• MeSH
• Urinary Tract Infections * etiology   drug therapy   classification   prevention & control   MeSH
• Humans MeSH
• Mannose * pharmacology   therapeutic use   MeSH
• Nitrofurantoin pharmacology   classification   therapeutic use   MeSH
• Carbohydrates pharmacology   classification   therapeutic use   MeSH
• Practice Guidelines as Topic MeSH
• Uropathogenic Escherichia coli metabolism   pathogenicity   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Anti-Bacterial Agents pharmacology   therapeutic use   MeSH
• Asymptomatic Infections MeSH
• Drug Resistance, Bacterial drug effects   MeSH
• Bacteriuria diagnosis   drug therapy   classification   MeSH
• Cystitis diagnosis   drug therapy   MeSH
• Hygiene standards   MeSH
• Urinary Tract Infections * diagnosis   drug therapy   MeSH
• Humans MeSH
• Nitrofurantoin pharmacology   therapeutic use   MeSH
• Recurrence MeSH
• Risk Factors MeSH
• Check Tag
• Humans MeSH

V České republice (ČR) bylo vystřídáno několik lékových forem léčivých přípravků s obsahem nitrofurantoinu. Nedávno byl ukončen specifický léčebný program, v rámci kterého byl do ČR dodáván nitrofurantoin v mikrokrystalické bezvodé formě. Nově je v ČR dostupný nitrofurantoin v makrokrystalické formě. Hlavním použitím je první volba v léčbě nekomplikovaných infekcí dolních močových cest (IDMC). Dále nalezne nitrofurantoin využití v případě profylaxe rekurentních IDMC. Makrokrystalická forma se vyznačuje lepší snášenlivostí a biologickou dostupností oproti mikrokrystalické formě. Doporučené dávkování uvedené v Souhrnu údajů o přípravku pro léčbu nekomplikovaných IDMC lze na základě zjištěných informací upřesnit na nitrofurantoin 50 mg po 6 hodinách, případně 100 mg po 8 hodinách. V indikaci nekomplikovaných IDMC má být makrokrystalický nitrofurantoin podáván po dobu minimálně 5 dnů. Kratší terapie (3 dny) může vést k selhání léčby.

In the Czech Republic, several dosage forms of medicinal products containing nitrofurantoin have been used. Recently, a specific treatment programme under which nitrofurantoin was supplied to the Czech Republic in the microcrystalline anhydrous form was terminated. Nitrofurantoin is now available in macrocrystalline form. Its primary indication is a first choice in treatment of uncomplicated lower urinary tract infections (IDMC). It is also used in the prophylaxis of recurrent IDMC. The macrocrystalline form is characterized by better tolerability and bioavailability compared to the microcrystalline form. The recommended dosage given in the Summary of Product Characteristics for the treatment of uncomplicated lower IDMC can be revised to nitrofurantoin 50 mg every 6 hours or 100 mg every 8 hours, based on the available information. In the therapy of uncomplicated lower IDMC, macrocrystalline nitrofurantoin should be administered for a minimum of 5 days. Shorter therapy (3 days) may lead to treatment failure.

• MeSH
• Anti-Infective Agents, Urinary administration & dosage   classification   MeSH
• Cystitis drug therapy   MeSH
• Adult MeSH
• Urinary Tract Infections * drug therapy   classification   prevention & control   MeSH
• Drug Interactions MeSH
• Humans MeSH
• Adolescent MeSH
• Nitrofurantoin * administration & dosage   pharmacokinetics   pharmacology   adverse effects   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Review MeSH

In the present study, we investigated the effect of acrylamide (ACR) exposure during pregnancy on the ovary of female adult offspring of two subsequent generations. Sixty-day-old Wistar albino female rats were given different doses of ACR (2.5 and 10 mg/kg/day) from day 6 of pregnancy until giving birth. Females from the first generation (AF1) were fed ad libitum, and thereafter, a subgroup was euthanized at 8 weeks of age and ovary samples were obtained. The remaining females were maintained until they reached sexual maturity (50 days old) and then treated in the same way as the previous generation to obtain the second generation of females (AF2). The histopathological examination indicated a high frequency of corpora lutea along with an increased number of antral follicles that reached the selectable stage mainly at a dose of 2.5 mg/kg/day. Interestingly, ACR exposure significantly increased the mRNA levels of CYP19 gene and its corresponding CYP19 protein expression in AF1 females. The TUNEL assay showed a significantly high rate of apoptosis in stromal cells except for dose of 2.5 mg/kg/day. However, in AF2 females, ACR exposure significantly increased the number of degenerating follicles and cysts while the number of growing follicles was reduced. Moreover, in both ACR-treated groups, estradiol-producing enzyme CYP19A gene and its corresponding protein were significantly reduced, and an excessive apoptosis was produced. We concluded that the ovarian condition of AF1 females had considerable similarity to the typical early perimenopausal stage, whereas that of AF2 females was similar to the late perimenopausal stage in women.

• MeSH
• Acrylamide toxicity   MeSH
• Apoptosis MeSH
• Aromatase * genetics   MeSH
• Furylfuramide MeSH
• Rats MeSH
• Humans MeSH
• Sex Ratio MeSH
• Rats, Wistar MeSH
• Pregnancy MeSH
• Prenatal Exposure Delayed Effects * chemically induced   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Anti-Bacterial Agents administration & dosage   adverse effects   therapeutic use   MeSH
• Drug Resistance, Microbial MeSH
• Bacterial Infections drug therapy   MeSH
• Bacteriuria diagnosis   MeSH
• Cystitis diagnosis   etiology   drug therapy   MeSH
• Urinary Tract Infections * diagnosis   etiology   drug therapy   MeSH
• Amoxicillin-Potassium Clavulanate Combination administration & dosage   poisoning   therapeutic use   MeSH
• Humans MeSH
• Nitrofurantoin administration & dosage   adverse effects   therapeutic use   MeSH
• Pyelonephritis diagnosis   etiology   drug therapy   MeSH
• Check Tag
• Humans MeSH

• MeSH
• Aminoglycosides administration & dosage   pharmacology   MeSH
• Drug Resistance, Bacterial MeSH
• Cystitis epidemiology   drug therapy   MeSH
• Fluoroquinolones administration & dosage   pharmacology   adverse effects   MeSH
• Fosfomycin administration & dosage   pharmacology   MeSH
• Urinary Tract Infections * epidemiology   microbiology   MeSH
• Community-Acquired Infections * epidemiology   microbiology   MeSH
• Pregnancy Complications, Infectious drug therapy   microbiology   MeSH
• Humans MeSH
• Male Urogenital Diseases drug therapy   microbiology   MeSH
• Nitrofurantoin administration & dosage   pharmacology   adverse effects   MeSH
• Postmenopause MeSH
• Pyelonephritis drug therapy   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH

Článek představuje výsledky studia antimikrobiálních a antimykotických vlastností derivátů 1,2,4-triazolu syntetizovanými na Katedře fyzikální a koloidní chemie Záporožské státní lékařské univerzity. Předchozí studie stanovily antimikrobiální a antimykotickou aktivitu derivátů 1,2,4-triazolu. Proto bylo účelné zkoumat mezi syntetizovanými sloučeninami vysoce účinné látky s antimikrobiálními a antimykotickými vlastnostmi. V první fázi našeho výzkumu byla provedena predikce akutní toxicity. Antimikrobiální a antimykotické vlastnosti byly provedeny metodou sériového ředění na kapalné živné půdě. Na tyto typy aktivit bylo zkoumáno 47 sloučenin různých tříd. Podle našeho výzkumu vykazovaly deriváty 3-amino-1,2,4-triazolu lepší účinnost než 3-thio-1,2,4-triazoly na Staphylococcus aureus a Candida albicans. Největší antimikrobiální a antimykotickou aktivitu vykazoval 5-(1Н-tetrazol-1-іl)methyl-4Н-1,2,4-triazol- 3-yl-1-(5-nitrofuran-2-yl)methanimin (11.6). Hlubší výzkum sloučeniny 11.6 byl proveden difuzí v agaru (jamková metoda). Studie ukázaly, že molekula 11.6 vykazovala antimikrobiální a antimykotický účinek na studované testovací kmeny v koncentraci 2 μg/ml. Proto může být tato sloučenina po zjištění její farmakologické bezpečnosti a toxicity vyvinuta jako užitečná léčivá látka.

This article presents the results of the study of the antimicrobial and antifungal properties among 1,2,4-triazole derivatives synthesized at the Department of Physical and Colloidal Chemistry of the Zaporizhzhia State Medical University. Previous studies have established the antimicrobial and antifungal activity of 1,2,4-triazole derivatives. Therefore, it was reasonable to investigate highly effective substances with antimicrobial and antifungal properties among synthesized compounds. In the first stage of our research, acute toxicity prediction was performed. The antimicrobial and antifungal properties were carried out by the method of “serial dilutions” on a liquid nutrient. Forty-seven compounds of the different classes were studied for these types of activities. According to our research, derivatives of 3-amino-1,2,4-triazole showed better performance than 3-thio-1,2.4-triazoles for Staphylococcus aureus and Candida albicans. 5-(1Н-tetrazole-1-іl)methyl-4Н- -1,2,4-triazole-3-yl-1-(5-nitrofuran-2-yl)methanimin (11.6) was showed the greatest antimicrobial and antifungal activity. Deeper research for compound 11.6 was done by diffusion in agar (method of “wells”). Studies have shown that molecule 11.6 showed antimicrobial and antifungal action to the studied test strains at a concentration of 2 μg/ml. Hence, this compound can be developed as a helpful therapeutic agent after establishing its safety pharmacology and toxicity.

• MeSH
• Agar MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Antifungal Agents pharmacology   MeSH
• Anti-Infective Agents pharmacology   MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Nitrofurans chemistry   pharmacology   MeSH
• Tetrazoles chemistry   pharmacology   MeSH
• Triazoles * chemistry   pharmacology   MeSH
• Check Tag
• Humans MeSH

The pregnane X receptor (PXR, NR1I2) is a xenobiotic-activated transcription factor with high levels of expression in the liver. It not only plays a key role in drug metabolism and elimination, but also promotes tumor growth, drug resistance, and metabolic diseases. It has been proposed as a therapeutic target for type II diabetes, metabolic syndrome, and inflammatory bowel disease, and PXR antagonists have recently been considered as a therapy for colon cancer. There are currently no PXR antagonists that can be used in a clinical setting. Nevertheless, due to the large and complex ligand-binding pocket (LBP) of the PXR, it is challenging to discover PXR antagonists at the orthosteric site. Alternative ligand binding sites of the PXR have also been proposed and are currently being studied. Recently, the AF-2 allosteric binding site of the PXR has been identified, with several compounds modulating the site discovered. Herein, we aimed to summarize our current knowledge of allosteric modulation of the PXR as well as our attempt to unlock novel allosteric sites. We describe the novel binding function 3 (BF-3) site of PXR, which is also common for other nuclear receptors. In addition, we also mention a novel allosteric site III based on in silico prediction. The identified allosteric sites of the PXR provide new insights into the development of safe and efficient allosteric modulators of the PXR receptor. We therefore propose that novel PXR allosteric sites might be promising targets for treating chronic metabolic diseases and some cancers.

• MeSH
• Allosteric Site MeSH
• Diabetes Mellitus, Type 2 * MeSH
• Furylfuramide MeSH
• Humans MeSH
• Ligands MeSH
• Pregnane X Receptor MeSH
• Receptors, Cytoplasmic and Nuclear MeSH
• Receptors, Steroid * metabolism   MeSH
• Xenobiotics MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Úvod: Antibiotika (ATB) jsou klíčové léčivé přípravky a mají nezpochybnitelné využití. Naneštěstí zejména neracionální používání ATB vede k rizikům především nežádoucích účinků, interakcí a vzniku rezistence. Cílem této práce bylo analyzovat spotřebu ATB pro systémové použití v České republice (ČR) v letech 2005-2019 a přinést závěry pro klinickou praxi. Metodika: Analýza spotřeby ATB pro systémové použití probíhala jako longitudinální retrospektivní analýza dat z databáze Státního ústavu pro kontrolu léčiv v letech 2005-2019 za použití standardní metodiky pro studium spotřeby léčiv typu DUR (Drug Utilization Review). Spotřeba ATB se vypočítala jako definované denní dávky (DDD) jednotlivých ATB na tisíc obyvatel za den (TID). Analyzována byla celková spotřeba ATB pro systémové použití v jednotlivých letech. Druhotně byly sledovány spotřeby pro jednotlivé zástupce nebo podskupiny a vyhodnoceny relativní indikátory kvality spotřeb ATB. Data byla popsána deskriptivní statistikou. Výsledky: Nejvyšší spotřeba ATB pro systémové použití byla zaznamenána v roce 2015, kdy dosáhla hodnoty 19,3338 DDD/TID. Nejpoužívanější skupinou ATB v průběhu celého sledovaného období byla β‑laktamová ATB (peniciliny). Nejvýznamnější změna spotřeby za sledované období proběhla ve skupině fluorochinolonů, kde byl pokles z roku 2005 do roku 2019 více než 2násobný. Zejména viditelný byl trend poklesu spotřeby norfloxacinu, který nastal v roce 2013. Nárůst ve spotřebě ATB byl sledován především u meropenemu, vankomycinu, cefuroxim‑axetilu, skupiny chráněných penicilinů a cefalosporinů II. a III. generace. Závěr: V celkovém hodnocení nepatřila ČR mezi státy s vysokou spotřebou ATB a četnějšími negativními výsledky stran relativních indikátorů kvality spotřeb ATB. V ČR docházelo zejména k možnému neracionálnímu nahrazování některých ATB a nárůstu spotřeby některých širokospektrých ATB.

Introduction: Antibiotics (ATB) are essential medicines and have unquestionable uses. Unfortunately, the irrational use of ATB leads to the risks of adverse effects, interactions, and the development of drug resistance. This study aimed to analyse ATB consumption for systemic use in the Czech Republic (CR) in 2005-2019 and provide conclusions for clinical practice. Methods: The analysis of ATB consumption for systemic use was performed as a longitudinal retrospective analysis of data from the State Institute for Drug Control database in the years 2005-2019 using the standard methodology for studying drug consumption of the DUR (Drug Utilization Review) type. ATB consumption was calculated as defined daily doses (DDD) of each ATB per thousand inhabitants per day (TID). The total consumption of ATB for systemic use in each year was analysed. Secondarily, consumption for individual representatives or subgroups was analysed and relative quality indicators of ATB consumption were evaluated. Results: The highest consumption of ATB for systemic use was observed in 2015 when it reached 19.3338 DDD/TID. β-lactam ATB (penicillins) was the most commonly used group of ATB throughout the study period. The most significant change in consumption over the period was in the fluoroquinolone group, where the decrease from 2005 to 2019 was more than 2-fold. The obvious was the downward trend in consumption of norfloxacin, which occurred in 2013. ATB consumption increased mainly for meropenem, vancomycin, cefuroxime-axetil, β-Lactamase-protected penicillins and the 2nd and 3rd generation cephalosporins. Conclusion: In the overall assessment, CR was not among the countries with high ATB consumption and frequent negative results in the relative quality indicators of ATB consumption. In particular, the possible irrational substitution of some ATB and an increase in the consumption of some broad-spectrum ATB was observed in CR.

• MeSH
• Anti-Bacterial Agents administration & dosage   MeSH
• Drug Resistance, Microbial MeSH
• beta-Lactams administration & dosage   MeSH
• Fluoroquinolones administration & dosage   MeSH
• Drug Utilization Review * trends   MeSH
• Drug Interactions MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Drug Substitution MeSH
• Drug-Related Side Effects and Adverse Reactions MeSH
• Nitrofurantoin administration & dosage   MeSH
• Penicillins administration & dosage   MeSH
• Retrospective Studies MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Humans MeSH
• Publication type
• Evaluation Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

• MeSH
• Amiodarone adverse effects   toxicity   MeSH
• Antirheumatic Agents adverse effects   toxicity   MeSH
• COVID-19 * diagnostic imaging   diagnosis   therapy   MeSH
• Humans MeSH
• Drug-Related Side Effects and Adverse Reactions MeSH
• Nitrofurantoin adverse effects   toxicity   MeSH
• Lung Diseases etiology   MeSH
• Pneumonia MeSH
• Tomography, X-Ray Computed MeSH
• Radiography, Thoracic MeSH
• Aged MeSH
• Toxic Actions MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH