Enhanced detection of hydrogen sulfide generated in cell culture using an agar trap method.

Lack of reliable methods to accurately measure hydrogen sulfide (H(2)S) produced in vitro has impeded research on the physiology of this gaseous mediator. Current in vitro methods involve measurement of H(2)S in cell culture media following incubation with H(2)S-releasing compounds. However, this method is inaccurate because H(2)S gas has a short life and thus evades detection.

The possible roles of food-derived bioactive peptides in reducing the risk of cardiovascular disease.

Vascular diseases such as atherosclerosis, stroke or myocardial infarction are a significant public health problem worldwide. Attempts to prevent vascular diseases often imply modifications and improvement of causative risk factors such as high blood pressure, obesity, an unfavorable profile of blood lipids or insulin resistance. In addition to numerous preventive and therapeutic drug regimens, there has been increased focus on identifying dietary compounds that may contribute to cardiovascular health in recent years.

Heme oxygenase-1 is a novel target and antioxidant mediator of S-adenosylmethionine.

The sulfur compound and dietary supplement S-adenosylmethionine (SAM) has been reported to have cytoprotective and antioxidant properties. However, the underlying mechanisms remain unresolved. The present study investigates the effect of SAM on the expression of the antioxidant stress proteins heme oxygenase-1 (HO-1) and ferritin in endothelial cells.

AAPS-FDA workshop white paper: microdialysis principles, application and regulatory perspectives.

Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment.

The chinchilla microdialysis model for the study of antibiotic distribution to middle ear fluid.

In cases of slow or limited penetration of an antibiotic to the site of infection such as in acute otitis media (the middle ear), plasma levels of the agent may not reflect the concentrations that are relevant in determining clinical outcome. There is a need for a model that allows prediction of the time-course of unbound, pharmacologically active drug levels in middle ear fluid (MEF). This article introduces microdialysis as a sampling tool to measure unbound antibiotic concentrations in the MEF of the chinchilla, and briefly summarizes the results of studies of MEF penetration of a cephalosporin, a macrolide, and a ketolide antibiotic using this technique.

Microdialysis studies of the distribution of antibiotics into chinchilla middle ear fluid.

For conditions such as acute otitis media, in which antibiotic penetration into middle ear fluid (MEF) may be slow or limited, antibiotic plasma levels may not reflect the concentrations at the site of infection that are relevant to clinical outcome. In such cases, a model is needed that will enable prediction of the time course of unbound, pharmacologically active antibiotic levels in MEF. We describe the use of microdialysis as a sampling tool for measurement of unbound antibiotic concentrations in the MEF of the awake, freely moving chinchilla.

The application of sample pooling methods for determining AUC, AUMC and mean residence times in pharmacokinetic studies.

For high-throughput screening in drug development, methods that can reduce analytical work are desirable. Pooling of plasma samples from an individual subject in the time domain to yield a single sample for analysis has been used to estimate the area under the concentration-time curve (AUC). We describe a pooling procedure for the estimation of the area under the first moment curve (AUMC).

Simultaneous intravenous and intramiddle-ear dosing to determine cefditoren influx and efflux clearances in middle ear fluid in freely moving chinchillas.

This study was conducted to determine cefditoren (CDTR) transport kinetics between plasma and middle ear fluid (MEF) by characterizing influx (CLin) and efflux (CLout) clearances expressed in terms of unbound concentrations and their ratio. Simultaneous intravenous bolus and intramiddle-ear dose were administered to two groups of chinchillas: normal control and infected. In vivo microdialysis was employed to determine protein-unbound CDTR levels in MEF.