Lead exposure of a fossorial rodent varies with the use of ammunition across the landscape.

Exposure to heavy metals has been documented in a wide range of wildlife species, but infrequently in ground squirrels. This is despite their tendency to be targets of recreational shooters and the accumulation of lead ammunition in the soil environments they inhabit. We analyzed lead and copper concentrations in liver (n = 116, n = 101) and femur (n = 116, n = 116) of Piute ground squirrels (Urocitellus mollis) and in soil (n = 75) on public lands in southwestern Idaho to understand how lead exposure may vary across a gradient of intensities and histories of shooting activity.

Photochemical Modification of the Extracellular Matrix to Alter the Vascular Remodeling Process.

Therapeutic interventions for vascular diseases aim at achieving long-term patency by controlling vascular remodeling. The extracellular matrix (ECM) of the vessel wall plays a crucial role in regulating this process. This study introduces a novel photochemical treatment known as Natural Vascular Scaffolding, utilizing a 4-amino substituted 1,8-naphthimide (10-8-10 Dimer) and 450 nm light.

Photochemically Aided Arteriovenous Fistula Creation to Accelerate Fistula Maturation.

Rates of arteriovenous fistula maturation failure are still high, especially when suboptimal size veins are used. During successful maturation, the vein undergoes lumen dilatation and medial thickening, adapting to the increased hemodynamic forces. The vascular extracellular matrix plays an important role in regulating these adaptive changes and may be a target for promoting fistula maturation.

Creating a Natural Vascular Scaffold by Photochemical Treatment of the Extracellular Matrix for Vascular Applications.

The development of bioscaffolds for cardiovascular medical applications, such as peripheral artery disease (PAD), remains to be a challenge for tissue engineering. PAD is an increasingly common and serious cardiovascular illness characterized by progressive atherosclerotic stenosis, resulting in decreased blood perfusion to the lower extremities. Percutaneous transluminal angioplasty and stent placement are routinely performed on these patients with suboptimal outcomes.

Photosensitized Oxidative Dimerization at Tyrosine by a Water-Soluble 4-Amino-1,8-naphthalimide.

The oxidation of proteins generates reactive amino acid (AA) residue intermediates, leading to protein modification and cross-linking. Aerobic studies with peptides and photosensitizers allow for the controlled generation of reactive oxygen species (ROS) and reactive AA residue intermediates, providing mechanistic insights as to how natural protein modifications form. Such studies have inspired the development of abiotic methods for protein modification and crosslinking, including applications of biomedical importance.

Solvent-Dependent Photophysics and Reactivity of Monomeric and Dimeric 4-Amino-1,8-Naphthalimides.

The solvent-dependent photophysics of two 4-amino-substituted 1,8-naphthalene imides () were studied using fluorescence spectroscopy and laser flash photolysis. The compounds were functionalized with water-soluble 2,2'(ethylenedioxy) diethylamine groups, yielding a monomer () and a dimer (). The radiative and nonradiative singlet-state deactivation processes of and were quantified in 10 solvents and at different pH values.

Evaluation needle length and density of microneedle arrays in the pretreatment of skin for transdermal drug delivery.

Solid silicon microneedle arrays with different needle lengths (ranging from 100 to 1100 microm) and needle densities (ranging from 400 to 11,900 needles/cm(2)) were used to penetrate epidermal membrane of human cadaver skin. After this pretreatment, the electrical resistance of the skin and the flux of acyclovir across the skin were monitored. A linear correlation between the acyclovir flux and the inverse of the skin electric resistance was observed.

Silicone elastomer uptake method for determination of free 1-alkyl-2-pyrrolidone concentration in micelle and hydroxypropyl-beta-cyclodextrin systems used in skin transport studies.

Previous investigations in our laboratory demonstrated how the polar head group and alkyl chain of amphiphilic chemical skin permeation enhancers contribute to enhancer potency. In those studies enhancers with n-alkyl chain lengths of eight or less were investigated. In order to investigate enhancers with longer n-alkyl chain lengths, enhancer-solubilizing agents should be considered.

Model analysis of flux enhancement across hairless mouse skin induced by chemical permeation enhancers.

Previous permeant partitioning studies with hairless mouse skin (HMS) in the presence of several chemical skin permeation enhancers have revealed that, when such enhancers induce significant skin permeability coefficient enhancement, it is accompanied by significant enhancement in the equilibrium uptake (partitioning) of the permeant into the intercellular lipid component of the stratum corneum (SC). Particularly, it was found that the 1-alkyl-2-pyrrolidones and the 1-alkyl-2-azacycloheptanones, at aqueous solution concentrations that gave skin permeation enhancement (E) of 10 for corticosterone (CS, the permeant), enhanced the equilibrium uptake of beta-estradiol (E2beta, a surrogate permeant) from the aqueous phase into the intercellular lipids of HMS SC by a factor of 5-7. This finding raised the question of whether this uptake enhancement induced by the permeation enhancer under equilibrium conditions would be essentially the same as that determined kinetically from time-dependent permeation experiments utilizing appropriate SC membrane models and Fick's laws of diffusion to treat the data.

Mechanistic study of chemical skin permeation enhancers with different polar and lipophilic functional groups.

In a previous study, the enhancement effects on the transport of a steroidal permeant along the hairless mouse skin (HMS) stratum corneum (SC) lipoidal pathway were investigated for two homologous series of chemical enhancers: the 1-alkyl-2-pyrrolidones and the 1-alkyl-2-azacycloheptanones. The objective of the present study was to extend this investigation to a broader range of enhancers in order that generalizations with regard to the mechanistic aspects of enhancer function might be established. Specific questions to be addressed included: (a) what is the nature of the microenvironment of the enhancer site of action? (b) what is the extent of the equilibrium uptake of the enhancer from its E = 10 aqueous enhancer solution (the aqueous concentration for which the enhancer induces a tenfold transport enhancement) into the HMS SC intercellular lipid "phase"? and (c) are the microenvironment of the enhancer site of action and that for the equilibrium enhancer uptake at E = 10 relatively independent of the molecular characteristics of the enhancers (as suggested by the earlier study)? Enhancers selected for this study included: a wide range of polar head group size and polarity; n-alkyl group chain lengths from C(4) to C(12); and enhancers in which a double bond is substituted for a single bond in the hydrocarbon chain (3-alkenols) from C(5) to C(9).

Mechanistic studies of branched-chain alkanols as skin permeation enhancers.

As part of a long-term effort to understand the structure/function relationship between chemical permeation enhancers and skin permeation enhancement, the present study examined the influence of hydrocarbon chain branching on the effectiveness of skin permeation enhancers of the type that possesses a polar group (e.g., the hydroxyl group) attached to a hydrocarbon chain(s).

Structure-activity relationship for chemical skin permeation enhancers: probing the chemical microenvironment of the site of action.

Studies were previously conducted in our laboratory on the influence of n-alkanols, 1-alkyl-2-pyrrolidones, N,N-dimethlyalkanamides, and 1,2-alkanediols as skin permeation enhancers on the transport of a model permeant, corticosterone (CS). The experiments were conducted with hairless mouse skin (HMS) in a side-by-side, two-chamber diffusion cell, with enhancer present in an aqueous buffer in both chambers. The purpose of the present study was to extend these studies and investigate in greater detail the hypothesis that a suitable semipolar organic phase may mimic the microenvironment of the site of enhancer action, and that the enhancer partitioning tendency into this organic phase may be used to predict the enhancer potency.

Mechanistic study of alkyl azacycloheptanones as skin permeation enhancers by permeation and partition experiments with hairless mouse skin.

In previous studies (Yoneto et al., 1995. J Pharm Sci 84:312-317; Kim et al.