Objective Innate immune protein C1q plays a dual role in the chronic inflammatory disease of atherosclerosis. Complement activation via C1q exacerbates pathology in the atherosclerotic lesion in later stages of the disease. However, in early stages of disease C1q is protective. We hypothesize that complement-independent activities of C1q are involved in reprogramming macrophage inflammatory polarization. Methods The influence of C1q on macrophage inflammatory responses during clearance of oxLDL was examined. Changes in cytokines at the gene and protein level were measured by quantitative PCR and ELISA assay. Results C1q modulated cytokine expression in Raw264.7 macrophages during ingestion of oxLDL. Levels of proinflammatory cytokines IL-1β and IL-6 were downregulated by C1q, whereas levels of the anti-inflammatory cytokine IL-10 were increased. In addition, data from an NFκB-luciferase gene reporter assay suggest that C1q suppresses activation of NFκB during lipoprotein clearance in macrophages, providing one mechanism by which C1q downregulates pro-inflammatory cytokine production. Conclusions C1q-polarization of macrophages toward an anti-inflammatory (M2-like) phenotype may be important in dampening inflammation in the early atherosclerotic lesion. Further investigation of molecular pathways targeted by C1q may provide novel therapeutic targets for this disease.
If you would like to write for this, or any other Emerald publication, then please use our Emerald for Authors service information about how to choose which publication to write for and submission guidelines are available for all. Please visit www.emeraldinsight.com/authors for more information. About Emerald www.emeraldinsight.comEmerald is a global publisher linking research and practice to the benefit of society. The company manages a portfolio of more than 290 journals and over 2,350 books and book series volumes, as well as providing an extensive range of online products and additional customer resources and services.Emerald is both COUNTER 4 and TRANSFER compliant. The organization is a partner of the Committee on Publication Ethics (COPE) and also works with Portico and the LOCKSS initiative for digital archive preservation. AbstractPurpose -The purpose of this paper is to systematically review online ethnography and its boundary challenges. The paper especially focusses on how researchers draw space boundaries, set time boundaries and engage their online field. Design/methodology/approach -The authors perform a systematic review of extant literature and identify 59 papers in 40 different journals as online ethnographies from various management disciplines. The authors perform both qualitative and quantitative analyses on papers in the sample. Findings -The paper identifies how online ethnographers both define boundaries and engage their online field. The paper shows that some of the advantages of online ethnography actually prompt researchers to favor-specific research designs over others.Research limitations/implications -The authors only focussed on articles adopting online ethnography in organization and management studies that are listed in Social Sciences Citation Index database. Online ethnographies in other research fields and indexes are not studied in this paper. Practical implications -The paper makes suggestions on how to complement existing online ethnographies to reach a more comprehensive practice of online ethnography. Social implications -The systematic review may help researchers to locate useful online ethnography examples across various management disciplines and may contribute to the maturation of online ethnography. Originality/value -The paper synthesizes emerging trends in online ethnography and identifies how specific advantages actually prompt online ethnographers to limit themselves in their research designs.
We investigated the efficiency of the cephamycin cefoxitin as an alternative to carbapenems for the treatment of urinary tract infections (UTIs) due to Escherichia coli producing CTX-M-type extended-spectrum -lactamases. The susceptible, UTIinducing E. coli CFT073-RR strain and its transconjugant CFT073-RR Tc (pbla CTX-M-15 ), harboring a bla CTX-M-15 carryingplasmid, were used for all experiments. MICs of cefoxitin (FOX), ceftriaxone (CRO), imipenem (IMP), and ertapenem (ETP) for CFT073-RR and CFT073-RR Tc (pbla CTX-M-15 ) were 4 and 4, 0.125 and 512, 0.5 and 0.5, and 0.016 and 0.032 g/ml, respectively. Bactericidal activity was similarly achieved in vitro against the two strains after 3 h of exposure to concentrations of FOX, IMI, and ETP that were 2 times the MIC, whereas CRO was not bactericidal against CFT073-RR Tc (pbla CTX-M-15 ). The frequencies of spontaneous mutants of the 2 strains were not higher for FOX than for IMP or ETP. In the murine model of UTIs, mice infected for 5 days were treated over 24 h. Therapeutic regimens in mice (200 mg/kg of body weight every 3 h or 4 h for FOX, 70 mg/kg every 6 h for CRO, 100 mg/kg every 2 h for IMP, and 100 mg/kg every 4 h for ETP) were chosen in order to reproduce the percentage of time that free-drug concentrations above the MIC are obtained in humans with standard regimens. All antibiotic regimens produced a significant reduction in bacterial counts (greater than 2 log 10 CFU) in kidneys and bladders for both strains (P < 0.001) without selecting resistant mutants in vivo, but the reduction obtained with CRO against CFT073-RR Tc (pbla CTX-M-15 ) in kidneys was significantly lower than that obtained with FOX. In conclusion, FOX appears to be an effective therapeutic alternative to carbapenems for the treatment of UTIs due to CTX-M-producing E. coli. Over the last decade, resistance to -lactams among Enterobacteriaceae has emerged as a major public health threat. This is mostly due to proliferation of extended-spectrum -lactamases (ESBLs), especially of the CTX-M-type, which have spread worldwide both in hospitals and the community (9). Escherichia coli isolates that produce CTX-M (especially CTX-M-15 in Western countries) are currently a serious cause of urinary tract infections (UTIs) in the community (36). Mortality in the most severe infections, particularly those evolving into bacteremia, is as high as 60% (27). In addition, associated resistance to other classes of antimicrobial agents is often observed in CTX-M producers, limiting the availability of therapeutic options. Carbapenems are widely regarded as the drug of choice for parenchymal infections due to ESBL-producing Enterobacteriaceae (35). However, several reports have described the emergence of resistance to carbapenems in Enterobacteriaceae by two mechanisms: (i) in vivo selection of porin-deficient mutants under therapy with carbapenems (11,20) and (ii) emergence of carbapenemases, reported extensively in Klebsiella pneumoniae (18, 30) and more recently in E. coli (18,29). The rise of ESBLs h...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.