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Janine JH Oosterhof G Jolanda Elving Ietse Stokroos Arie van nieuw Amerongen Henny C van der Mei Henk J Busscher 《Biofouling》2013,29(6):347-353
The integrity of biofilms on voice prostheses used to rehabilitate speech in laryngectomized patients causes unwanted increases in airflow resistance, impeding speech. Biofilm integrity is ensured by extracellular polymeric substances (EPS). This study aimed to determine whether synthetic salivary peptides or mucolytics, including N-acetylcysteine and ascorbic acid, influence the integrity of voice prosthetic biofilms. Biofilms were grown on voice prostheses in an artificial throat model and exposed to synthetic salivary peptides, mucolytics and two different antiseptics (chlorhexidine and Triclosan). Synthetic salivary peptides did not reduce the air flow resistance of voice prostheses after biofilm formation. Although both chlorhexidine and Triclosan reduced microbial numbers on the prostheses, only the Triclosan-containing positive control reduced the air flow resistance. Unlike ascorbic acid, the mucolytic N-acetylcysteine removed most EPS from the biofilms and induced a decrease in air flow resistance. 相似文献
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Yongqi Deng Zhiwei Yang Gerald W. Shipps Sie-Mun Lo Robert West Joyce Hwa Shuqin Zheng Constance Farley Jean Lachowicz Margaret van Heek Alan S. Bass Dinesh P. Sinha Craig R. Mahon Mark E. Cartwright 《Bioorganic & medicinal chemistry letters》2013,23(3):791-796
Inhibitors based on a benzo-fused spirocyclic oxazepine scaffold were discovered for stearoyl-coenzyme A (CoA) desaturase 1 (SCD1) and subsequently optimized to potent compounds with favorable pharmacokinetic profiles and in vivo efficacy in reducing the desaturation index in a mouse model. Initial optimization revealed potency preferences for the oxazepine core and benzylic positions, while substituents on the piperidine portions were more tolerant and allowed for tuning of potency and PK properties. After preparation and testing of a range of functional groups on the piperidine nitrogen, three classes of analogs were identified with single digit nanomolar potency: glycine amides, heterocycle-linked amides, and thiazoles. Responding to concerns about target localization and potential mechanism-based side effects, an initial effort was also made to improve liver concentration in an available rat PK model. An advanced compound 17m with a 5-carboxy-2-thiazole substructure appended to the spirocyclic piperidine scaffold was developed which satisfied the in vitro and in vivo requirements for more detailed studies. 相似文献
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Emma C. Wall Katharine Cartwright Matthew Scarborough Katherine M. Ajdukiewicz Patrick Goodson James Mwambene Eduard E. Zijlstra Stephen B. Gordon Neil French Brian Faragher Robert S. Heyderman David G. Lalloo 《PloS one》2013,8(7)
Mortality from bacterial meningitis in African adults is significantly higher than those in better resourced settings and adjunctive therapeutic interventions such as dexamethasone and glycerol have been shown to be ineffective. We conducted a study analysing data from clinical trials of bacterial meningitis in Blantyre, Malawi to investigate the clinical parameters associated with this high mortality.
Methods
We searched for all clinical trials undertaken in Blantyre investigating bacterial meningitis from 1990 to the current time and combined the data from all included trial datasets into one database. We used logistic regression to relate individual clinical parameters to mortality. Adults with community acquired bacterial meningitis were included if the CSF culture isolate was consistent with meningitis or if the CSF white cell count was >100 cells/mm3 (>50% neutrophils) in HIV negative participants and >5 cells/mm3 in HIV positive participants. Outcome was measured by mortality at discharge from hospital (after 10 days of antibiotic therapy) and community follow up (day 40).Results
Seven hundred and fifteen episodes of bacterial meningitis were evaluated. The mortality rate was 45% at day 10 and 54% at day 40. The most common pathogens were S.pneumoniae (84% of positive CSF isolates) and N.meningitidis (4%). 607/694 (87%) participants tested were HIV antibody positive. Treatment delays within the hospital system were marked. The median presenting GCS was 12/15, 17% had GCS<8 and 44.9% had a seizure during the illness. Coma, seizures, tachycardia and anaemia were all significantly associated with mortality on multivariate analysis. HIV status and pneumococcal culture positivity in the CSF were not associated with mortality. Adults with community acquired bacterial meningitis in Malawi present with a severe clinical phenotype. Predictors of high mortality are different to those seen in Western settings. Optimising in-hospital care and minimising treatment delays presents an opportunity to improve outcomes considerably. 相似文献8.
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Ali C Akyildiz Lambert Speelman Harald van Brummelen Miguel A Gutiérrez Renu Virmani Aad van der Lugt Anton FW van der Steen Jolanda J Wentzel Frank JH Gijsen 《Biomedical engineering online》2011,10(1):25