Changes in interstitial fluid flow, mass transport and the bone cell response in microgravity and normogravity.

In recent years, our scientific interest in spaceflight has grown exponentially and resulted in a thriving area of research, with hundreds of astronauts spending months of their time in space. A recent shift toward pursuing territories farther afield, aiming at near-Earth asteroids, the Moon, and Mars combined with the anticipated availability of commercial flights to space in the near future, warrants continued understanding of the human physiological processes and response mechanisms when in this extreme environment. Acute skeletal loss, more severe than any bone loss seen on Earth, has significant implications for deep space exploration, and it remains elusive as to why there is such a magnitude of difference between bone loss on Earth and loss in microgravity. The removal of gravity eliminates a critical primary mechano-stimulus, and when combined with exposure to both galactic and solar cosmic radiation, healthy human tissue function can be negatively affected. An additional effect found in microgravity, and one with limited insight, involves changes in dynamic fluid flow. Fluids provide the most fundamental way to transport chemical and biochemical elements within our bodies and apply an essential mechano-stimulus to cells. Furthermore, the cell cytoplasm is not a simple liquid, and fluid transport phenomena together with viscoelastic deformation of the cytoskeleton play key roles in cell function. In microgravity, flow behavior changes drastically, and the impact on cells within the porous system of bone and the influence of an expanding level of adiposity are not well understood. This review explores the role of interstitial fluid motion and solute transport in porous bone under two different conditions: normogravity and microgravity.

Development of dried blood spot quality control materials for adenosine deaminase severe combined immunodeficiency and LC-MS/MS method for their characterization.

Adenosine deaminase severe combined immunodeficiency (ADA-SCID) is an autosomal recessive disorder in which a lack of ADA enzyme prevents the maturation of T- and B-cells; early intervention is crucial for restoring immune function in affected neonates. ADA is responsible for purine metabolism and-in its absence-adenosine, deoxyadenosine, and S-adenosylhomocysteine build up and can be detected in the blood. Preparing dried blood spot (DBS) quality control (QC) materials for these analytes is challenging because enrichments are quickly metabolized by the endogenous ADA in normal donor blood. Adding an inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), has been previously reported to minimize enzyme activity, although this adds additional cost and complexity. We describe an alternative method using unnatural L-enantiomer nucleosides (L-adenosine and 2'-deoxy-L-adenosine) which eliminates the need for enzyme inhibition. We also present a novel method for characterization of the materials using liquid chromatography mass spectrometry to quantify the analytes of interest.

Microengineered vascular systems for drug development.

Recent advances in microfabrication technologies and advanced biomaterials have allowed for the development of in vitro platforms that recapitulate more physiologically relevant cellular components and function. Microengineered vascular systems are of particular importance for the efficient assessment of drug candidates to physiological barriers lining microvessels. This review highlights advances in the development of microengineered vascular structures with an emphasis on the potential impact on drug delivery studies. Specifically, this article examines the development of models for the study of drug delivery to the central nervous system and cardiovascular system. We also discuss current challenges and future prospects of the development of microengineered vascular systems.