5-HT
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This study aimed to determine the effect of complex training (CT) on post-activation performance enhancement (PAPE) effect magnitude, 5- and 30-m linear sprint, 5-0-5 change-of-direction (COD), back squat (BS) and hip thrust (HT) one-repetition maximum [1RM], and jumping performance (countermovement jump [CMJ], drop jump [DJ], and broad jump [BJ]). The PAPE effect was elicited before and after each intervention by 3 BS repetitions at 90% 1RM and verified by CMJ performance. Twenty-four soccer players were randomly and equally assigned to 6 weeks of either medium (MED; [65-70%1RM]) or high-intensity (HIGH; [80-85%1RM]) CT performed twice a week. The HIGH group significantly improved their 5-m time (p < 0.001; effect size [ES] = 1.91), 30-m time (p = 0.001; ES = 0.66), BS 1RM (p = 0.019; ES = 0.19) and HT 1RM (p = 0.035; ES = 0.26), BJ length (p = 0.012; ES = 0.62) and DJ height (p = 0.002; ES = 0.57) from pre- to post-intervention. The MED group significantly improved their 5-m time (p = 0.004; ES = 0.52), BS 1RM (p = 0.019; ES = 0.36) and BJ length (p = 0.012; ES = 0.7). Significantly shorter 5-m sprint time (p = 0.001; ES = 1.63) and greater DJ height percentage increase (p < 0.001; ES = 1.81) were found in the HIGH group compared to the MED group. Moreover, a significant main effect of the group, indicating a higher PAPE response in the MED group compared to the HIGH group for CMJ peak power output, was observed at both pre- and post-CT intervention (p = 0.045; η2 = 0.171). Six weeks of either medium or high-intensity CT could be used to enhance jumping performance, linear speed and lower-body maximum strength among soccer players. Superior improvements in acceleration and DJ might be expected after high-intensity CT than medium intensity. Medium-intensity CT can improve PAPE response.
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- Gapulsid,
- MeSH
- benzamidy * terapeutické užití MeSH
- deprese komplikace MeSH
- dyspepsie farmakoterapie psychologie MeSH
- escitalopram škodlivé účinky terapeutické užití MeSH
- kombinovaná farmakoterapie metody MeSH
- lidé MeSH
- selektivní inhibitory zpětného vychytávání serotoninu * terapeutické užití MeSH
- senioři MeSH
- úzkost komplikace MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Předčasná ejakulace je jednou z běžných sexuálních poruch mužů. V naší studii jsme se zaměřili na předčasnou ejakulaci jako možný problém celého sexuálního páru. Hodnotili jsme možný vliv předčasné ejakulace mužů na vznik sexuální dysfunkce u jejich partnerek a následné odstranění této ženské dysfunkce pouze léčbou mužů. Z 95 párů bylo do pilotní studie zařazeno 50 párů, které splnily daná kritéria na základě diagnostických nástrojů. U mužů byla potvrzena předčasná ejakulace, u žen sexuální dysfunkce, jejímž zdrojem byla pouze předčasná ejakulace. Výsledky škály Arizona Sexual Experience Scale-Male a Female vykazují Spearmanovu korelaci před léčbou (R = 0,68) a po 6 měsících léčby (R = 0,90). Dále jsme potvrdili vztah mezi Arizona Sexual Experience Scale-Female a Female Sexual Function Index před léčbou (R = 0,42) a po léčbě (R = 0,59). Všechna data byla potvrzena Mannovým-Whitneyovým testem. Výsledky naší pilotní studie poukazují na málo prozkoumaný fakt, že předčasná ejakulace není pouze problémem mužů, ale může se stát následným sexuálním problémem celého páru. Výsledky této pilotní studie představují důležité zjištění o pozitivním účinku léčby mužů s předčasnou ejakulací na následnou sexuální dysfunkci jejich sexuálních partnerek.
Premature ejaculation is one of the common sexual disorders of men. In our study we focused on premature ejaculation as a possible problem for the entire sexual couple. We evaluated the possible effect of men premature ejaculation on the development of sexual dysfunction in their wives and the subsequent elimination of this female dysfunction if only men are treated. Out of 95 couples, 50 couples who met the given criteria based on the diagnostic tools were included in the pilot study. In men, premature ejaculation was confirmed, in women, sexual dysfunction, the source of which was only premature ejaculation. Results of the Arizona Sexual Experience Scale-Male and Female relationship are characterized by Spearman’s correlation before treatment (R = 0.68), after 6 months of treatment (R = 0.90). Furthermore, we confirmed the relationship between Arizona Sexual Experience Scale-Female and Female Sexual Function Index before treatment (R = 0.42) and after treatment (R = 0.59). All data were confirmed by the Mann-Whitney test. The results of our pilot study point to the little-explored fact that premature ejaculation is not only a problem for men, but can also form a subsequent sexual problem for the couple as a whole. The results of this pilot study represent important findings regarding the positive effect of treatment of men with premature ejaculation on the resulting sexual dysfunction in their sexual partners.
- MeSH
- lidé MeSH
- paroxetin aplikace a dávkování terapeutické užití MeSH
- pilotní projekty MeSH
- předčasná ejakulace * diagnóza farmakoterapie MeSH
- průzkumy a dotazníky MeSH
- selektivní inhibitory zpětného vychytávání serotoninu MeSH
- sexuální dysfunkce fyziologická diagnóza MeSH
- sexuální dysfunkce psychické diagnóza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Histological transformation (HT) in Waldenström's macroglobulinemia (WM) is a rare complication and despite growing literature in the last years, no consensus recommendations exist. Consensus Panel 6 (CP6) of the 12th International Workshop on Waldenström's Macroglobulinemia (IWWM-12) was convened to review the current data on transformed WM and make recommendations on its diagnosis and management. The key recommendations from IWWM-12 CP6 included: (1) in case of suspected HT, tissue biopsy is the gold standard for diagnosis; (2) the initial work-up should comprise 18FDG-PET/CT for the evaluation of disease extent and, for patients with clinical suspicion or for high-risk patients (CNS-IPI, multiple and/or specific extranodal involvements), cerebrospinal fluid examination and brain MRI; (3) standard dose chemoimmunotherapy (CIT) such as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone) or R-CHP + polatuzumab vedotin are the preferred front-line regimen; (4) CNS prophylaxis and consolidation with autologous stem cell transplantation (SCT) can be considered according to de novo diffuse large B-cell lymphoma (DLBCL) guidelines; (5) T-cell-engaging therapies (CAR T-cells, bispecific antibodies) should be used in the relapse/refractory setting according to international guidelines for DLBCL and local access to these therapies. Key unanswered questions include the role of TP53 abnormalities and CXCR4 mutations on the risk of HT, the prognostic role of clonal relationship between WM and HT, the optimal front-line therapy (addition of novel agents to CIT, dose-intensive CIT, consolidation with autologous SCT), and the sequence of T-cell-engaging therapies. International collaboration and consideration of and inclusion in clinical trials is critical to address these issues in a rare patient population.
Emočně nestabilní adolescenti představují rozsáhlou skupinu pacientů, kterými se v současnosti zabývají pedopsychiatrická pracoviště, jak ambulantního, tak lůžkového charakteru. Převážnou většinu tvoří adolescentní dívky, které přicházejí zejména pro úzkostně depresivní symptomatiku, sebepoškozování a suicidální chování. Emoční nestabilita v adolescenci představuje spektrum závažnosti, počínaje emoční labilitou obvyklou v dospívání, až po poruchy ve vývoji osobnosti, které mohou v nejzávažnějším případě vyústit do emočně nestabilní – hraniční poruchy osobnosti. Terapie vyžaduje integrovaný přístup, s důrazem na psychoterapii a rodinnou terapii, a také indikovanou farmakoterapii.
Emotionaly unstable adolescents represent a large group of patients currently dealt with pedopsychiatric facilities, both outpatient and inpatient. The vast majority are adolescent girl who come mainly for anxiety - depressive symptoms, self harm and suicidal behavior. Emotional instability in adolescence represents a spektrum of severity, starting with emotional lability common in adolescence, up to disturbances in personality development, which in the most serious case can reset in emotionally unstable - bordeline personality disorder. Therapy requires an integrated approach, with an emphasis on psychotherapy and family therapy, as well as indicated pharmacotherapy.
- MeSH
- dialektická behaviorální terapie metody MeSH
- hraniční porucha osobnosti * epidemiologie psychologie MeSH
- lidé MeSH
- mladiství * MeSH
- pokus o sebevraždu psychologie MeSH
- psychoterapie metody MeSH
- sebepoškozování MeSH
- selektivní inhibitory zpětného vychytávání serotoninu MeSH
- Check Tag
- lidé MeSH
- mladiství * MeSH
The intestine hosts the largest immune system and peripheral nervous system in the human body. The gut‒brain axis orchestrates communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Here, using a human three-dimensional in vitro culture model, we investigated the effects of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Serotonin attenuated the tumor necrosis factor-induced proinflammatory response, mostly by affecting the expression of chemokines. Serotonin affected the phenotype and distribution of tissue-migrating monocytes, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, our results show that serotonin plays a crucial role in communication among gut-brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of inflammation. In vivo studies focused on the role of neuromodulators in gut inflammation have shown controversial results, highlighting the importance of human experimental models. Moreover, our results emphasize the importance of human health research in human cell-based models and suggest that the serotonin signaling pathway is a new therapeutic target for inflammatory bowel disease.
The novel diiron amine complexes [Fe2Cp2(CO)(NH2R')(μ-CO){μ-CN(Me)(Cy)}]CF3SO3 [R' = H, 3; Cy, 4; CH2CH2NH2, 5; CH2CH2NMe2, 6; CH2CH2(4-C6H4OMe), 7; CH2CH2(4-C6H4OH), 8; Cp = η5-C5H5, Cy = C6H11 = cyclohexyl] were synthesized in 49-92 % yields from [Fe2Cp2(CO)2(μ-CO){μ-CN(Me)(Cy)}]CF3SO3, 1a, using a straightforward two-step procedure. They were characterized by IR and multinuclear NMR spectroscopy, and the structure of 7 was confirmed through X-ray diffraction analysis. Complexes 3-8 and the acetonitrile adducts [Fe2Cp2(CO)(NCMe)(μ-CO){μ-CN(Me)(R)}]CF3SO3 (R = Cy, 2a; Me, 2b; Xyl = 2,6-C6H3Me2, 2c) were assessed for their water solubility, octanol-water partition coefficient and stability in physiological-like solutions. The in vitro antiproliferative activity of 2a-c and 3-8 was tested on seven human cancer cell lines (A2780, A2780R, PC3, A549, MCF7, HOS and HT-29), while the selectivity was evaluated using normal MRC-5 cells. Overall, the complexes exhibited variable cytotoxicity, with IC50 values reaching the low micromolar range for 3, 7 and 8 in A2780 and A2780R cells, along with significant selectivity. Targeted experiments covered cell cycle modification, induction of cell death, mitochondrial membrane potential, ROS production and interaction with DNA and bovine serum albumin (BSA) as a model protein. The interaction of 3 with BSA was further investigated through computational studies. Results showed a negligible increase in intracellular ROS levels (except for 2b) and insignificant changes in mitochondrial membrane potential.
- MeSH
- aminy chemie farmakologie MeSH
- komplexní sloučeniny chemie farmakologie chemická syntéza MeSH
- lidé MeSH
- ligandy MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- proliferace buněk * účinky léků MeSH
- protinádorové látky * farmakologie chemie chemická syntéza MeSH
- screeningové testy protinádorových léčiv * MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- železo chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro. OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717). METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using TEAE data from participants with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). Incidences of TEAEs matching terms from each search were stratified by SSRI/SNRI use. RESULTS: Of 2257 DAYBREAK participants, 274 (12.1%) used an SSRI/SNRI. No participants had TEAEs matching the SA narrow search terms. There was no significant difference in the percentage of participants with ⩾1 TEAE matching the SA broad search for those on versus off SSRIs/SNRIs (on: 12.4%, n = 34/274; off: 15.6%, n = 310/1982, nominal p = 0.1630). CONCLUSION: MedDRA searches showed no increase in TEAEs potentially associated with SA with concomitant SSRI/SNRI and ozanimod use.
- MeSH
- antidepresiva škodlivé účinky MeSH
- indany * MeSH
- inhibitory zpětného vychytávání serotoninu a noradrenalinu * škodlivé účinky MeSH
- lidé MeSH
- oxadiazoly * MeSH
- roztroušená skleróza * chemicky indukované MeSH
- selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky MeSH
- serotonin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Effort-based decision-making is particularly relevant to psychiatric conditions where motivation deficits are prominent features. Despite its clinical significance, the neurochemical mechanisms of this cognitive process remain unclarified. This study explores the impact of serotonin synthesis inhibition (PCPA) and modulation of serotonin release and 5-HT1A receptor agonism (8-OH-DPAT) on effort-based decision-making in rats. Adult male rats were trained in a modified T-maze task where they could obtain a high reward for climbing a mesh barrier or a low reward for no extra effort. Following training, rats received either acute 8-OH-DPAT treatment or subchronic PCPA treatment and were tested on their choices between high- and low-effort arms. The goal-arm choices and goal-arm entrance latencies were recorded. Next, homovanillic acid and 5-hydroxyindoleacetic acid, metabolites of dopamine and serotonin, respectively, were quantified in the rats' prefrontal cortex, striatum, and hippocampus. 8-OH-DPAT significantly increased low-effort, low-reward choices and increased goal-arm latency. In contrast, PCPA treatment did not affect these measures. Both PCPA and 8-OH-DPAT significantly decreased 5-hydroxyindoleacetic acid levels in the prefrontal cortex and the hippocampus. 8-OH-DPAT treatment was also associated with decreased homovanillic acid levels in the hippocampus. Our findings suggest that the overall reduction of serotonin levels alone does not affect effort-based decision-making and highlights the possible role of the hippocampus and the 5-HT1A receptor in this cognitive process.
- MeSH
- 8-hydroxy-2-(di-N-propylamino)tetralin * farmakologie MeSH
- agonisté serotoninového receptoru 5-HT1 farmakologie MeSH
- bludiště - učení účinky léků fyziologie MeSH
- chování zvířat účinky léků MeSH
- krysa rodu rattus MeSH
- odměna MeSH
- potkani Sprague-Dawley MeSH
- rozhodování * fyziologie účinky léků MeSH
- serotonin * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Syndrom Dravetové je závažnou vývojovou a epileptickou encefalopatií se začátkem v kojeneckém věku, která se projevuje farmakorezistentní epilepsií a četnými komorbiditami. Typická je provokace záchvatů zvýšenou teplotou. Léčba onemocnění je obtížná. V chronické medikaci by měl být první volbou valproát, dalšími přidanými léky klobazam, stiripentol, fenfluramin, kanabidiol, topiramát. Pacienti musí být vybaveni SOS medikací pro zvládnutí záchvatů v domácím prostředí. V léčbě je nutné se vyhnout blokátorům sodíkových kanálů, aplikace fenytoinu v epileptickém statu je však přípustná. Kromě protizáchvatové léčby je nutné věnovat pozornost i nefarmakologické léčbě komorbidit.
Dravet syndrome is a developmental and epileptic encephalopathy starting in infancy and its main features are drug -resistant epilepsy and several co-morbidities. Seizures are typically provoked by increased temperature. The treatment of Dravet syndrome is challenging. The first antiseizure drug should be valproic acid, while clobazam, stiripentol, fenfluramine, canabidiol or topiramate are usually added later. All the patients must have rescue medication for home management of seizures. Sodium channel blockers should not be used for chronic treatment, but phenytoin can be administered to stop status epilepticus. Non-pharmacological treatment of co-morbidities should be addressed as well.
- Klíčová slova
- stiripentol, fenfluramin,
- MeSH
- dioxolany aplikace a dávkování farmakologie terapeutické užití MeSH
- epilepsie myoklonické * farmakoterapie patologie MeSH
- kanabidiol aplikace a dávkování farmakologie terapeutické užití MeSH
- klobazam aplikace a dávkování farmakologie terapeutické užití MeSH
- komorbidita MeSH
- kyselina valproová aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé MeSH
- selektivní inhibitory zpětného vychytávání serotoninu aplikace a dávkování farmakologie terapeutické užití MeSH
- topiramat aplikace a dávkování farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
