Sex hormone levels in patients with sudden cardiac arrest.

Background: Sex hormones are known to have significant effects on the pathophysiology of cardiovascular disease.

Objective: The purpose of this study was to study the association between sex hormone levels and sudden cardiac arrest (SCA).

Methods: In the ongoing Oregon Sudden Unexpected Death Study (catchment population approximately 1 million), cases of SCA were compared with matched controls.

Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease.

Background: Recent genome-wide association studies (GWAS) have identified novel loci associated with sudden cardiac death (SCD). Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD).

A common missense variant in the neuregulin 1 gene is associated with both schizophrenia and sudden cardiac death.

Background: Both schizophrenia and epilepsy have been linked to increased risk of sudden cardiac death (SCD). We hypothesized that DNA variants within genes previously associated with schizophrenia and epilepsy may contribute to an increased risk of SCD.

Objective: To investigate the contribution to SCD susceptibility of DNA variants previously implicated in schizophrenia and epilepsy.

Anti-tumor activity of liposome encapsulated fluoroorotic acid as a single agent and in combination with liposome irinotecan.

To test the hypothesis that co-delivery of synergistic drug combinations in the same liposome provides a better anti-tumor effect than the drugs administered in separate liposomes, fluoroorotic acid (FOA) alone and in combination with irinotecan (IRN) were encapsulated in liposomes and evaluated for their anti-tumor activity in the C26 colon carcinoma mouse model. A new chaotropic loading strategy was devised wherein FOA was dissolved in 7 M urea to increase its solubility. This enabled the passive loading of FOA into liposomes at a high concentration.

Synthesis and properties of star-comb polymers and their doxorubicin conjugates.

We describe a six-step synthesis to water-soluble doxorubicin (DOX)-loaded biodegradable PEGylated star-comb polymers with favorable pharmaceutical properties by atom transfer radical polymerization (ATRP) starting with a commercially available tripentaerythritol carrying eight reactive sites. The low polydispersity polymers degrade in a stepwise manner into lower molecular weight (MW) fragments by 15 days at 37 °C at either pH 5.0 or pH 7.

Antitumor effect of folate-targeted liposomal doxorubicin in KB tumor-bearing mice after intravenous administration.

The effect of folate-targeted liposomal doxorubicin (FTL-Dox) has been well characterized in folate receptor (FR) overexpressing tumors in vitro, particularly in KB human carcinoma cells. However, there are few studies evaluating the in vivo efficacy of FTL-Dox in KB murine xenograft models. In this study, we investigated the antitumor activity of FTL-Dox injected intravenously in mice bearing KB tumors.

Design, synthesis, and biological evaluation of a robust, biodegradable dendrimer.

PEGylated dendrimers are attractive for biological applications due to their tunable pharmacokinetics and ability to carry multiple copies of bioactive molecules. The rapid and efficient synthesis of a robust and biodegradable PEGylated dendrimer based on a polyester-polyamide hybrid core is described. The architecture is designed to avoid destructive side reactions during dendrimer preparation while maintaining biodegradability.

Synthesis and in vivo antitumor efficacy of PEGylated poly(l-lysine) dendrimer-camptothecin conjugates.

Polymer conjugates of camptothecin (CPT) have been pursued as a solution to the difficulties present in treating cancers with CPT and its derivatives. Covalent attachment of CPT to a polymer can improve solubility, increase blood circulation time, enhance tumor uptake, and significantly improve efficacy of the drug. In this report, we describe a novel polymer conjugate of CPT using a core-functionalized, symmetrically PEGylated poly(l-lysine) (PLL) dendrimer.

The influence of polymer topology on pharmacokinetics: differences between cyclic and linear PEGylated poly(acrylic acid) comb polymers.

Water-soluble polymers for the delivery of chemotherapeutic drugs passively target solid tumors as a consequence of reduced renal clearance and the enhanced permeation and retention (EPR) effect. Elimination of the polymers in the kidney occurs due to filtration through biological nanopores with a hydrodynamic diameter comparable to the polymer. Therefore we have investigated chemical features that may broadly be grouped as "molecular architecture" such as: molecular weight, chain flexibility, number of chain ends and branching, to learn how they impact polymer elimination.