PURPOSE: Adrenal venous sampling (AVS) performed to distinguish unilateral and bilateral primary aldosteronism (PA) is invasive and poorly standardized. This study aimed to identify non-invasive characteristics that can select the patients with unilateral PA who could bypass AVS before surgery. METHODS: A single-center study collected a total of 450 patients with PA. Development and validation cohorts included 242 and 208 patients. The AVS was successful in 150 and 138 patients from the cohorts, and the unilateral PA was found in 96 and 94 patients, respectively. Clinical factors independently associated with lateralized AVS in multivariable logistic regression were used to construct a unilateral PA prediction score (SCORE). RESULTS: The proposed SCORE was calculated as a sum of the prevalence of adrenal nodule on computed tomography (2 points) and plasma/serum aldosterone concentration ≥ 165 ng/L after the saline infusion test (SIT) (1 point). Importantly, the SCORE = 3 points identified 48% of unilateral PA patients with a specificity of 100% in the development cohort. The zero rate of false-positive classifications was preserved with the same cut-off value in the validation cohort. CONCLUSIONS: AVS could be omitted before surgery in patients with typical Conn ́s adenoma provided the aldosterone concentration ≥ 165 ng/L after the SIT.

• Publikační typ
• časopisecké články MeSH

The gateway reflex is a mechanism by which neural inputs regulate chemokine expression at endothelial cell barriers, thereby establishing gateways for the invasion of autoreactive T cells into barrier-protected tissues. In this study, we hypothesized that rod photoreceptor dysfunction causes remodeling of retinal neural activity, which influences the blood-retinal barrier and the development of retinal inflammation. We evaluated this hypothesis using Gnat1rd17 mice, a model of night blindness with late-onset rod-cone dystrophy, and experimental autoimmune uveoretinitis (EAU). Retinal remodeling and its effect on EAU development were investigated by transcriptome profiling, target identification, and functional validation. We showed that Gnat1rd17 mice primarily underwent alterations in their retinal dopaminergic system, triggering the development of an exacerbated EAU, which was counteracted by dopamine replacement with L-DOPA administered either systemically or locally. Remarkably, dopamine acted on retinal endothelial cells to inhibit NF-κB and STAT3 activity and the expression of downstream target genes such as chemokines involved in T cell recruitment. These results suggest that rod-mediated dopamine release functions in a gateway reflex manner in the homeostatic control of immune cell entry into the retina, and the loss of retinal dopaminergic activity in conditions associated with rod dysfunction increases the susceptibility to autoimmune uveitis.

• MeSH
• buněčné linie MeSH
• dopamin metabolismus   MeSH
• endoteliální buňky metabolismus   patologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• NF-kappa B metabolismus   MeSH
• retina metabolismus   patologie   MeSH
• transkripční faktor STAT3 metabolismus   MeSH
• uveitida metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Warfarin is widely used anticoagulant drug for a variety of diseases (thromboembolic disease, atrial fibrillation, etc.). It has three most important parallel metabolic pathways, CYP1A2, CYP3A4 and CYP2C9. Terbinafine is a potent CYP2D6 inhibitor. A possible drug interaction could lead to an increased pharmacological effect of the above drugs. Enzyme induction with CYP3A4, CYP2C9, CYP1A2 inducers may have occurred. Case report: We present a case report of an 88-year-old male patient who has been successfully anticoagulated with warfarin due to atrial fibrillation. He was orally administered terbinafine to treat onychomycosis. Two weeks after initiation of this drug the patient experienced dizziness and feelings of instability, for which he was admitted to the neurology department. A low-efficient INR level was found at the baseline, presumably due to warfarin interaction with terbinafine. The induction of liver enzymes lasts 10-14 days, which matches the introduction of the antifungal agent. Conclusion: Combined therapy with warfarin and oral terbinafine is actually rarely prescribed but, if used, their interaction can have serious consequences in many clinical situations for which anticoagulation therapy with warfarin is indicated.

• MeSH
• antifungální látky aplikace a dávkování   škodlivé účinky   MeSH
• antikoagulancia aplikace a dávkování   škodlivé účinky   MeSH
• aplikace orální MeSH
• fibrilace síní farmakoterapie   MeSH
• lékové interakce * MeSH
• lidé MeSH
• onychomykóza farmakoterapie   MeSH
• senioři nad 80 let MeSH
• terbinafin aplikace a dávkování   škodlivé účinky   MeSH
• warfarin aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2 self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 120-min IVSA sessions under a fixed ratio FR1, which significantly reduced the number of the active lever-pressing, the number of infusions, and the cannabinoid intake. Pretreatment with JMV2959 suggested reduction of the WIN55,212-2-seeking/relapse-like behavior tested in rats on the twelfth day of the forced abstinence period. On the contrary, pretreatment with ghrelin significantly increased the cannabinoid IVSA as well as enhanced the relapse-like behavior. Co-administration of ghrelin with JMV2959 abolished/reduced the significant efficacy of the GHS-R1A antagonist in the cannabinoid IVSA. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of THC-induced CPP. The THC-CPP development was reduced after the simultaneous administration of JMV2959 with THC during conditioning. JMV2959 also significantly reduced the THC-induced behavioral stimulation in the LABORAS cage. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of cannabinoids.

• MeSH
• autoaplikace MeSH
• chování zvířat účinky léků   MeSH
• glycin analogy a deriváty   farmakologie   MeSH
• intravenózní podání MeSH
• kanabinoidy aplikace a dávkování   farmakologie   MeSH
• krysa rodu rattus MeSH
• operantní podmiňování účinky léků   MeSH
• podmiňování (psychologie) účinky léků   MeSH
• posilování (psychologie) MeSH
• potkani Wistar MeSH
• receptory ghrelinu antagonisté a inhibitory   MeSH
• triazoly farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by gradual loss of upper and lower motor neurons and their pathways, usually without affecting the extraocular and sphincter muscles. The cause of the disease is not yet known. It is a chain of subsequent events, ending in programmed cell death in selective neuronal subpopulations. The prognosis for survival is rather short with a median of 2 to 4 years. Survival may be prolonged based on prompt diagnosis, ALS subtype and proper management with supportive treatment (tracheostomy, gastrostomy, etc.). According to the clinical picture, the typical form of ALS with upper and lower motoneuron involvement and progressive bulbar paralysis with bulbar muscle involvement is observed. The ALS form with progressive muscle atrophy, where only the lower motoneuron is affected, and primary lateral sclerosis with only upper motoneuron damage are rare. Familiar forms of ALS (FALS) associated with specific genes (the most common is C9orf72) have been discovered. FALS is usually associated with dementia (frontotemporal lobar dementia, FTLD), behavioral disorders, cognitive dysfunction and impairment of executive functions. The diagnosis of ALS is determined by excluding other conditions and utilizing clinical examinations, laboratory and genetic tests and nerve conduction/needle electromyography studies (EMG). Needle EMG records abnormal activities at rest and looks for neurogenic patterns during muscle contraction. Motor evoked potentials after transcranial magnetic stimulation remain the test of choice to identify impairment of upper motor neurons. New biochemical, neurophysiological and morphological biomarkers are extensively studied as early diagnostic and prognostic factors and have implications for clinical trials, research and drug development.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVE: A survey among medical students of all medical schools in the Czech Republic was conducted to investigate attitudes and views of psychiatry and career choice of psychiatry. METHODS: A Czech version of the Attitudes to Psychiatry Scale (APS) and a questionnaire surveying demographic characteristics and choices of future specialty were distributed to all medical students of eight medical schools in the Czech Republic via the schools' internal communication systems in the form of an anonymous online questionnaire. RESULTS: Out of a total of 10,147 medical students in the Czech Republic (academic year 2019/2020), 2418 students participated in the survey (response rate 23.8%). Psychiatry as a non-exclusive career choice was considered by 31.3% respondents; child and adolescent psychiatry was considered by 15.4% respondents. Psychiatry as the only choice was considered by 1.6%, and child and adolescent psychiatry was not considered at all. The interest in both specialties was declining since the first year of study. The status of psychiatry among other medical specialties was perceived as low; students were rather discouraged from entering psychiatry by their families. They did not feel encouraged by their teachers to pursue career in psychiatry despite the fact that they were interested in psychiatry. They also felt uncomfortable with patients with mental illness. CONCLUSIONS: Despite high enthusiasm for psychiatry in the first year of medical school, only a small proportion of medical students consider to choose psychiatry, and especially child and adolescent psychiatry, as a career at the end of medical school.

• MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• postoj zdravotnického personálu MeSH
• postoj MeSH
• průzkumy a dotazníky MeSH
• psychiatrie * MeSH
• studenti lékařství * MeSH
• volba povolání MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Deschloroketamine (2-(methylamino)-2-phenyl-cyclohexanone) is a ketamine analog belonging to a group of dissociative anesthetics, which have been distributed within the illicit market since 2015. However, it was also being sold as 'ketamine' misleading people to believe that they were getting genuine ketamine. Dissociative anesthetics have also come to the attention of the psychiatric field due to their potential properties in the treatment of depression. At present, there is a dearth of information on deschloroketamine related to its metabolism, biodistribution, and its mechanism of action. We have therefore carried out a metabolomics study for deschloroketamine via non-targeted screening of urine samples employing liquid chromatography combined with high-resolution mass spectrometry. We developed and validated a multiple reaction monitoring method using a triple quadrupole instrument to track metabolites of deschloroketamine. Furthermore, significant metabolites of deschloroketamine, (trans-dihydrodeschloroketamine, cis- and trans-dihydronordeschloroketamine, and nordeschloroketamine), were synthesized in-house. The prepared standards were utilized in the developed multiple reaction monitoring method. The quantification method for serum samples provided intra-day accuracy ranging from 86% to 112% with precision of 3% on average. The concentrations of cis/trans-dihydronordeschloroketamines and trans-dihydrodeschloroketamine were lower than 10 ng/mL, nordeschloroketamine and deschloroketamine ranged from 0.5 to 860 ng/mL in real samples. The quantification method for brain tissue provided intra-day accuracy ranging from 80% to 125% with precision of 7% on average. The concentrations of cis/trans-dihydronordeschloroketamines and trans-dihydrodeschloroketamine ranged from 0.5 to 70 ng/g, nordeschloroketamine and deschloroketamine varied from 0.5 to 4700 ng/g in real samples.

• MeSH
• chromatografie kapalinová MeSH
• ketamin agonisté   krev   chemická syntéza   farmakokinetika   MeSH
• krysa rodu rattus MeSH
• mozek metabolismus   MeSH
• tandemová hmotnostní spektrometrie přístrojové vybavení   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Animals' reactions to novel objects vary not only with zoological taxa and their ecology but also in the types of presented stimuli, the context, and individual characteristics. Behavioral reactions can vary from extremely neophobic (avoiding novel objects) to extremely neophilic (intense exploration of novel objects); most often, a mixture of these behavioral patterns appears. In primates, reactions toward novel objects vary according to species, age, sex, population, and the types of objects. Most experiments in this field have used a free exploration design with food or non-food objects. Here, we tested the reactions of captive male rhesus macaques using various stimuli, motivation levels, rewards, and time limits. We found that the monkeys explored and manipulated novel objects in various contexts, with little evidence of a neophobic response; however, environment, types of stimuli, and other parameters of the test can significantly affect monkeys' reactions.

• MeSH
• chování zvířat * MeSH
• Macaca mulatta fyziologie   MeSH
• odměna MeSH
• pátrací chování * MeSH
• zvířata v ZOO MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) affects 1-2% of people over 60 years of age and presents a high risk of developing a neurodegenerative disorder from the group of synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Therefore, screening tools are needed. In 2007, the rapid eye movement sleep behavior disorder screening questionnaire (RBD-SQ) was developed and has been translated into several languages. The aim of study was to assess the validity and reliability of the Czech version of the RBD-SQ in a mixed population of sleep clinic patients, supplemented by healthy volunteers and RBD patients. METHODS: Participants included 81 iRBD patients, 205 patients with other sleep disorders (obstructive sleep apnea, insomnia, restless legs syndrome and periodic limb movement disorder, other parasomnias, or central hypersomnias including narcolepsy) and 20 healthy volunteers. RESULTS: The mean RBD-SQ score in the iRBD patients was 9.4 ± 2.8 points, and in the non-RBD group it was 4.5 ± 3.0 (P < 0.0001). Receiver -operator analysis yielded an area under the curve of 0.864, suggesting good diagnostic performance of the scale. When using a cut-off value for positivity of 5 points, sensitivity was 0.89 and specificity was 0.62. CONCLUSIONS: The Czech version of the RBD-SQ is a sensitive tool for screening for iRBD patients and helps to identify subjects for complete clinical workup.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• plošný screening metody   MeSH
• porucha chování v REM spánku diagnóza   MeSH
• překládání MeSH
• průzkumy a dotazníky * MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• validační studie MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: 5-methoxy-N,N-dimethyltryptamine (hereinafter referred to as 5-MeO-DMT) is a psychedelic substance found in the secretion from the parotoid glands of the Bufo alvarius toad. Inhalation of vapor from toad secretion containing 5-MeO-DMT has become popular in naturalistic settings as a treatment of mental health problems or as a means for spiritual exploration. However, knowledge of the effects of 5-MeO-DMT in humans is limited. AIMS: The first objective of this study was to assess sub-acute and long-term effects of inhaling vapor from dried toad secretion containing 5-MeO-DMT on affect and cognition. The second objective was to assess whether any changes were associated with the psychedelic experience. METHODS: Assessments at baseline, within 24 h and 4 weeks following intake, were made in 42 individuals who inhaled vapor from dried toad secretion at several European locations. RESULTS: Relative to baseline, ratings of satisfaction with life and convergent thinking significantly increased right after intake and were maintained at follow-up 4 weeks later. Ratings of mindfulness also increased over time and reached statistical significance at 4 weeks. Ratings of depression, anxiety, and stress decreased after the session, and reached significance at 4 weeks. Participants that experienced high levels of ego dissolution or oceanic boundlessness during the session displayed higher ratings of satisfaction with life and lower ratings of depression and stress. CONCLUSION: A single inhalation of vapor from dried toad secretion containing 5-MeO-DMT produces sub-acute and long-term changes in affect and cognition in volunteers. These results warrant exploratory research into therapeutic applications of 5-MeO-DMT.

• MeSH
• aplikace inhalační MeSH
• dospělí MeSH
• duševní poruchy farmakoterapie   epidemiologie   psychologie   MeSH
• halucinogeny aplikace a dávkování   MeSH
• kognice účinky léků   fyziologie   MeSH
• lidé MeSH
• methoxydimethyltryptaminy aplikace a dávkování   MeSH
• následné studie MeSH
• osobní uspokojení * MeSH
• ropuchy MeSH
• vaping psychologie   MeSH
• všímavost metody   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH