Ciprofloxacin has antifibrotic effects in scleroderma fibroblasts via downregulation of Dnmt1 and upregulation of Fli1

Systemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs. The present study was undertaken to examine the effects of ciprofloxacin, a fluoroquinolone antibiotic implicated in matrix remodeling, on dermal and lung fibroblasts obtained from SSc patients. Dermal and lung fibroblasts from SSc patients and healthy subjects were treated with ciprofloxacin. Western blotting was used to analyze protein levels and RT-PCR was used to measure in RNA expression. The pharmacologic inhibitor UO126 was used to block Erk1/2 signaling. SSc dermal fibroblasts demonstrated a significant decrease in collagen type I mRNA and protein levels after antibiotic treatment, while healthy dermal fibroblasts were less sensitive to ciprofloxacin, downregulating collagen only at the protein levels. Connective tissue growth factor (CCN2) gene expression was significantly reduced and matrix metalloproteinase (MMPI) levels were enhanced after ciprofloxacin treatment to a similar extent in healthy and SSc fibroblasts. Ciprofloxacin induced Erk1/2 phosphorylation, and Erk1/2 blockade completely prevented MMP1 upregulation. However. Smad1 and Smad3 activation in response to TGF beta was not affected. The expression of friend leukemia integration factor 1 (Fli1). a transcriptional repressor of collagen, was increased after treatment with ciprofloxacin only in SSc fibroblasts, and this was accompanied by a decrease in the levels of DNA methyltransferase 1 (Dnmt1). Similar effects were observed in SSc-interstitial lung disease (ILD) lung fibroblasts. In summary, our study demonstrates that ciprofloxacin has antifibrotic actions in SSc dermal and lung fibroblasts via the downregulation of Dnmt1, the upregulation of Fli1 and induction of MMPI gene expression via an Erk1/2-dependent mechanism. Thus, our data suggest that ciprofloxacin may he an attractive therapy for SSc skin and lung fibrosis.

Effectiveness of the association of dexamethasone with antibiotic therapy in pediatric patients with bacterial meningitis

Effectiveness of the association of dexamethasone with antibiotic therapy in pediatric patients with bacterial meningitis Objective: To evaluate the efficacy of the association of corticosteroids and the standard treatment of bacterial meningitis in pediatric patients. Methods: A systematic review of the literature was conducted through the MEDLINE database. Only randomized controlled trials comparing dexamethasone with placebo in the treatment of pediatric patients with bacterial meningitis were included. Results: Eight articles met the inclusion criteria and were selected for analysis. There were no difference in mortality (p = 0.86), and incidence of neurological (p = 0.41) and auditory (p = 0.48) sequelae between the groups. Conclusion: There are no benefits in associating corticosteroids with the standard treatment of bacterial meningitis in pediatric patients.

Applying validated quality indicators to surgical antibiotic prophylaxis in a Brazilian hospital: Learning what should be learned

Background: Compliance with the best surgical antibiotic prophylaxis practice is usually low despite many published guidelines. Objective: This study investigated compliance with the Hospital Infection Control Committee guideline for antibiotic prophylaxis in a Brazilian hospital using quality indicators. Methods: A retrospective study was carried out from November 2009 to March 2010. Medical records from adult inpatients undergoing cardiac, neurologic, and orthopedic clean surgeries were included. The full compliance index was considered 100% when the antibiotic prophylaxis showed adequacy in all evaluated attributes. Analyses were conducted with 5% significance. Results: Medical records from 101 cardiac, 128 neurologic, and 519 orthopedic surgical patients were evaluated. The compliance index was 4.9%, and the compliance index according to specialty was 5.8%, 3.1%, and 3.0%, respectively, for orthopedic, neurologic, and cardiac surgeries. The attribute route of administration produced the best outcomes, whereas the attribute duration of antibiotic prophylaxis produced the worst. No association was identified between compliance to the attributes and patient characteristics. Conclusion: This study showed a low level of adherence to Hospital Infection Control Committee guidelines for antibiotic prophylaxis. This suggests that different strategies should be implemented to promote the best possible practice in the field of antibiotic prophylaxis with greater surgeon engagement. Copyright (C) 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Clinical and surgical evaluation of the indication of postoperative antibiotic prescription in third molar surgery

Objective. The aim of this study was to evaluate the need for antibiotic prescription in third molar surgery. Study design. A double-blind randomized study was carried out with 71 patients from CODONT (Dentistry Center of the Police of Sao Paulo). Amoxicillin, clindamycin, or no medication was administered for 7 days immediately after surgery. The participants evaluated the presence of pain, edema, interincisal distance (ID), presence of infection, Pell and Gregory classification, rescue analgesia, osteotomy, and odontosection. Results. There was no difference (P < .05) between antibiotics and control over the surgery duration, dose, visual analog scale (VAS), ID, and edema, yet significant differences were seen over time for VAS, edema, and ID. Conclusions. Antibiotic prescription should not be indicated in all clinical conditions, yet it is necessary to correctly evaluate factors such as systemic condition of the patient, skill of the operator, and contamination of the surgical environment. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012; 114(suppl 5):S26-S31)

Tuning the reaction products of ruthenium and ciprofloxacin for studies of DNA interactions

This work presents two potential metallo-drugs, the ionic (C17H19FN3O3)(3)[RuCl6]center dot 3H(2)O (1) and the coordination [Ru(C17H17FN3O3)(3)]center dot 4H(2)O (2) compounds, obtained by the combination of ruthenium(III) and ciprofloxacin in different synthetic conditions. The ESI MS spectrum of 1 displayed a main peak at m/z = 994.6, assigned to the gaseous phase adduct (ciprofloxacin)(3)center dot H+, while 2 featured peaks at m/z 1093.3 and 547.1 ascribed to [Ru(C17H17FN3O3)(3)center dot H+-4H(2)O](+) and [Ru(C17H17FN3O3)(3)center dot 2H(+)-4H(2)O](2+). Thermal analysis corroborated the proposed water content for both complexes. Absorption spectra of the compounds in aqueous medium are dominated by ciprofloxacin transitions in the UV region but displayed weak bands in the visible region, assigned to ligand field transitions. The cyclic voltammograms of 2 exhibited a quasi-reversible process ascribed to the Ru(II)/(III) redox pair at -0.25V (vs. SHE) while 1 displayed this process at -0.11 V, showing that the central ruthenium ion is stabilized in the (III) oxidation state by the coordination to the hard oxygen atoms of ciprofloxacin. The solubility of 1 is pH dependent (as well as free ciprofloxacin) while 2 is fully water soluble and stable under physiological pH for at least 48 h. The compounds are also stable under incubation conditions (stomach pH and 37 degrees C) without significant pH lowering. An interaction study of 2 with ct-DNA showed a value of K-b = 2.47 (+/- 0.89) x 10(4) mol(-1) L for the intrinsic binding constant.

The first report of the qnrB19, qnrS1 and aac(6 ')-Ib-cr genes in urinary isolates of ciprofloxacin-resistant Escherichia coli in Brazil

In this study, we investigated the presence of plasmid-mediated quinolone resistance (PMQR) genes among 101 ciprofloxacin-resistant urinary Escherichia coli isolates and searched for mutations in the quinolone-resistance-determining regions (QRDRs) of the DNA gyrase and topoisomerase IV genes in PMQR-carrying isolates. Eight isolates harboured the qnr and aac(6')-Ib-cr genes (3 qnrS1, 1 qnrB19 and 4 aac(6')-Ib-cr). A mutational analysis of the QRDRs in qnr and aac(6')-Ib-cr-positive isolates revealed mutations in gyrA, parC and parE that might be associated with high levels of resistance to quinolones. No mutation was detected in gyrB. Rare gyrA, parC and parE mutations were detected outside of the QRDRs. This is the first report of qnrB19, qnrS1 and aac(6')-Ib-cr-carrying E. coli isolates in Brazil.