Novel fatty acyl apoE mimetic peptides have increased potency to reduce plasma cholesterol in mice and macaques.

Ac-hE18A-NH is a dual-domain apoE mimetic peptide that possesses the putative receptor binding domain from apoE (LRKLRKRLLR, denoted hE; residues 141-150) covalently attached to lipid-associating peptide 18A. Like apoE, Ac-hE18A-NH reduces plasma cholesterol in animal models and exhibits anti-inflammatory properties independent of its cholesterol-reducing effect. Ac-hE18A-NH has already undergone phase I clinical trials as a lipid-lowering agent.

Topical iontophoretic administration of acyclovir for the episodic treatment of herpes labialis: a randomized, double-blind, placebo-controlled, clinic-initiated trial.

Background: Multiple studies of the use of acyclovir for the treatment of herpes labialis have suggested that the nominal efficacy of the topical formulation is the result of inadequate penetration of the drug into the target site of infection, the basal epidermis.

Methods: We developed a low-voltage, wireless, hand-held, computer-controlled, iontophoretic applicator to enhance the skin penetration of topical acyclovir in the treatment of herpes labialis. We performed a multicenter, placebo-controlled, clinic-initiated, pilot trial of a single, topical, iontophoretic application of 5% acyclovir cream for the episodic treatment of herpes labialis among 200 patients with an incipient cold sore outbreak at the erythema or papular/edema lesion stage.

Imaging infections with antibodies. A quantitative autoradiographic analysis.

Radiolabeled IgG has recently been demonstrated to effectively image infections. A potential but unproven mechanism for this localization is the specific binding of IgG to Fc receptors on the surface of inflammatory cells in infections. In an animal model of soft tissue infection, quantitative autoradiography was used to measure 125I-labeled IgG and albumin in tissues with a spatial resolution sufficient to associate these proteins with cellular morphology.

Endothelial communication. State of the art lecture.

By virtue of its location at the interface of flowing blood and vascular tissue, the endothelial cell monolayer is in a unique position for interactions with soluble and cellular elements of the blood on one side and with component cells of the vascular tissue on the other. This brief review outlines humoral and contact-mediated endothelial communication with other cells, particularly the resident cells of the vessel wall. Evidence for gap junctional communication channels between endothelium and vascular cells is summarized and discussed in relation to endothelial ion channel activity.

Absolute quantitative autoradiography of low concentrations of [125I]-labeled proteins in arterial tissue.

We developed a method for absolute quantitative autoradiographic measurement of very low concentrations of [125I]-labeled proteins in arterial tissue using Kodak NTB-2 nuclear emulsion. A precise linear relationship between measured silver grain density and isotope concentration was obtained with uniformly labeled standard sources composed of epoxy-embedded gelatin containing glutaraldehyde-fixed [125I]-albumin. For up to 308-day exposures of 1 micron-thick tissue sections, background grain densities ranged from about two to eight grains/1000 micron 2, and the technique was sensitive to as little as about one grain/1000 micron 2 above background, which correspond to a radioactivity concentration of about 2 x 10(4) cpm/ml.

Endothelial cell perturbation and low-density lipoprotein. Quantitative autoradiography.

The focal entry and accumulation of LDL within the arterial wall of the normal animal may represent an early stage in the development of the atherosclerotic plaque. Concentrations of LDL 10 to 100 times normal medial concentrations might be difficult to clear from the arterial wall, permitting accumulation of lipid. Elevated LDL concentrations, in proximity to smooth muscle cells, appear to stimulate SMC proliferation.

Local variation in arterial wall permeability to low density lipoprotein in normal rabbit aorta.

Normal rabbits were injected intravenously with horseradish peroxidase (HRP) and 125I-labeled human low density lipoprotein (LDL), and the aortas were perfusion-fixed. Subsequent visualization of HRP in the aortas was produced by reaction of the tissue with diaminobenzidine and hydrogen peroxide. The luminal surface of the aortas showed many small punctate foci of brown reaction product to the HRP, which represented penetration of the HRP into the vessel wall.