Oběhové přetížení (transfusion-associated circulatory overload, TACO) a poškození plic způsobené transfuzí (transfusion-related acute lung injury, TRALI) významnou měrou přispívají k morbiditě a mortalitě v souvislosti s transfuzí. Tato případová studie popisuje 28letou pacientku přepravenou k lékaři s dušností po transfuzi. Diagnostické vyšetření zahrnovalo fyzikální vyšetření, rentgenové vyšetření, základní laboratorní testy a echokardiografické vyšetření. Problematické bylo stanovení diagnózy, kdy bylo nutno – vzhledem k omezeným poznatkům v této oblasti, nedostatečně definovaným diagnostickým kritériím a absenci specifických léčebných intervencí – se rozhodnout mezi TACO, TRALI nebo kombinací obojího. Tyto problémy zdůrazňují potřebu přesnějšího rozpoznávání a vypracování strategií léčby těchto komplikací v souvislosti s transfuzí.
Transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) represent significant contributors to transfusion-related morbidity and mortality. This case study involves a 28-year-old female patient presenting with shortness of breath following a transfusion. The diagnostic approach relied on physical examination, chest x-ray, basic laboratory tests, and echocardiography. The challenges included difficulty in establishing the diagnosis between TACO, TRALI, or a combination thereof due to limited awareness, poorly defined diagnostic criteria, and the lack of specific therapeutic interventions. These complexities underscore the need for enhanced recognition and management strategies for these transfusion-associated complications.
- MeSH
- akutní poškození plic vyvolané transfuzí diagnostické zobrazování krev patologie terapie MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- elektrokardiografie MeSH
- furosemid aplikace a dávkování MeSH
- lidé MeSH
- plicní edém * diagnostické zobrazování etiologie patologie terapie MeSH
- potransfuzní reakce * diagnostické zobrazování krev patologie terapie MeSH
- rentgendiagnostika hrudníku MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
An imbalance in coagulation is associated with cardiovascular events. For prevention and treatment, anticoagulants, currently mainly xabans and gatrans, are used. The purpose of the present study was to provide a head-to-head comparison since there are no studies directly evaluating these novel anticoagulants. An additional aim was to find whether selected anthropological and biochemical factors can affect their anticoagulant properties as they are used in fixed doses. In this cross-sectional study, blood from 50 generally healthy donors was collected, and coagulation responses to dabigatran, argatroban, rivaroxaban, and apixaban, at a concentration of 1 μM, were analyzed. Heparin was used as a positive control. Prothrombin time (PT) expressed as international normalized ratio (INR) and activated partial thromboplastin time (aPTT) were measured and compared. Rivaroxaban was the most active according to PT/INR while argatroban according to aPTT. The ex vivo anticoagulant effect measured by INR correlated inversely with body mass index (BMI) in all four anticoagulants tested. Shortening of aPTT was associated with higher cholesterol and triglyceride levels. No sex-related differences were observed in response to the anticoagulant treatments. As this was an ex vivo study and pharmacokinetic factors were not included, the influence of BMI is of high therapeutic importance.
