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SUMMARY Thirty-seven patients with liver cirrhosis (16 without ascites: group 1; 21 with untreated ascites at the first onset: group 2) were studied during controlled sodium intake (40 mmol/day). Renal plasma flow, glomerular filtration rate, urinary sodium excretion, plasma sodium and potassium, plasma renin activity, plasma aldosterone concentration, blood volume, and arterial pressure were evaluated. All the patients had normal renal perfusion, plasma sodium and potassium, and arterial pressure. Mean plasma renin activity and plasma aldosterone concentration were significantly depressed in group 1 (p<0.001, p<0005 respectively) compared with 21 normal controls in identical experimental conditions. This was possibly a consequence of expanded blood volume (p

Purpose Fortification of foods with vitamin D may be a population-based solution to low vitamin D intake. We performed modelling of vitamin D from diet, fortified foods and supplements in a population of Danish women 18-50 years, a risk group of vitamin D deficiency, to inform fortification policies on safe and adequate levels. Methods Based on individual habitual dietary vitamin D intake of female participants from the Danish National Survey of Dietary Habits and Physical Activity (DANSDA) (n = 855), we performed graded intake modelling to predict the intake in six scenarios increasing the vitamin D intake from a habitual diet without fish to habitual diet including fish, fortified foods and supplements (40/80 µg). Four different foods were used as potential foods to fortify with vitamin D. Results The vitamin D intake was below the Average Requirement (AR) of 7.5 µg/day for 88% of the assessed women. Safe levels of intake (< 100 µg/day) were observed after adding four different fortified foods (plain yoghurt, cheese, eggs and crisp-bread) contributing with a total of 20 µg/day and a vitamin D supplement of 40 µg/day to the habitual diet. Consumption of fish, fortified foods and a vitamin D supplement of 80 µg resulted in intakes above the Tolerable Upper Intake Level (UL) < 100 µg/day. Conclusions In a Danish female population with a low vitamin D intake, low-dose fortification of different foods with vitamin D may be an effective and safe population-based approach.

BackgroundSingle photon emission computed tomography (SPECT) is an indispensable tool in the determination of the in vivo fate of polymeric micelles. However, for this purpose, the micelles need to be radiolabeled, and almost all radiolabeling procedures published to date involve the conjugation of a chelating agent to the constituting polymer, which could actually affect their biodistribution. In this paper, we report a new facile method for radiolabeling polystyrene-b-poly(ethylene oxide) diblock copolymer micelles without the necessity of any chemical modification. Instead, we entrap the radiolabel (i.e., 111In) in the micellar core during the formation of the micelles by using tropolone as lipophilic ligand.MethodsMicelles were prepared by emulsifying a polymer solution in chloroform with a buffer containing 111In and lipophilic ligand tropolone, by stirring for about 2 h. The produced micelles were physically characterized by means of dynamic light scattering and transmission electron microscopy. The biological properties of the radiolabeled micelles were determined by means of in vivo and ex vivo evaluation. SPECT analysis was done on Balb/c-nu mice, after administration of 1 mg micelles containing 22 MBq of 111In. SPECT images were obtained over 24 h. Biodistribution of the micelles was assessed also ex vivo.ResultsThe radiolabeling method is robust and reproducible with constant radiolabeling efficiency (~30 %) even at indium concentrations that are much higher than the necessary for in vivo studies, and the radiolabel retention is more than 80 % in mouse serum at 48 h. Radiolabeled micelles having hydrodynamic radius of 97 ± 13 nm have been successfully evaluated in vivo and ex vivo in non-tumor-bearing mice, revealing significant blood circulation up to at least 24 h post injection, with low accumulation in most organs except for the liver and spleen, which are the natural organs for clearance of nanoparticles.ConclusionsAn easy and robust radiolabeling method has been developed, and its applicability is demonstrated in animal studies, showing its value for future investigation of polymeric micelles as nanocarriers in tumor-bearing mice.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0167-x) contains supplementary material, which is available to authorized users.

In the treatment of neuroendocrine tumors (NETs), complete surgical removal of malignancy is generally desirable, because it offers curative results. Preoperative guidance with radiolabeled somatostatin analogs, commonly used for NET diagnosis and preoperative planning, is limited by its low resolution, with the risk that tumor margins and small metastases will be incompletely resected with subsequent recurrence. A single hybrid probe combining radiotracer and optical dye would enable high-resolution optical guidance, also during surgery. In the current study, the hybrid labeled somatostatin analog Cy5-DTPA-Tyr 3 -octreotate (DTPA is diethylene triamine pentaacetic acid) was synthesized and evaluated for its ability to specifically trace NET cells in vitro and in an animal model. The performance of the hybrid tracer was compared with that of octreotate with only radiolabel or only optical label. Methods: The binding affinity and internalization capacity of Cy5-DTPA-Tyr 3 -octreotate were assessed in vitro. Biodistribution profiles and both nuclear and optical in vivo imaging of Cy5-111 In -DTPA-Tyr 3 -octreotate were performed in NET-bearing mice and compared with the performance of 111 In-DTPA-Tyr 3 -octreotate. Results: In vitro studies showed a low receptor affinity and internalization rate for Cy5-DTPA-Tyr 3 -octreotate. The dissociation constant value was 387.7 ± 97.9 nM for Cy5-DTPA-Tyr 3 -octreotate, whereas it was 120.5 ± 18.1 nM for DTPA-Tyr 3 -octreotate. Similarly, receptor-mediated internalization reduced from 33.76% ± 1.22% applied dose for DTPA-Tyr 3 -octreotate to 1.32% ± 0.02% applied dose for Cy5-DTPA-Tyr 3 -octreotate. In contrast, in vivo and ex vivo studies revealed similar tumor uptake values of Cy5-111 In-DTPA-Tyr 3 -octreotate and 111 In -DTPA-Tyr 3 -octreotate (6.93 ± 2.08 and 5.16 ± 1.27, respectively). All organs except the kidneys showed low background radioactivity, with especially low activities in the liver, and high tumor-to-tissue ratios were achieved-both favorable for the tracer's toxicity profile. Hybrid imaging in mice confirmed that the nuclear and fluorescence signals colocalized. Conclusion: The correlation between findings with the optical and the nuclear probes underlines the potential of combining SPECT imaging with fluorescence guidance and shows the promise of this novel hybrid peptide for preoperative and intraoperative imaging of NET.