Biologically synthesized silver nanoparticles as potent antibacterial effective against multidrug-resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the most worrisome infectious bacteria due to its intrinsic and acquired resistance against several antibiotics and the recalcitrance of its infections; hence, the development of novel antimicrobials effective against multidrug-resistant P. aeruginosa is mandatory. In this work, silver nanoparticles obtained by green synthesis using a leaf extract and fungi were tested against a battery of clinical strains from cystic fibrosis, pneumonia and burnt patients, some of them with multidrug resistance. Both nanoparticles showed a potent antibacterial effect, causing severe damage to the cell wall, membrane and DNA, and inducing the production of reactive oxygen species. Moreover, the nanoparticles derived from fungi showed synergistic antibacterial effects with the antibiotics meropenem and levofloxacin for some clinical strains and both kinds of nanoparticles were nontoxic for larvae of the moth Galleria mellonella, encouraging further research for their implementation in the treatment of P. aeruginosa infections.

Inhibition of quorum-sensing-dependent virulence factors and biofilm formation of clinical and environmental Pseudomonas aeruginosa strains by ZnO nanoparticles.

UNLABELLED: Quorum quenching decreases Pseudomonas aeruginosa virulence factors and biofilm formation, alleviating infections in animal models. Nevertheless, it is usually performed in laboratory strains such as PAO1 and PA14, and studies involving clinical or environmental isolates are scarce. In this work, the effects of ZnO nanoparticles, a potent quorum and virulence quencher for the PAO1 strain, were tested in six clinical strains from cystic fibrosis patients, a furanone C-30 resistant clinical strain from urine, two PA14 gallium resistant mutants, a PA14 C-30 resistant mutant and four environmental isolates. ZnO nanoparticles effectively decreased elastase, pyocyanin, and biofilm formation for most of the strains; regardless their origin or their resistance against the canonical quorum quencher C-30 or the novel antimicrobial gallium. The data indicate ZnO nanoparticles may have a broad spectrum for the quorum quenching of relevant strains and that may be an alternative to treat Ps. aeruginosa recalcitrant infections. SIGNIFICANCE AND IMPACT OF THE STUDY: Virulence inhibition by quorum quenchers in Pseudomonas aeruginosa is usually tested in laboratory strains and studies of their effects in relevant clinical and environmental strains are scarce. This study is significant as the effects of ZnO nanoparticles in QS-dependent virulence factor production were tested in six clinical strains from cystic fibrosis patients, a C-30 resistant clinical strain from urine, two PA14 gallium resistant mutants, a PA14 C-30 resistant mutant, and four environmental isolates. ZnO nanoparticles decreased elastase, pyocyanin, and biofilms for most of the strains; indicating they have broad spectrum and may be an alternative to treat Ps. aeruginosa infections.

Antioxidant activity of topiramate: an antiepileptic agent.

A number of experimental and clinical reports suggest the involvement of oxidative stress in pathophysiology of epilepsy. Topiramate, a new antiepileptic drug, induces antioxidant effect in epileptic animals. However, to date, no further studies appear to be carried out in order to demonstrate the ability of topiramate to act as antioxidant. Therefore, the objective of this work was to evaluate the in vitro superoxide (O2(·-)), hydroxyl radical (OH·), hypochlorous acid (HOCl), hydrogen peroxide (H2O2), singlet oxygen ((1)O2) and peroxynitrite (ONOO(-)) scavenging capacity of topiramate in comparison with reference compounds. In addition, we investigated the possible antitumour activity of this compound in some cancer cell lines. Topiramate displays a scavenging capacity compared to the reference compound, with the exception of ONOO(-), although it was less efficient than nordihydroguaiaretic acid, dimethylthiourea, ascorbic acid, sodium pyruvate and glutathione for O2(·-), OH·, HOCl, H2O2 and (1)O2(P < 0.0001), respectively, and not induced significant growth inhibition in cancer cell lines. The direct antioxidant properties of topiramate could explain the neuroprotective effects attributed to this compound and suggest its use as chemopreventive agent in a future.

Proteolytic activity in Serratia marcescens clinical isolates.

Exoproteinase production was demonstrated in 64 clinical isolates of S. marcescens. A significant relationship was found between the site of origin (autopsy material, hemocultures, various other sources), proteinase activity, and LD50 of the analyzed isolates. The number of exoproteinases varied during a 14-h incubation in batch cultures; the most frequently found was a 57.5-kDa proteinase which was observed in all analyzed strains. The exoproteinase production was shown to be related to strain virulence.

Aminoglycoside resistance patterns of Serratia marcescens strains of clinical origin.

Aminoglycoside resistance patterns of 147 Serratia marcescens strains of clinical origin were studied. All strains analysed belonged to three different bacterial populations. The periods of study and the institutions the strains were isolated from correlated significantly with the resistance patterns shown by the strains. The most frequent resistance patterns found were the following: ACC (6')-I at the Hospital Infantil de México (Children's Hospital of México), and ANT (2'') + AAC(6')-I at the Instituto Nacional de Pediatría (INPed or National Institute of Pediatrics) in Mexico City. Furthermore, the isolation frequency of aminoglycoside-sensitive strains decreased remarkably at the INPed over a 12-year period. These results suggest that there has been a selection of Serratia marcescens strains that are very resistant to aminoglycosides.

Biotyping of Serratia marcescens strains of clinical origin.

One hundred and ninety five Serratia marcescens strains of clinical origin isolated at the Children's Hospital of Mexico (Hospital Infantil de México) in 1978 and at the National Institute of Pediatrics (Instituto Nacional de Pediatría) in Mexico City in 1977 and from 1988 to 1989, were studied and compared. All strains were identified using the biotyping system described by Grimont and Grimont, without modification. The most numerous biogroup found was A5/8, and the frequencies of isolation of each biotype varied depending on the institution where it was isolated and the period of study.

Desarrollo de la produccion de inmunoglobulinas humanas especificas. II.Comparacion de tecnicas para titulacion in vivo e in vitro de antitoxina tetanica. / Development of the production of specific human immunoglobulins. II. Comparison of techniques for in vivo and in vitro titration of tetanus antitoxin

Se compararon tres metodos para titulacion in vivo e in vitro para la determinacion cuantitativa de antitoxina tetanica en el laboratorio, con objeto de seleccionar un metodo practico para control de donadores hiperinmunizados con toxoide tetanico, en el proceso de produccion de inmunoglobulina humana antitetanica. El metodo de hemaglutinacion con globulos humanos sensibilizados con cloruro de cromo da una (excelente correlacion con la neutralizacion in vivo (r= 0.926), mejor que ELISA (r= 0.823), por lo que se considera adecuada para este trabajo

Desarrollo de la produccion de inmunoglobulinas humanas especificas. III Produccion de un lote de prueba de inmunoglobulina especifica antitetanica. / Development of the production of specific human immunoglobulinas.III. Production of a test batch of antitetanic specific immunoglobulins

Se presenta un estudio para la preparacion a escala de laboratorio de inmunoglobulina humana hiperinmune antitetanica. El plasma hiperinmune se obtuvo inmunizando voluntarios con 2 esquemas de vacunacion distintos, lograndose un titulo promedio de 42,72 Ul/ml de plasma. El fraccionamiento se llevo a cabo por el metodo 6 y 9 de Cohn original. A partir de un plasma con una potencia de 39 Ul/ml se llego a una inmunoglobulina con 220 Ul/ml lo qual representa una concentracion de 5.64 veces el titulo inicial. El rendimiento a lo largo del proceso fue de 20% menos de lo reportado en otras plantas fraccionadoras lo cual se considero relativamente aceptable en una etapa inicial del trabajo. El estudio permite concluir que se cuenta con la tecnologia necesaria en el Instituto Nacional de Higiene, para la elaboracion de este producto a mayor escala