Dietary calcium supplementation has been to alter calcium metabolism and prevent hypertension in spontaneously hypertensive rats (SHR). Likewise, microgravity alters calcium metabolism. It is possible that the alteration of calcium metabolism caused by different levels of dietary calcium or microgravity change skeletal muscle properties. The purpose of this investigation was to determine whether spaceflight and/or dietary calcium causes alteration of properties in skeletal muscle from SHR.
Nine-week-old male SHR, fed either high- (2.0%, HCa) or low-calcium (0.2%, LCa) diets, were flown on an 18-day shuttle flight. They were assigned to four groups (n=7/group): control (ground-based) with LCa or HCa, spaceflight with LCa, or HCa. After the spaceflight, the soleus muscle was dissected and analyzed histochemically and biochemically.
Spaceflight caused a slow-to-fast fiber transition that did not differ between diet groups. Cross-sectional areas of a single muscle fiber were not modified by dietary calcium in either control or spaceflight groups. The changes of succinate dehydrogenase activity in Type I fibers in response to spaceflight was higher in the LCa diet (+23.7%) than the HCa diet group (+12.8%). Conversely, in Type IIa fibers the response to spaceflight was lower in the LCa (-9.6%) than the HCa (-19.2%) group. These findings suggest that the effect of dietary calcium on fiber type composition and fiber size may be smaller than that of spaceflight, while dietary calcium may inhibit the alteration of oxidative metabolism of muscle fibers by spaceflight in SHR.
Recent advances in sensitivity of analytical instrumentation has resulted in the routine practice of low-volume blood sampling in pre-clinical pharmacokinetic studies. Mice, the species of choice in oncology, have a limited blood volume; hence demand a small volume sampling strategy to avoid unwanted physiological side effects. When assessing drug exposure in mice, a serial sampling methodology requires less than 20 μl of blood per time point in order to comply with animal welfare guidelines.
Various microsampling techniques have been employed in pharmacokinetic studies to achieve exact sampling of low blood volumes. The aim of this work was to explore capillary microsampling as an alternative methodology to dried blood spot sampling for the analysis of whole blood in mouse pharmacokinetic studies. Concentration-time profiles of both blood sampling techniques were compared following intravenous administration of four compounds to female Balb C mice. In each case pharmacokinetic parameters from the two different sampling methods were equivalent.
Compared to dried blood spots, capillary microsampling provided an inexpensive, reliable and robust method for low volume sampling in the pre-clinical pharmacokinetic setting. In vivo and bioanalytical workflows were integrated with the result of improving laboratory efficiency and lowering consumable costs. Compared to the previous blood spot method there was an improvement in animal welfare through faster handling times due to refined microsampling procedures.
There has been a great challenge of research and discovery of novel medicinal leads against swine influenza since 2009. Rational drug design utilizing pharmacoinformatics tools has been augmented now-a-days for in-silico screening of lead compounds prior to experimental synthesis, structural elucidation, biological evaluation and finally clinical trials to make the cost efficient drug design and discovery research. There is hardly any specific chemotherapeutics for the treatment against deadly swine influenza viral infection. Therefore, it is an urgent need to design and develop new anti-viral lead compounds active against swine influenza. Quantitative structure activity relationship (QSAR) has been used to develop models that correlate biological activity of angelicin compounds derived from published literature and their computed structural properties. The approach started by generation of a series of descriptors including topological, three dimensional, constitutional, functional groups and atom fragment indices respectively solely calculated from the compounds in the data set. In this study, data set consists of 53 angelicin compounds along with their inhibitory concentration 50% (IC50, μM) against H1N1 swine influenza virus. Genetic algorithm-multiple linear regression (GA-MLR) analysis technique has been to generate a number of QSAR models. The models were validated statistically incorporating training and test set approaches. Finally, structure-based molecular docking study has been performed for interpretation of the mode of binding of the angelicin compounds toward H1N1 target. QSAR and molecular docking analysis of these congeners have not yet been reported. Therefore, this study has significant impact for designing of the highly active compounds in this series that are useful for the treatment of swine influenza. In-silico structure based docking model could be helpful for design and screening of congeneric compounds having mode of binding similarity.