RESUMO
ABSTRACT Escherichia coli and Klebsiella pneumoniae are the most common pathogens causing urinary tract infections in humans and animals. Close contact between humans and companion animals can facilitate the spread of multidrug resistant pathogens between both species. The objective of the research was to characterize extended-spectrum ß-lactamases (ESBL) -producing E. coli and K. pneumoniae isolated from dogs with urinary tract infections in the metropolitan area of Valle del Aburrá (Antioquia, Colombia). Three-hundred seventy-one urine samples collected from March 2018 to March 2019 in a veterinary clinical laboratory were analyzed. E. coli and K. pneumoniae isolates were detected in chromogenic agar and identified by biochemical tests. Susceptibility testing was performed by disc diffusion and ESBL production was evaluated by the double disk test in all isolates. MIC determination of ESBL-positive isolates were performed on the automated VITEK®2 system. Multiple PCR was used for the detection of CTX-M beta-lactamases (group 1, 2, 9 and 8/25), SHV, TEM, and AmpC of plasmid origin in ESBL-positive isolates. In total 22 out 371 isolates were positive for ESBL production by double disc test, 11 E. coli (ESBL-Ec) and 11 K. pneumoniae (ESBL-Kp). The multiple PCR detected CTX-M group 1 in the 22 ESBL-positive isolates. Multi-drug resistance was observed in all ESBL-producing isolates. In conclusion, a high frequency of antibiotic multi-resistance was found in ESBL-Ec and ESBL-Kp. The main ESBL detected was CTX-M group 1, which also prevails in human isolates.
RESUMEN Escherichia coli y Klebsiella pneumoniae son los patógenos más comunes causantes de infecciones en tracto urinario en humanos y animales. El contacto estrecho con los animales de compañía puede favorecer la diseminación de patógenos multiresistentes entre ambas especies. El objetivo de la investigación fue caracterizar E. coli (Ec -BLEE) y K. pneumo-niae (Kp -BLEE) productores de betalactamasas de espectro extendido provenientes de aislados de caninos con infecciones del tracto urinario del Área Metropolitana del Valle de Aburrá. 371 muestras de orina de caninos colectadas entre marzo de 2018 y marzo 2019 en un laboratorio clínico veterinario fueron analizadas. E. coli y K. pneumoniae se detectaron en agar cromogénico y se identificaron mediante pruebas bioquímicas. La prueba de susceptibilidad se realizó por difusión en disco y la producción de BLEE se evaluó por test de doble disco en todos los aislados. La determinación de la CIM en aislados positivos a BLEE se realizó en el sistema automatizado VITEK®2. Se utilizó PCR múltiple para la detección de betalactamasas tipo CTX-M (grupo 1, 2, 9 y 8/25), SHV, TEM y AmpC de origen plasmídico en aislados positivos a BLEE. Un total de 22 de 371 aislados fueron positivos a BLEE por test de doble disco, 11 E. coli (Ec -BLEE) y 11 K. pneumoniae (Kp-BLEE). La PCR detectó CTX-M grupo 1 en los 22 aislados positivos a BLEE. Se observó multirresistencia en todos los aislamientos productores de BLEE. En conclusión, se encontró una alta frecuencia de multirresistencia en Ec-BLEE y Kp-BLEE. La principal BLEE detectada fue CTX-M grupo 1, que también predomina en aislados humanos.
RESUMO
Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson's disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH+) and microglia markers (Iba-1+; CD68+) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68+/ Iba-1+ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions. Graphical Abstract MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.