- MeSH
- antikoagulancia * farmakologie MeSH
- arginin * analogy a deriváty MeSH
- dabigatran farmakologie MeSH
- dospělí MeSH
- hemokoagulace * účinky léků MeSH
- index tělesné hmotnosti MeSH
- INR MeSH
- kyseliny pipekolové * farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- parciální tromboplastinový čas MeSH
- protrombinový čas MeSH
- průřezové studie MeSH
- pyrazoly farmakologie MeSH
- pyridony farmakologie farmakokinetika MeSH
- rivaroxaban * farmakologie MeSH
- sulfonamidy farmakologie 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
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Wild strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were tested in an experimental hyperbaric chamber to determine the possible effect of hyperbaric oxygen on the susceptibility of these strains to the antibiotics ampicillin, ampicillin + sulbactam, cefazolin, cefuroxime, cefoxitin, gentamicin, sulfamethoxazole + trimethoprim, colistin, oxolinic acid, ofloxacin, tetracycline, and aztreonam during their cultivation at 23 °C and 36.5 °C. Ninety-six-well inoculated microplates with tested antibiotics in Mueller-Hinton broth were cultured under standard incubator conditions (normobaric normoxia) for 24 h or in an experimental hyperbaric chamber (HAUX, Germany) for 24 h at 2.8 ATA of 100% oxygen (hyperbaric hyperoxia). The hyperbaric chamber was pressurised with pure oxygen (100%). Both cultures (normoxic and hyperoxic) were carried out at 23 °C and 36.5 °C to study the possible effect of the cultivation temperature. No significant differences were observed between 23 and 36.5 °C cultivation with or without the 2-h lag phase in Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Cultivation in a hyperbaric chamber at 23 °C and 36.5 °C with or without a 2-h lag phase did not produce significant changes in the minimum inhibitory concentration (MIC) of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. For the tested strains of Pseudomonas aeruginosa, the possible effect of hyperbaric oxygen on their antibiotic sensitivity could not be detected because the growth of these bacteria was completely inhibited by 100% hyperbaric oxygen at 2.8 ATA under all hyperbaric conditions tested at 23 °C and 36.5 °C. Subsequent tests with wild strains of pseudomonads, burkholderias, and stenotrophomonads not only confirmed the fact that these bacteria stop growing under hyperbaric conditions at a pressure of 2.8 ATA of 100% oxygen but also indicated that inhibition of growth of these bacteria under hyperbaric conditions is reversible.
- MeSH
- ampicilin farmakologie MeSH
- anaerobní bakterie MeSH
- antibakteriální látky farmakologie MeSH
- Bacteria MeSH
- Escherichia coli MeSH
- hyperbarická oxygenace * MeSH
- Klebsiella pneumoniae MeSH
- kombinace léků trimethoprim a sulfamethoxazol farmakologie MeSH
- kyslík MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- oxidační stres MeSH
- pseudomonádové infekce * MeSH
- Pseudomonas aeruginosa MeSH
- sulbaktam MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- diabetes mellitus 2. typu * diagnóza farmakoterapie komplikace MeSH
- diabetes mellitus diagnóza farmakoterapie MeSH
- hypertenze diagnóza farmakoterapie MeSH
- indapamid aplikace a dávkování terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- komplikace diabetu MeSH
- lidé středního věku MeSH
- lidé MeSH
- telmisartan aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The potential as a cancer therapeutic target of the recently reported hotspot binding region close to Lys508 of the β-catenin armadillo repeat domain was not exhaustively explored. In order to get more insight, we synthesized novel N-(heterocyclylphenyl)benzenesulfonamides 6-28. The new compounds significantly inhibited Wnt-dependent transcription as well as SW480 and HCT116 cancer cell proliferation. Compound 25 showed binding mode consistent with this hotspot binding region. Compound 25 inhibited the growth of SW480 and HCT116 cancer cells with IC50's of 2 and 0.12 μM, respectively, and was superior to the reference compounds 5 and 5-FU. 25 inhibited the growth of HCT-116 xenografted in BALB/Cnu/nu mice, reduced the expression of the proliferation marker Ki67, and significantly affected the expression of cancer-related genes. After incubation with human and mouse liver microsomes, 25 showed a higher metabolic stability than 5. Compound 25 aims to be a promising lead for the development of colorectal cancer anticancer therapies.
- MeSH
- beta-katenin * metabolismus antagonisté a inhibitory MeSH
- HCT116 buňky MeSH
- jaterní mikrozomy metabolismus MeSH
- lidé MeSH
- myši inbrední BALB C * MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- proliferace buněk * účinky léků MeSH
- protinádorové látky * farmakologie chemická syntéza chemie MeSH
- sulfonamidy * farmakologie chemie chemická syntéza MeSH
- vztahy mezi strukturou a aktivitou MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Burns are a major global healthcare concern, often complicated by the presence of bacteria such as Pseudomonas aeruginosa in the wounds. Silver-based dressings are commonly used in the treatment of burns but can cause skin irritation and delay healing time. Medical-grade honey (MGH) provides an interesting alternative. This study investigated the antimicrobial effects and possible cytotoxicity of L-Mesitran Soft (MGH-gel) and its individual components, Medihoney (Manuka), Flammazine (silver sulphadiazine), and silver nitrate (AgNO3) in an ex vivo human burn wound model. Bacterial survival and wound healing parameters, including re-epithelialization and keratinocyte proliferation were assessed. L-Mesitran, Flammazine, and AgNO3 reduced P. aeruginosa numbers below detection levels. L-Mesitran Soft exhibited a significantly stronger antimicrobial effect compared to Medihoney. The individual components of L-Mesitran contributed significantly to its antibacterial efficacy, thus suggesting synergistic activities. Moreover, L-Mesitran, Flammazine, and AgNO3 slightly inhibited re-epithelialization while Medihoney treatment resulted in a complete lack of re-epithelialization and keratinocyte proliferation. Furthermore, clinical cases illustrated the effectiveness of MGH therapy in infected burns. Overall, L-Mesitran Soft had similar effects as silver-based products on bacterial load and epidermal regeneration, but outperformed Medihoney. Therefore, supplemented MGH could be used as an effective alternative to silver-based dressings for P. aeruginosa-infected burns.
The therapeutic potential of targeting PI3K/AKT/PTEN signalling in B-cell malignancies remains attractive. Whilst PI3K-α/δ inhibitors demonstrate clinical benefit in certain B-cell lymphomas, PI3K signalling inhibitors have been inadequate in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in part, due to treatment related toxicities. Clinically, AKT inhibitors exhibit a differentiated tolerability profile offering an alternative approach for treating patients with B-cell malignancies. To explore how AKT inhibition complements other potential therapeutics in the treatment of DLBCL patients, an in vitro combination screen was conducted across a panel of DLCBL cell lines. The AKT inhibitor, capivasertib, in combination with the BCL-2 inhibitor, venetoclax, produced notable therapeutic benefit in preclinical models of DLBCL. Capivasertib and venetoclax rapidly induced caspase and PARP cleavage in GCB-DLBCL PTEN wildtype cell lines and those harbouring PTEN mutations or reduced PTEN protein, driving prolonged tumour growth inhibition in DLBCL cell line and patient derived xenograft lymphoma models. The addition of the rituximab further deepened the durability of capivasertib and venetoclax responses in a RCHOP refractory DLBCL in vivo models. These findings provide preclinical evidence for the rational treatment combination of AKT and BCL-2 inhibitors using capivasertib and venetoclax respectively alongside anti-CD20 antibody supplementation for treatment of patients with DLBCL.
- MeSH
- apoptóza účinky léků MeSH
- bicyklické sloučeniny heterocyklické * farmakologie terapeutické užití MeSH
- difúzní velkobuněčný B-lymfom * farmakoterapie patologie MeSH
- fosfohydroláza PTEN metabolismus MeSH
- lidé MeSH
- myši SCID MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- protokoly protinádorové kombinované chemoterapie * farmakologie terapeutické užití MeSH
- protoonkogenní proteiny c-akt * metabolismus MeSH
- protoonkogenní proteiny c-bcl-2 * antagonisté a inhibitory metabolismus MeSH
- pyrimidiny * farmakologie terapeutické užití MeSH
- pyrroly farmakologie terapeutické užití MeSH
- rituximab farmakologie terapeutické užití MeSH
- sulfonamidy * farmakologie terapeutické užití MeSH
- xenogenní modely - testy protinádorové aktivity * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- nintedanib, pirfenidon, voštiny,
- MeSH
- adherence pacienta MeSH
- antifibrotické látky * farmakologie terapeutické užití MeSH
- centra terciární péče MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- idiopatická plicní fibróza * dějiny diagnostické zobrazování farmakoterapie mikrobiologie MeSH
- kašel farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- plicní hypertenze farmakoterapie MeSH
- prognóza MeSH
- sildenafil citrát farmakologie terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Sildenafil citrate has low oral bioavailability, systemic adverse effects, and a relatively delayed action. These issues may be addressed through direct transdermal delivery to the penis. This study aims to investigate the microemulsion formulation of the drug for effective transdermal delivery. Sildenafil citrate was formulated as a microemulsion using clove oil, dimethyl sulphoxide, phosphate buffer (pH 7), propylene glycol, Tween®80, and distilled water. Different proportions of these components were used to create six formulations of the microemulsion (F1-F6), which were then characterised by their physical appearance and clarity, pH, viscosity, conductivity, percent transmission, and droplet size. Furthermore, the stability, content analysis, in-vitro drug release, and transdermal permeation of sildenafil citrate from the generated drug-loaded microemulsions were studied. All prepared formulas contained nano-sized oil droplets (less than 20 nm), and the pH values were within the range of skin pH; however, two formulas were not transparent. Additionally, all formulations were thermodynamically stable, passing freeze-thaw, heating-cooling, and centrifugation tests. Next, the formulas demonstrated zero-order release kinetics, indicating that they can provide a sustained release profile for sildenafil citrate. Finally, the microemulsion formulation exhibited a 2.8-fold enhancement in skin permeation compared with that of the sildenafil citrate suspension. The prepared microemulsions demonstrated beneficial physical properties and skin permeation profiles that are promising for the local administration of sildenafil citrate.
- Klíčová slova
- mikroemulze,
- MeSH
- aplikace kožní * MeSH
- emulze MeSH
- hřebíčkový olej MeSH
- krysa rodu rattus MeSH
- lékové formy MeSH
- modely u zvířat MeSH
- permeabilita MeSH
- příprava léků metody MeSH
- sildenafil citrát * aplikace a dávkování farmakokinetika farmakologie MeSH
- stabilita léku MeSH
- suspenze MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- klinická studie MeSH
A series of new unique acetylene derivatives of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonamide 3a-f and 6a-f were prepared by reactions of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonyl chlorides with acetylene derivatives of amine. A series of new hybrid systems containing quinoline and 1,2,3-triazole systems 7a-h were obtained by reactions of acetylene derivatives of quinoline-5-sulfonamide 6a-d with organic azides. The structures of the obtained compounds were confirmed by 1H and 13C NMR spectroscopy and HR-MS spectrometry. The obtained quinoline derivatives 3a-f and 6a-f and 1,2,3-triazole derivatives 7a-h were tested for their anticancer and antimicrobial activity. Human amelanotic melanoma cells (C-32), human breast adenocarcinoma cells (MDA-MB-231), and human lung adenocarcinoma cells (A549) were selected as tested cancer lines, while cytotoxicity was investigated on normal human dermal fibroblasts (HFF-1). All the compounds were also tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis. Only the acetylene derivatives of 8-hydroxyquinoline-5-sulfonamide 3a-f were shown to be biologically active, and 8-hydroxy-N-methyl-N-(prop-2-yn-1-yl)quinoline-5-sulfonamide (3c) showed the highest activity against all three cancer lines and MRSA isolates. Its efficacies were comparable to those of cisplatin/doxorubicin and oxacillin/ciprofloxacin. In the non-cancer HFF-1 line, the compound showed no toxicity up to an IC50 of 100 μM. In additional tests, compound 3c decreased the expression of H3, increased the transcriptional activity of cell cycle regulators (P53 and P21 proteins), and altered the expression of BCL-2 and BAX genes in all cancer lines. The unsubstituted phenolic group at position 8 of the quinoline is the key structural fragment necessary for biological activity.
- MeSH
- antibakteriální látky * farmakologie chemie chemická syntéza MeSH
- chinoliny * chemie farmakologie chemická syntéza MeSH
- Enterococcus faecalis účinky léků MeSH
- lidé MeSH
- mikrobiální testy citlivosti * MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- protinádorové látky * farmakologie chemie chemická syntéza MeSH
- racionální návrh léčiv MeSH
- Staphylococcus aureus účinky léků MeSH
- sulfonamidy * farmakologie chemie chemická syntéza MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
