The Institute for Safe Medication Practices and the American Society of Health-System Pharmacists have advocated for removing all injectable promethazine from inpatient and outpatient settings; however, this drug is still being used despite the risk for tissue necrosis, gangrene, and possible amputation when it inadvertently is given by the subcutaneous or intra-arterial route. This article describes alternative injectable medications that can be selected based on patient comorbidities, indications, and clinician experience.

• MeSH
• injekce subkutánní MeSH
• injekce MeSH
• lidé MeSH
• promethazin * aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Ceramides are key components of the skin's permeability barrier. In atopic dermatitis, pathological hydrolysis of ceramide precursors - glucosylceramides and sphingomyelin - into lysosphingolipids, specifically glucosylsphingosine (GS) and sphingosine-phosphorylcholine (SPC), and free fatty acids (FFAs) has been proposed to contribute to impaired skin barrier function. This study investigated whether replacing ceramides with lysosphingolipids and FFAs in skin lipid barrier models would exacerbate barrier dysfunction. When applied topically to human stratum corneum sheets, SPC and GS increased water loss, decreased electrical impedance, and slightly disordered lipid chains. In lipid models containing isolated human stratum corneum ceramides, reducing ceramides by ≥ 30% significantly increased permeability to four markers, likely due to loss of long-periodicity phase (LPP) lamellae and phase separation within the lipid matrix, as revealed by X-ray diffraction and infrared spectroscopy. However, when the missing ceramides were replaced by lysosphingolipids and FFAs, no further increase in permeability was observed. Conversely, these molecules partially mitigated the negative effects of ceramide deficiency, particularly with 5%-10% SPC, which reduced permeability even compared to control with "healthy" lipid composition. These findings suggest that while ceramide deficiency is a key factor in skin barrier dysfunction, the presence of lysosphingolipids and FFAs does not aggravate lipid structural or functional damage, but may provide partial compensation, raising further questions about the behavior of lyso(sphingo)lipids in rigid multilamellar lipid environments, such as the stratum corneum, that warrant further investigation.

• MeSH
• biologické modely MeSH
• ceramidy * metabolismus   MeSH
• fosforylcholin analogy a deriváty   MeSH
• kůže * metabolismus   MeSH
• kyseliny mastné neesterifikované metabolismus   MeSH
• lidé MeSH
• lysofosfolipidy metabolismus   MeSH
• permeabilita účinky léků   MeSH
• sfingosin analogy a deriváty   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

During development, tooth germs undergo various morphological changes resulting from interactions between the oral epithelium and ectomesenchyme. These processes are influenced by the extracellular matrix, the composition of which, along with cell adhesion and signaling, is regulated by metalloproteinases. Notably, these include matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs), and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs). Our analysis of previously published scRNAseq datasets highlight that these metalloproteinases show dynamic expression patterns during tooth development, with expression in a wide range of cell types, suggesting multiple roles in tooth morphogenesis. To investigate this, Marimastat, a broad-spectrum inhibitor of MMPs, ADAMs, and ADAMTSs, was applied to ex vivo cultures of mouse molar tooth germs. The treated samples exhibited significant changes in tooth germ size and morphology, including an overall reduction in size and an inversion of the typical bell shape. The cervical loop failed to extend, and the central area of the inner enamel epithelium protruded. Marimastat treatment also disrupted proliferation, cell polarization, and organization compared with control tooth germs. In addition, a decrease in laminin expression was observed, leading to a disruption in continuity of the basement membrane at the epithelial-mesenchymal junction. Elevated hypoxia-inducible factor 1-alpha gene (Hif-1α) expression correlated with a disruption to blood vessel development around the tooth germs. These results reveal the crucial role of metalloproteinases in tooth growth, shape, cervical loop elongation, and the regulation of blood vessel formation during prenatal tooth development.NEW & NOTEWORTHY Inhibition of metalloproteinases during tooth development had a wide-ranging impact on molar growth affecting proliferation, cell migration, and vascularization, highlighting the diverse role of these proteins in controlling development.

• MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus   genetika   MeSH
• inhibitory matrixových metaloproteinas farmakologie   MeSH
• kyseliny hydroxamové farmakologie   MeSH
• metaloproteasy metabolismus   genetika   MeSH
• moláry embryologie   růst a vývoj   metabolismus   enzymologie   MeSH
• morfogeneze MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• odontogeneze * MeSH
• proliferace buněk * MeSH
• vývojová regulace genové exprese MeSH
• zubní zárodek embryologie   metabolismus   enzymologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. Moreover, chemogenetic analysis revealed central amygdala as critical for linking appetitive emotional states with spatial contexts. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.

• MeSH
• amfetamin farmakologie   MeSH
• amygdala fyziologie   MeSH
• hipokampus * fyziologie   MeSH
• konsolidace paměti * fyziologie   MeSH
• krysa rodu rattus MeSH
• mozek fyziologie   MeSH
• neurony fyziologie   metabolismus   MeSH
• nucleus accumbens * fyziologie   MeSH
• odměna * MeSH
• paměť fyziologie   MeSH
• podněty MeSH
• prefrontální mozková kůra fyziologie   MeSH
• rozpomínání * fyziologie   MeSH
• strojové učení MeSH
• tegmentum mesencephali - area ventralis * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The forskolin-induced swelling assay (FIS) in patient-derived intestinal organoids (PDIOs), used to determine in vitro responsiveness to elexacaftor/tezacaftor/ivacaftor (ETI), showed variability in swelling among PDIOs obtained from people with CF (pwCF) carrying the same F508del/F508del CFTR genotype. We aimed to characterise the effect of ETI on the transcriptional activity of PDIOs-derived cells to understand the intracellular processes triggered by ETI and the differences in treatment response. Six high- and six low-responding PDIOs to ETI, derived from F508del/F508del pwCF, were incubated with or without ETI for 2 to 6 h. Gene expression was assessed using 3'-mRNA sequencing and modelled using negative binomial models. Incubation with ETI resulted in a significant upregulation of several biological processes: mostly related to chemokines and signalling, chemotaxis, and tissue development processes. No changes were observed in abundance of the CFTR transcripts or in CFTR-related gene sets and pathways. The genes and pathways associated with ETI did not overlap with those whose expression changed with time only. PDIOs with a high FIS response did not significantly differ in any interpretable gene from the FIS-low organoids. The changes in the PDIOs gene expression upon the exposure to ETI cannot explain differences in the magnitude of PDIOs FIS-measured response to ETI. In conclusion, on incubation with ETI, genes of the CFTR-related pathways do not change their transcriptional activity; instead, overexpression was observed in genes of inflammatory-like cytokine response and receptor activation pathways.

• MeSH
• aktivátory chloridových kanálů terapeutické užití   farmakologie   MeSH
• aminofenoly * terapeutické užití   farmakologie   MeSH
• benzodioxoly * terapeutické užití   farmakologie   MeSH
• chinolony * farmakologie   terapeutické užití   MeSH
• cystická fibróza * genetika   farmakoterapie   MeSH
• fixní kombinace léků MeSH
• indoly * farmakologie   MeSH
• lidé MeSH
• organoidy * metabolismus   MeSH
• protein CFTR genetika   MeSH
• pyrazoly * farmakologie   MeSH
• pyridiny farmakologie   MeSH
• pyrrolidiny farmakologie   MeSH
• pyrroly farmakologie   MeSH
• stanovení celkové genové exprese metody   MeSH
• střeva účinky léků   MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Depression therapy has been linked to negative effects on energy metabolism, which can be attributed to various factors, including an ongoing inflammatory process commonly seen in metabolic disorders. Unhealthy lifestyle choices of patients and the impact of antidepressants on body weight and lipid and glucose metabolism also contribute to these metabolic side effects. Although not as pronounced as other psychopharmaceuticals, the increasing use of antidepressants raises concerns about their potential impact on public health. The study aimed to evaluate the short- and long-term effects of the antidepressant citalopram and its long-term combination with a special diet on metabolic parameters in mice. METHODS: Animals were randomly divided into 5 groups - control, control + special diet, citalopram (10 mg/kg for 35 days), citalopram + special diet (10 mg/kg for 35 days), and citalopram (10 mg/kg for 7 days). After a described time of administration, animals were anesthetized, blood and fat and liver tissues were collected. Biochemical parameters of lipid metabolism (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and glucose were analyzed using spectrophotometry and relevant adipokines and cytokines were evaluated by ELISA. RESULTS: After a week of application of citalopram, we observed dyslipidemia that persisted even at the end of the 5-week experiment. Furthermore, after 5 weeks of citalopram administration, we observed a significant decrease in body weight gain and decreased leptin levels. Changes in lipid metabolism, higher levels of adipokines leptin and PAI-1 were observed due to the special diet after 5 weeks. CONCLUSIONS: Our research suggests that the effects of citalopram and a diet on the metabolism of mice can be significant, both in the short term (1 week) and in the long term (5 weeks).

• MeSH
• citalopram * škodlivé účinky   aplikace a dávkování   farmakologie   MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• dyslipidemie * chemicky indukované   krev   metabolismus   MeSH
• glukosa * metabolismus   MeSH
• játra metabolismus   účinky léků   MeSH
• krevní glukóza metabolismus   účinky léků   MeSH
• leptin * krev   metabolismus   MeSH
• lipidy * krev   MeSH
• metabolismus lipidů * účinky léků   MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Nově se do terapie tuberkulózy v dětském věku dostávají moderní léky, tablety rozpustné v ústech. léky jsou k dispozici buď v kombinované formě (dohromady izoniasid + rifampicin + pyrazinamid nebo izoniasid + rifampicin) nebo samostatně (izoniasid a etambutol). léčba je indikována převážně pro nejmladší věkové skupiny.

Contemporary pharmaceutical agents, specifically orodispersible tablets, are now entering the management of tuberculosis in children. the pharmaceuticals are available in two forms: either in combination (isoniaside+rifamp icin+pyrazinamide, isoniazid+rifampicin) or as monotherapy (isoniaside, ethambutol). the treatment is primarily indicated for the youngest age groups.

• MeSH
• antituberkulotika * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• aplikace orální MeSH
• dítě MeSH
• ethambutol aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• isoniazid aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• kombinovaná terapie * metody   MeSH
• lékové formy MeSH
• lidé MeSH
• rifampin aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• tuberkulóza diagnóza   farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH

Příručka a pracovní sešit, který se zaměřuje na regulaci dopaminu v rámci péče o psychické zdraví a zvládání závislostí. Určeno široké veřejnosti.; Tento praktický průvodce vznikl jako doplněk k obsáhlejší úspěšné knize Dopamin (Triton 2022). Autorka vychází ze základní myšlenky, že hojnost sama o sobě je stresorem, který celosvětově přispívá k rostoucímu počtu závislostí, depresí, úzkostí a sebevražd. Zavádí pojem paradox hojnosti: čím bohatší je země a čím dostupnější je léčba duševních poruch, tím nešťastnější, depresivnější a úzkostnější jsou její obyvatelé. Neustálé vystavování se rychlým požitkům mění mozek. Trpíme stresem z nadbytku. Sešit je určen každému, kdo se rozhodne změnit způsoby, jimiž se odměňuje. Pomůže vám lépe se zorientovat v problematice patologického potěšení a bolesti. Díky množství interaktivních cvičení a inspirativních příkladů budete schopni přesněji určit návykové látky a způsoby chování, o jejichž omezení či změně uvažujete. Získáte návod, jak si naplánovat, zahájit a úspěšně dokončit dopaminový půst, dopracovat se k přenastavení drah odměny v mozku a v konečném důsledku vést zdravější, spokojenější a plnohodnotnější život.

• MeSH
• dopamin MeSH
• duševní zdraví MeSH
• návykové chování * MeSH
• rozvoj osobnosti MeSH
• self-management MeSH
• střídmost MeSH
• zdravý životní styl MeSH
• Publikační typ
• populární práce MeSH
• příručky MeSH

• Konspekt
• Psychopatologie
• NLK Obory
• psychologie, klinická psychologie
• zdravotní výchova
• NLK Publikační typ
• pracovní sešity

• Klíčová slova
• ICHTHAMOL,
• MeSH
• kvartérní amoniové sloučeniny * chemie   terapeutické užití   MeSH
• lékové formy MeSH
• péče o kůži MeSH
• příprava léků MeSH

Bisoprolol is a second-generation, highly selective beta-1 adrenergic receptor antagonist with various beneficial effects in patients with heart failure. Interindividual variability in response to bisoprolol is known, and finding the optimal dose for individual patients with heart failure is still challenging. This pilot study included patients treated with bisoprolol for chronic heart failure with reduced ejection fraction. Between November 2022 and November 2023, one to six blood samples were collected from these patients to determine the trough serum concentration of bisoprolol. At the same time, the values of selected clinical variables were recorded. Bisoprolol concentrations ranged from 1.1 to 65.0 μg/L and correlated with both the daily dose and the dose per kilogram of body weight. However, wide variability in measured serum concentrations of bisoprolol was observed at the same daily dose and in apparent weight-adjusted clearance. Patients classified as NYHA III-IV received a 33% higher dose per kilogram of body weight than patients in NYHA I-II but achieved 165% higher serum concentrations of bisoprolol. An inverse correlation was found between diastolic blood pressure and dose per kilogram of body weight, and a positive correlation between N-terminal pro-B-type natriuretic peptide and both dose per kilogram of body weight and serum bisoprolol concentration. A wide variability in patients' serum concentrations of bisoprolol achieved after taking the same dose has been observed. A significantly higher concentration-to-dose ratio and a significantly lower weight-adjusted apparent clearance were demonstrated in patients with reduced cardiac function, reduced renal function, and taking the combination with amiodarone. These patients may be more prone to overdose with bisoprolol.

• MeSH
• antagonisté beta-1-adrenergních receptorů * krev   aplikace a dávkování   farmakokinetika   terapeutické užití   MeSH
• bisoprolol * krev   aplikace a dávkování   farmakokinetika   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování léčiv MeSH
• pilotní projekty MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srdeční selhání * farmakoterapie   krev   patofyziologie   MeSH
• tepový objem účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH