Antibacterial and antibiofilm activity of permanently ionized quaternary ammonium fluoroquinolones.

A series of quaternary ammonium fluoroquinolones was obtained by exhaustive methylation of the amine groups present at the 7-position of fluoroquinolones, including ciprofloxacin, enoxacin, gatifloxacin, lomefloxacin, and norfloxacin. The synthesized molecules were tested for their antibacterial and antibiofilm activities against Gram-positive and Gram-negative human pathogens, i.e. Staphylococcus aureus and Pseudomonas aeruginosa. The study showed that the synthesized compounds are potent antibacterial agents (MIC values at the lowest 6.25 µM) with low cytotoxicity in vitro as assessed on the BALB 3T3 mouse embryo cell line. Further experiments proved that the tested derivatives are able to bind to the DNA gyrase and topoisomerase IV active sites in a fluoroquinolone-characteristic manner. The most active quaternary ammonium fluoroquinolones, in contrast to ciprofloxacin, reduce the total biomass of P. aeruginosa ATCC 15442 biofilm in post-exposure experiments. The latter effect may be due to the dual mechanism of action of the quaternary fluoroquinolones, which also involves disruption of bacterial cell membranes. IAM-HPLC chromatographic experiments with immobilized artificial membranes (phospholipids) showed that the most active compounds were those with moderate lipophilicity and containing a cyclopropyl group at the N1 nitrogen atom in the fluoroquinolone core.

Predictors of the maximal oxygen consumption in adult patients with type 1 diabetes treated with personal insulin pumps.

AIMS/INTRODUCTION: Regular physical activity for adults with type 1 diabetes mellitus improves cardiorespiratory fitness (CF) and quality of life. The aim of our study was to evaluate clinical and biochemical features that might be associated with CF in a homogenous group of adults with type 1 diabetes mellitus who are all treated with a personal insulin pump (continuous subcutaneous insulin infusion). MATERIALS AND METHODS: We assessed CF in 62 patients (74.2% of whom were men) who fulfilled the eligibility criteria. To determine maximal oxygen consumption, the march-running test on the treadmill was carried out. Two hours before the test, the patients consumed a defined meal covered by a dose of rapid acting insulin analog that was reduced by 25% from their regular dose. Basal insulin infusion was reduced by 50% for an hour. Additionally, the Perceived Stress Scale-10 questionnaire was used to measure the perception of stress. RESULTS: There was no episode of severe hypoglycemia during or after the test. In the final model, independent predictors of maximal oxygen consumption were sex, body fat percentage, lactate at 20 min after CF test and Perceived Stress Scale-10 score. Of interest, neither short-term (continuous glucose monitoring) nor long-term (glycosylated hemoglobin) metabolic control parameters were predictors of CF. CONCLUSIONS: In our selected homogenous group of patients with type 1 diabetes mellitus treated with personal insulin pumps, higher CF was associated with a lower percentage of body fat, male sex, higher lactate level after the CF test and the Perceived Stress Scale-10 score. The proposed protocol in our cohort proved to be safe with regard to glycemic control.

Furcellaran-Coated Microcapsules as Carriers of Cyprinus carpio Skin-Derived Antioxidant Hydrolysate: An In Vitro and In Vivo Study.

Carp skin gelatine hydrolysate (CSGH) may be a possible bioactive peptide source, as promising antioxidant properties have been noted during in vivo testing. Hence, the present study focused on improving the bioavailability of the antioxidant peptides from CSGH and on the use of furcellaran (FUR), which can protect the biopeptides during digestion in the gastrointestinal tract. Therefore, in this study, microcapsules coated with furcellaran and containing CSGH cores were prepared. The structural properties of the sample were determined using FT-IR and SEM analysis. The antioxidant properties of hydrolysate, uncoated, and encapsulated samples were investigated. In vivo analysis included determination of its safety in an animal organism and evaluation of the lipid profile, antioxidant blood status, and mRNA expression of some genes involved in antioxidant status in Wistar rats. The results showed no adverse effects of microencapsulated protein hydrolysates in laboratory animals. Nonetheless, there was a statistically significant rise in the level of total antioxidant status blood serum among animals consuming CSGH and not inducing oxidative stress. This can be viewed as a promising indication of the positive effects of antioxidant properties tested in vivo. The process of CSGH microencapsulation in FUR cause a decrease in antioxidant hydrolysate activity, both in vitro, as well as in healthy Wistar rats. When considering the results of the presented diverse therapeutic potential, further research on CSGH being a potential bioactive peptide source used as a functional food or nutraceutical, but with a different microencapsulation coating, is encouraged.

Synthesis and biological evaluation of hybrid quinolone-based quaternary ammonium antibacterial agents.

A series of novel fluoroquinolone-Safirinium dye hybrids was synthesized by means of tandem Mannich-electrophilic amination reactions from profluorophoric isoxazolones and antibiotics bearing a secondary amino group at position 7 of the quinoline ring. The obtained fluorescent spiro fused conjugates incorporating quaternary nitrogen atoms were characterized by 1H NMR, IR, MS, and elemental analysis. All the synthetic analogues (3a-h and 4a-h) were evaluated for their in vitro antimicrobial, bactericidal, and antibiofilm activities against a panel of Gram positive and Gram-negative pathogenic bacteria. The most active Safirinium Q derivatives of lomefloxacin (4d) and ciprofloxacin (4e) exhibited molar-based antibacterial activities comparable to the unmodified drugs and displayed considerable inhibitory potencies in E. coli DNA gyrase supercoiling assays with IC50 values in the low micromolar range. Zwiterionic hybrids were noticeably less lipophilic than the parent quinolones in micellar electrokinetic chromatography (MECK) experiments. The tests performed in the presence of phenylalanine-arginine ß-naphthylamide (PAßN) or carbonyl cyanide m-chlorophenylhydrazone (CCCP) revealed that the conjugates are to some extent subject to bacterial efflux and cellular accumulation, respectively. Moreover, the hybrids did not exhibit notable cytotoxicity towards the HEK 293 control cell line and demonstrated low propensity for resistance development, as exemplified for compounds 3g and 4b. Finally, molecular docking experiments revealed that the synthesized compounds were able to bind in the fluoroquinolone-binding mode at S. aureus DNA gyrase and S. pneumoniae topoisomerase IV active sites.

Evaluation of the potential use of a carp (Cyprinus carpio) skin gelatine hydrolysate as an antioxidant component.

Gelatine hydrolysates are of increasing interest as potential ingredients used in various health-promoting functional foods. Cyprinus carpio skin gelatine hydrolysates can be a potential source of bioactive peptides with antioxidant properties. Therefore, the aim of this research was to evaluate the potential use of a carp skin gelatine hydrolysate with proven antioxidant properties as a bioactive compound in functional foods as well as its stability under various processing conditions. The analysis of the hydrolysate included its characterisation (ζ-potential, particle size distribution), solubility, antioxidant ability and stability (DPPH, FRAP, chelating properties) under various conditions (heating, pH and NaCl). Additionally, an analysis of residual environmental pollutants (heavy metals, dioxins and pesticides) was also conducted. The hydrolysate had high solubility over a range of pH values from 2 to 12 (84%-98%), and its antioxidant properties remained stable in low concentration NaCl solutions as well as after being heated at temperatures between 40 and 100 °C. The hydrolysate was not contaminated with heavy metals, dioxins or pesticides. According to our study, carp skin hydrolysates can be incorporated into food processing systems without significant loss of their antioxidant activities.

Muscle and intestinal damage in triathletes.

The aim of the paper was to assess indicators of muscle and intestinal damage in triathletes. The study involved 15 triathletes whose objective for the season was to start in the XTERRA POLAND 2017 event (1,500-m swimming, 36-km cycling, and 10-km mountain running). Before the 14-week preparatory period, the competitors' body composition was measured, aerobic capacity was tested (graded treadmill test) and blood samples were collected to determine markers showing the level of muscle and intestinal damage. Subsequent tests for body composition were carried out before and after the competition. Blood samples for biochemical indicators were collected the day before the competition, after the completed race, and 24 and 48 hours later. A significant decrease in body mass was observed after completing the race (-3.1±1.5%). The mean maximal oxygen uptake level among the studied athletes equalled 4.9±0.4 L·min-1, 58.8±4.5 mL·kg-1·min-1. The significant increase in concentrations of cortisol, c-reactive protein and myoglobin after the competition, significantly correlated with the significant increase in zonulin concentration (post 1h: r = 0.88, p = 0.007, r = 0,79, p = 0.001, r = 0.78, p = 0.001, and post 12h: r = 0.75, p = 0.01, r = 0.71, p = 0.011, r = 0.83, p = 0.02). No significant changes in the concentration of tumour necrosis factor alpha among the examined competitors were noted at following stages of the study. The results of our research showed that in order to monitor overload in the training of triathletes, useful markers reflecting the degree of muscle and intestinal damage include cortisol, testosterone, testosterone to cortisol ratio, c-reactive protein, myoglobin and zonulin. Changes in muscle cell damage markers strongly correlated with changes in zonulin concentration at particular stages of the study. Thus, one can expect that the concentrations of markers depicting the level of muscle cell damage after an intense and long-lasting effort will significantly influence the level of the intestinal barrier.