete involves sex hormones, such as the steroids testosterone and estradiol. A wealth of studies in both nonhuman animals and humans have shown that a rise in testosterone levels before and after winning a competition enhances the motivation to compete. There is strong evidence for acute behavioral effects in response to steroid hormones. Intriguingly, a substantial testosterone surge following a win also appears to improve an individual's performance in later contests resulting in a higher probability of winning again. These effects may occur via androgen and estrogen pathways modulating dopaminergic regions, thereby behavior on longer timescales. Hormones thus not only regulate and control social behavior but are also key to adult neurobehavioral plasticity. Here, we present literature showing hormone-driven behavioral effects that persist for extended periods of time beyond acute effects of the hormone, highlighting a fundamental role of sex steroid hormones in adult neuroplasticity. We provide an overview of the relationship between testosterone, motivation measured from objective effort, and their influence in enhancing subsequent effort in competitions. Implications for an important role of testosterone in enabling neuroplasticity to improve performance will be discussed.

[Myocardial infarction in the young - our results and experience]. / Infarkt myokardu v mladom veku - nase výsledky a skúsenosti.

AIMS: Coronary artery disease in young adults is important task of contemporary cardiology. Presented our results experience and opinion were obtained by our long term investigation of myocardial infarction in young patients under 40 years. METHODS: Two sets of patients were examined - 78 patients (74 men, 4 women) hospitalised in pretrombolytic era in prospective 8 years follow up (1984-1992) and 39 patients (35 men, 4 women) admitted during period 2000-2010 analysed retrospective. RESULTS: Myocardial infarction in young age belongs roughly to two different groups with considerable overlap in pathogenetic mechanisms: 1. angiographycally normal coronary arteries or unilocular nonsignificant atherosclerotic stenosis (less 50%) in 25-30% with thrombotic occlusion of one infarct related artery probably with substantial vasospastic component. Patients were younger (average 31.7 ± 3.7 years), dominant risk factors smoking, hyperlipidemia, excessive physical and emotional stress. Disease course and prognosis are favourable. 2. premature accelerated atherosclerosis with significant (more 50%) in 70-75 % often multivessel affection. Pts were significantly older (average 35.8 ± 2.6 years; < 0.001) bad risk factors profile, worse clinical course and poor long-term prognosis. CONCLUSIONS: Study of myocardial infarction in young adults indicates: great role of risk factors, mainly smoking, hyperlipidemia, family history and type A behaviour, hostility with participation of low education level and social inequality (unemployment). Noticeable are hypercoagulable states and trauma. Dominancy of men (90-95%). Prognosis depends on age, extend of coronary atherosclerosis and residual cardiac function. Disease picture has not been changed during last 30 years. Aggressive control over risk factors is unavoidable. Current requirement is to evaluate impact of modern treatment strategy on long-term survival. Key words: coronary artery disease - myocardial infarction at young age.

[Natriuretic peptides in patients with aortic stenosis]. / Nátriuretické peptidy pri aortovej stenóze.

INTRODUCTION: The aim of this research was to, in patients with severe (tight) aortic stenosis (AoS), evaluate a) an association between clinical and some haemodynamic characteristics and natriuretic peptides (ANP, BNP) concentrations and b) usefulness of these hormones in the decision making on the next therapeutic steps. METHODS: Echocardiography and 6-minut exertion walking test were performed in 23 consecutive patients (12 men, 11 women; age 67 +/- 7 years) and 20 controls together with ANP and BNP measurements from three plasma samples before, immediately after and 20 minutes after the exertion test. RESULTS: There was high inter-individual variability in the ANP and BNP concentrations in patients with AoS. All ANP and BNP were significantly higher than in the controls (ANP 1, 2, 3, p < 0.001; BNP 1, 2, 3, p < 0.001). Only the ANP levels increased significantly after the exercise (ANP 1 vs. ANP 2 = 0.011; ANP 2 vs. ANP 3 p = 0.037). We identified significant correlations between aortic peak gradient and BNP 1, 2 (r = 0.821, p < 0.001) and ANP 1, with BNP correlations being stronger. We did not find any correlations with aortic valve area and the left ventricle mass. The hormone levels were non-significantly increased depending on NYHA classification. Exercise did not improve validity ofANP and BNP measurement. Their values had high sensitivity but low specificity in detecting critical AoS. CONCLUSION: ANP and mainly BNP helped to exclude severe AoS but they were not useful in detecting lower, orderline gradients. We did not prove ANP and BNP to be significant factors in decision making about the timing of AoS surgery.

The physiological actions of isoflavone phytoestrogens.

Isoflavones are a subgroup of phytoestrogens, natural plant substances with structure similar to 17-beta-estradiol and capable of binding to estrogen receptors (ERs). Isoflavones possess higher affinity to ERbeta than to ERalpha and may have a potency to activate both genomic and non-genomic estrogen signaling pathways. In addition, isoflavones interact with the metabolism of steroid hormones. Therefore, the actions of isoflavones are rather complex and may be related to large number of factors, which are not satisfactorily identified yet. Recently, isoflavones have come into focus of interest due to several reports about their positive effect on human health, in particular prevention of hormone-dependent cancers, cardiovascular diseases, osteoporosis, adverse menopausal manifestations and age-related cognitive decline. Isoflavones may bring new insights into the mechanisms of physiological regulations and increase the possibilities of medical interventions.

Cardiovascular diseases and molecular variants of the renin-angiotensin system components in Slovak population.

Cardiovascular diseases associated with molecular variants of individual components of renin-angiotensin system are reported to constitute inherited predisposition in humans. Molecular variant frequencies are race- and population-dependent. We examined frequencies of the M235T variant of angiotensinogen gene and I/D polymorphism of gene for angiotensin-converting enzyme in Slovak population: in hypertensive patients, coronary heart disease (CHD), dilated cardiomyopathy (DCM) and myocardial infarction (MI) patients compared to healthy subjects. Frequency of M235T was significantly increased in hypertensive, CHD and DCM patients compared to controls (0.48 and 0.50 vs. 0.40, p < 0.001). Significant increase in D allele frequency compared to controls was observed in the group of patients after MI (0.58 vs. 0.50, p < 0.001), CHD (0.59 vs. 0.50, p < 0.001) and DCM (0.60 vs. 0.50, p < 0.001). These results correlate with other Caucasian populations. In Slovak population, M235T is associated with increased blood pressure and D allele of ACE gene is associated with MI, chronic CHD and DCM, rather than with hypertension. Our results suggest that in Slovak population, D alelle and M235T variant represent a risk factor for several cardiovascular diseases and these polymorphisms might have a cumulative effect on development of cardiovascular diseases.

Saccadic eye movement related potentials.

The saccadic eye movement related potentials (SEMRPs) enable to study brain mechanisms of the sensorimotor integration. SEMRPs provide insight into various cognitive mechanisms related to planning, programming, generation and execution of the saccadic eye movements. SEMRPs can be used to investigate pathophysiological mechanisms of several disorders of the central nervous system. Here we shortly summarize basic findings concerning the significance of SEMRP components, their relationship to the functional brain asymmetry and visual attention level as well as changes related to certain neuropsychological disorders.

Chaotic EEG patterns during recall of stressful memory related to panic attack.

Chaotic transitions likely emerge in a wide variety of cognitive phenomena and may be linked to specific changes during the development of mental disorders. They represent relatively short periods in the behavior of a system, which are extremely sensitive to very small changes. This increased sensitivity has been suggested to occur also during retrieval of stressful emotional experiences because of their fragmentary, temporally and spatially disorganized character. To test this hypothesis we recorded EEG during retrieval of fearful memories related to panic attack in 7 patients and retrieval of anxiety-related memories in 11 healthy controls. Nonlinear data analysis of EEG records showed a statistically significant increase in degree of chaotic dynamics after retrieval of stressful memories in majority of patients as well as in control subjects. This change correlated with subjective intensity of anxiety induced during the memory retrieval. The data suggest a role of nonlinear changes of neural dynamics in the processing of stressful anxiety-related memories, which may play an important role in the pathophysiology of panic disorder.

Initial experiences with novel therapy for pulmonary hypertension in Slovakia.

Pulmonary hypertension (PH) is the most serious and potentially devastating chronic disorder of the pulmonary circulation with diverse etiologies and pathogenesis characterized by abnormal increased vasoconstriction and vascular remodelling. Current specific therapy of PH is based on an understanding of its pathogenesis and is acting through pathogenic pathways and therefore changes therapeutic strategy, effectively improves clinical course and prolongs life. The authors discuss the actual classification, pathogenesis in short and particularly actual treatment modalities and the impact on the natural history of this disorder. In chronic thromboembolic pulmonary hypertension is pulmonary endarterectomy if correct indicated the curable method, warranted substantial improvement of life quality and survival. These novel therapies of PH were absent in Slovakia until recently. The authors present initial experiences, results of PH management up to date on the basis of cooperation with PH centres in Austria and Czech Republic (Tab. 1, Fig. 6, Ref. 32).

Extrastriate area V5 (MT) and its role in the processing of visual motion.

Extrastriate area V5 was identified in many primates including humans. V5 represents an important substrate for visual motion processing. Neurons in this area show a sharp preference for direction and speed of visual stimuli. Neuronal activity correlates with the ability to detect and discriminate motion in several psychophysical paradigms. The nature of neuronal representation of motion in V5 is much debated currently. The following article provides a summary of basic anatomical, neurophysiological, neuropsychological, and behavioural data related to the role of area V5 in the processing of visual motion information.

Endothelial dysfunction and the clinical application.

The vascular endothelium is a large organ that secretes numerous factors regulating vascular tone, cell growth, platelet and leukocyte interactions and thrombogenesis. Endothelial dysfunction is an early event in atherogenesis and is also important in establish coronary artery disease. Over the past decade a noninvasive technique has evolved to evaluate flow-mediated vasodilation, an endothelium-dependent function. Procedure is realised on the brachial artery. The stimulus provokes the endothelium to release nitric oxide with subsequent vasodilation that can be imaged and quantitated as the index of vasomotor function. (Fig. 1, Ref. 2.).

