Simi Patel

Background: The purpose of this study was to investigate the capabilities of a novel optical wide-field imaging technology known as spatial frequency domain imaging to quantitatively assess reconstructive tissue status. Methods: Twenty-two cutaneous pedicle flaps were created on 11 rats based on the inferior epigastric vessels. After baseline measurement, all flaps underwent vascular ischemia, induced by clamping the supporting vessels for 2 hours ; normal saline was injected into the control flap and hypertonic-hyperoncotic saline solution was injected into the experimental flap. Flaps were monitored for 2 hours after reperfusion. The spatial frequency domain imaging system was used for quantitative assessment of flap status over the duration of the experiment. Results: All flaps demonstrated a significant decline in oxyhemoglobin and tissue oxygen saturation in response to occlusion. Total hemoglobin and deoxyhemoglobin were increased markedly in the selective venous occlusion group. After reperfusion and the administration of solutions, oxyhemoglobin and tissue oxygen saturation in those flaps that survived gradually returned to baseline levels. However, flaps for which oxyhemoglobin and tissue oxygen saturation did not show any signs of recovery appeared to be compromised and eventually became necrotic within 24 to 48 hours in both occlusion groups. Conclusions: Spatial frequency domain imaging technology provides a quantitative, objective method of assessing tissue status. This study demonstrates the potential of this optical technology to assess tissue perfusion in a very precise and quantitative way, enabling wide-field visualization of physiologic parameters. The results of this study suggest that spatial frequency domain imaging may provide a means for prospectively identifying dysfunctional flaps well in advance of failure. Copyright © 2010 by the American Society of Plastic Surgeons.

© 2015 American Neurological Association. Objective Mutations in the gene encoding the prion protein are responsible for approximately 10 to 15% of cases of prion disease in humans, including Creutzfeldt-Jakob disease. Here, we report on the discovery of a previously unreported C-terminal PrP mutation in a CJD patient exhibiting a disease similar to the rare VV1 subtype of sporadic CJD and investigate the role of this mutation in prion replication and transmission. Methods We generated transgenic mice expressing human PrP with the V129 polymorphism and A224V mutation, denoted Tg mice, and inoculated them with different subtypes of sCJD prions. Results Transmission of sCJD VV2 or MV2 prions was accelerated in Tg mice, compared to Tg mice, with incubation periods of ∼110 and ∼210 days, respectively. In contrast, sCJD MM1 prions resulted in longer incubation periods in Tg mice, compared to Tg mice. Prion strain fidelity was maintained in Tg mice inoculated with sCJD VV2 or MM1 prions, despite the altered replication kinetics. Interpretation Our results suggest that A224V is a risk factor for prion disease and modulates the transmission behavior of CJD prions in a strain-specific manner, arguing that residues near the C-terminus of PrP are important for controlling the kinetics of prion replication.

© 2014 American Heart Association, Inc.Background: Early afterdepolarizations are triggers of cardiac arrhythmia driven by L-type Ca2+ current reactivation or sarcoplasmic reticulum Ca2+ release and Na+/Ca2+ exchange. In large mammals the positive action potential plateau promotes ICaL reactivation, and the current paradigm holds that cardiac EAD dynamics are dominated by interaction between ICaL and the repolarizing K+ currents. However, EADs are also frequent in the rapidly repolarizing mouse action potential, which should not readily permit ICaL reactivation. This suggests that murine EADs exhibit unique dynamics, which are key for interpreting arrhythmia mechanisms in this ubiquitous model organism. We investigated these dynamics in myocytes from arrhythmia-susceptible calcium calmodulin-dependent protein kinase II delta C -overexpressing mice, and via computational simulations. Methods and Results: In Tg myocytes, β-adrenergic challenge slowed late repolarization, potentiated sarcoplasmic reticulum Ca2+ release, and initiated EADs below the ICaL activation range. These EADs were abolished by caffeine and tetrodotoxin, suggesting that sarcoplasmic reticulum Ca2+ release and Na+ current, but not late INa, are required for EAD initiation. Simulations suggest that potentiated sarcoplasmic reticulum Ca2+ release and Na+/Ca2+ exchange shape late action potential repolarization to favor nonequilibrium reactivation of INa and thereby drive the EAD upstroke. Action potential clamp experiments suggest that lidocaine eliminates virtually all inward current elicited by EADs, and that this effect occurs at concentrations for which lidocaine remains specific for inactivated Na+ channels. This strongly suggests that previously inactive channels are recruited during the EAD upstroke, and that nonequilibrium INa dynamics underlie murine EADs. Conclusions: Nonequilibrium reactivation of INa drives murine EADs.