cGMP-Elevating Compounds and Ischemic Conditioning Provide Cardioprotection Against Ischemia and Reperfusion Injury via Cardiomyocyte-Specific BK Channels.

Background: The nitric oxide-sensitive guanylyl cyclase/cGMP-dependent protein kinase type I signaling pathway can afford protection against the ischemia/reperfusion injury that occurs during myocardial infarction. Reportedly, voltage and Ca-activated K channels of the BK type are stimulated by cGMP/cGMP-dependent protein kinase type I, and recent ex vivo studies implicated that increased BK activity favors the survival of the myocardium at ischemia/reperfusion. It remains unclear, however, whether the molecular events downstream of cGMP involve BK channels present in cardiomyocytes or in other cardiac cell types.

Phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate in dogs with naturally occurring malignant tumors.

OBJECTIVE To conduct a phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate (HA-Pt) in dogs with naturally occurring malignant tumors. ANIMALS 18 healthy rats, 9 healthy mice, and 16 dogs with cancer. PROCEDURES HA-Pt was prepared and tested by inductively coupled plasma mass spectrometry; DNA-platinum adduct formation and antiproliferation effects of cisplatin and HA-Pt were compared in vitro.

Development and Validation of an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) Method for Quantitative Analysis of Platinum in Plasma, Urine, and Tissues.

Cisplatin, a platinum chemotherapeutic, is one of the most commonly used chemotherapeutic agents for many solid tumors. In this work, we developed and validated an inductively coupled plasma mass spectrometry (ICP-MS) method for quantitative determination of platinum levels in rat urine, plasma, and tissue matrices including liver, brain, lungs, kidney, muscle, heart, spleen, bladder, and lymph nodes. The tissues were processed using a microwave accelerated reaction system (MARS) system prior to analysis on an Agilent 7500 ICP-MS.

Hyaluronan-Lysine Cisplatin Drug Carrier for Treatment of Localized Cancers: Pharmacokinetics, Tolerability, and Efficacy in Rodents and Canines.

The purpose of this study was to develop a safe and efficacious drug delivery platform for sustained release of cisplatin after locoregional administration. We successfully synthesized hyaluronan-cisplatin nanoconjugates (HA-Lys-Pt) using an N-Ac-lysine linker, which formed a thermodynamically stable five-membered ring with the platinum. The conjugate was characterized for release kinetics, in vitro anti-proliferative activity, degradability, impurity content, formation of Pt-DNA adducts, pharmacokinetics, tolerability in rodents and canines, and for efficacy in rodents.

Development of thrombus-resistant and cell compatible crimped polyethylene terephthalate cardiovascular grafts using surface co-immobilized heparin and collagen.

Short-term patency of polyethylene terephthalate (PET) cardiovascular grafts is determined mainly by the inherent thrombogenicity and improper endothelialization following grafts implantation. The aim of the present study was to immobilize heparin to develop thrombus resistant grafts. Additionally, collagen was co-immobilized to enhance the host cell compatibility.