Impact of pH on activity of trimethoprim, fosfomycin, amikacin, colistin and ertapenem in human urine.

OBJECTIVE: Although major impairment of activity at lower pH values has been reported for fluoroquinolones, acidification is a widely recommended practice for the prophylaxis and treatment of uncomplicated urinary tract infections (UTIs). Until now, there is little evidence for the influence of pH on the activity on other antimicrobial classes in urine. METHODS: Bacterial growth curves of Staphylococcus aureus (ATCC 29213), Klebsiella oxytoca (ATCC 700324), Proteus mirabilis (ATCC 14153), Escherichia coli (ATCC 25922) and Enterococcus faecalis (ATCC 29212) were performed in Mueller-Hinton broth and in pooled human urine with a pH of between 5.0 and 8.0. Bacterial killing of trimethoprim, fosfomycin, amikacin, colistin and ertapenem against the five strains (where appropriate) was determined consecutively at concentrations equal to the MIC. RESULTS: While no difference in the bacterial growth of E. coli, S. aureus, P. mirabilis and K. oxytoca was observed at different pH values, bacterial growth of E. faecalis was significantly reduced at low pH. Acidification to pH 5 impaired the antimicrobial activity of all investigated antibiotics, i.e. the net effect of bacterial growth and killing resulted in increased colony-forming units/ml at the end of the experiment. CONCLUSION: The present in vitro findings indicate that acidification of urine during the treatment of UTIs should be carefully considered. While growth curves of one strain supports the concept of therapeutic or prophylactic acidification during UTIs, the most common pathogen, E. coli, was not affected by low pH. Independent of the investigated strain or antibiotic, pH values below 6 lead to a reduction of antimicrobial activity.

Macrophage-elicited loss of estrogen receptor-α in breast cancer cells via involvement of MAPK and c-Jun at the ESR1 genomic locus.

Estrogen receptor-α (ERα, ESR1) is a pivotal transcriptional regulator of breast cancer physiology and is targeted by endocrine therapies. Loss of ERα activity or expression is an indication of endocrine resistance and is associated with increased risk of tumor recurrence and worse prognosis. In this study, we sought to investigate whether elements of the tumor microenvironment, namely macrophages, would impact on ERα and we found that macrophage-derived factors caused loss of ERα expression in breast cancer cells. Conditioned media from macrophages caused activation of several intracellular pathways in breast cancer cells of which c-Src, protein kinase c and mitogen-activated protein kinase (MAPK) were essential for loss of ERα expression. Moreover, a prolonged hyperactivation of MAPK was observed. The activation of this kinase cascade resulted in recruitment of extracellular signal regulated kinase 2 (ERK2) directly to chromatin at the ESR1 gene locus in a process that was dependent upon activation and recruitment of the c-Jun transcription factor. Thus, we identify a novel mechanism for loss of ERα expression in breast cancer cells via macrophage activation of kinase cascades in the cancer cells causing transcriptional repression of the ESR1 gene by a direct chromatin action of a c-Jun/ERK2 complex. The findings in this study support an alternative mechanism, not intrinsic to the tumor cell but derived from the cross-talk with the tumor microenvironment, that could lead to endocrine resistance and might be targeted therapeutically to prevent loss of ERα expression in breast tumors.

Effects of dietary supplementation of synbiotics and phytobiotics on performance, caecal coliform population and some oxidant/antioxidant parameters of broilers.

The current study was conducted to evaluate the effects of dietary supplementation of synbiotics and phytobiotics on performance, small intestine weight, pH and caecal coliform counts of broilers. The influences of synbiotics and phytobiotics on oxidant/antioxidant status in the blood of broilers were also assessed. A total of 200 broiler chicks were randomly allotted to four dietary treatments, either fed a basal diet or the same diet supplemented with 1 g/kg synbiotic, 1 g/kg phytobiotic or 1 g/kg synbiotic plus 1 g/kg phytobiotic. The diet supplemented with both synbiotic and phytobiotic had no effect on body weight, body weight gain, feed intake and feed efficiency of broilers at the end of the study (p > 0.05). Neither small intestine weight nor pH was affected by any of the treatments. Supplementation of both synbiotic and phytobiotic to diet decreased the caecal coliform count (p < 0.01). Addition of synbiotics and phytobiotics in combination significantly increased plasma malondialdehyde (MDA) levels (p ≤ 0.05), whereasphytobiotic addition alone showed only a slight increase. Similarly, elevated nitric oxide (NO) level was recorded in the synbiotic- and phytobiotic-fed group and in the phytobiotic-fed group (p ≤ 0.001). Superoxide dismutase (SOD) activities did not differ between the groups. In conclusion, dietary supplementation of synbiotic and phytobiotic improved the gut health by decreasing the caecal total coliform count, but growth performance was not affected by the supplementations. Further investigations are needed to determine the effects of phytobiotics on oxidative/antioxidative metabolism as regards their compositional analysis.

Effect of different dietary levels of Yucca schidigera powder on the performance, blood parameters and egg yolk cholesterol of laying quails.

A total of 135 laying quails (Coturnix coturnix japonica), 9 weeks old, were divided into three dietary treatment groups. Three replicates were assigned to each treatment group consisting of 15 birds per cage. The diet was supplemented with 0, 100 and 200 ppm Yucca schidigera powder and given ad libitum to the quails for a period of 14 weeks. Body weight, egg production, feed consumption and feed efficiency were not different due to dietary treatments among the groups. Increased egg weight was determined in the control group. Yucca powder supplementation decreased serum glucose, cholesterol triglyceride level in laying quails. Serum total protein concentration was not changed by dietary treatments but albumin level was decreased in quails fed 100 ppm yucca powder. Egg yolk cholesterol concentration was not significantly different among the groups but tended to decline (11.5%) as a result of yucca supplementation. Red Blood Cell (RBC) and White Blood Cell (WBC) counts, packed cell volume (PCV), mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) were not affected by supplementation of yucca powder. However, haemoglobin (HB) concentration was slightly increased and mean corpuscular haemoglobin concentration (MCHC) was significantly increased by 200 ppm yucca powder supplementation to the diet.