Safety and biodistribution of XC001 (encoberminogene rezmadenovec) gene therapy in rats: a potential therapy for cardiovascular diseases.

Adenovirus-mediated gene therapy holds promise for the treatment of cardiovascular diseases such as refractory angina. However, potential concerns around immunogenicity and vector dissemination from the target injected tissue require evaluation. This study was undertaken to evaluate the safety and biodistribution of XC001, a replication-deficient adenovirus serotype 5 vector expressing multiple isoforms of human vascular endothelial growth factor (VEGF), following direct administration into normal rat myocardium.

Pharmacokinetics of Sirolimus in a Novel Liposome Delivery System in Selected Ocular Tissues and Plasma Following a Single Subconjunctival Injection in Dutch Belted Rabbits.

To determine the pharmacokinetics of a proprietary liposomal sirolimus (LS) formulation in ocular tissues and plasma following a single subconjunctival (SCJ) injection in Dutch belted rabbits (DBR). Analytical methods for detection of LS in plasma, aqueous humor (AH), vitreous humor (VH), retina, combined retina/choroid/retinal pigment epithelium, sclera, and iris/ciliary body were developed to examine samples. Thirty male DBR were subconjunctivally injected in both eyes with 0.

Sample preparation and digestion for proteomic analyses using spin filters.

We describe the use of commercially available microcentrifugation devices (spin filters) for cleanup and digestion of protein samples for mass spectrometry analyses. The protein sample is added to the upper chamber of a spin filter with a > or = 3000 molecular weight cutoff membrane and then washed prior to resuspension in ammonium bicarbonate. The protein is then reduced, alkylated, and digested with trypsin in the upper chamber and the peptides are recovered by centrifugation through the membrane.

Global shifts in protein sumoylation in response to electrophile and oxidative stress.

Human small ubiquitin-like modifier (sumo) proteins include sumo-1 and the less studied, nearly identical sumo-2 and sumo-3 proteins. Whereas the structurally related ubiquitin molecule targets proteins for degradation, sumo provides a distinct, yet poorly understood regulatory signal. Protein sumoylation is sensitive to diverse cellular stresses, yet the targets of sumoylation in stress are unknown.

Affective discrimination and the implicit learning process.

A modified version of the mere exposure effect paradigm was utilized in an implicit artificial grammar learning task in an attempt to develop a procedure that would be more sensitive in assesing nonconscious learning processes than the methods currently utilized within the field of implicit learning. Subjects were presented with stimuli generated from a finite-state artificial grammar and then had to either (a) decide if novel items conformed to the rule structure of the grammar or (b) rate the degree to which they liked novel items. Because the latter task was the more indirect of the two procedures, subjects' ability to discriminate between well-formed and ill-formed items on this liking task was taken as a more sensitive piece of evidence of implicit learning, compared to performance on the rule conformity task.

Implicit and explicit learning: differential effects of affective states.

Two experiments using a standard artificial grammar paradigm were conducted to examine the role of affective states, specifically anxiety and depression, on implicit learning. The main purpose was to broaden the range of human functioning explored through the application of the robustness principle in the evolutionary framework recently developed by Reber which predicts that cognitive processes which rely upon unconscious, implicit processes should be less affected by affective states than those which rely upon conscious, explicit processes. In Study 1 (N = 60), high test anxiety was associated with performance deficits in the explicit components of the task; no differences were found in the implicit phases of the task.

The rat's preference for sucrose, polycose and their mixtures.

In one-bottle tests (30 min/day) food-deprived rats consumed significantly more 2% Polycose than 2% sucrose, and yet in two-bottle choice tests they did not consistently prefer Polycose to sucrose. A previously proposed explanation for this effect is that rats habituate, or develop oral satiety, to the flavor of sucrose more rapidly than to Polycose, and sucrose satiety generalizes to Polycose. This idea was not supported by the results of sequential 15-min one-bottle tests: the intake of 2% sucrose did not suppress subsequent Polycose intake.

The conditioning of aversions to familiar and preferred flavours: a new aversion therapy model.

The present study examined the ability of rats to develop aversions to familiar flavours and to flavours that they had previously acquired a preference for. Rats were first conditioned to prefer a CS+ flavour over a CS- flavour by pairing CS+ intake with the consumption of a starch solution (16% Polycose). A second group was exposed to the same training but preference conditioning was prevented by inhibiting starch digestion with the drug acarbose.