Low toxicity ß-cyclodextrin-caged 4,4'-bipyridinium-bis(siloxane): synthesis and evaluation.

The toxicity of viologens can be significantly reduced by including them in tight [2]rotaxane structures alongside ß-cyclodextrin, thus turning them into candidates of pharmaceutical interest. Here, we report a synthesis pathway for a benign viologen, by capping a small ß-cyclodextrin-caged molecule, the 4,4'-bipyridine, with minimal-length presynthesized axle-stopper segments of the propyl-3-pentamethyldisiloxane type. After 90 min from the oral administration to laboratory mice, the product concentration in the bloodstream reaches a value equivalent to 0.634% of the initial dose of 800 mg·kg(-1). As compared to the nude viologen having the same structure, which proved to be lethal in doses of 40 mg·kg(-1), the product induces reversible morphological changes in the liver, kidney, lung, and cerebellum, up to a dose of 400 mg·kg(-1), with higher dosages giving rise to a chronic slow evolution.

Synthesis and biological evaluation of new 2-azetidinones with sulfonamide structures.

New series of N-(arylidene)hydrazinoacetyl sulfonamides 4a1-6, 4b1-6 and N-(4-aryl-3-chloro-2-oxoazetidin-1-yl)aminoacetyl sulfonamides 5a1-6, 5b1-6 were synthesized. The structures of the new derivatives was confirmed using spectral methods (FT-IR, 1H-NMR, 13C-NMR). The antibacterial activities of these compounds against Gram positive (Staphylococcus aureus ATCC 6583, Staphylococcus epidermidis ATCC 12228, Enterococcus faecalis ATCC 25912) and Gram negative (Klebsiella pneumoniae CIP 53153, Proteus vulgaris CIP 104989, Citrobacter freundii CIP 5732, Enterobacter cloacae CIP 103475, Escherichia coli ATCC 25922, Pseudomonas aeruginosa CIP 82118) bacterial strains were evaluated using the broth micro-dilution method. Compound 4a2 displayed the highest antibacterial activity, especially against Staphylococcus epidermidis, Enterococcus faecalis and Pseudomonas aeruginosa. The antioxidant potential of the synthesized compounds was also investigated according to ferric reducing power, total antioxidant activity and DPPH radical scavenging assays. All tested compounds showed excellent antioxidant activity in comparison with sulfadiazine and sulfisoxazole which were used as parent sulfonamides. Moreover, some of them showed an antioxidant activity comparable with that of ascorbic acid. In general, the compounds designed based on a sulfadiazine skeleton (compounds 4a1-6, 5a1-6) are more active than those obtained from sulfisoxazole (compounds 4b1-6, 5b1-6), and the N-(arylidene)hydrazinoacetyl sulfonamide derivatives 4a1-6, 4b1-6 are more active than their azetidionone analogues 5a1-6, 5b1-6.

Changes in concentrations of fluoroquinolones and of ciprofloxacin-resistant Enterobacteriaceae in chicken feces and manure stored in a heap.

This study evaluated the impact of storing chicken manure on the degradation of enrofloxacin (ENR) and ciprofloxacin (CIP), and on the survival of CIP-resistant Enterobacteriaceae. At 24 d of age, half of 8900 chickens received ENR for 5 d. After the animals departed, their manure was stored in two heaps for 63 d. Enterobacteriaceae were cultured on media containing 0 to 32 mg L⁻¹ of CIP. A total of 320 isolates were fingerprinted using enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) to evaluate community structure. Initial concentrations of ENR and CIP in the heap were 22 and 1.8 mg kg⁻¹, respectively. Seventy-three percent of the two fluoroquinolones were eliminated during storage. The administration of ENR led to a 5.1 log₋10 decrease in Enterobacteriaceae concentrations and emergence of CIP-resistant bacteria, which became dominant in the feces. concentrations decreased 1.2 to 2.3 log₋10 2 d after the heaps were made and continued to decline during storage. No resistant were found by Day 63. The highest CIP minimum inhibitory concentration (MIC) values observed among isolates of and of both and sp. were 128 and 4 mg L⁻¹, respectively. The dominant ERIC-PCR profiles changed over time. There was no relationship between genotype and resistance-isolated strains to CIP. Storing chicken manure in heaps appeared to be an effective way of limiting the entrance of CIP-resistant E. coli into the environment but did not prevent the dissemination of fluoroquinolones after land spreading.

Geographical Variations in Virulence Factors and Antimicrobial Resistance Amongst Staphylococci Isolated From Dogs From the United Kingdom and Romania.

The objective of this study was to compare virulence and resistance factors of mucosal and cutaneous staphylococci from dogs with pyoderma in the UK and Romania, two countries with different approaches to antimicrobial use in companion animals. Staphylococcal isolates (n = 166) identified to the species level as being Staphylococcus pseudintermedius or coagulase negative (CoNS) were analyzed for their antimicrobial resistance (AMR) profile and presence of resistance and virulence genes. Of the investigated isolates, 26 were methicillin-resistant S. pseudintermedius (MRSP), 89 were methicillin-susceptible S. pseudintermedius (MSSP) and 51 were coagulase negative staphylococci (CoNS). A significantly larger number of isolates originating from Romania were resistant to clindamycin, tetracycline, and chloramphenicol compared to the UK isolates (P < 0.05). Resistance to amoxicillin-clavulanic acid, gentamicin, and trimethoprim-sulphamethoxazole was more evident in UK isolates. Fusidic acid resistance was common in Staphylococcus spp. isolates from both countries. Most isolates carried virulence factors associated with siet (exfoliative toxin) and luk (leucocidin) genes. All MRSP UK isolates exhibited fusidic acid resistance genes whilst this was very rare in the MRSP isolates from Romania. The chlorhexidine resistance gene qacA/B was frequently identified in CoNS isolates from the UK (P < 0.001). The current study documented differences in antimicrobial resistance profiles of Staphylococcus spp. isolates from dogs in two geographical locations in Europe, which could reflect differences in antimicrobial prescribing patterns. The study also highlights the need for further studies and interventions on antimicrobial use, prescribing patterns and AMR surveillance in companion animals in Romania.

Bacteriological agents which play a role in the development of infertility.

This study was carried out to determine the prevalence of the bacterial agents Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae (N. gonorrhoeae), Mycoplasma hominis (M. hominis) and Ureaplasma urealyticum (U. urealyticum) and the conditions which may play a role in the development of female infertility, in the county of Iasi in North-Eastern Romania. Cervical and blood samples were collected from 176 infertile women and 45 pregnant women in the third trimester. Classical methods and real time PCR were applied to each cervical sample to detect the presence of these sexually transmitted microorganisms; the ELISA method was applied to blood samples to detect C. trachomatis antibodies (IgA, IgM and IgG). The proportion of C. trachomatis IgG was significantly higher in the infertile group (23.8%) than in the pregnant group (4.4%), p < 0.05. For C. trachomatis antigen (Ag) and N. gonorrhoeae Ag no differences were observed between the two groups. The prevalence of mycoplasma genital infections was higher in the pregnant group (U. urealyticum - 53.3% and M. hominis - 20%) than in the infertile group (U. urealyticum - 39.7% and M. hominis - 7.3%). Higher rate of co-infection with C. trachomatis and mycoplasma were observed among the infertile women (25.7%) than among the pregnant women (7.7%). This combination could be involved in the appearance of pelvic inflammatory disease (PID) and its sequela, including infertility. C. trachomatis IgG determination still remains the gold standard for the diagnosis of PID and should be used as a screening test for the prediction of tubal damage in infertile women. In view of the large number of cases involving the co-existence of genital infections with C. trachomatis, M. hominis and U. urealyticum, it is clearly necessary to perform screening for all three microorganisms among all women of reproductive age but especially those who are infertile.