[The importance of electrocardiographic changes at rest during exercise in deciding to perform immediate ("ad hoc") percutaneous transluminal coronary angioplasty]. / Význam elektrokardiografických zmien v pokoji a pri zát'azi pre rozhodnutie o bezprostredne vykonanej ("ad hoc") perkutánnej transluminálnej koronárnej angioplastike.

In 100 patients (75 men and 25 women, mean age 53 years) who had "ad hoc" percutaneous transluminal coronary angioplasty (PTCA) on one or two vessels retrospectively the ECG records were evaluated (signs of necrosis or ischaemia) at rest and/or after exercise and compared with the finding of major obstruction (complete occlusion, stenosis > 50%) on coronarography. In obstruction of the ramus interventricularis anterior the positive ECG finding was consistent with the area of the impaired blood supply in 87%, in case of obstruction of the right coronary artery in 79%, in obstruction of the ramus circumflexus in 90%. In concurrent obstruction of two coronaries despite a 100% positive ECG no close topical correlation was found between coronarography and ECG. On the whole no reliable consistency was found between ECG and kinetic disorders detected by echocardiography. The results indicate that topical analysis of ECG ischaemic findings in patients with coronary arterial disease before planned coronarography contributes to the decision to make "ad hoc" PTCA in affections of one artery. In affections of two arteries ECG is of no particular value.

[Treatment of pseudoaneurysms with injection of thrombin]. / Liecba pseudoaneuryziem injekciou trombínu.

OBJECTIVES: To introduce and assess the efficacy and risks associated with a new treatment method of post-catheterization pseudoaneurysms. METHODS: Thrombin injection was indicated in patients with failure of compression therapy during 24 hours. Patients with a cavity volume < 1 cm3, with a pseudoaneurysm causing compression or haemorrhagic shock were excluded. A needle is introduced under local anaesthesia with ultrasound guidance, its tip is placed thoroughly in the centre of the cavity. Subsequently, under colour-flow mapping, thrombin solution with concentration of 1000 IU/ml is cautiously injected, which results in instantaneous thrombosis of the pseudoaneurysm cavity. RESULTS: Thrombin injection was used in 17 patients during a period of 12 months. 12 of them were women, 6 patients with valvular disease, 2 after intervention and 5 anticoagulated. The method was successful in 16 patients. In 5 of them, a small residual cavity persisted, which was not suitable for re-injection, and was closed completely after a few minutes of compression by a ultrasound transducer. There were no thrombotic complications. CONCLUSION: Although compression remains the method of choice, thrombin injection is a highly effective, quick and, with necessary precautions, safe alternative to surgical treatment of pseudoaneurysms, mainly in anticoagulated patients.

[80th anniversary of the Slovak Medical Society in Bratislava (1920-2000), and its significance in the development of medicine in Slovakia]. / Osemdesiat rokov Spolku slovenskych lekarov v Bratislave (1920-2000) a jeho vyznam pre vyvoj mediciny na Slovensku.

The establishment of the Slovak Medical Society (SMS) in Bratislava on 13th June 1920 (until 1939, the society was included into the Czechoslovak Medical Society) represents one of the most important milestones in the modern history of Slovak medicine. It was founded in direct consequence of the establishment of the first faculty of the Comenius University, namely the Medical Faculty. SMS began to issue its own journal Bratislavské lekárske listy (Bratislava Medical Journal) which was the first medical journal published in Slovakia after the origin of the Czechoslovak Republic. Eighty years of the existence of SMS which by its 2500 members forms the largest medical association, prove that the share of this society and its contribution to the development of Slovak medicine are essential. For many years, the society has been the only forum for Slovak physicians and scientific workers of the Medical Faculty where they could meet and increase their expertise. The society has witnessed also the significant material and moral support and co-operation between Czech and Slovak physicians during the period of the first Czechoslovak Republic.

Value of echocardiography in results evaluation of transcatheter atrial septal defect closure in adults.

Transcatheter closure of secundum atrial septal defect using Amplatzer occluder is accepted treatment modality. Transthoracic (TTE) and transoesophageal (TEE) echocardiography provides indispensable informations in the selection of eligible atrial septal defects, evaluates the exact size, location and morphology of the defect. In the closure procedure assistance of TEE enables precise determination of device size, correct placement of the device and immediate and follow-up closure results assessment. The present prospective study was performed in order to investigate the value of both approaches--TTE and TEE in the intermediate-term follow-up. Before, during transcatheter defect closure and in the follow-up echocardiography studies [TTE and TEE] were performed in 33 adult patients with secundum atrial septal defect with fulfilled TEE criteria. Correct placement of the device without interference with surrounding structures under TEE monitoring was possible in all patients. Immediate complete closure was achieved in 49% of patients, after 3 months in 94%. TEE findings corresponded well with TTE. In the follow-up echocardiographic signs of right ventricle overload retreated. Results indicate that TEE provides valued data for the selection and closure procedure. TTE is a sufficient reliable approach for results evaluation in intermediate follow-up. Echocardiography plays crucial role in the safety and efficacy assessment of transcatheter treatment of secundum atrial septal defect.