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- Bang, Charlotte Sahlberg, 1967-, et al.
(författare)
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Multiresistant uropathogenic extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2 (CORM-2).
- 2014
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Ingår i: Microbial Pathogenesis. - London : Elsevier. - 0882-4010 .- 1096-1208. ; 66, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Carbon monoxide (CO) releasing molecules (CO-RMs) have been shown to inhibit growth of commensal Escherichia coli (E. coli). In the present study we examined the effect of CORM-2 on uropathogenic E. coli (UPEC) that produces extended-spectrum β-lactamase (ESBL). Viability experiments showed that CORM-2 inhibited the growth of several different ESBL-producing UPEC isolates and that 500 μM CORM-2 had a bactericidal effect within 4 h. The bactericidal effect of CORM-2 was significantly more pronounced than the effect of the antibiotic nitrofurantoin. CORM-2 demonstrated a low level of cytotoxicity in eukaryotic cells (human bladder epithelial cell line 5637) at the concentrations and time-points where the antibacterial effect was obtained. Real-time RT-PCR studies of different virulence genes showed that the expression of capsule group II kpsMT II and serum resistance traT was reduced and that some genes encoding iron acquisition systems were altered by CORM-2. Our results demonstrate that CORM-2 has a fast bactericidal effect against multiresistant ESBL-producing UPEC isolates, and also identify some putative UPEC virulence factors as targets for CORM-2. CO-RMs may be candidate drugs for further studies in the field of finding new therapeutic approaches for treatment of uropathogenic ESBLproducing E. coli.
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| 2. |
- Bang, Charlotte Sahlberg, 1967-, et al.
(författare)
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The antibacterial effect of nitric oxide against ESBL-producing uropathogenic E-coli is improved by combination with miconazole and polymyxin B nonapeptide
- 2014
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Ingår i: BMC Microbiology. - London : BioMed Central. - 1471-2180. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nitric oxide (NO) is produced as part of the host immune response to bacterial infections, including urinary tract infections. The enzyme flavohemoglobin, coded by the hmp gene, is involved in protecting bacterial cells from the toxic effects of NO and represents a potentially interesting target for development of novel treatment concepts against resistant uropathogenic bacteria. The aim of the present study was to investigate if the in vitro antibacterial effects of NO can be enhanced by pharmacological modulation of the enzyme flavohemoglobin.Results: Four clinical isolates of multidrug-resistant extended-spectrum beta-lactamase (ESBL)-producing uropathogenic E. coli were included in the study. It was shown that the NO-donor substance DETA/NO, but not inactivated DETA/NO, caused an initial growth inhibition with regrowth noted after 8 h of exposure. An hmp-deficient strain showed a prolonged growth inhibition in response to DETA/NO compared to the wild type. The imidazole antibiotic miconazole, that has been shown to inhibit bacterial flavohemoglobin activity, prolonged the DETA/NO-evoked growth inhibition. When miconazole was combined with polymyxin B nonapeptide (PMBN), in order to increase the bacterial wall permeability, DETA/NO caused a prolonged bacteriostatic response that lasted for up to 24 h.Conclusion: An NO-donor in combination with miconazole and PMBN showed enhanced antimicrobial effects and proved effective against multidrug-resistant ESBL-producing uropathogenic E. coli.
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| 3. |
- d'Amore, Francesco, et al.
(författare)
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Phase II trial of zanolimumab (HuMax-CD4) in relapsed or refractory non-cutaneous peripheral T cell lymphoma
- 2010
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 150:5, s. 565-573
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy and safety of zanolimumab (HuMax-CD4) in patients with relapsed or refractory peripheral T Cell lymphoma (PTCL) was evaluated. Twenty-one adult patients with relapsed or refractory CD4+ PTCL of non-cutaneous type (angioimmunoblastic T cell lymphoma (AITL) n = 9, PTCL-not otherwise specified (NOS) n = 7, anaplastic large cell lymphoma (ALCL) n = 4 and enteropathy type T cell lymphoma n = 1) were treated in a single-arm multi-centre study, with weekly intravenous infusions of zanolimumab 980 mg for 12 weeks. Median age was 69 years (range 26-85). Seventeen of the patients had advanced stage disease (Ann Arbor stages III-IV). Objective tumour responses were obtained in 24% of the patients with two complete responses unconfirmed (CRu) and three partial responses (PR). One of the CRus lasted more than 252 d. Responses were obtained in different PTCL entities: AITL (n = 3), ALCL (n = 1) and PTCL-NOS (n = 1). In general, the trial drug was well tolerated with no major toxicity. Zanolimumab at a dose of 980 mg weekly demonstrated clinical activity and an acceptable safety profile in this poor-prognosis patient population, suggesting that the potential benefit combining zanolimumab with standard chemotherapy in the treatment of PTCL should be investigated.
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| 4. |
- Persson, Jonas, et al.
(författare)
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Efficacy and safety of clopidogrel after PCI with stenting in patients on oral anticoagulants with acute coronary syndrome
- 2011
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Ingår i: EUROINTERVENTION. - : EUROPA EDITION, 5, RUE SAINT-PANTALEON, BP 61508, TOULOUSE CEDEX 6, 31015, FRANCE. - 1774-024X. ; 6:9, s. 1046-1052
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate crude cardiovascular risk in patients with acute coronary syndrome (ACS) who are on oral anticoagulants (OAC) after percutaneous coronary intervention with stents (PCI-S) and also to evaluate if the patients on OAC after PCI-S benefit from clopidogrel. less thanbrgreater than less thanbrgreater thanMethods and results: Data from RIKS-HIA and SCAAR on patients admitted to coronary care units 1997 to 2005, undergoing PCI-S (n=27,972), were evaluated. OAC were prescribed to 4.2% (n=1,183) of the patients and they had higher crude 1-year mortality than the non-OAC group, (3.6% [n=421 vs. 1.5% [n= 413], p=0.008), but after adjusting for pre-treatment patient characteristics there were no significant difference in 1-year mortality (adjusted risk ratio [adj. RR] 0.82 [95% CI 0.58-1.16]). Of patients on OAC, 56% (n=659) were also on clopidogrel at discharge. Incidence of death or myocardial infarction (MI) within one year did not differ between the clopidogrel and non-clopidogrel group, adj. RR 0.93 (95% Cl 0.65-1.34). Triple therapy (OAC, clopidogrel plus aspirin) was associated with four times higher risk of any bleeding than OAC plus aspirin, adj. RR 4.27 (95% Cl 1.2-15.1) but a lower incidence of death or MI than OAC plus clopidogrel adj. RR 0.63 (95% Cl 0.40-0.99) less thanbrgreater than less thanbrgreater thanConclusions: Patients discharged on OAC after PCI-S in ACS have higher crude 1-year mortality than patients not on OAC, largely explained by age and comorbidities. Adding clopidogrel is not associated with lower incidence of death or MI at one year. Triple therapy is associated with higher risk of any bleeding than OAC plus aspirin but lower risk of death or MI than OAC plus clopidogrel.
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