Xantusia gracilis

Number of Pages: 2Integrative BiologyEarth and Planetary Science

Graptemys ernsti

Number of Pages: 2Integrative BiologyGeological Science

Graptemys pearlensis

Number of Pages: 4Integrative BiologyGeological Science

Graptemys barbouri

Number of Pages: 2Integrative BiologyGeological Science

Amphibians and Reptiles of United States Department of Defense Installations

The U.S. Department of Defense (DoD) occupies approximately 10.1 million ha of land within the U.S. spanning most ecosystems contained therein. To date, no comprehensive agency-wide inventory of amphibian and reptile species has been compiled. We developed an amphibian and reptile species inventory for 415 DoD installations/sites and evaluated species diversity. The amphibian and reptile species confirmed present on DoD sites represent 66% of the total native species documented in the continental U.S. Snakes are the most widespread group found on DoD lands. Of the military services, Army sites have the greatest number of confirmed species, federally listed, state-listed, and At-risk species. There are 24 federally listed (threatened or endangered), 55 state- listed, and 70 At-risk species confirmed present on DoD sites. Thirty non-native and native transplant amphibian and reptile species/subspecies are also confirmed present on DoD sites. Lastly, we verified that approximately half of the military sites evaluated in this study have at least one venomous snake species confirmed present. Our study results assist directly with ongoing management and conservation of amphibian and reptile species on DoD lands and confirm military lands comprise a significant contribution to biodiversity conservation

Modelling arterial wall drug concentrations following the insertion of a drug-eluting stent

A mathematical model of a drug-eluting stent is proposed. The model considers a polymer region, containing the drug initially, and a porous region consisting of smooth muscle cells embedded in an extracellular matrix. An analytical solution is obtained for the drug concentration both in the target cells and the interstitial region of the tissue in terms of the drug release concentration at the interface between the polymer and the tissue. When the polymer region and the tissue region are considered as a coupled system it can be shown, under certain assumptions, that the drug release concentration satisfies a Volterra integral equation which must be solved numerically in general. The drug concentrations, both in the cellular and extracellular regions, are then determined from the solution of this integral equation and used in deriving the mass of drug in the cells and extracellular space

Vascular Regeneration by Local Growth Factor Release Is Self-Limited by Microvascular Clearance

Background— The challenge of angiogenesis science is that stable sustained vascular regeneration in humans has not been realized despite promising preclinical findings. We hypothesized that angiogenic therapies powerfully self-regulate by dynamically altering tissue characteristics. Induced neocapillaries increase drug clearance and limit tissue retention and subsequent angiogenesis even in the face of sustained delivery. Methods and Results— We quantified how capillary flow clears fibroblast growth factor after local epicardial delivery. Fibroblast growth factor spatial loading was significantly reduced with intact coronary perfusion. Penetration and retention decreased with transendothelial permeability, a trend diametrically opposite to intravascular delivery, in which factor delivery depends on vascular leak, but consistent with a continuum model of drug transport in perfused tissues. Model predictions of fibroblast growth factor sensitivity to manipulations of its diffusivity and transendothelial permeability were validated by conjugation to sucrose octasulfate. Induction of neocapillaries adds pharmacokinetic complexity. Sustained local fibroblast growth factor delivery in vivo produced a burst of neovascularization in ischemic myocardium but was followed by drug washout and a 5-fold decrease in fibroblast growth factor penetration depth. Conclusions— The very efficacy of proangiogenic compounds enhances their clearance and abrogates their pharmacological benefit. This self-limiting property of angiogenesis may explain the failures of promising proangiogenic therapies.National Institutes of Health (U.S.) (Grant R01 GM 49039

Diffusion-limited binding explains binary dose response for local arterial and tumour drug delivery

Background:  Local drug delivery has transformed medicine, yet it remains unclear how drug efficacy depends on physicochemical properties and delivery kinetics. Most therapies seek to prolong release, yet recent studies demonstrate sustained clinical benefit following local bolus endovascular delivery. Objectives:  The purpose of the current study was to examine interplay between drug dose, diffusion and binding in determining tissue penetration and effect. Methods:  We introduce a quantitative framework that balances dose, saturable binding and diffusion, and measured the specific binding parameters of drugs to target tissues. Results:  Model reduction techniques augmented by numerical simulations revealed that impact of saturable binding on drug transport and retention is determined by the magnitude of a binding potential, Bp, ratio of binding capacity to product of equilibrium dissociation constant and accessible tissue volume fraction. At low Bp ( 40), drug transport exhibits threshold dependence on applied surface concentration. Conclusions:  In this paradigm, drugs and antibodies with large Bp penetrate faster and deeper into tissues when presented at high concentrations. Threshold dependence of tissue transport on applied surface concentration of paclitaxel and rapamycin may explain threshold dose dependence of in vivo biological efficacy of these drugs.Hertz FoundationNational Institutes of Health (U.S.) (R01 G 49039)Johnson & Johnson. Pharmaceutical Research & Development (Cordis

Graptemys pulchra

Number of Pages: 2Integrative BiologyGeological Science