- Klíčová slova
- SeHCAT test,
- MeSH
- cholestyraminová pryskyřice farmakologie terapeutické užití MeSH
- kvalita života MeSH
- lidé MeSH
- malabsorpční syndromy * diagnóza dietoterapie farmakoterapie patologie MeSH
- mikroživiny MeSH
- nukleární lékařství - oddělení nemocnice metody MeSH
- prevalence MeSH
- vitaminy MeSH
- žlučové kyseliny a soli * genetika metabolismus MeSH
- Check Tag
- lidé MeSH
Background/Objectives: Tacrine is a centrally active non-competitive reversible acetylcholinesterase inhibitor. It also exerts antagonising activity against N-methyl-D-aspartate receptors. Tacrine was approved for the treatment of Alzheimer's disease in 1993, but was withdrawn from clinical use in 2013 because of its hepatotoxicity and gastrointestinal side effects. Nevertheless, tacrine is currently facing a renewed wave of interest primarily due to several new tacrine-incorporated hybrids and derivates. There were two specific aims for this study: firstly, to explain the mechanisms of the adverse action of tacrine, as a distinctive example of a highly effective acetylcholinesterase inhibitor; and secondly to check whether luminal impedance planimetry is feasible for preclinical testing of possible side effects of compounds potentially toxic to the gastrointestinal tract. Methods: Six experimental pigs were used as the animal model in this study. Five major parameters were evaluated: luminal pressure (mmHg), estimated diameter (mm), cross-sectional area (mm2), distensibility (mm2/mmHg), and zone compliance (mm3/mmHg). All measurements were performed before and 360 min after intragastric administration of 200 mg tacrine (at the porcine tacrine Tmax). Results: This study consistently demonstrated an increase in luminal pressure (a directly measured indicator) for the particular balloon filling volumes used, and inversely a reciprocal decrease in the other parameters after tacrine administration. Conclusions: Endoscopic luminal impedance planimetry is a feasible method to evaluate functional response of the lower oesophageal sphincter to tacrine in experimental pigs. Tacrine did not compromise the function of the lower oesophageal sphincter either toward oesophageal spasms or, in contrast, decreased competence of the lower oesophageal sphincter.
- Publikační typ
- časopisecké články MeSH
In this study, we have focused on a multiparametric microbiological analysis of the antistaphylococcal action of the iodinated imine BH77, designed as an analogue of rafoxanide. Its antibacterial activity against five reference strains and eight clinical isolates of Gram-positive cocci of the genera Staphylococcus and Enterococcus was evaluated. The most clinically significant multidrug-resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant S. aureus (VRSA), and vancomycin-resistant Enterococcus faecium, were also included. The bactericidal and bacteriostatic actions, the dynamics leading to a loss of bacterial viability, antibiofilm activity, BH77 activity in combination with selected conventional antibiotics, the mechanism of action, in vitro cytotoxicity, and in vivo toxicity in an alternative animal model, Galleria mellonella, were analyzed. The antistaphylococcal activity (MIC) ranged from 15.625 to 62.5 μM, and the antienterococcal activity ranged from 62.5 to 125 μM. Its bactericidal action; promising antibiofilm activity; interference with nucleic acid, protein, and peptidoglycan synthesis pathways; and nontoxicity/low toxicity in vitro and in vivo in the Galleria mellonella model were found to be activity attributes of this newly synthesized compound. In conclusion, BH77 could be rightfully minimally considered at least as the structural pattern for future adjuvants for selected antibiotic drugs. IMPORTANCE Antibiotic resistance is among the largest threats to global health, with a potentially serious socioeconomic impact. One of the strategies to deal with the predicted catastrophic future scenarios associated with the rapid emergence of resistant infectious agents lies in the discovery and research of new anti-infectives. In our study, we have introduced a rafoxanide analogue, a newly synthesized and described polyhalogenated 3,5-diiodosalicylaldehyde-based imine, that effectively acts against Gram-positive cocci of the genera Staphylococcus and Enterococcus. The inclusion of an extensive and comprehensive analysis for providing a detailed description of candidate compound-microbe interactions allows the valorization of the beneficial attributes linked to anti-infective action conclusively. In addition, this study can help with making rational decisions about the possible involvement of this molecule in advanced studies or may merit the support of studies focused on related or derived chemical structures to discover more effective new anti-infective drug candidates.
- MeSH
- antibakteriální látky farmakologie chemie MeSH
- antiinfekční látky * farmakologie MeSH
- Enterococcus MeSH
- methicilin rezistentní Staphylococcus aureus * MeSH
- mikrobiální testy citlivosti MeSH
- rafoxanid farmakologie MeSH
- Staphylococcus aureus MeSH
- Staphylococcus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Background: Increasing rates of acquired resistance have justified the critical need for novel antimicrobial drugs. One viable concept is the modification of known drugs. Methods & results: 21 mafenide-based compounds were prepared via condensation reactions and screened for antimicrobial efficacy, which demonstrated promising activity against both Gram-positive and Gram-negative pathogens, pathogenic fungi and mycobacterial strains (minimum inhibitory concentrations from 3.91 μM). Importantly, they retained activity against a panel of superbugs (methicillin- and vancomycin-resistant staphylococci, enterococci, multidrug-resistant Mycobacterium tuberculosis) without any cross-resistance. Unlike mafenide, most of its imines were bactericidal. Toxicity to HepG2 cells was also investigated. Conclusion: Schiff bases were significantly more active than the parent drug, with iodinated salicylidene and 5-nitrofuran/thiophene-methylidene scaffolds being preferred in identifying the most promising drug candidates.
The greatest threat and medicinal impact within gram-positive pathogens are posed by two bacterial genera, Staphylococcus and Enterococcus. Chalcones have a wide range of biological activities and are recognized as effective templates in medicinal chemistry. This study provides comprehensive insight into the anti-staphylococcal and anti-enterococcal activities of two recently published brominated and chlorinated pyrazine-based chalcones, CH-0y and CH-0w. Their effects against 4 reference and 12 staphylococcal and enterococcal clinical isolates were evaluated. Bactericidal action, the activity in combination with selected conventional antibiotics, the study of post-antimicrobial effect (PAE, PAE/SME), and in vitro and in vivo toxicity, were included. In CH-0y, anti-staphylococcal activity ranging from MIC = 15.625 to 62.5 μM, and activity against E. faecium from 31.25 to 62.5 μM was determined. In CH-0w, anti-staphylococcal activity ranging from 31.25 to 125 μM, and activity against E. faecium and E. faecalis (62.5 μM) was revealed. Both CH-0y and CH-0w showed bactericidal action, beneficial impact on bacterial growth delay within PAE and PAE/SME studies, and non/low toxicity in vivo. Compared to CH-0w, CH-0y seems to have higher anti-staphylococcal and less toxic potential. In conclusion, chalcones CH-0y and CH-0w could be considered as structural pattern for future adjuvants to selected antibiotic drugs.
- Publikační typ
- časopisecké články MeSH
Arthroderma benhamiae, jehož nepohlavní stadium nemá v současnosti jméno, proto je označováno jako Trichophyton sp., je zoofilní dermatofyt, který je stále častějším původcem mykotických onemocnění kůže v Evropě. Zdrojem jsou v našich podmínkách nejčastěji morčata, králíci či jiní hlodavci. Klinicky se podobá mykotickým infekcím způsobeným Microsporum canis. Ve Woodově světle fluoreskuje zelenožlutě. Lékem volby je celkové podávání terbinafinu, z lokálních antimykotik je možno použít ciclopiroxolamin či naftifin. Autoři popisují případ 43leté ženy s tineou na palci levé ruky způsobenou Arthroderma benhamiae léčenou úspěšně terbinafinem. Zdrojem onemocnění bylo morče.
Arthroderma benhamiae, whose asexual stadium has not been named yet, is therefore referred to as Trichophyton sp. It is a zoophilic dermatophyte which is more and more commonly reported as causative agents of mycotic skin diseases in Europe. In our conditions, the source of infection are usually guinea pigs, rabbits or other rodents. Clinically, it resembles mycotic infections caused by Microsporum canis. During Wood lamp examination green-yellow fluorescence is observed. The treatment of choice is systemic administration of terbinafine, topically are used ciclopiroxolamin and naftifin. The authors describe a case of 43-year-old woman, whose left thumb was affected by tinea caused by Artrodermna benhamiea and successfully treated with terbinafine. The source of the infection was a guinea pig. Key words: Arthroderma benhamiae - mycosis - dermatophyte - mycology - terbinafine
- MeSH
- acyklovir aplikace a dávkování terapeutické užití MeSH
- antibakteriální látky MeSH
- antivirové látky MeSH
- Arthrodermataceae * patogenita MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- klarithromycin aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- mykózy diagnóza etiologie farmakoterapie MeSH
- naftaleny aplikace a dávkování terapeutické užití MeSH
- palec ruky patologie MeSH
- pyridony aplikace a dávkování terapeutické užití MeSH
- tinea diagnóza etiologie MeSH
- zoonózy MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
