Infectious diseases, including bacterial, fungal, and viral, have once again gained urgency in the drug development pipeline after the recent COVID-19 pandemic. Tuberculosis (TB) is an old infectious disease for which eradication has not yet been successful. Novel agents are required to have potential activity against both drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis (Mtb), the causative agent of TB. In this study, we present a series of 2-phenyl-N-(pyridin-2-yl)acetamides in an attempt to investigate their possible antimycobacterial activity, cytotoxicity on the HepG2 liver cancer cell line, and-as complementary testing-their antibacterial and antifungal properties against a panel of clinically important pathogens. This screening resulted in one compound with promising antimycobacterial activity-compound 12, MICMtb H37Ra = 15.625 μg/mL (56.26 μM). Compounds 17, 24, and 26 were further screened for their antiproliferative activity against human epithelial kidney cancer cell line A498, human prostate cancer cell line PC-3, and human glioblastoma cell line U-87MG, where they were found to possess interesting activity worth further exploration in the future.

• MeSH
• acetamidy * chemie   farmakologie   MeSH
• antifungální látky farmakologie   chemie   chemická syntéza   MeSH
• antituberkulotika farmakologie   chemie   MeSH
• buňky Hep G2 MeSH
• lidé MeSH
• mikrobiální testy citlivosti * MeSH
• Mycobacterium tuberculosis * účinky léků   MeSH
• nádorové buněčné linie MeSH
• proliferace buněk * účinky léků   MeSH
• protinádorové látky farmakologie   chemie   MeSH
• pyridiny chemie   farmakologie   MeSH
• SARS-CoV-2 účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Using an active targeting approach of chemotherapeutics-loaded nanocarriers (NCs) with monoclonal antibodies is a potential strategy to improve the specificity of the delivery systems and reduce adverse reactions of chemotherapeutic drugs. Specific targeting of the human epidermal growth factor receptor-2 (HER-2), expressed excessively in HER-2-positive breast cancer cells, can be achieved by conjugating NCs with an anti-HER-2 monoclonal antibody. We constructed trastuzumab-conjugated chitosan iodoacetamide-coated NCs containing doxorubicin (Tras-Dox-CHI-IA-NCs) as a tumor-targeted drug delivery system, during the study. Chitosan-iodoacetamide (CHI-IA) was synthesized and utilized to prepare trastuzumab-conjugated NCs (Tras-NCs). The morphology, physicochemical properties, drug loading, drug release, and biological activities of the NCs were elucidated. The Tras-NCs were spherical, with a particle size of approximately 76 nm, and had a positive zeta potential; after incorporating the drug, the size of the Tras-NC increased. A prolonged, 24-h drug release from the NCs was achieved. The Tras-NCs exhibited high cellular accumulation and significantly higher antitumor activity against HER-2-positive breast cancer cells than the unconjugated NCs and the drug solution. Therefore, Tras-Dox-CHI-IA-NCs could be a promising nanocarrier for HER-2-positive breast cancer.

• MeSH
• chitosan * chemie   MeSH
• doxorubicin chemie   MeSH
• jodacetamid MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• monoklonální protilátky chemie   MeSH
• nádory prsu * farmakoterapie   MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• trastuzumab MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Liver sinusoidal endothelial cells (LSECs) play a crucial role in regulating the hepatic function. Endoglin (ENG), a transmembrane glycoprotein, was shown to be related to the development of endothelial dysfunction. In this study, we hypothesized the relationship between changes in ENG expression and markers of liver sinusoidal endothelial dysfunction (LSED) during liver impairment. Male C57BL/6J mice aged 9-12 weeks were fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet (intrahepatic cholestasis) or choline-deficient l-amino acid defined high-fat diet (CDAA-HFD) (non-alcoholic steatohepatitis (NASH)). Significant increases in liver enzymes, fibrosis, and inflammation biomarkers were observed in both cholestasis and NASH. Decreased p-eNOS/eNOS and VE-cadherin protein expression and a significant increase in VCAM-1 and ICAM-1 expression were detected, indicating LSED in both mouse models of liver damage. A significant reduction of ENG in the DDC-fed mice, while a significant increase of ENG in the CDAA-HFD group was observed. Both DDC and CDAA-HFD-fed mice showed a significant increase in MMP-14 protein expression, which is related to significantly increased levels of soluble endoglin (sENG) in the plasma. In conclusion, we demonstrated that intrahepatic cholestasis and NASH result in an altered ENG expression, predominantly in LSECs, suggesting a critical role of ENG expression for the proper function of liver sinusoids. Both pathologies resulted in elevated sENG levels, cleaved by MMP-14 expressed predominantly from LSECs, indicating sENG as a liver injury biomarker.

• MeSH
• acetamidy * MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• endoglin metabolismus   MeSH
• endoteliální buňky metabolismus   MeSH
• intrahepatální cholestáza * MeSH
• matrixová metaloproteinasa 14 MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nealkoholová steatóza jater * patologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are major causes of hospital-acquired infections and sepsis. Due to increasing antibiotic resistance, new treatments are needed. Mesenchymal stem cells (MSCs) have antimicrobial effects, which can be enhanced by preconditioning with antibiotics. This study investigated using antibiotics to strengthen MSCs against MRSA and P. aeruginosa. MSCs were preconditioned with linezolid, vancomycin, meropenem, or cephalosporin. Optimal antibiotic concentrations were determined by assessing MSC survival. Antimicrobial effects were measured by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and antimicrobial peptide (AMP) gene expression. Optimal antibiotic concentrations for preconditioning MSCs without reducing viability were 1 μg/mL for linezolid, meropenem, and cephalosporin and 2 μg/mL for vancomycin. In MIC assays, MSCs preconditioned with linezolid, vancomycin, meropenem, or cephalosporin inhibited MRSA or P. aeruginosa growth at lower concentrations than non-preconditioned MSCs (p ≤ 0.001). In MBC assays, preconditioned MSCs showed enhanced bacterial clearance compared to non-preconditioned MSCs, especially when linezolid and vancomycin were used against MRSA (p ≤ 0.05). Preconditioned MSCs showed increased expression of genes encoding the antimicrobial peptide genes hepcidin and LL-37 compared to non-preconditioned MSCs. The highest hepcidin expression was seen with linezolid and vancomycin preconditioning (p ≤ 0.001). The highest LL-37 expression was with linezolid preconditioning (p ≤ 0.001). MSCs' preconditioning with linezolid, vancomycin, meropenem, or cephalosporin at optimal concentrations enhances their antimicrobial effects against MRSA and P. aeruginosa without compromising viability. This suggests preconditioned MSCs could be an effective adjuvant treatment for antibiotic-resistant infections. The mechanism may involve upregulation of AMP genes.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• antimikrobiální peptidy MeSH
• cefalosporiny farmakologie   MeSH
• hepcidiny farmakologie   terapeutické užití   MeSH
• lidé MeSH
• linezolid farmakologie   terapeutické užití   MeSH
• meropenem farmakologie   terapeutické užití   MeSH
• methicilin rezistentní Staphylococcus aureus * MeSH
• mezenchymální kmenové buňky * MeSH
• mikrobiální testy citlivosti MeSH
• Pseudomonas aeruginosa genetika   MeSH
• stafylokokové infekce * mikrobiologie   MeSH
• vankomycin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Influenza A and B viruses cause epidemics every year, with approximately 3-5 million serious cases and about 290,000 to 650,000 deaths worldwide. Most patients die from bacterial complications of influenza. The aim of our study was to describe the clinical pictures of influenza and the development of the complications in seniors over 65 years of age, who were treated in University Hospital Pilsen. The course of the disease and changes in laboratory parameters were evaluated with regard to the method of treatment performed. METHODS: A descriptive retrospective study was performed. Clinical and laboratory data of seniors with the diagnosis of influenza were extracted from electronic medical records and later analysed. The data were processed with Excel 2016 and Statistica. RESULTS: A collection of 261 seniors, of whom 218 were hospitalized and 43 treated in an outpatient setting, has been studied. Patients who later developed complications had elevated values of CRP, procalcitonin, urea, and creatinine. The antiviral drug oseltamivir was administered to 226 of 261 seniors. Forty-seven seniors (18.0%) died from influenza and its complications (severe pneumonia with acute respiratory insufficiency or heart failure). CONCLUSIONS: The course of influenza in seniors was usually more severe and required hospitalization along with antiviral treatment. The mortality rate in the monitored group exceeded 18%. Annual timely vaccination, but also other preventive measures, and maybe considering other risk groups are methods to prevent severe or even fatal cases of influenza.

• MeSH
• antivirové látky * terapeutické užití   MeSH
• chřipka lidská * epidemiologie   komplikace   MeSH
• hospitalizace statistika a číselné údaje   MeSH
• lidé MeSH
• oseltamivir terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• virus chřipky A izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Pneumonie patří v dětském věku mezi častá infekční onemocnění. Jejich průběh může být nekomplikovaný, avšak mohou také vést k respiračnímu selhání, které vyžaduje hospitalizaci na jednotce intenzivní a resuscitační péče. Součástí léčby respiračního selhání je podpora či náhrada plicních funkcí pomocí oxygenoterapie, neinvazivní a invazivní umělé plicní ventilace a dále postupy zahrnující aplikaci inhalačního oxidu dusnatého, či pronační polohu. V případech, kdy tyto metody selhávají, je nezbytná mimotělní podpora životních funkcí. V následující kazuistice popisujeme komplikovaný průběh pneumonie u šestiletých dvojčat, jejichž zdravotní stav vyžadoval z důvodu kritických plicních funkcí připojení na mimotělní oběh s membránovou oxygenací.

Pneumonia is a common infectious disease in childhood. Its course may be uncomplicated, but it can also lead to respiratory failure requiring hospitalisation in the paediatric intensive care unit. The treatment of respiratory insufficiency includes support or replacement of lung function by oxygen therapy, non-invasive and invasive mechanical ventilation, and procedures such as inhaled nitric oxide or prone positioning. In situations where these methods fail, extracorporeal life support is necessary. In the following case report, we discuss the complicated course of pneumonia in six-year-old twins whose medical condition required connection to extracorporeal membrane oxygenation due to critical lung function.

• MeSH
• ceftriaxon farmakologie   terapeutické užití   MeSH
• dítě MeSH
• dvojčata MeSH
• infekce respiračními syncytiálními viry diagnóza   farmakoterapie   klasifikace   komplikace   MeSH
• koinfekce etiologie   klasifikace   mikrobiologie   MeSH
• lidé MeSH
• linezolid farmakologie   terapeutické užití   MeSH
• mimotělní membránová oxygenace * metody   MeSH
• pneumonie pneumokoková diagnóza   farmakoterapie   komplikace   MeSH
• pneumonie * diagnóza   etiologie   farmakoterapie   klasifikace   mikrobiologie   MeSH
• rentgendiagnostika hrudníku metody   MeSH
• respirační insuficience diagnóza   etiologie   komplikace   terapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

V období covidové pandemie ustoupila chřipka do pozadí. Její prevalence dramaticky poklesla vlivem zavedení protiepidemických opatření. Po jejich rozvolnění se chřipka vrátila v nezměněné síle a stále představuje významný zdravotní problém postihující nejvíce osoby ve věkové kategorii nad 65 let. Pozitivum proběhlé pandemie vyvolané podobným respiračním virem lze spatřovat v rozšíření spektra a dostupnosti diagnostických testů. Včasná diagnostika je u léčby chřipky zásadní, protože jediné dostupné antivirotikum oseltamivir je účinné pouze tehdy, pokud je nasazeno do dvou dní od začátku příznaků. Nedostatečné spektrum antivirotik ještě zdůrazňuje význam pravidelné vakcinace u rizikových osob nejen proti chřipce, ale i proti pneumokokovým a hemofilovým onemocněním, která představují nejčastější původce bakteriálních superinfekcí nasedajících na chřipkou vyvolané postižení dolních cest dýchacích. Právě bakteriální superinfekce je nejvýznamnější příčinou mortality u chřipky.

During the covid pandemic, influenza took a back seat. Its prevalence dropped dramatically due to the introduction of anti-epidemic measures. Following their relaxation, influenza has returned unchanged and continues to be a major health problem, affecting mostly people over 65 years of age. The positive aspect of the pandemic caused by a similar respiratory virus is the widening of the range and availability of diagnostic tests. Early diagnosis is essential in the treatment of influenza because the only available antiviral drug, oseltamivir, is only effective if given within 2 days of the onset of symptoms. The inadequate spectrum of antivirals further emphasizes the importance of regular vaccination in persons at risk not only against influenza but also against pneumococcal and haemophilus diseases, which are the most common causative agents of bacterial superinfections superimposed on influenza-induced lower respiratory tract involvement. It is bacterial superinfection that is the most important cause of mortality in influenza.

• MeSH
• antivirové látky MeSH
• chřipka lidská * MeSH
• lidé MeSH
• oseltamivir terapeutické užití   MeSH
• vakcinace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVE: To provide additional information on the transport of the new anti-seizure medications lacosamide, perampanel, and zonisamide in breast milk and breastfed infants. METHODS: Between 2013 and 2022, concentrations of anti-seizure medications were measured in six women with epilepsy (each drug in two patients) using high-performance liquid chromatography. Additionally, concentrations were determined after two consecutive pregnancies in women receiving lacosamide and one woman receiving zonisamide. In all cases, anti-seizure medication concentrations were measured in the maternal serum and breast milk, and five cases, in the infant serum. RESULTS: For lacosamide, the ratios of breast milk/maternal serum concentration varied between 0.77 and 0.93, the ratios of infant/maternal serum concentrations were 0.16 and 0.35, and the ratios of infant serum/milk concentrations were 0.21 and 0.38. For perampanel, the ratios of breast milk/maternal serum concentration were 0.01 and 0.10 and the ratio of infant/maternal serum concentration was 0.36. For zonisamide, the ratios of breast milk/maternal serum concentration varied between 0.76 and 1.26, the ratios of infant/maternal serum concentrations between 0.44 and 0.85, and the ratios of infant serum/milk concentrations between 0.55 and 1.05. CONCLUSIONS: Breastfeeding is recommended for women using lacosamide, perampanel, and zonisamide. However, the actual exposure can only be accurately evaluated by determining the serum concentration of anti-seizure medication in breastfed infants.

• MeSH
• kojenec MeSH
• kojení * škodlivé účinky   MeSH
• lakosamid MeSH
• lidé MeSH
• nitrily * MeSH
• pyridony * MeSH
• těhotenství MeSH
• zonisamid MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Levetiracetam is an anticonvulsive drug increasingly used in paediatric populations. Ontogenesis may alter its pharmacokinetics, demanding dose individualisation of levetiracetam in paediatric populations. We therefore aimed to explore levetiracetam pharmacokinetics and to propose its optimal dosing in the paediatric population. METHODS: Individual levetiracetam pharmacokinetic parameters were calculated based on therapeutic drug monitoring data, using a one-compartmental model, and regression models were used to explore possible covariates. RESULTS: 56 patients aged from 47 days to 18 years were included in the analysis. The median (IQR) volume of distribution and clearance of levetiracetam were 0.7 (0.58-0.85) L/kg and 0.123 (0.085-0.167) L/hour/kg, respectively. Levetiracetam pharmacokinetics were influenced by postnatal age, body size descriptors and renal functional status. CONCLUSIONS: Based on observed relationships, an individualised loading dose of 26.2 mg/kg body weight and maintenance dose of 20.7 mg/mL/min of estimated glomerular filtration rate were calculated as optimal. Since we observed increased levetiracetam clearance in association with valproate co-medication, caution should be used when combining these two drugs.

• MeSH
• antikonvulziva * MeSH
• dítě MeSH
• kyselina valproová * MeSH
• levetiracetam MeSH
• lidé MeSH
• monitorování léčiv MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• peramivir,
• MeSH
• analýza dat * MeSH
• antivirové látky farmakologie   MeSH
• chřipka lidská * diagnóza   epidemiologie   komplikace   prevence a kontrola   MeSH
• lidé MeSH
• oseltamivir aplikace a dávkování   terapeutické užití   MeSH
• preventabilní nemoci MeSH
• rizikové faktory MeSH
• vakcinace * statistika a číselné údaje   MeSH
• vakcíny proti chřipce MeSH
• zanamivir aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Česká republika MeSH