The literature documenting the value of drug-like molecules found in natural products is vast. Although many dietary and herbal remedies have been found to be effective for treating intestinal inflammation, the identification of their active components has lagged behind. In this study, we find that a major ginger component, furanodienone (FDN), is a selective pregnane X receptor (PXR) ligand with agonistic transcriptional outcomes. We show that FDN binds within a sub-pocket of the PXR ligand binding domain (LBD), with subsequent alterations in LBD structure. Using male mice, we show that orally provided FDN has potent PXR-dependant anti-inflammatory outcomes that are colon-specific. Increased affinity and target gene activation in the presence of synergistically acting agonists indicates further opportunities for augmenting FDN activity, efficacy and safety. Collectively, these results support the translational potential of FDN as a therapeutic agent for the treatment and prevention of colonic diseases.

• MeSH
• Anti-Inflammatory Agents pharmacology   chemistry   MeSH
• Furans pharmacology   MeSH
• Colitis drug therapy   chemically induced   metabolism   pathology   MeSH
• Colon drug effects   pathology   metabolism   MeSH
• Humans MeSH
• Ligands MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Pregnane X Receptor * metabolism   genetics   MeSH
• Inflammation drug therapy   metabolism   MeSH
• Zingiber officinale * chemistry   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

• 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

Quorum Sensing allows bacteria to sense their population density via diffusible N-acyl homoserine lactone (N-HL) signaling molecules. Upon reaching a high enough cell density, bacteria will collectively exhibit a phenotype. Until recently, methods used for detection of N-HLs have not considered the chirality of these molecules and it was assumed that only the L-enantiomer was produced by bacteria. The production and effects of D-N-HLs have rarely been studied. In this work, the temporal production of D-N-HLs by the plant pathogen Pectobacterium atrosepticum and the human pathogen Pseudomonas aeruginosa are reported. Both bacteria produced D-N-HLs in significant amounts and in some cases their concentrations were higher than other low abundance L-N-HLs. Previously unreported D-enantiomers of N-3-oxoacyl and N-3-hydroxyacyl homoserine lactones were detected in P. atrosepticum. Interestingly, L-N-HLs produced in the lowest concentrations had relatively higher amounts of their corresponding D-enantiomers. Potential sources of D-N-HLs and their significance are considered.

• MeSH
• Acyl-Butyrolactones * pharmacology   MeSH
• Bacteria MeSH
• 4-Butyrolactone MeSH
• Homoserine pharmacology   MeSH
• Lactones MeSH
• Humans MeSH
• Pectobacterium * MeSH
• Pseudomonas aeruginosa MeSH
• Quorum Sensing genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't 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

Low solubility of reactants or products in aqueous solutions can result in the enzymatic catalytic reactions that can occur in non-aqueous solutions. In current study we investigated aqueous solutions containing different organic solvents / deep eutectic solvents (DESs) that can influence the protease enzyme's activity, structural, and thermal stabilities. Retroviral aspartic protease enzyme is responsible for the cleavage of the polypeptide precursors into mature viral components, a very crucial step for virus life cycle. In molecular dynamic simulations (MDS), the complex of the protease enzyme with Darunavirwas found highly stable in urea aqueous solution compared to when with the ethylene glycol (EG) or glycerol solvents. Particularly, in different organic solvents the presence of Darunavir induced protein-protein interactions within the protease homodimer. For the systems with EG or glycerol solvents, the flap domains of the enzyme formed an "open" conformation which lead to a weak binding affinity with the drug. Conserved D25 and G27 residues among this family of the aspartic protease enzymes made a stable binding with Darunavir in the urea systems. Unfolding of the protease dimer was initiated due to self-aggregation for the EG or glycerol organic solvents, which formed an "open" conformation for the flap domains. On the contrary lack of such clustering in urea solvent, the protease showed conventional structural folding in the presence or absence of the drug molecule. These novel findings may help to better understand the protease enzymes, which could be controlled by deep eutectic solvents.

• MeSH
• Darunavir MeSH
• Ethylene Glycol * MeSH
• Glycerol * MeSH
• Urea pharmacology   chemistry   MeSH
• Peptide Hydrolases MeSH
• Solvents chemistry   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't 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