Stability testing of gadoteridol and gadobenate dimeglumine formulations under exposure to high-intensity focused ultrasound.

OBJECTIVE: Contrast-enhanced MRI could be useful to guide high-intensity focused ultrasound treatment (HIFU), but the effects of HIFU on gadolinium-based agents is not known. Here, we tested in vitro the stability of gadoteridol and gadobenate dimeglumine, two widely used MR contrast agents, after exposure to HIFU at power levels typically applied in the clinical practice. METHODS: 0.5 M (gadoteridol and gadobenate dimeglumine) and diluted formulations (1:10 gadoteridol in saline) were exposed to different HIFU sequences. Unexposed and exposed solutions were characterized by high-performance liquid chromatography in terms of concentration of gadolinium complex, free gadolinium and free ligand. RESULTS: Gadoteridol formulation after treatment showed concentrations of the complex not significantly different from control. Free Gd and/or free ligand concentrations in the order of 0.002/0.004% w/w, were observed occasionally without significant correlation with intensity and duration of exposure to HIFU. Gadobenate dimeglumine formulation after treatment showed complex assay content values, by-products (0.24-0.26%) and free BOPTA levels (0.07%) comparable to control sample within the experimental error. CONCLUSION: In the range of conditions explored, HIFU exposure did not induce significant dissociations of gadoteridol and gadobenate dimeglumine, nor a detectable increase in the concentration of free species. ADVANCES IN KNOWLEDGE: Our study strengthens the hypothesis that gadolinium-based contrast agents are stable during HIFU treatment for body applications (e.g. thermal ablation of uterine fibroids).

Palliative sedation at end of life - a systematic literature review.

Palliative sedation at the end of life to handle unmanageable symptoms has been much debated. A systematic literature review in three phases including a content analysis of 15 articles published between the years 1990 and 2005 has been conducted. The aim was to describe the phenomenon of 'palliative sedation at the end of life' from a nursing perspective. The results can be summarised in three themes: 'Important factors leading to the patient receiving sedation at the end of life', 'Attitudes to palliative sedation at the end of life' and 'Nurses' experience of palliative sedation at the end of a patient's life'. Together, the themes show that palliative sedation is a phenomenon that could be described as sedation given to fewer than 40% of dying patients during their last 4 days of life. It is usually given because of the patient's pain, agitation and/or dyspnoea. Professionals usually have positive attitudes towards it and their view differs from that of the public's view regarding it as continuously deep sedation, whereas the public regards it as being close to euthanasia. Studies focusing on nursing care during palliative sedation are hard to find and this underlines the importance of further research in this area to elucidate the nurses' role during palliative sedation.

Water exchange across the erythrocyte plasma membrane studied by HR-MAS NMR spectroscopy.

Water exchange across the plasma membrane of erythrocytes (red blood cells (RBCs)) was studied by means of high-resolution magic angle spinning (HR-MAS) NMR spectroscopy. Under HR-MAS conditions, the centrifugal force causes the splitting of RBC suspensions into a two-phase system composed of a central core of cell free water and an outer layer of tightly packed cells. Water belonging to each of these phases gives rise to two separated resonances. Chemical exchange between them is not detectable on the chemical shift or saturation transfer (ST) NMR time scale because of the physical separation between the phases. When the RBCs are dispersed and immobilized within a matrix made of cross-linked albumin, the splitting into a two-phase system is prevented and a single exchange-averaged peak for water is detected in (1)H HR-MAS NMR spectra. The lineshape of this peak is dependent on transmembrane exchange kinetics, since MAS averages out all the anisotropic magnetic interactions that are responsible for additional line-broadening under conventional liquid conditions. Line-shape analysis according to a two-site exchange model yielded a residence lifetime on the order of about 10 ms (at 37 degrees C) for a water molecule within the intracellular compartment, which is not too far from the generally accepted value of 9.6-14.8 ms.

HR-MAS of cells: A "cellular water shift" due to water-protein interactions?

Under HR-MAS conditions, cells are subjected to high centrifugal forces that may cause irreversible cell damage. First, conditions have been defined to monitor and keep to a minimum unwanted effects in HR-MAS spectra arising from the loss of cell integrity. Then, the HR-MAS spectra of reasonably intact cells have been analyzed. Cell suspensions subjected to MAS rates as low as 1 kHz split into a two-compartment system that is composed of a cell-rich phase (H(2)O(i)) and a cell-free phase (H(2)O(o)). Each of these phases is characterized by its own water (1)H-NMR signal. Transport of water molecules between the cell-rich and cell-free compartments is limited by the very low contact area between the two compartments, and water exchange dynamics consequently fall into the slow exchange limit on the NMR timescale. Since the exchange between the two water populations is "frozen," the separation between the H(2)O(o) and H(2)O(i) water signals (Deltanu(water)) detected in an HR-MAS experiment is not affected by chemical exchange but reflects only chemical differences in the two environments. Different cell lines show a different Deltanu(water), leading to the concept of "cellular water shift." This shift roughly correlates with the cellular protein content, supporting the view that the most important determinant of the cellular water shift is the interaction between water and proteins in the intracellular compartment.

Modulation of the antioxidant activity of HO* scavengers by albumin binding: a 19F-NMR study.

The interaction between different HO(z.rad;) radical scavengers in a three-component antioxidant system has been investigated by means of 19F-NMR spectroscopy. This system is composed of bovine serum albumin (BSA), trolox, and N-(4-hydroxyphenyl)-trifluoroacetamide (CF(3)PAF). The antioxidant capacity of BSA and trolox has been assessed by measuring the amount of trifluoroacetamide (TFAM) arising from the radical mediated decomposition of CF(3)PAF. When assayed separately, both trolox and BSA behaved as antioxidants, as they were effective to protect CF(3)PAF from HO* radical-mediated decomposition. By contrast, trolox enhanced the production of TFAM in the presence of BSA, thus behaving as a pro-oxidant. Urate, carnosine, glucose, and propylgallate showed antioxidant properties both with or without BSA. CF(3)PAF and trolox were found to bind to BSA with association constants in the order of 5 x 10(3)M(-1) and to compete for the same binding sites. These results have been discussed in terms of BSA-catalysed cross-reactions between trolox-derived secondary radicals and CF(3)PAF.