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Transgastric endoscopic splenectomy in a porcine model appears technically feasible. Additional long-term survival experiments are planned.

Quantitative, single-voxel proton NMR spectroscopy of normal brain was performed in five adult beagle dogs using the cerebral water signal as an internal intensity reference. The same brain regions were then rapidly isolated and frozen using a pneumatic biopsy drill, perchloric acid extracted, and analyzed by biochemical assay and high-resolution NMR spectroscopy. The concentrations of the major resonances in the in vivo and in vitro spectra were compared, and good agreement was found between the different measurements. The in vivo spectra contained three peaks at 3.21, 3.04, and 2.02 ppm, which are usually assigned to trimethylamines (TMA), creatines, and N-acetyl derivatives (NAc), which corresponded to be the following metabolite concentration values: 1.7 +/- 0.6, 7.7 +/- 2.1, and 10.9 +/- 2.7 mumol/g wet weight respectively. In vitro, the following metabolite concentrations were measured: glycerophosphocholine (GPC) 1.3 +/- 0.2, phosphocholine (PC) 0.5 +/- 0.1, phosphocreatine (PCr) 2.6 +/- 0.4, creatine (Cr) 5.9 +/- 1.4, and N-Acetyl aspartate (NAA) 8.9 +/- 1.8 mumol/g wet weight. Therefore, the 3.21 ppm resonance observed in the in vivo spectrum is predominantly GPC and PC in a ratio of 2.6:1, the 3.04 ppm resonance is Cr and PCr in a ratio of 2.3:1, and the 2.02 ppm resonance is predominantly (approximately 80%) NAA with small contributions from N-acetylaspartylglutamate (NAAG) and glutamate. The data presented here validate the technique of water referencing as a simple and convenient means of quantitating single-voxel in vivo proton NMR spectra of the brain.

Alginate-poly-L-lysine-alginate (APA) microcapsules have been explored as vehicles for therapeutic drug and cell delivery. The permselectivity of these capsules provides a unique means of controlled drug release and immunoisolation of encapsulated cells. Immunoisolation is especially attractive as it abrogates the need for chronic immunosuppressive therapy and opens up the possibility for the delivery of numerous cell sources including xenogeneic grafts. APA microcapsules containing cellular therapeutics have proven effective in the short-term treatment of a wide range of diseases requiring enzyme or endocrine replacement therapy, including type I diabetes. If these microcapsules could be noninvasively monitored with X-ray imaging modalities (i.e., fluoroscopy, CT, and digital subtraction angiography), questions such as the ideal transplantation site, the best means of delivery, and the long-term survival of grafts could be better addressed. We have developed two novel alginate-based radiopaque microcapsule formulations containing either barium sulfate (Ba X-Caps) or bismuth sulfate (Bi X-Caps). As compared to conventional, nonradiopaque APA capsules, Ba X-Caps and Bi X-Caps containing human cadaveric islets resulted in a decrease in cellular viability of less than 5% up to 14 days after encapsulation. Both radiopaque capsules were found to be permeable to lectins < or =75 kDa, but were impermeable to lectins > or =120 kDa, thus ensuring the blockage of the penetration of antibodies while allowing free diffusion of insulin and nutrients. The glucose-responsive insulin secretion of the radiopaque encapsulated human islets was found to be unaltered compared to that of unlabeled controls, with human C-peptide levels ranging from 3.21 to 2.87 (Ba X-Caps) and 3.23 to 2.87 (Bi X-Caps) ng/islet at 7 and 14 days postencapsulation, respectively. Using fluoroscopy, both Ba X-Caps and Bi X-Caps could be readily visualized as single radiopaque entities in vitro. Furthermore, following transplantation in vivo in mice and rabbits, single capsules could be identified with no significant change in contrast for at least 2 weeks. This study represents the first attempt at making radiopaque microcapsules for X-ray guided delivery and imaging of cellular therapeutics. While human cadaveric islets were used as a proof-of-principle, these radiopaque capsules may have wide ranging therapeutic applications for a variety of cell types.

This study identified that medication diluents contribute substantially to the total IV volume received by critically ill patients. Saline as the primary medication diluent compared with dextrose 5% in water is associated with hyperchloremia, a possible risk factor for acute kidney injury.