| 1. |
- Ahrén, Maria, et al.
(author)
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Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement
- 2010
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In: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:8, s. 5753-5762
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Journal article (peer-reviewed)abstract
- Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study. We report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in NI RI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3-5 nm) gadolinium oxide (DEG-Gd2O3) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy. X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd2O3 nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd2O3 nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r(1) and r(2) values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd2O3. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is. an extremely high MR signal at the cellular and molecular level.
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| 2. |
- Gustafsson, Håkan, et al.
(author)
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Magnetic and Electron Spin Relaxation Properties of (GdxY1-x)(2)O-3 (0 <= x <= 1) Nanoparticles Synthesized by the Combustion Method. Increased Electron Spin Relaxation Times with Increasing Yttrium Content
- 2011
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In: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:13, s. 5469-5477
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Journal article (peer-reviewed)abstract
- The performance of a magnetic resonance imaging contrast agent (CA) depends on several factors, including the relaxation times of the unpaired electrons in the CA. The electron spin relaxation time may be a key factor for the performance of new CAs, such as nanosized Gd2O3 particles. The aim of this work is, therefore, to study changes in the magnetic susceptibility and the electron spin relaxation time of paramagnetic Gd2O3 nanoparticles diluted with increasing amounts of diamagnetic Y2O3. Nanoparticles of (GdxY1-x)(2)O-3 (0 <= x <= 1) were prepared by the combustion method and thoroughly characterized (by X-ray diffraction, transmission electron microscopy, thermogravimetry coupled with mass spectroscopy, photoelectron spectroscopy, Fourier transform infrared spectroscopy, and magnetic susceptibility measurements). Changes in the electron spin relaxation time were estimated by observations of the signal line width in electron paramagnetic resonance spectroscopy, and it was found that the line width was dependent on the concentration of yttrium, indicating that diamagnetic Y2O3 may increase the electron spin relaxation time of Gd2O3 nanoparticles.
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| 3. |
- Gustafsson, Håkan, 1976-, et al.
(author)
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Magnetic and Electron Spin Relaxation Properties of (GdxY1-x)2O3 (0 ≤ x ≤ 1) Nanoparticles Synthesized by the Combustion Method. Increased Electron Spin Relaxation Times with Increasing Yttrium Content
- 2011
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In: The Journal of Physical Chemistry C. - United States : American Chemical Society. - 1932-7447 .- 1932-7455. ; 115:13, s. 5469-5477
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Journal article (peer-reviewed)abstract
- The performance of a magnetic resonance imaging contrast agent (CA) depends on several factors, including the relaxation times of the unpaired electrons in the CA. The electron spin relaxation time may be a key factor for the performance of new CAs, such as nanosized Gd2O3 particles. The aim of this work is, therefore, to study changes in the magnetic susceptibility and the electron spin relaxation time of paramagnetic Gd2O3 nanoparticles diluted with increasing amounts of diamagnetic Y2O3. Nanoparticles of (GdxY1-x)2O3 (0 e x e 1) were prepared by the combustion method and thoroughly characterized (by X-ray di.raction, transmission electron microscopy, thermogravimetry coupled with mass spectroscopy, photoelectron spectroscopy, Fourier transform infrared spectroscopy, and magnetic susceptibility measurements). Changes in the electron spin relaxation time were estimated by observations of the signal line width in electron paramagnetic resonance spectroscopy, and it was found that the line width was dependent on the concentration of yttrium, indicating that diamagnetic Y2O3 may increase the electron spin relaxation time of Gd2O3 nanoparticles.
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| 4. |
- Hedlund, Anna, et al.
(author)
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Gd2O3 nanoparticles in hematopoietic cells for MRI contrast enhancement
- 2011
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In: International journal of nano medicine. - Manchester, UK : Dove Medical Press Ltd. - 1178-2013. ; 6, s. 3233-3240
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Journal article (peer-reviewed)abstract
- As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and in recent time there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd2O3) nanoparticles generate higher relaxivity than currently available Gd chelates: In addition, the Gd2O3 nanoparticles have promising properties for MRI cell tracking. The aim of the present work was to study cell labeling with Gd2O3 nanoparticles in hematopoietic cells and to improve techniques for monitoring hematopoietic stem cell migration by MRI. Particle uptake was studied in two cell lines: the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd2O3 nanoparticles and it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by electron microscopy and MRI, and analyzed for particle content by inductively coupled plasma sector field mass spectrometry. Results showed that particles were intracellular, however, sparsely in Ba/F3. The relaxation times were shortened with increasing particle concentration. Relaxivities, r1 and r2 at 1.5 T and 21°C, for Gd2O3 nanoparticles in different cell samples were 3.6–5.3 s-1 mM-1 and 9.6–17.2 s-1 mM-1, respectively. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. However, the increased uptake did not increase the relaxation rate for THP-1 as for Ba/F3, probably due to aggregation and/or saturation effects. Viability of treated cells was not significantly decreased and thus, it was concluded that the use of Gd2O3 nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells. In conclusion, Gd2O3 nanoparticles are a promising material to achieve positive intracellular MRI contrast; however, further particle development needs to be performed.
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| 5. |
- Hu, Zhangjun, et al.
(author)
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Highly Water-Dispersible Surface-Modified Gd2O3 Nanoparticles for Potential Dual-Modal Bioimaging
- 2013
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In: Chemistry - A European Journal. - : Wiley-VCH Verlagsgesellschaft. - 0947-6539 .- 1521-3765. ; 19:38, s. 12658-12667
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Journal article (peer-reviewed)abstract
- Water-dispersible and luminescent gadolinium oxide (GO) nanoparticles (NPs) were designed and synthesized for potential dual-modal biological imaging. They were obtained by capping gadolinium oxide nanoparticles with a fluorescent glycol-based conjugated carboxylate (HL). The obtained nanoparticles (GO-L) show long-term colloidal stability and intense blue fluorescence. In addition, L can sensitize the luminescence of europium(III) through the so-called antenna effect. Thus, to extend the spectral ranges of emission, europium was introduced into L-modified gadolinium oxide nanoparticles. The obtained Eu-III-doped particles (Eu:GO-L) can provide visible red emission, which is more intensive than that without L capping. The average diameter of the monodisperse modified oxide cores is about 4nm. The average hydrodynamic diameter of the L-modified nanoparticles was estimated to be about 13nm. The nanoparticles show effective longitudinal water proton relaxivity. The relaxivity values obtained for GO-L and Eu:GO-L were r(1)=6.4 and 6.3s(-1)mM(-1) with r(2)/r(1) ratios close to unity at 1.4T. Longitudinal proton relaxivities of these nanoparticles are higher than those of positive contrast agents based on gadolinium complexes such as Gd-DOTA, which are commonly used for clinical magnetic resonance imaging. Moreover, these particles are suitable for cellular imaging and show good biocompatibility.
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| 6. |
- Mamhidir, Anna-Greta, et al.
(author)
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Deficient knowledge of multidrug-resistant bacteria and preventive hygiene measures among primary healthcare personnel
- 2011
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In: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 67:4, s. 756-762
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Journal article (peer-reviewed)abstract
- AIM:This paper is a report of a study conducted to describe primary healthcare personnel's knowledge of multidrug-resistant and preventive hygiene measures.BACKGROUND:The group of patients at risk for multi-drug resistant bacteria is largely cared for in primary care. Knowledge of multidrug-resistant and hygiene preventive measures among primary healthcare personnel is therefore essential.METHOD:A descriptive and comparative questionnaire survey among primary healthcare personnel was performed in 2008. In total, five urban and rural primary healthcare centres situated in one county in central Sweden were included. Convenient sampling was used and 10 physicians, 38 district nurses and 10 nursing assistants participated. Knowledge/medical facts concerning multidrug-resistant and hygiene preventive measures were investigated and data were analysed using a quantitative approach.RESULTS:Knowledge/medical facts concerning several aspects of multidrug-resistant bacteria, particularly Extended-Spectrum-Beta-Lactamase producing bacteria, were deficient as was knowledge of different aspects of hygiene preventive measures. Physicians showed significantly better results than district nurses and nursing assistants did. Awareness of proper hand-washing as an effective preventive method and use of aprons in nursing care was high among all participants. Staff who knew they had cared for these patients had significantly better results than the others did.CONCLUSION:Our findings suggest that evidence-based education of multidrug-resistant and hygiene preventive measures, in primary health with subsequent follow-ups should become a prioritized clinician and management concern. Research is needed that focus implementation of evidence-based educations, staff attitudes and responsibilities related to the work with patients at risk of multidrug-resistant bacteria.
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| 7. |
- Randmaa, Maria, 1957-, et al.
(author)
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SBAR improves communication and safety climate and decreases incident reports due to communication errors in an anaesthetic clinic : a prospective intervention study
- 2014
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In: BMJ Open. - : BMJ. - 2044-6055. ; 4:1
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Journal article (peer-reviewed)abstract
- Objectives: We aimed to examine staff members’ perceptions of communication within and between different professions, safety attitudes and psychological empowerment, prior to and after implementation of the communication tool Situation-Background-Assessment-Recommendation (SBAR) at an anaesthetic clinic. The aim was also to study whether there was any change in the proportion of incident reports caused by communication errors.Design: A prospective intervention study with comparison group using preassessments and postassessments. Questionnaire data were collected from staff in an intervention (n=100) and a comparison group (n=69) at the anaesthetic clinic in two hospitals prior to (2011) and after (2012) implementation of SBAR. The proportion of incident reports due to communication errors was calculated during a 1-year period prior to and after implementation.Setting: Anaesthetic clinics at two hospitals in Sweden.Participants: All licensed practical nurses, registered nurses and physicians working in the operating theatres, intensive care units and post anaesthesia care units at anaesthetic clinics in two hospitals were invited to participate.Intervention: Implementation of SBAR in an anaesthetic clinic.Primary and secondary outcomes: The primary outcomes were staff members’ perception of communication within and between different professions, as well as their perceptions of safety attitudes. Secondary outcomes were psychological empowerment and incident reports due to error of communication.Results: In the intervention group, there were statistically significant improvements in the factors “Between-group communication accuracy” (p=0.039) and “Safety climate” (p=0.011). The proportion of incident reports due to communication errors decreased significantly (p<0.0001) in the intervention group, from 31% to 11%.Conclusions: Implementing the communication tool SBAR in anaesthetic clinics was associated with improvement in staff members’ perception of communication between professionals and their perception of the safety climate as well as with a decreased proportion of incident reports related to communication errors.
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| 8. |
- Sabater-Lleal, Maria, et al.
(author)
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Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease.
- 2014
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
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Journal article (peer-reviewed)abstract
- Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung function (spirometry) for association with carotid intima-media thickness (cIMT) in 3,378 subjects with multiple CAD risk factors, and for association with CAD in a case-control study of 5,775 CAD cases and 7,265 controls. SNPs rs2865531, located in the CFDP1 gene, and rs9978142, located in the KCNE2 gene, were significantly associated with CAD. In addition, SNP rs9978142 and SNP rs3995090 located in the HTR4 gene, were associated with average and maximal cIMT measures. Genetic risk scores combining the most robustly spirometry-associated SNPs from the literature were modestly associated with CAD, (odds ratio (OR) (95% confidence interval (CI95) = 1.06 (1.03, 1.09); P-value = 1.5×10-4, per allele). In conclusion, our study suggests that some genetic loci implicated in determining human lung function also influence cIMT and susceptibility to CAD. The present results should help elucidate the molecular underpinnings of the co-morbidity observed across COPD and CAD.
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| 9. |
- van der Harst, Pim, et al.
(author)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Journal article (peer-reviewed)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 10. |
- Zetterling, Maria, et al.
(author)
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Cortisol and adrenocorticotropic hormone dynamics in the acute phase of subarachnoid haemorrhage
- 2011
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In: British Journal of Neurosurgery. - : Informa UK Limited. - 0268-8697 .- 1360-046X. ; 25:6, s. 684-692
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Journal article (peer-reviewed)abstract
- Objective. An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimising care in the acute phase of SAH. Patients. Fifty-five patients with spontaneous SAH were evaluated regarding morning concentrations of serum (S)-cortisol and P-adrenocorticotropic hormone (ACTH) 7 days after the bleeding. In a subgroup of 20 patients, the diurnal changes of S-cortisol and P-ACTH were studied and urine (U)-cortisol was measured. The relationships of hormone concentrations to clinical and radiological parameters and to outcome were assessed. Results. S-cortisol and P-ACTH were elevated the day of SAH. S-cortisol concentrations below reference range were uncommon. Early global cerebral oedema was associated with higher S-cortisol concentrations at admission and a worse World Federation of Neurological Surgeons (WFNS) and Reaction Level Scale 85 grade. Global cerebral oedema was shown to be a predictor of S-cortisol at admittance. Patients in better WFNS grade displayed higher U-cortisol. All patients showed diurnal variations of S-cortisol and P-ACTH. A reversed diurnal variation of S-cortisol was more frequently found in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-cortisol peaks occurred especially in periods of secondary brain ischaemia. Conclusion. There was an HPA response acutely after SAH with an increase in P-ACTH and S-cortisol. Higher U-cortisol in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-cortisol at admission and was a predictor of S-cortisol concentrations. Global cerebral oedema may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischaemia, indicating a possible connection between brain ischaemia and ACTH suppression.
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