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Objective/ Background: Various oral formulations of cholecalciferol are available in world. To ensure optimal and appropriate delivery and absorption of these formulations, it is important to study their bioavailability and biodistribution within the human body. Gamma scintigraphy is a technique used to map various drug formulations as it traverses the human body in real-time. Combining this information with the pharmacokinetic data (pharmacoscintigraphy) gives valuable information about the release and absorption mechanisms of drug formulations, including the ability of a formulation to reach a specific target location, the rate of erosion in comparison with in vitro dissolution data, and the impact of absorption windows on bioavailability. It is required to study the bioavailability and biodistribution of specific cholecalciferol formulations before prescribing. Method: We evaluated the bioavailability and biodistribution pattern, transit time, and gastrointestinal clearance of a single dose of Calcirol® soft gelatin capsule 60,000 IU [an oral cholecalciferol (vitamin D) formulation] using pharmacoscintigraphy. Six male healthy adult volunteers were administered with a single oral dose of Calcirol® soft gelatin capsule labeled with technetium-99m. Post-dosing, Sequential static gamma imaging for 24 hrs was performed to evaluate the biodistribution and serial venous blood samples were collected till day 27 for the estimation of the plasma levels of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol levels. Different pharmacokinetic parameters were calculated. Results and Discussion: This was the first pharmacoscintography study in the world to demonstrate the favorable biodistribution of Calcirol® soft gelatin capsules, supporting its use for vitamin D supplementation. The overall absorption of Calcirol® soft gelatin capsule was 93.23%, which was fully from the small intestine. The small intestinal residence time was around 16 h. [Table-1] shows the different pharmacokinetic parameters of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol. Results shows that exogenous cholecalciferol in the form of soft gelatin capsule achieves a sufficient level of 25-hydroxycholecalciferol (>60 ng/ml) within 6 hr of oral intake. No adverse event was noted.{Table 1} Conclusion: An in-depth understanding of Cholecalciferol absorption pattern can be achieved using pharmacoscintigraphy. [ABSTRACT FROM AUTHOR]

Motivation: One bottleneck in high-throughput protein crystallography is interpreting an electron-density map, that is, fitting a molecular model to the 3D picture crystallography produces. Previously, we developed Acmi (Automatic Crystallographic Map Interpreter), an algorithm that uses a probabilistic model to infer an accurate protein backbone layout. Here, we use a sampling method known as particle filtering to produce a set of all-atom protein models. We use the output of Acmi to guide the particle filters sampling, producing an accurate, physically feasible set of structures. Results: We test our algorithm on 10 poor-quality experimental density maps. We show that particle filtering produces accurate all-atom models, resulting in fewer chains, lower sidechain RMS error and reduced R factor, compared to simply placing the best-matching sidechains on Acmis trace. We show that our approach produces a more accurate model than three leading methods—Textal, Resolve and ARP/WARP—in terms of main chain completeness, sidechain identification and crystallographic R factor. Availability: Source code and experimental density maps available at http://ftp.cs.wisc.edu/machine-learning/shavlik-group/programs/acmi/ Contact: dimaio@cs.wisc.edu [ABSTRACT FROM AUTHOR]