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We performed susceptibility testing using the microdilution method to determine the in-vitro activity of tigecycline against 393 Acinetobacter baumannii clinical isolates collected in 2006 from 19 hospitals in Taiwan. Significant proportions of the isolates were resistant to imipenem (44%), ciprofloxacin (75%), amikacin (69%), sulbactam (34%) and all four antibiotics (22%), and susceptibility to tigecycline among these different resistant phenotypes of A. baumannii varied from 71% to 82%. The minimum inhibitory concentration (MIC) of tigecycline ranged from 0.6 to 16 microg/mL (MIC(50) 2 microg/mL; MIC(90) 4 microg/mL). The cumulative curve of tigecycline MICs showed that when the MIC cut-offs were set at 2 microg/mL and 4 microg/mL, 80.9% and 93.1% of the isolates were susceptible, respectively. As tigecycline will be used in the future for infections caused by multidrug-resistant A. baumannii because of limited antibiotic choice, and as resistance to tigecycline in A. baumannii isolates may develop following antibiotic exposure, continuous monitoring of the susceptibility of A. baumannii isolates to tigecycline is warranted.
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The quinolones involved were moxifloxacin (N = 24), ciprofloxacin (N = 11) and levofloxacin (N = 3). Sepharose-RIA was positive in 12 cases (31.57%) and BAT in 27 (71.05%). With Sepharose-RIA, 8 (21%) were positive to ciprofloxacin, 7 (18.4%) to moxifloxacin and 7 (18.4%) to levofloxacin. With BAT, 23 (60.5%) were positive to ciprofloxacin, 12 (31.6%) to moxifloxacin and 8 (21%) to levofloxacin. The specificity of the Sepharose-RIA was demonstrated by inhibition tests. To confirm that the BAT results observed were IgE mediated, the PI3K inhibitor wortmannin was used, with this compound inhibiting the BAT when stimulated with anti-IgE and the different quinolones, but not when fMLP was used as the basophil stimulator. Sepharose-RIA and BAT were repeated in positive cases 1 year later, detecting a decrease in all cases, with four becoming negative.
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Of 338 isolates, MRSA rate was 50.0%. Among MRSA isolates (n = 169), 81.7% were associated to MLST CC5, 68.8% had spa t149/SCCmec I, and more than 85% were co-resistant to ciprofloxacin, clindamycin, erythromycin and gentamicin; 8.9% (n = 15) were associated to MLST CC8, 14 of them had spa t148/SCCmec IV, and more than 70% were co-resistant to ciprofloxacin, clindamycin and erythromycin. Among MSSA isolates (n = 169), there was a higher diversity of spa types (n = 56) compared to MRSA isolates (n = 17), 27.2% were associated to MLST CC8, 23.7% were resistant to erythromycin and clindamycin resistance exceeded 20%.
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A total of 1324 bacterial pathogens representing more than 70 species were isolated. The most common species were Haemophilus influenzae (26.0%), Streptococcus pneumoniae (22.8%), Staphylococcus aureus (14.4%), and Staphylococcus epidermidis (8.4%). H. influenzae was most frequently isolated among patients aged 1-18 years, while S. aureus was most prevalent among those >65 years. Drug resistance was prevalent: Of H. influenzae isolates, 25.3% were β-lactamase positive and 27.2% of S. pneumoniae isolates were penicillin-intermediate/ resistant; of S. aureus isolates, 13.7% were methicillin-resistant (MRSA), and of these, 65.4% were ciprofloxacin-resistant, while 45.9% of S. epidermidis isolates were methicillin-resistant (MRSE), and, of these, 47.1% were ciprofloxacin-resistant. Besifloxacin was more potent than comparator fluoroquinolones overall, and particularly against Gram-positive bacteria. Against ciprofloxacin-resistant MRSA and MRSE, besifloxacin was four-fold to ≥ 128-fold more potent than other fluoroquinolones.
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3Mix and Vitapex((R)) can be used as a root canal treatment agent in pulpally involved primary teeth.
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In the present work, the development, optimization, and validation (including a whole stability study) of a fast, reliable, and comprehensive method for the analysis of ten anticancer drugs in hospital and urban wastewater is described. Extraction of these pharmaceutical compounds was performed using automated off-line solid-phase extraction followed by their determination by ultra-performance liquid chromatography coupled to a triple quadrupole-linear ion trap mass spectrometer. Target compounds include nine cytotoxic agents: cyclophosphamide, ifosfamide, docetaxel, paclitaxel, etoposide, vincristine, tamoxifen, methotrexate, and azathioprine; and the cytotoxic quinolone, ciprofloxacin. Method detection limits (MDL) ranged from 0.8 to 24 ng/L. Levels found of cytostatic agents in the hospital and wastewater influents did not differ significantly, and therefore, hospitals cannot be considered as the primary source of this type of contaminants. All the target compounds were detected in at least one of the influent samples analyzed: Ciprofloxacin, cyclophosphamide, tamoxifen, and azathioprine were found in most of them and achieving maximum levels of 14.725, 0.201, 0.133, and 0.188 μg/L, respectively. The rest of target cancer drugs were less frequently detected and at values ranging between MDL and 0.406 μg/L. Furthermore, a feasible, useful, and advantageous approach based on information acquisition tool (information-dependent acquisition) was used for the screening of human metabolites in hospital effluents, where the hydroxy tamoxifen, endoxifen, and carboxyphosphamide were detected.
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When a benzenesulfonyl moiety (BS) was bound to the N-piperazinyl ring of antibacterial fluoroquinolones (AMFQs) norfloxacin (NOR) or ciprofloxacin (CIP), the resulting benzenesulfonyl-fluoroquinolone (BSFQs) analogs showed an improved in vitro activity against Gram-positive strains. A bioisosterical replacement of the sulfonyl group for a carbonyl group led to the benzenecarboxamide-fluoroquinolones (BCFQs) that showed a similar trend in the antibacterial activity and spectrum. The BSFQs and BCFQs are considered members of the "dual targeting" fluoroquinolones, targeting both DNA gyrase and topoisomerase IV. To disclose the real contribution of the BS/BC moiety in anti-staphylococcal activity, a 3D-QSAR analysis that included calculation of theoretical molecular descriptors and pharmacophore generation was performed. Previous and present QSAR results have confirmed the positive influence on activity of small electron donating p-substituent on the BS or BC moiety. The generated phamacophore model showed that both phenyl and SO2/CO groups are involved in the interaction with receptor. We postulate that the enhanced potency of BSFQs against Staphylococcus aureus compared to CIP and NOR could be caused by the presence of the BS moiety that resulted in enhanced binding to DNA gyrase of Sa. Additionally, their greater ability to enter bacterial cells by diffusion and a reduced susceptibility to FQ-specific efflux pumps could also make a contribution.
Management of Type 1 diabetes is burdensome, both to the individual and society, costing over 100 billion dollars annually. Despite the widespread use of glucose monitoring and new insulin formulations, many individuals still develop devastating secondary complications. Pancreatic islet transplantation can restore near normal glucose control in diabetic patients, without the risk of serious hypoglycemic episodes that are associated with intensive insulin therapy. Providing sufficient islet mass is important for successful islet transplantation. However, donor characteristics, organ procurement and preservation affect the isolation outcome. At University of Illinois at Chicago (UIC) we developed a successful isolation protocol with an improved purification gradient. The program started in January 2004 and more than 300 isolations were performed up to November 2008. The pancreata were sent in cold preservation solutions (UW, University of Wisconsin or HTK, Histidine-Tryptophan Ketoglutarate) to the Cell Isolation Laboratory at UIC for islet isolation. Pancreatic islets were isolated using the UIC method, which is a modified version of the method originally described by Ricordi et al. As described in Part I: Digestion and Collection of Pancreatic Tissue, human pancreas was trimmed, cannulated, perfused, and digested. After collection and at least 30 minutes of incubation in UW solution, the tissue was loaded in the cell separator (COBE 2991, Cobe, Lakewood, CO) for purification. Following purification, islet yield (expressed as islet equivalents, IEQ), tissue volume, and purity was determined according to standard methods. Isolated islets were cultured in CMRL-1066 media (Mediatech, Herndon, VA), supplemented with 1.5% human albumin, 0.1% insulin-transferrin-selenium (ITS), 1 ml of Ciprofloxacin, 5 ml o f 1M HEPES, and 14.5 ml of 7.5% Sodium Bicarbonate in T175 flasks at 37 degrees C overnight culture before islets were transplanted or used for research.