Using the chequerboard technique we studied the in vitro activity of the broad spectrum antibiotic fosfomycin in combination with vancomycin, rifampicin, linezolid, quinupristin/ dalfopristin, ...cefazolin, meropenem and moxifloxacin against two Staphylococcus epidermidis strains (ATCC 12228, DSM 3269) and five Staphylococcus aureus isolates (ATCC 29213, DSM 683, DSM 46320, GISA 323/93, MRSA 3558/00). The phenomena of ‘trailing’ and ‘skipped wells’ did not present a problem. Synergy was the most common effect of all drugs tested in combination with fosfomycin; only combination with vancomycin showed antagonism for two of seven isolates. Using a killing-curve technique fosfomycin showed cidal activity, where increasing the drug concentration above the MIC did not enhance killing velocity. Inhibitory concentrations of vancomycin plus fosfomycin against DSM 46320 caused effects identical to those observed with vancomycin alone. The combination of fosfomycin plus linezolid exerted the bacteriostatic effect found with linezolid alone. Fosfomycin plus quinupristin/dalfopristin exhibited the bactericidal effect found with fosfomycin alone (in contrast to the rapidly bactericidal effect of quinupristin/dalfopristin). Electron microscopy showed that fosfomycin given in combination with linezolid, quinupristin/dalfopristin or moxifloxacin (substances that do not cause morphological alterations when given alone) resulted in ‘cauliflower-shaped’ distortion as caused by fosfomycin alone. Our in vitro data indicate considerable potential for fosfomycin used in combination with other antistaphylococcal antimicrobials, especially linezolid or quinupristin/dalfopristin.
Coastal marine ecosystems experience dynamic fluctuations in seawater carbonate chemistry. The importance of this variation in the context of ocean acidification requires knowing what aspect of ...variability biological processes respond to. We conducted four experiments (ranging from 3 to 22 days) with different variability regimes (pH
7.4-8.1) assessing the impact of diel fluctuations in carbonate chemistry on the early development of the mussel Mytilus galloprovincialis. Larval shell growth was consistently correlated to mean exposures, regardless of variability regimes, indicating that calcification responds instantaneously to seawater chemistry. Larval development was impacted by timing of exposure, revealing sensitivity of two developmental processes: development of the shell field, and transition from the first to the second larval shell. Fluorescent staining revealed developmental delay of the shell field at low pH, and abnormal development thereof was correlated with hinge defects in D-veligers. This study shows, for the first time, that ocean acidification affects larval soft-tissue development, independent from calcification. Multiple developmental processes additively underpin the teratogenic effect of ocean acidification on bivalve larvae. These results explain why trochophores are the most sensitive life-history stage in marine bivalves and suggest that short-term variability in carbonate chemistry can impact early larval development.
Ketamine is an anesthetic drug that also has antidepressant properties, with quick action. Despite the great number of studies showing its effectiveness as a treatment for major depression, there is ...little information about its effects on postpartum depression, as pharmacological treatments bring risks to the health of both mother and child. Thus, this study aimed to evaluate the effects of prolonged treatment with subanesthetic doses of ketamine in a rat model of postpartum depression. Female dams were induced to postpartum depression by the maternal separation model from lactating day (LD) 2-12. They were divided into four groups: one control and three experimental groups, which were treated with different doses of ketamine (5, 10 or 20 mg/kg) from LD 2-21 i.p. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day 2 through 90. Ketamine causes poor maternal care, with few neurochemical alterations. However, the highest dose used in this study had an antidepressant effect. Regarding the male offspring, indirect exposure to ketamine through breast milk caused few behavioral changes during infancy, but they were not permanent, as they faded in adulthood. Nevertheless, this exposure was able to cause alterations in their monoaminergic neurotransmission systems that were found in both infancy and adulthood periods.
Postpartum depression is a mentally disabling disease with multifactorial etiology that affects women worldwide. It can also influence child development and lead to behavioral and cognitive ...alterations. Despite the high prevalence, the disease is underdiagnosed and poorly studied. To study the postpartum depression caused by maternal separation model in rats, dams were separated from their litter for 3 h daily starting from lactating day (LD) 2 through LD12. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day (PND) 2 through PND90. The stress caused by the dam-offspring separation led to poor maternal care and a transient increase in anxiety in the offspring detected during infancy. The female offspring also exhibited a permanent impairment in sociability during adult life. These changes were associated with neurochemical alterations in the prefrontal cortex and hippocampus, and low TSH concentrations in the dams, and in the hypothalamus, hippocampus and striatum of the offspring. These results indicate that the postpartum depression resulted in a depressive phenotype, changes in the brain neurochemistry and in thyroid economy that remained until the end of lactation. Changes observed in the offspring were long-lasting and resemble what is observed in children of depressant mothers.
•Maternal separation caused maternal behavior dysfunction.•Maternal separation induced depressive behavior and hormonal phenotype on dams.•Maternal separation changed dam’s brain neurochemistry and thyroid economy.•Maternal separation caused long-lasting impairment in offspring’s sociability.•Maternal separation changed offspring’s brain neurochemistry in adulthood.
We have recently documented the efficacy of a highly concentrated probiotic preparation (VSL#3) in the prevention of flare-up in patients with chronic pouchitis. The aim of this study was to compare ...probiotic therapy with VSL#3 versus placebo in the ability to prevent the onset of acute pouchitis during the first year after ileal pouch-anal anastomosis.
Forty consecutive patients who underwent ileal pouch-anal anastomosis for ulcerative colitis were randomized to receive either VSL#3 (1 packet containing 900 billion bacteria/day) (n = 20) or an identical placebo (n = 20) immediately after ileostomy closure for 1 year. The patients were assessed clinically, endoscopically, and histologically after 1, 3, 6, 9, and 12 months. Health-related quality of life was assessed using the Inflammatory Bowel Disease Questionnaire.
Two of the 20 patients (10%) treated with VSL#3 had an episode of acute pouchitis compared with 8 of the 20 patients (40%) treated with placebo (log-rank test,
z = 2.273;
P < 0.05). Treatment with VSL#3 determined a significant improvement in Inflammatory Bowel Disease Questionnaire score, whereas this was not the case with placebo.
Treatment with VSL#3 is effective in the prevention of the onset of acute pouchitis and improves quality of life of patients with ileal pouch-anal anastomosis.
The aim of this study was to compare the influence of rifaximin and neomycin on faecal flora in rats. The study was performed on 18 Wistar rats (three groups of six male animals). Group 1 received ...rifaximin (50 mg kg−1/day), group 2, neomycin (50 mg kg−1/day) and group 3 was used as control. Drugs were administered orally, once daily for 3 days. Faecal specimens, collected from each rat on day 3, were cultured for the quantitative and qualitative determination of aerobic microorganisms. Rifaximin treatment produced a marked reduction in the number of total aerobic bacteria and Salmonellae; neomycin caused reduction in Salmonellae, but did not cause statistically significant changes in total aerobic bacterial count. The binding of neomycin with faeces could explain this limited activity, which does not correlate with the in vitro susceptibility of the organism affected. These results confirm that rifaximin is suitable for topical treatment to reduce selected bacterial load in the gut intestines.
Background & Aims: Pouchitis is the major long-term complication after ileal pouch–anal anastomosis for ulcerative colitis. Most patients have relapsing disease, and no maintenance treatment study ...has been performed. We evaluated the efficacy of a probiotic preparation (VSL#3) containing 5 × 1011 per gram of viable lyophilized bacteria of 4 strains of lactobacilli, 3 strains of bifidobacteria, and 1 strain of Streptococcus salivarius subsp. thermophilus compared with placebo in maintenance of remission of chronic pouchitis. Methods: Forty patients in clinical and endoscopic remission were randomized to receive either VSL#3, 6 g/day, or an identical placebo for 9 months. Patients were assessed clinically every month and endoscopically and histologically every 2 months or in the case of a relapse. Fecal samples were collected for stool culture before and after antibiotic treatment and each month during maintenance treatment. Results: Three patients (15%) in the VSL#3 group had relapses within the 9-month follow-up period, compared with 20 (100%) in the placebo group (P < 0.001). Fecal concentration of lactobacilli, bifidobacteria, and S. thermophilus increased significantly from baseline levels only in the VSL#3-treated group (P < 0.01). Conclusions: These results suggest that oral administration of this new probiotic preparation is effective in preventing flare-ups of chronic pouchitis.
GASTROENTEROLOGY 2000;119:305-309
The objective of the study was to investigate possible changes in vancomycin serum levels induced by cardio-pulmonary bypass (CPB). Ten cardiac patients (seven males, three females, aged between 56 ...and 81), who underwent cardiac surgery requiring CPB, took part in the study. Vancomycin (15 mg kg−1) was intravenously infused over 60 min before anaesthesia and blood samples were taken at appropriate times after drug administration (0, 0.5, 1, 6, 8 h), after starting CPB (0, 5, 30 and 60 min) and after aortic unclamping (0, 5, 30, 60, 120 min). Drug serum concentrations were determined by means of a fluorescence polarization immunoassay. The area under the concentration–time curve (AUC) measured during CPB were compared with the AUC extrapolated in the same interval by fitting a two-compartment pharmacokinetic model to drug concentrations obtained before and after CPB. Five minutes after starting CPB vancomycin serum levels decreased, on average, by 40.9% and remained steadily lower than the expected values over the next 60 min. In the same interval, the measured AUC was 31.7% lower than the expected AUC. In no instance did serum levels fall below the MIC for most common pathogens (1–2 mg l−1). At aortic unclamping serum levels slightly rebounded but tended to remain lower than the expected concentrations over the next 120 min. In conclusion, during CPB vancomycin serum levels invariably decreased but, at the dose employed (15 mg kg−1), remained in a potentially effective range for antimicrobial prophylaxis.
We investigated the in vitro influence of HAF on the antibacterial activity of moxifloxacin against Escherichia coli ATCC 10798, Escherichia coli K-12, Proteus rettgeri (Sanelli), Staphylococcus ...aureus ATCC 25923 Staphylococcus aureus NCTC 1808 and Staphylococcus epidermidis ATCC 12228. Human ascitic fluid was obtained from 6 cirrhotic patients by paracentesis. The interaction effect was evaluated by the checkerboard technique. Our results indicate the ability of human ascitic fluid to reduce minimum inhibitory concentrations of moxifloxacin against Gram-negative bacteria, but not against Gram-positives.
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