| 1. |
- Bang, Charlotte Sahlberg, 1967-, et al.
(författare)
-
Multiresistant uropathogenic extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2 (CORM-2).
- 2014
-
Ingår i: Microbial Pathogenesis. - London : Elsevier. - 0882-4010 .- 1096-1208. ; 66, s. 29-35
-
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.
|
|
| 2. |
- Bang, Charlotte Sahlberg, 1967-, et al.
(författare)
-
The antibacterial effect of nitric oxide against ESBL-producing uropathogenic E-coli is improved by combination with miconazole and polymyxin B nonapeptide
- 2014
-
Ingår i: BMC Microbiology. - London : BioMed Central. - 1471-2180. ; 14
-
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.
|
|
| 3. |
- d'Amore, Francesco, et al.
(författare)
-
Phase II trial of zanolimumab (HuMax-CD4) in relapsed or refractory non-cutaneous peripheral T cell lymphoma
- 2010
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 150:5, s. 565-573
-
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.
|
|
| 4. |
- Faucherre, Samuel, et al.
(författare)
-
Short and Long-Term Controls on Active Layer and Permafrost Carbon Turnover Across the Arctic
- 2018
-
Ingår i: Journal of Geophysical Research - Biogeosciences. - : American Geophysical Union (AGU). - 2169-8953 .- 2169-8961. ; 123:2, s. 372-390
-
Tidskriftsartikel (refereegranskat)abstract
- Decomposition of soil organic matter (SOM) in permafrost terrain and the production of greenhouse gases is a key factor for understanding climate change-carbon feedbacks. Previous studies have shown that SOM decomposition is mostly controlled by soil temperature, soil moisture, and carbon-nitrogen ratio (C:N). However, focus has generally been on site-specific processes and little is known about variations in the controls on SOM decomposition across Arctic sites. For assessing SOM decomposition, we retrieved 241 samples from 101 soil profiles across three contrasting Arctic regions and incubated them in the laboratory under aerobic conditions. We assessed soil carbon losses (Closs) five times during a 1 year incubation. The incubated material consisted of near-surface active layer (ALNS), subsurface active layer (ALSS), peat, and permafrost samples. Samples were analyzed for carbon, nitrogen, water content, δ13C, δ15N, and dry bulk density (DBD). While no significant differences were observed between total ALSS and permafrost Closs over 1 year incubation (2.3 ± 2.4% and 2.5 ± 1.5% Closs, respectively), ALNS samples showed higher Closs (7.9 ± 4.2%). DBD was the best explanatory parameter for active layer Closs across sites. Additionally, results of permafrost samples show that C:N ratio can be used to characterize initial Closs between sites. This data set on the influence of abiotic parameter on microbial SOM decomposition can improve model simulations of Arctic soil CO2 production by providing representative mean values of CO2 production rates and identifying standard parameters or proxies for upscaling potential CO2 production from site to regional scales.
|
|
| 5. |
- Kropp, Heather, et al.
(författare)
-
Shallow soils are warmer under trees and tall shrubs across Arctic and Boreal ecosystems
- 2021
-
Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- Soils are warming as air temperatures rise across the Arctic and Boreal region concurrent with the expansion of tall-statured shrubs and trees in the tundra. Changes in vegetation structure and function are expected to alter soil thermal regimes, thereby modifying climate feedbacks related to permafrost thaw and carbon cycling. However, current understanding of vegetation impacts on soil temperature is limited to local or regional scales and lacks the generality necessary to predict soil warming and permafrost stability on a pan-Arctic scale. Here we synthesize shallow soil and air temperature observations with broad spatial and temporal coverage collected across 106 sites representing nine different vegetation types in the permafrost region. We showed ecosystems with tall-statured shrubs and trees (>40 cm) have warmer shallow soils than those with short-statured tundra vegetation when normalized to a constant air temperature. In tree and tall shrub vegetation types, cooler temperatures in the warm season do not lead to cooler mean annual soil temperature indicating that ground thermal regimes in the cold-season rather than the warm-season are most critical for predicting soil warming in ecosystems underlain by permafrost. Our results suggest that the expansion of tall shrubs and trees into tundra regions can amplify shallow soil warming, and could increase the potential for increased seasonal thaw depth and increase soil carbon cycling rates and lead to increased carbon dioxide loss and further permafrost thaw.
|
|
| 6. |
- Mahajan, Anubha, et al.
(författare)
-
Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
-
Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
|
|
| 7. |
- Persson, Jonas, et al.
(författare)
-
Efficacy and safety of clopidogrel after PCI with stenting in patients on oral anticoagulants with acute coronary syndrome
- 2011
-
Ingår i: EUROINTERVENTION. - : EUROPA EDITION, 5, RUE SAINT-PANTALEON, BP 61508, TOULOUSE CEDEX 6, 31015, FRANCE. - 1774-024X. ; 6:9, s. 1046-1052
-
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.
|
|
| 8. |
- Sahlberg Bang, Charlotte, 1967-
(författare)
-
Carbon monoxide and nitric oxide as antimicrobial agents : focus on ESBL-producing uropathogenic E.coli
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Urinary tract infections (UTI) are common in humans and most often caused by uropathogenic Escherichia coli (E. coli). Extended-spectrum beta-lactamase (ESBL)-producing E. coli are increasing worldwide and they are frequently multidrug-resistant with limited treatment options. The overall aim of this thesis was to study the role of the host-derived factors nitric oxide (NO) and carbon monoxide (CO) as antimicrobial agents against ESBL-producing uropathogenic strains of E. coli (UPEC).The NO-donor DETA/NO caused a temporary growth inhibition in ESBL-producing UPEC. The antibacterial effect of DETA/NO was improved when DETA/NO was combined with miconazole, a pharmacological inhibitor of NO-protective mechanisms. Combination treatment with DETA/NO, miconazole and polymyxin B nonapeptid prolonged the bacteriostatic effect in the majority of examined isolates. The CO-donor CORM-2 showed a pronounced antibacterial effect in ESBL-producing UPEC with a fast bactericidal effect. Moreover, CORM-2 was shown to reduce the bacterial viability of ESBL-producing UPEC grown under biofilm-like conditions and to decrease the bacterial colonization of human bladder epithelial cells. A microarray analysis was performed to define transcriptomic targets of CORM-2 after a single exposure and after repeated exposure to CORM-2. Many processes were affected by CORM-2, including a downregulation in energy metabolism and biosynthesis pathways and upregulation of the SOS response and DNA repair. Repeated exposure to CORM-2 did not change the gene expression patterns or fold changes and the growth inhibitory response to CORM-2 was not altered after repeated exposure.In conclusion, NO- and CO-donors have antibacterial effects against ESBL-producing UPEC and may be interesting candidates for development of new antibiotics to treat UTI caused by multidrug-resistant uropathogens.
|
|
| 9. |
- Yang, Changwon, et al.
(författare)
-
One-dimensional numerical simulation of CFB combustion: Improvement of hydrodynamic models for accurate prediction of pressure and particle size distributions
- 2023
-
Ingår i: Fuel. - 0016-2361. ; 346
-
Tidskriftsartikel (refereegranskat)abstract
- This study aims to improve the accuracy of one-dimensional numerical simulations of circulating fluidized bed (CFB) boilers by evaluating models related to solid properties, such as attrition, fragmentation, cyclone efficiency, and bed material discharge. The study validates models for estimating solids holdup and particle size distribution (PSD) using experimental results from a 12 MWth CFB boiler. The study found that accurate prediction of solid axial holdup and local PSD requires proper consideration of attrition and fragmentation, and the simulation results show that attrition has a more significant effect on numerical analysis performance than fragmentation. By using appropriate values for sand attrition constant (5E-7), char attrition constant (6E-6), and coal:1.5, sand:1.2, and char(ash):1.2 fragmentation constants, the pressure distribution measured from experiments was best predicted. The simulation successfully predicted the particle PSD distribution at a specific location in the CFB boiler and pressure change by height, similar to the experimental results In addition, this study investigated the accuracy of 3D computational fluid dynamics (CFD) simulations using solid properties obtained through 1D simulation as initial conditions compared to those based on experimental conditions. The results revealed that 3D CFD simulations using the solid properties from 1D numerical analysis are more accurate, implying that 1D-3D co-simulation approach is a good strategy to increase the simulation performance.
|
|
| 10. |
- Zhang, Yue-Jiao, et al.
(författare)
-
Probing the Electronic Structure of Heterogeneous Metal Interfaces by Transition Metal Shelled Gold Nanoparticle-Enhanced Raman Spectroscopy
- 2016
-
Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 120:37, s. 20684-20691
-
Tidskriftsartikel (refereegranskat)abstract
- In heterogeneous catalysis, characterization of heterogeneous metal interfaces of bimetallic catalysts is a crucial step to elucidate the catalytic performance and is a key to develop advanced catalysts. However, analytical techniques such as X-ray photoelectron spectroscopy can only work in vacuum conditions and are difficult to use for in situ analysis. Here, we present efficient and convenient core-shell nano particle-enhanced Raman spectroscopy to explore the in situ electronic structures of heterogeneous interfaces (Au@Pd and Au@Pt core-shell NPs) by varying the shell thickness. The experimental observations reported here clearly show that Pd donates electrons to Au, while Pt accepts electrons from Au at the heterogeneous interfaces. This conclusion gains further support from ex situ X-ray photoelectron spectroscopy results. The Au core greatly affects the electronic structures of both the Pd and Pt shells as well as catalytic behaviors. Finally, the as prepared core-shell nanoparticles were used to demonstrate their improved catalytic properties in real electrocatalytic systems such as methanol oxidation and oxygen reduction reactions.
|
|
