Publikace se zaměřuje na farmakorezistenci u schizofrenie, deprese, úzkosti a obsedantně-kompulzivní poruchy. Určeno odborné veřejnosti.; Publikace se zaměřuje na problematiku rezistence vůči psychofarmakům u pacientů se závažnými duševními onemocněními, jako jsou schizofrenie, bipolární porucha, deprese, vybrané úzkostné stavy a obsedantně-kompulzivní porucha. Autorka přináší přehled výzkumných metod a vývoje v oblasti léčby farmakorezistentních stavů a zároveň popisuje slepé cesty a výzkumné přístupy, které se původně jevily jako slibné, ale v praxi se ukázaly jako neúčinné. Vysvětluje mechanismy působení psychofarmak a rozkrývá genetické základy farmakogenomiky, které pomáhají objasnit individuální variace v účincích léků. Odhaluje také složitost výzkumu a metodologické nástrahy, jež ovlivňují interpretaci studií na poli farmakorezistence. Kniha je cenným zdrojem informací pro odborníky, kteří se chtějí zorientovat v komplexnosti farmakorezistentních stavů a efektivněji podporovat své pacienty na cestě k zotavení.

• MeSH
• duševní poruchy MeSH
• léková rezistence MeSH
• psychotropní léky MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Psychiatrie
• NLK Obory
• psychiatrie
• psychofarmakologie

Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group. In a mega-analysis, we investigated the associations between BMI, diagnosis or medication and FA. Lower FA was associated with both BD and BMI in six white matter tracts, including the corpus callosum and thalamic radiation. Higher BMI or BD were uniquely associated with lower FA in three and six white matter tracts, respectively. People not receiving lithium treatment had a greater negative association between FA and BMI than people treated with lithium in the posterior thalamic radiation and sagittal stratum. In three tracts BMI accounted for 10.5 to 17% of the negative association between the number of medication classes other than lithium and FA. Both overweight/obesity and BD demonstrated lower FA in some of the same regions. People prescribed lithium had a weaker association between BMI and FA than people not on lithium. In contrast, greater weight contributed to the negative associations between medications and FA. Obesity may add to brain alterations in BD and may play a role in effects of medications on the brain.

• MeSH
• anizotropie MeSH
• bílá hmota * patologie   diagnostické zobrazování   metabolismus   MeSH
• bipolární porucha * patologie   metabolismus   MeSH
• dospělí MeSH
• index tělesné hmotnosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozek patologie   MeSH
• obezita * patologie   metabolismus   komplikace   MeSH
• šedá hmota MeSH
• zobrazování difuzních tenzorů metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses. METHODS: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we developed a scoring system for NDP load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and gender with bootstrap replications. RESULTS: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and specific learning disorders. Patients with higher NDP load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.

• MeSH
• bipolární porucha * genetika   MeSH
• dospělí MeSH
• fenotyp * MeSH
• hyperkinetická porucha genetika   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• multifaktoriální dědičnost genetika   MeSH
• neurovývojové poruchy genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The perception of a voice in the absence of an external auditory source-an auditory verbal hallucination-is a characteristic symptom of schizophrenia. To better understand this phenomenon requires integration of findings across behavioural, functional, and neurochemical levels. We address this with a locally adapted MEGA-PRESS sequence incorporating interleaved unsuppressed water acquisitions, allowing concurrent assessment of behaviour, blood-oxygenation-level-dependent (BOLD) functional changes, Glutamate + Glutamine (Glx), and GABA, synchronised with a cognitive (flanker) task. We acquired data from the anterior cingulate cortex (ACC) of 51 patients with psychosis (predominantly schizophrenia spectrum disorder) and hallucinations, matched to healthy controls. Consistent with the notion of an excitatory/inhibitory imbalance, we hypothesized differential effects for Glx and GABA between groups, and aberrant dynamics in response to task. Results showed impaired task performance, lower baseline Glx and positive association between Glx and BOLD in patients, contrasting a negative correlation in healthy controls. Task-related increases in Glx were observed in both groups, with no significant difference between groups. No significant effects were observed for GABA. These findings suggest that a putative excitatory/inhibitory imbalance affecting inhibitory control in the ACC is primarily observed as tonic, baseline glutamate differences, rather than GABAergic effects or aberrant dynamics in relation to a task.

• MeSH
• cingulární gyrus metabolismus   patofyziologie   MeSH
• dospělí MeSH
• GABA * metabolismus   MeSH
• glutamin metabolismus   MeSH
• halucinace * metabolismus   patofyziologie   MeSH
• kognice * fyziologie   MeSH
• kyselina glutamová * metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladý dospělý MeSH
• psychotické poruchy * metabolismus   patofyziologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: This study aimed to investigate the impact of bleaching agents based on carbamide or hydrogen peroxide on dental ceramics in vitro, utilizing scanning electron microscopy (SEM) and elemental analysis via inductively coupled plasma optical emission spectroscopy (ICP-OES). METHODS: CAD/CAM ceramics (IPS e.max®CAD, IPS Empress®CAD, Vitablocs® Mark II, Celtra Duo, and inCoris TZI) were treated with bleaching agents using either 10%, 20%, 30% carbamide peroxide or with 35%, and 40% hydrogen peroxide. RESULTS: Surface elemental release was not significantly affected by the type or concentration of bleaching agent (p>0.05). Ion release in feldspathic ceramics was significantly higher than in other ceramic materials (p⟨0.0001). Microstructural surface changes were observed in all materials except for lithium disilicate and zirconia-reinforced lithium silicate ceramics. CONCLUSIONS: All bleaching agents tested in this study showed a similar impact within each material type tested regarding total mass loss, elemental composition, or surface structure. CLINICAL RELEVANCE: Lithium disilicate and zirconia-reinforced lithium silicate ceramics were the most resistant to bleaching agents. In contrast, feldspathic ceramic showed the highest ion release and surface deterioration when exposed to all bleaching agents tested.

• MeSH
• design s pomocí počítače * MeSH
• karbamidperoxid * chemie   MeSH
• keramika * chemie   MeSH
• látky na bělení zubů * chemie   MeSH
• mikroskopie elektronová rastrovací MeSH
• peroxid vodíku * chemie   MeSH
• povrchové vlastnosti MeSH
• testování materiálů MeSH
• zirkonium chemie   MeSH
• zubní porcelán * chemie   MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The European Medicines Agency has recommended a series of restrictions on the use of sodium valproate (valproate) following research linking its exposure in utero to adverse congenital and neurodevelopmental effects in offspring. Recent research has highlighted a potential increased risk of neurodevelopmental disorders in children born to males taking valproate prior to conception. Clinicians and patients require guidance regarding suitable alternatives. AIM: To provide an overview of suitable alternatives to valproate in the management of bipolar disorder. METHOD: A narrative review was conducted. Only medications with an established evidence base in managing different phases of bipolar disorder and endorsed within clinical practice guidelines were considered. Eligible guidelines included those (i) where recommendations were informed by a formal guideline development process and (ii) published in English within the last 15 years. REPROTOX® was chosen as the primary information source regarding reproductive safety of alternative medications. RESULTS: Of all second-generation antipsychotics, quetiapine should be considered a first-line alternative to valproate. Lithium has been associated with an increased risk of cardiac malformations, especially Ebstein anomaly, following in utero exposure. However, given its robust efficacy as an antimanic agent and the absolute risk of cardiac abnormalities being low, it's use can still be considered in individuals of child-bearing potential with appropriate monitoring. Carbamazepine treatment should be avoided due to concerns for teratogenicity. Although considered safe in pregnancy, lamotrigine is largely effective at preventing relapse of bipolar depression. Thus, lamotrigine offers limited clinical utility as an alternative to valproate. CONCLUSION: Specific recommendations are made regarding alternatives to valproate in managing bipolar disorder.

• MeSH
• antimanika * škodlivé účinky   terapeutické užití   MeSH
• antipsychotika * škodlivé účinky   terapeutické užití   MeSH
• bipolární porucha * farmakoterapie   MeSH
• kyselina valproová * škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• management nemoci * MeSH
• těhotenství MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

The distribution and morphology of neuronal degeneration were observed and analyzed in each sector of the zona incerta in a lithium‐pilocarpine (LiCl) Wistar rat model of status epilepticus in 12, 15, 18, 21, and 25‐day‐old rats and survival intervals of 4, 8, 12, 24, and 48 hours. Status epilepticus was induced via intraperitoneal (IP) injection of LiCl (3 mmol/kg) 24 hours before an injection of pilocarpine (40 mg/kg, IP). Motor seizures were suppressed by paraldehyde (0.3‐0.6 ml/kg, IP) two hours after status epilepticus onset. Animals were anesthetized using urethane and perfused with phosphate‐buffered saline followed by 4% paraformaldehyde. Brains were sectioned and Nissl stained for map guidance, with fluoro‐Jade B fluorescence used to detect degenerated neurons. Fluoro‐jade B‐positive neurons were plotted to a standard stereotaxic atlas, their distribution was quantified, and their long‐axis diameter was measured. Fluoro‐jade B‐positive neurons were found in pups aged 15 days and older 24 hours after status epilepticus, in which their numbers increased, and their perikaryon size decreased with advancing age. Thus, neuronal damage severity was dependent on age and survival interval. Neuronal damage was only found in the rostral sector of the zona incerta, a region that exhibits a small number of inhibitory neurons and is reciprocally connected to the limbic cortex. This system of hyperactivity, coupled with inhibitory neurons, may be the underlying cause of the neuronal degeneration and explain why it was confined to the rostral sector of the zona incerta.

• MeSH
• chlorid lithný toxicita   MeSH
• degenerace nervu * patologie   etiologie   MeSH
• fluoresceiny MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• neurony * patologie   MeSH
• novorozená zvířata MeSH
• pilokarpin toxicita   MeSH
• potkani Wistar MeSH
• status epilepticus * patologie   chemicky indukované   komplikace   MeSH
• věkové faktory MeSH
• zona incerta * patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Tato kazuistika popisuje případ 32leté ženy trpící bipolární afektivní poruchou, která byla hospitalizována na psychiatrickém oddělení CNS Centra Třinec kvůli ztrátě hlasu trvající 10 měsíců. Pacientka byla v psychiatrické péči od roku 2013, kdy byla přijata na oddělení krátce po porodu dcery, a to s psychotickými projevy. V roce 2014 se u ní projevily příznaky manické fáze, což vedlo k nutnosti hospitalizace a nasazení lithia jako stabilizátoru nálady. V roce 2023, po pečlivém somatickém vyšetření z důvodu dlouhotrvající ztráty hlasu, byla vyloučena organická příčina obtíží. Na základě vyšetření se ukázalo, že ztráta hlasu by mohla být způsobena nežádoucím účinkem lithia, což bylo potvrzeno dalším sledováním stavu pacientky. Tato kazuistika zdůrazňuje důležitost důkladného vyšetření a sledování vedlejších účinků psychofarmak u pacientů s bipolární afektivní poruchou.

This case study describes a 32-year-old woman suffering from bipolar affective disorder who was hospitalized in the psychiatric department of CNS Center Třinec due to a voice loss lasting 10 months. The patient had been under psychiatric care since 2013, when she was admitted to the unit shortly after the birth of her daughter, presenting with psychotic symptoms. In 2014, she exhibited signs of a manic episode, necessitating hospitalization and the initiation of lithium as a mood stabilizer. In 2023, following a thorough somatic examination due to the prolonged voice loss, an organic cause for her difficulties was ruled out. Based on the assessment, it appeared that the voice loss may have been caused by a side effect of lithium, which was confirmed by further monitoring of the patient's condition. This case study underscores the importance of comprehensive evaluation and monitoring for side effects of psychotropic medications in patients with bipolar affective disorder.

• MeSH
• afonie * chemicky indukované   terapie   MeSH
• bipolární porucha farmakoterapie   komplikace   MeSH
• dospělí MeSH
• lidé MeSH
• lithium * škodlivé účinky   terapeutické užití   MeSH
• nežádoucí účinky léčiv MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

This study investigated the striatopallidal complex's involvement in status epilepticus (SE) caused by morphological neurodegenerative changes in a post-natal immature developing brain in a lithium-pilocarpine male Wistar albino rat model of mesial temporal lobe epilepsy. One hundred experimental pups were grouped by age as follows: 12, 15, 18, 21, and 25 days. SE was induced by lithium-pilocarpine. Brain sections were microscopically examined by Fluoro-Jade B fluorescence stain at intervals of 4, 12, 24, and 48 h and 1 week after SE. Each interval was composed of four induced SE pups and a control. Fluoro-Jade B positive neurons in the dorsal striatum (DS) were screened and plotted on stereotaxic rat brain maps. The DS showed consistent neuronal damage in pups aged 18, 21, and 25 days. The peak of the detected damage was observed in pups aged 18 days, and the start of the morphological sequela was observed 12 h post SE. The neuronal damage in the DS was distributed around its periphery, extending medially. The damaged neurons showed intense Fluoro-Jade B staining at the intervals of 12 and 24 h post SE. SE neuronal damage was evidenced in the post-natal developing brain selectively in the DS and was age-dependent with differing morphological sequela.

• MeSH
• corpus striatum * patologie   metabolismus   MeSH
• epilepsie temporálního laloku * patologie   chemicky indukované   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• neurony patologie   metabolismus   MeSH
• pilokarpin MeSH
• potkani Wistar MeSH
• status epilepticus * patologie   chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability. The resin blend of polyethylene glycol diacrylate and N-vinylpyrrolidone, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photoinitiator, was used, mixed with IMQ nanocrystals in water. The final microneedle-patches had 36 cylindrical microneedles arranged in a square grid, measuring approximately 600 μm in height and 500 μm in diameter. They contained 5wt% IMQ, which is equivalent to a commercially available cream. The homogeneity of IMQ distribution in the matrix was higher for nanocrystals compared to usual crystalline form. The release of IMQ from the patches was determined ex vivo in natural skin and revealed a 48% increase in efficacy for nanocrystal formulations compared to the crystalline form of IMQ.

• MeSH
• 3D tisk * MeSH
• aplikace kožní MeSH
• imichimod * chemie   aplikace a dávkování   MeSH
• jehly * MeSH
• kožní absorpce MeSH
• kůže metabolismus   MeSH
• lékové transportní systémy přístrojové vybavení   MeSH
• mikroinjekce přístrojové vybavení   MeSH
• nanočástice * chemie   aplikace a dávkování   MeSH
• polyethylenglykoly chemie   aplikace a dávkování   MeSH
• povidon chemie   MeSH
• rozpustnost * MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH