• MeSH
• akomodace oka účinky léků   MeSH
• atropin * aplikace a dávkování   farmakologie   MeSH
• axiální délka oka účinky léků   MeSH
• lidé MeSH
• mladiství MeSH
• myopie * farmakoterapie   terapie   MeSH
• oční roztoky aplikace a dávkování   MeSH
• progrese nemoci MeSH
• sourozenci MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

The relative inhibitory activities of diazabicyclooctanes (avibactam, relebactam, zidebactam, nacubactam, durlobactam), boronic acid derivatives (vaborbactam, taniborbactam, xeruborbactam), and penicillin-based sulfone derivative enmetazobactam were evaluated against several intrinsic and acquired class C β-lactamases. By contrast to vaborbactam and enmetazobactam, taniborbactam, xeruborbactam, and all diazabicyclooctanes demonstrated effective activities against most AmpC enzymes. Notably, durlobactam exhibited the most pronounced inhibitory effect. Interstingly, the chromosomal AmpC of Acinetobacter baumannii was the least sensitive enzyme to the newly developed β-lactamase inhibitors.

• MeSH
• Acinetobacter baumannii * účinky léků   enzymologie   MeSH
• antibakteriální látky * farmakologie   chemie   MeSH
• azabicyklické sloučeniny * farmakologie   chemie   MeSH
• bakteriální proteiny * antagonisté a inhibitory   metabolismus   MeSH
• beta-laktamasy * metabolismus   MeSH
• bicyklické sloučeniny heterocyklické farmakologie   chemie   MeSH
• cyklooktany MeSH
• inhibitory beta-laktamasy * farmakologie   chemie   MeSH
• kyseliny boronové * farmakologie   chemie   MeSH
• laktamy MeSH
• mikrobiální testy citlivosti * MeSH
• peniciliny farmakologie   chemie   MeSH
• piperidiny MeSH
• sulfony farmakologie   chemie   MeSH
• Publikační typ
• časopisecké články MeSH

This study aims to describe movement disorders secondary to cocaine use. To our knowledge, while these presentations have been previously reported in the literature, a comprehensive review has not been published yet. We searched six databases from 1986 to 2022 without language restriction. Case reports, case series, and literature reviews have been analysed to find associations between cocaine use and movement disorders. The present study encompasses epidemiology, clinical manifestations, pathophysiology, and diagnostic challenges of abnormal movements associated with cocaine use. This review highlights the importance of proper initial evaluation and investigation taking into account the broad spectrum of differential diagnoses and exclusion of primary movement disorders. The role of the dopaminergic system in movement disorders is reviewed. Cocaine use is associated with movement disorders such as dystonia, parkinsonism, akathisia, and tics. The complex interaction of multiple factors, including other neurological conditions, such as Tourette syndrome, and additional substances of abuse is discussed. The presentation of these manifestations is often heterogeneous and does not follow a specific pattern. In this way, future research is needed to improve our understanding of the pathophysiological mechanisms and develop novel drug targets for these disorders. Increased awareness among the general public and policymakers could translate into reduced stigma and improved care.

• MeSH
• kokain škodlivé účinky   MeSH
• lidé MeSH
• pohybové poruchy * diagnóza   etiologie   patofyziologie   MeSH
• poruchy spojené s užíváním kokainu komplikace   epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

There are currently no pharmacological treatments for cocaine use disorder. Recently there has been a great deal of interest in the potential of psychedelic drugs such as psilocybin to treat psychiatric disorders. Human studies have indicated that a single administration of psilocybin can have long-lasting effects. Few preclinical studies have examined a role for psilocybin in addiction models. The goal of the current study was to determine whether psilocybin would enhance extinction following cocaine self-administration in male and female mice and rats and thus result in an attenuation of cue-induced drug-seeking. In experiments in mice, 16 female and 19 male mice underwent 8d of cocaine self-administration (0.5 mg/kg/infusion) and extinction training. Immediately following extinction trials, mice were injected with vehicle or 1.0 mg/kg psilocybin. Following the conclusion of extinction training, mice were tested for cue-induced reinstatement. In experiments in rats, 24 female and 23 male rats underwent 15d of cocaine self-administration (0.8 mg/kg/infusion) and extinction training. Immediately following extinction trials, rats were injected with vehicle, 1.0 mg/kg psilocybin, or 2.5 mg/kg psilocybin. Following the conclusion of extinction training, rats were tested for cue-induced reinstatement. Psilocybin administered following extinction trials had no effect, as both female and male mice and rats demonstrated significant cue-induced reinstatement. These data suggest that psilocybin is ineffective at altering cocaine-seeking behavior in the paradigm and doses used in the current study. It remains to be seen whether treatment with psilocybin under different conditions may be useful in the long-standing goal of finding pharmacotherapies to treat CUD.

• MeSH
• autoaplikace * MeSH
• chování při shánění drogy * účinky léků   MeSH
• extinkce (psychologie) * účinky léků   MeSH
• halucinogeny * farmakologie   aplikace a dávkování   MeSH
• inhibitory vychytávání dopaminu farmakologie   aplikace a dávkování   MeSH
• kokain * farmakologie   aplikace a dávkování   MeSH
• krysa rodu rattus MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• operantní podmiňování účinky léků   MeSH
• podněty * MeSH
• pohlavní dimorfismus MeSH
• poruchy spojené s užíváním kokainu farmakoterapie   psychologie   MeSH
• potkani Sprague-Dawley MeSH
• psilocybin * farmakologie   aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: In the battle against multidrug-resistant bacterial infections, ceftazidime- avibactam (CZA) stands as a pivotal defense, particularly against carbapenemresistant (CR) Gram-negative pathogens. However, the rise in resistance against this drug poses a significant threat to its effectiveness, highlighting the critical need for in-depth studies about its resistance mechanisms. METHODS: This research focuses on the genomic characterization of CR- and CZA-resistant Escherichia coli (n=26) and Klebsiella pneumoniae (n=34) strains, harboring the blaNDM and/or blaOXA-48-like genes, at a major Lebanese tertiary care medical center, using whole genome sequencing (WGS). RESULTS: Our findings revealed a notable prevalence of blaNDM in all K. pneumoniae strains isolates, with 27 of these also harboring blaOXA-48. On the other hand, E. coli strains predominantly carried the blaNDM-5 gene. Whole genome sequencing (WGS) identified a predominance of ST383 among K. pneumoniae strains, which possessed a multi-replicon IncFIB-IncHI1B plasmid harboring the blaNDM-5. Additionally, various Inc group plasmids in K. pneumoniae across multiple sequence types were found to carry the blaNDM. Similarly, diverse STs of E. coli were observed to carry blaNDM-5 on different plasmids. DISCUSSION: The study underscores NDM carbapenemases as a paramount resistance mechanism in Lebanon,jeopardizing critical last-resort treatments. It also illuminates the role of varied sequence types and mobile genetic elements in the spread of NDM resistance,stressing the urgent need for strategies to mitigate this threat, especially in nosocomial infections.

• MeSH
• antibakteriální látky * farmakologie   MeSH
• azabicyklické sloučeniny * farmakologie   MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• beta-laktamasy * genetika   metabolismus   MeSH
• ceftazidim * farmakologie   MeSH
• centra terciární péče MeSH
• Enterobacteriaceae rezistentní na karbapenemy genetika   účinky léků   izolace a purifikace   MeSH
• Escherichia coli * genetika   účinky léků   MeSH
• fixní kombinace léků * MeSH
• genom bakteriální MeSH
• karbapenemy * farmakologie   MeSH
• Klebsiella pneumoniae * genetika   účinky léků   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mnohočetná bakteriální léková rezistence * genetika   MeSH
• plazmidy genetika   MeSH
• přenos genů horizontální MeSH
• sekvenování celého genomu * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Libanon MeSH

Therapeutic options for Alzheimer's disease are limited. Dual compounds targeting two pathways concurrently may enable enhanced effect. The study focuses on tacrine derivatives inhibiting acetylcholinesterase (AChE) and simultaneously N-methyl-D-aspartate (NMDA) receptors. Compounds with balanced inhibitory potencies for the target proteins (K1578 and K1599) or increased potency for AChE (K1592 and K1594) were studied to identify the most promising pro-cognitive compound. Their effects were studied in cholinergic (scopolamine-induced) and glutamatergic (MK-801-induced) rat models of cognitive deficits in the Morris water maze. Moreover, the impacts on locomotion in the open field and AChE activity in relevant brain structures were investigated. The effect of the most promising compound on NMDA receptors was explored by in vitro electrophysiology. The cholinergic antagonist scopolamine induced a deficit in memory acquisition, however, it was unaffected by the compounds, and a deficit in reversal learning that was alleviated by K1578 and K1599. K1578 and K1599 significantly inhibited AChE in the striatum, potentially explaining the behavioral observations. The glutamatergic antagonist dizocilpine (MK-801) induced a deficit in memory acquisition, which was alleviated by K1599. K1599 also mitigated the MK-801-induced hyperlocomotion in the open field. In vitro patch-clamp corroborated the K1599-associated NMDA receptor inhibitory effect. K1599 emerged as the most promising compound, demonstrating pro-cognitive efficacy in both models, consistent with intended dual effect. We conclude that tacrine has the potential for development of derivatives with dual in vivo effects. Our findings contributed to the elucidation of the structural and functional properties of tacrine derivatives associated with optimal in vivo pro-cognitive efficacy.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• antagonisté excitačních aminokyselin farmakologie   MeSH
• bludiště - učení * účinky léků   MeSH
• cholinesterasové inhibitory * farmakologie   MeSH
• dizocilpinmaleát * farmakologie   MeSH
• kognice * účinky léků   MeSH
• krysa rodu rattus MeSH
• paměť účinky léků   MeSH
• potkani Wistar * MeSH
• receptory N-methyl-D-aspartátu * antagonisté a inhibitory   metabolismus   MeSH
• skopolamin MeSH
• takrin * farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Radiomic features are usually used to predict target variables such as the absence or presence of a disease, treatment response, or time to symptom progression. One of the potential clinical applications is in patients with Parkinson's disease. Robust radiomic features for this specific imaging method have not yet been identified, which is necessary for proper feature selection. Thus, we are assessing the robustness of radiomic features in dopamine transporter imaging (DaT). For this study, we made an anthropomorphic head phantom with tissue heterogeneity using a personal 3D printer (polylactide 82% infill); the bone was subsequently reproduced with plaster. A surgical cotton ball with radiotracer (123I-ioflupane) was inserted. Scans were performed on the two-detector hybrid camera with acquisition parameters corresponding to international guidelines for DaT single photon emission tomography (SPECT). Reconstruction of SPECT was performed on a clinical workstation with iterative algorithms. Open-source LifeX software was used to extract 134 radiomic features. Statistical analysis was made in RStudio using the intraclass correlation coefficient (ICC) and coefficient of variation (COV). Overall, radiomic features in different reconstruction parameters showed a moderate reproducibility rate (ICC = 0.636, p <0.01). Assessment of ICC and COV within CT attenuation correction (CTAC) and non-attenuation correction (NAC) groups and within particular feature classes showed an excellent reproducibility rate (ICC > 0.9, p < 0.01), except for an intensity-based NAC group, where radiomic features showed a good repeatability rate (ICC = 0.893, p <0.01). By our results, CTAC becomes the main threat to feature stability. However, many radiomic features were sensitive to the selected reconstruction algorithm irrespectively to the attenuation correction. Radiomic features extracted from DaT-SPECT showed moderate to excellent reproducibility rates. These results make them suitable for clinical practice and human studies, but awareness of feature selection should be held, as some radiomic features are more robust than others.

• MeSH
• jednofotonová emisní výpočetní tomografie * MeSH
• lidé MeSH
• nortropany * MeSH
• počítačové zpracování obrazu * metody   MeSH
• radiomika MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Bacterial resistance surveillance is one of the main outputs of microbiological laboratories and its results are important part of antimicrobial stewardship (AMS). In this study, the susceptibility of specific bacteria to selected antimicrobial agents was tested. The susceptibility of 90 unique isolates of pathogens of critical priority obtained from clinically valid samples of ICU patients in 2017-2021 was tested. 50% of these fulfilled difficult-to-treat resistance (DTR) criteria and 50% were susceptible to all antibiotics included in the definition. 10 Enterobacterales strains met DTR criteria, and 2 (20%) were resistant to colistin (COL), 2 (20%) to cefiderocol (FCR), 7 (70%) to imipenem/cilastatin/relebactam (I/R), 3 (30%) to ceftazidime/avibactam (CAT) and 5 (50%) to fosfomycin (FOS). For Enterobacterales we also tested aztreonam/avibactam (AZA) for which there are no breakpoints yet. The highest MIC of AZA observed was 1 mg/l, MIC range in the susceptible cohort was 0.032-0.064 mg/l and in the DTR cohort (incl. class B beta-lactamase producers) it was 0.064-1 mg/l. Two (13.3%) isolates of Pseudomonas aeruginosa (15 DTR strains) were resistant to COL, 1 (6.7%) to FCR, 13 (86.7%) to I/R, 5 (33.3%) to CAT, and 5 (33.3%) to ceftolozane/tazobactam. All isolates of Acinetobacter baumannii with DTR were susceptible to COL and FCR, and at the same time resistant to I/R and ampicillin/sulbactam. New antimicrobial agents are not 100% effective against DTR. Therefore, it is necessary to perform susceptibility testing of these antibiotics, use the data for surveillance (including local surveillance) and conform to AMS standards.

• MeSH
• antibakteriální látky * farmakologie   terapeutické užití   MeSH
• azabicyklické sloučeniny * MeSH
• aztreonam MeSH
• cefalosporiny * MeSH
• cefiderokol MeSH
• gramnegativní bakterie MeSH
• kolistin farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• Pseudomonas aeruginosa MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Chronic treatment with acetylcholinesterase inhibitors may be a promising therapeutic strategy for treatment of cardiovascular diseases. The aim of our study was to analyze the changes in blood pressure (BP) and heart rate (HR) during 14 days of treatment with two different acetylcholinesterase inhibitors - pyridostigmine (PYR) having only peripheral effects or donepezil (DON) with both peripheral and central effects. In addition, we studied their effects on the cardiovascular response to restraint stress and on sympathovagal control of HR in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). SHR were characterized by elevated BP and increased low-frequency component of systolic BP variability (LF-SBPV), but their cardiac vagal tone and HR variability (HRV) were reduced compared with WKY. Chronic treatment with either acetylcholinesterase inhibitor decreased HR and increased HRV in both strains. PYR treatment slightly decreased BP and LF-SBPV in the dark phase of the day. Neither drug significantly altered BP response to stress, but PYR attenuated HR increase during restraint stress. Regarding sympathovagal balance, acute methylatropine administration caused a greater increase of HR in WKY than in SHR. Chronic PYR or DON treatment enhanced HRV and HR response to methylatropine (vagal tone) in WKY, whereas PYR but not DON treatment potentiated HRV and vagal tone in SHR. In conclusion, vagal tone was lower in SHR compared with WKY, but was enhanced by chronic PYR treatment in both strains. Thus, chronic peripheral, but not central, acetylcholinesterase inhibition has major effects on HR and its variability in both normotensive and hypertensive rats.

• MeSH
• acetylcholinesterasa MeSH
• cholinesterasové inhibitory farmakologie   terapeutické užití   MeSH
• deriváty atropinu * MeSH
• donepezil farmakologie   MeSH
• hypertenze * farmakoterapie   MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• pyridostigmin-bromid * farmakologie   MeSH
• srdeční frekvence MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• Zaficefta, avibaktam,
• MeSH
• aortální chlopeň mikrobiologie   MeSH
• azabicyklické sloučeniny aplikace a dávkování   terapeutické užití   MeSH
• bakteriální endokarditida * chirurgie   etiologie   farmakoterapie   komplikace   MeSH
• bakteriální léková rezistence MeSH
• ceftazidim aplikace a dávkování   terapeutické užití   MeSH
• chirurgická náhrada chlopně škodlivé účinky   MeSH
• fixní kombinace léků MeSH
• gramnegativní bakterie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mimotělní membránová oxygenace MeSH
• nozokomiální pneumonie * diagnóza   etiologie   farmakoterapie   MeSH
• renální insuficience MeSH
• Stenotrophomonas maltophilia účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• kazuistiky MeSH