Thirty years of telemetry-based data acquisition for cardiovascular drug safety evaluation: Applications and optimization.

Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the years to improve both the data quality and the well being of our animal subjects. Of particular interest for us has been the use of telemetry-based data acquisition for conducting studies on cardiovascular (CV) function.

Biomarkers of tissue remodeling predict survival in patients with pulmonary hypertension.

Background: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in vascular and right ventricular remodeling in pulmonary hypertension (PH). MMP2, MMP9, TIMP1, and TIMP4 were measured in plasma and their potential as biomarkers for PH was evaluated.

Methods: Consecutive patients undergoing right heart catheterization for suspected PH were included in this study (patients with mPAP ≥25mmHg were classed as having PH; those with mPAP <25mmHg served as non-PH controls).

Membrane lipids determine the antibiotic activity of the lantibiotic gallidermin.

Lantibiotics, a group of lanthionine-containing peptides, display their antibiotic activity by combining different killing mechanisms within one molecule. The prototype lantibiotic nisin was shown to possess both inhibition of peptidoglycan synthesis and pore formation in bacterial membranes by interacting with lipid II. Gallidermin, which shares the lipid II binding motif with nisin but has a shorter molecular length, differed from nisin in pore formation in several strains of bacteria.

Affinity and kinetics of different heparins binding to P- and L-selectin.

Selectins are adhesion receptors that participate in inflammation and tumor cell metastasis. The anti-inflammatory and antimetastatic activities of heparins have been related partly to their ability to interact with P- and L-selectin. The recent findings that various heparins differ in antimetastatic activity were explained by differences in their P- and L-selectin binding ability.

The role of lipid II in membrane binding of and pore formation by nisin analyzed by two combined biosensor techniques.

Nisin, a peptide antibiotic, efficiently kills bacteria through a unique mechanism which includes inhibition of cell wall biosynthesis and pore formation in cytoplasmic membranes. Both mechanisms are based on interaction with the cell wall precursor lipid II which is simultaneously used as target and pore constituent. We combined two biosensor techniques to investigate the nisin activity with respect to membrane binding and pore formation in real time.

The detection of UV-induced membrane damages by a combination of two biosensor techniques.

Ketoprofen is an important anti-inflammatory drug, but its dermal application is limited because of the photosensitizing properties causing phototoxic reactions of the skin when exposed to UV light. We have recently investigated the peroxide formation of ketoprofen in solutions of linoleic acid during UV irradiation. To continue these studies and focus on UV-induced changes in membrane integrity and barrier function we established an in vitro model using two biosensor techniques simultaneously.