A Perspective on Clinical Trials for Citizens: Relatively Safe, Relatively Effective, Relatively Cheap
Peter T. Kissinger
Clinical trials are in the news. Most scientists, and fewer citizens, have any familiarity with the complications, the history and the regulation of clinical trials. This is a lighthearted look at all three, not a definitive treatise. While expectations run high for new medical interventions, reality suggests caution, but not too much caution. Balancing the financial risk of novel therapies (both to develop and to apply them), their availability in a timely manner and the risk of adverse events requires compromises which are inevitably unacceptable to most of us. While we do not say it, we instinctively know that drugs can only be relatively safe, relatively effective and relatively cheap versus allowing disease to continue unabated. Without this relativistic approach, we will inevitably be disappointed. To expect safety and effectiveness in an absolute sense denies the fact that each time patients receive a new prescription, they are volunteering for a clinical trial of one. A better system for integrating information from all these “n of 1” trials might well be helpful, but we have no means yet of doing this.
Desorption Electrospray Ionization (DESI) Mass Spectrometry: A brief introduction and overview
Justin M. Wiseman and Brian C. Laughlin
A recent advancement in mass spectrometry is the ability to examine samples situated outside the vacuum system in the ambient environment with minimal sample preparation. This article presents an introduction to desorption electrospray ionization (DESI) mass spectrometry and an overview of recent literature and emerging methods. In DESI, electrically charged droplets are directed at the sample of interest; ions are generated of the sample constituents and are collected and mass analyzed in a standard commercial mass spectrometer. This method promises rapid, high-throughput analysis combined with the sensitivity and specificity of the mass spectrometer. Applications related to counterfeit tablet identification, metabolomics, and two-dimensional chemical imaging of biological tissues are briefly discussed.
Application of Proteomics Technologies to Biomarker Discovery and Development – Challenges and Solutions
In recent years, proteomic technologies have led to enormous advances in basic research and medicine. The impact these technologies can have on a more complete understanding of the processes of life is only now beginning to be realized. On the clinical side, proteomics is viewed as a promising new approach that will speed the discovery and validation of protein biomarkers that correlate with disease and allow for assessment of therapeutic regimens. However, despite many significant technological developments, serious challenges remain. For instance, greater sensitivity in detecting proteins from complex mixtures and easy access to fast and cost-effective assays to validate promising markers are improvements that will allow the field of proteomics to have a much greater impact. In this article, we will discuss how INCAPS is tackling these two challenges to offer unique proteomic capabilities to its customers.
Automated Measurement of Amphetamine-Induced Focused Stereotypy in Rats and Harmaline-Induced Tremor in Mice: An Introduction to the Force Plate Actimeter
S. Katner, N. Nikolaidis, J. Markham, and S. Clevenger
Until now, researchers were required to use a multitude of different behavioral measurement devices for quantification of various behaviors associated with disease models and drug development. This included photo-cell beam boxes to quantify locomotion (1) and rearing activity (2), rotometers to quantify rotational activity (3), and subjective human scoring for stereotypical behaviors (10, 11). In addition, many of these devices work for either rats or mice, but not both species, further compounding the amount of equipment required to quantify behaviors. This article highlights use of the BASi Force Plate Actimeter to objectively quantify amphetamine-induced focused stereotypy in rats, as well as harmaline-induced tremor in mice.
Comparison of Automated and Manual Oral Dosing on the Absorption, Conversion, and Locomotor-Activating Effects of Nicotine
James E. Woods II, Chandrani P. Gunaratna, Robyn R. Guinn, Bruce P. Solomon, Chester T. Duda, and Candice B. Kissinger
The accurate assessment of a new drug candidate’s pharmacokinetic and pharmacodynamic profile are essential components of the drug development process. Given the importance of these characteristics, knowledge of potential influencing factors such as stress becomes crucial. This study examined the effect of low-stress, automated intragastric dosing compared to higher-stress, manual gavage dosing on the absorption phase of nicotine’s pharmacokinetic curve, conversion of nicotine to cotinine, and nicotine-induced locomotor stimulation in Sprague Dawley rats. Nicotine (1 mg/kg) was either automatically infused directly into the stomach or manually dosed using the typical gavage needle and syringe. Immediately following nicotine administration, a rapid blood sampling method (every 5 min) was conducted and motor activity was recorded for 60 min. Each rat received both an automated infusion and a manually-injected dose of nicotine in a cross-over design. The results indicated that nicotine absorption was more rapid when automatically dosed, but this effect did not significantly alter the conversion of nicotine to cotinine. Also, no significant differences in motor activity were found between manual and automated dosing. The results suggest that the method of dosing can influence the pharmacokinetics of a drug and should be considered a factor in study designs.
LC/MSMS Methods for Quantitative Determination of Mycophenolic Acid in Human Plasma
Tom Fleischmann, James Merdink, Sue Faulconbridge and Tony Clarke
- Handbook of Microdialysis
- The Demon under the Microscope
- The Body Hunters
- Waters Corporation and Prosolia, Inc. Collaborate on DESI
- Aptuit, Inc. Acquires SSCI
- George W. Sledge Receives 2006 Brinker Award
- 2007 Charles N. Reilley Award