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Abstract Background Sulfur mustard (SM) is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE) cells and bronchial/tracheal epithelial (BTE) cells. Cell viability, expression of proinflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF), and expression of inducible nitric oxide synthase (iNOS) were examined, since these proinflammatory cytokines/mediators are import indicators of tissue inflammatory responses. We suggest that the influence of roxithromycin on SM-induced inflammatory reaction could play an important therapeutic role in the cytotoxicity exerted by this toxicant. Results MTS assay and Calcein AM/ethidium homodimer (EthD-1) fluorescence staining showed that roxithromycin decreased SM cytotoxicity in both SAE and BTE cells. Also, roxithromycin inhibited the SM-stimulated overproduction of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF at both the protein level and the mRNA level, as measured by either enzyme-linked immunosorbent assay (ELISA) or real-time RT-PCR. In addition, roxithromycin inhibited the SM-induced overexpression of iNOS, as revealed by immunocytochemical analysis using quantum dots as the fluorophore. Conclusion The present study demonstrates that roxithromycin has inhibitory effects on the cytotoxicity and inflammation provoked by SM in human respiratory epithelial cells. The decreased cytotoxicity in roxithromycin-treated cells likely depends on the ability of the macrolide to down-regulate the production of proinflammatory cytokines and/or mediators. The results obtained in this study suggest that macrolide antibiotics may serve as potential vesicant respiratory therapeutics through mechanisms independent of their antibacterial activity.

AbstractContamination of heavy metals and antibiotics would threaten the water and soil resources. Phytoremediation can be potentially used to remediate metal and antibiotics contaminated sites. The current study was carried out over a period of 12 months to assess the efficiency of the macrophytes Typha domingensis and Cyperus papyrus with different substrate materials to remove heavy metals and two antibiotics, roxithromycin and levofloxacin, from wastewater for reuse in agriculture. The concentrations of seven heavy metals (copper, nickel, iron, cadmium, zinc, lead, and chromium) in water and plant tissues were determined. The results showed that C. papyrus had a greater capacity than T. domingensis to remove biochemical oxygen demand (BOD) (80.69%), chemical oxygen demand (COD) (69.87%), and ammonium (NH4+) (69.69%). Cyperus papyrus was more effective in retaining solid pollutants. The bioaccumulation factors (BCF) roots of C. papyrus were higher levels of most metals than those of T. domingensis. The highest root–rhizome translocation factor (TF) values of C. papyrus were higher than T. domingensis. The bacterial indicators (total and fecal coliforms, as well as Faecal streptococci) and the potential pathogens (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) showed removal efficiencies ranging between 96.9% and 99.8%. The results indicated that the two systems could significantly reduce the concentration of antibiotics in wastewater, with roxithromycin showing higher elimination rates than levofloxacin. The results showed maximum removal of the heavy metals in constructed wetlands CWs planted with T. domingensis. The presence of zeolite and C. papyrus in the effluent of CWs significantly improved treatment capacity and increased pollutant removal efficiency.

Subtherapeutic antibiotic use in ruminant feeding to optimize rumen fermentation may lead to residues in meat and milk (6), as well as an increase in the inhibition of ruminal bacterial populations (7). For this reason, in 2006, the European Union banned the use of antibiotics as growth promoters in livestock feeding due to potential toxicities to host animals, potential rumen microbial adaptation, and risk of the presence of residues of these compounds in milk and meat, with potential effects on human health (8). ; In the present study, sensitive and mutant colonies of some ruminal bacterial species isolated from sheep, cattle, and buffalo were detected. We counted and considered "mutant colonies" the bacterial colonies grown in the clear inhibition zone in the Kirby–Bauer disk diffusion susceptibility test. Detected mutant colonies were higher in buffalo than in cattle and sheep. Duricef and metronidazole caused no mutations in any species. The others formed mutant colonies, where roxithromycin = polymyxin = chloramphenicol = gentamicin streptomycin = piperacillin > erythromycin > vancomycin = cefoperazone = cefotaxime > roxithromycin > polymyxin > chloramphenicol). The number of sensitive isolates of the different ruminant species for all the antibiotics was highest in buffalo, followed by cattle and then sheep (P < 0.05). We could conclude that subtherapeutic antibiotic use in ruminant feeding may lead to the formation of antibiotic-resistant mutant colonies, making their subtherapeutic effect nonexistent.

Subtherapeutic antibiotic use in ruminant feeding to optimize rumen fermentation may lead to residues in meat and milk (6), as well as an increase in the inhibition of ruminal bacterial populations (7). For this reason, in 2006, the European Union banned the use of antibiotics as growth promoters in livestock feeding due to potential toxicities to host animals, potential rumen microbial adaptation, and risk of the presence of residues of these compounds in milk and meat, with potential effects on human health (8). ; In the present study, sensitive and mutant colonies of some ruminal bacterial species isolated from sheep, cattle, and buffalo were detected. We counted and considered "mutant colonies" the bacterial colonies grown in the clear inhibition zone in the Kirby–Bauer disk diffusion susceptibility test. Detected mutant colonies were higher in buffalo than in cattle and sheep. Duricef and metronidazole caused no mutations in any species. The others formed mutant colonies, where roxithromycin = polymyxin = chloramphenicol = gentamicin streptomycin = piperacillin > erythromycin > vancomycin = cefoperazone = cefotaxime > roxithromycin > polymyxin > chloramphenicol). The number of sensitive isolates of the different ruminant species for all the antibiotics was highest in buffalo, followed by cattle and then sheep (P < 0.05). We could conclude that subtherapeutic antibiotic use in ruminant feeding may lead to the formation of antibiotic-resistant mutant colonies, making their subtherapeutic effect nonexistent.

Background. Ciprofloxacin-resistant Campylobacter jejuni isolates obtained from infected patients in Australia have not been detected in studies of isolates from specific geographic areas. The Australian government has prohibited the use of fluoroquinolone in food-producing animals. To assess the impact of this policy, we have examined the antimicrobial susceptibility of isolates from 5 Australian states. Methods. We conducted a period-prevalence survey of the susceptibility of C. jejuni isolates to 10 antimicrobial agents. C. jejuni isolates obtained from 585 patients from 5 Australian states (Queensland, South Australia, Tasmania, Victoria, and Western Australia) were identified by means of notifiable disease databases and were systematically selected from September 2001 to August 2002. Results. Among locally acquired infections, only 2% of isolates (range, 0%-8% in different states) were resistant to ciprofloxacin. The locally acquired isolates also exhibited resistance to sulfisoxazole (55%), ampicillin (46%), roxithromycin (38%), tetracycline (7%), nalidixic acid (6%), chloramphenicol (3%), erythromycin (3%), gentamicin (2%), and kanamycin (0.2%). Treatment with antimicrobial agents in the 4 weeks before onset was not associated with ciprofloxacin resistance. Conclusions. The very low level of ciprofloxacin resistance in C. jejuni isolates likely reflects the success of Australia's policy of restricting use of fluoroquinolones in food-producing animals.

Background. Ciprofloxacin-resistant Campylobacter jejuni isolates obtained from infected patients in Australia have not been detected in studies of isolates from specific geographic areas. The Australian government has prohibited the use of fluoroquinolone in food-producing animals. To assess the impact of this policy, we have examined the antimicrobial susceptibility of isolates from 5 Australian states. Methods. We conducted a period-prevalence survey of the susceptibility of C. jejuni isolates to 10 antimicrobial agents. C. jejuni isolates obtained from 585 patients from 5 Australian states (Queensland, South Australia, Tasmania, Victoria, and Western Australia) were identified by means of notifiable disease databases and were systematically selected from September 2001 to August 2002. Results. Among locally acquired infections, only 2% of isolates (range, 0%-8% in different states) were resistant to ciprofloxacin. The locally acquired isolates also exhibited resistance to sulfisoxazole (55%), ampicillin (46%), roxithromycin (38%), tetracycline (7%), nalidixic acid (6%), chloramphenicol (3%), erythromycin (3%), gentamicin (2%), and kanamycin (0.2%). Treatment with antimicrobial agents in the 4 weeks before onset was not associated with ciprofloxacin resistance. Conclusions. The very low level of ciprofloxacin resistance in C. jejuni isolates likely reflects the success of Australia's policy of restricting use of fluoroquinolones in food-producing animals.

This is a post-print version of the published article: Gonzalez-Gil, L., Mauricio-Iglesias, M., Serrano, D., Lema, J. M., & Carballa, M. (2018). Role of methanogenesis on the biotransformation of organic micropollutants during anaerobic digestion. Science of The Total Environment, 622, 459-466. https://doi.org/10.1016/j.scitotenv.2017.12.004 ; Several studies showed that some organic micropollutants (OMPs) are biotransformed during anaerobic digestion (AD). Yet, most of them aim at reporting removal efficiencies instead of understanding the biotransformation process. Indeed, how each of the main AD stages (i.e., hydrolysis, acidogenesis, and methanogenesis) contribute to OMP biotransformation remains unknown. This study focuses on investigating the role of methanogenesis, the most characteristic step of AD, to OMP removal. More specifically, the sorption and the biotransformation of 20 OMPs by methanogenic biomass were analyzed determining their concentrations in both liquid and solid phases. Sorption onto methanogenic biomass displayed a similar behavior as reported for digested sludge. Most of the OMPs were biotransformed to a medium extent (35–70%) and only sulfamethoxazole was completely removed. Comparing these results with those reported for the complete AD process, methanogenesis was proven to play a key role, accounting for more than 50% of the OMP biotransformation (except for roxithromycin) during AD. An increase in the organic loading rate from 1 to 2 g COD/L d, typical loads employed in sewage sludge anaerobic digesters, did not exert a clear cometabolic effect on the OMPs biotransformation. It is hypothesized that biotransformation occurs in both liquid and solid phases because no link between the partition coefficient (Kd) and the overall biotransformation efficiency was found. These findings allow a better understanding of the OMPs fate under anaerobic conditions, which is necessary to design efficient biological mitigation strategies ; This research was funded by the Spanish Government (AEI) ...