After intravenous injection, particles larger than red blood cells will be trapped in the first capillary bed that they encounter. This is the principle of lung perfusion imaging in nuclear medicine, where macroaggregated albumin (MAA) is radiolabeled with (99m)Tc, infused into a patient's arm vein, and then imaged with gamma scintigraphy. Our aim was to evaluate if monosized microspheres could replace (99m)Tc-MAA. Biodegradable poly(L-lactide) microspheres containing chelating bis(picolylamine) end groups were prepared by a flow focusing method on a microfluidic glass chip and were of highly homogeneous size (9.0 +/- 0.4 microm). The microspheres were radiolabeled with [(99m)Tc(H(2)O)(3)(CO)(3)](+) and then evaluated in mice for lung perfusion imaging. Fifteen minutes after injection, 79.6 +/- 3.8% of the injected activity was trapped in the lungs of mice. Monosized biodegradable radioactive microspheres are, thus, appropriate lung perfusion imaging agents. Other sizes of these highly uniform microspheres have the potential to improve diagnostic and therapeutic approaches in diverse areas of medicine.
For many applications, polymer microspheres (MS) should possess a monodisperse size distribution. With such uniformity they are able to deliver precise amounts of drug per MS, optimize the release kinetics of an encapsulated drug, obtain repeatable in vivo biodistributions to different organs and tissues, and obtain the maximum protection of (protein) drugs from degradation. This review classifies monodisperse polymer MS according to their methods of production and gives examples of the formation of uniform MS and their applications in the medical field. In the literature, the term 'monodisperse' is often used inaccurately, and this article attempts to rectify this by clearly defining monodispersity in terms of the coefficient of variation and the polydispersity index, the two statistical quantities most frequently used to describe the size distribution of MS.
Malignant hyperthermia can result from mutations in the ryanodine receptor that favor anesthetic-induced Ca2+ release. Zullo et al. find that membrane potential modulates the effect of the volatile anesthetic halothane on skeletal muscle ryanodine receptors possessing the Y524S mutation.
41 C/1h): interestingly mortality rate was dramatically decreased in trained (t) CASQ1-null mice compared to un-trained (un-t) controls: 16% vs. 86%, respectively. In tCASQ1-null mice, the increase in core temperature during exposure to heat-stress (i.e. hyperthermia) was lower than in un-t mice, and their EDL muscles displayed a lowered threshold of response when exposed to increasing [caffeine] during in-vitro contracture test (IVCT). Several other parameters were assessed in muscle samples: aerobic training succeeded in decreasing mitochondrial damage (14.853.9% vs. 752.3%), mitochondrial efficiency by increasing of 34% the cytochrome-c oxidase activity, while decreasing SERCA's and also Ca 2þ -dependent proteolytic activity. Additionally, training also reduced lipid peroxidation (elevated in un-tCASQ1-null mice) in isolated sarcoplasmic reticulum and mitochondria membranes: À45 and À35 %, respectively. In conclusion, aerobic training protects CASQ1null mice from HS, an effect essentially mediated by a significant reduction in oxidative stress and fiber damage.
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