Journal of pharmacological and toxicological methods
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J Pharmacol Toxicol Methods · May 2012
Improvement in ARDS experimental model installation: low mortality rate and maintenance of hemodynamic stability.
Many experimental models using lung lavage have been developed for the study of acute respiratory distress syndrome (ARDS). The original technique has been modified by many authors, resulting in difficulties with reproducibility. There is insufficient detail on the lung injury models used, including hemodynamic stability during animal preparation and drawbacks encountered such as mortality. The authors studied the effects of the pulmonary recruitment and the use of fixed tidal volume (Vt) or fixed inspiratory pressure in the experimental ARDS model installation. ⋯ There were no differences between the three study groups, with no disadvantage in method of lung recruitment, either fixed tidal volume or fixed inspiratory pressure, regarding the number of lung lavages necessary to obtain the ARDS animal model. Furthermore, the three different procedures resulted in good hemodynamic stability of the animals, and low mortality rate.
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J Pharmacol Toxicol Methods · Jan 2012
Establishment of a novel objective and quantitative method to assess pain-related behavior in monosodium iodoacetate-induced osteoarthritis in rat knee.
Pain in osteoarthritis (OA) patients can be present at rest but typically worsens with movement of the affected joint. However, useful assessment methods of movement-induced pain in animal models are limited. Here, we describe the reduction of spontaneous activity in a rat model of OA as an objective and quantifiable behavioral pain that can predict the analgesic activity of a variety of agents following single-dose administration. ⋯ This study indicates that unlike standard measures of analgesia such as alteration in thermal or mechanical sensitivity, measurement of spontaneous activity is a validated method for measuring the effects of analgesics in rats with OA knee joints. Moreover, the animals require no habituation, and thus behavioral observation subjectivity is eliminated.
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J Pharmacol Toxicol Methods · Sep 2011
Noninvasive cardiac output monitoring with bioreactance as an alternative to invasive instrumentation for preclinical drug evaluation in beagles.
Non-invasive measurement of cardiac output (CO) using bioreactance signals (NICOM) was recently validated in swine and human adults. The present study was designed to test the hypothesis that NICOM flow measurements can accurately measure CO and detect acute drug-induced changes in aortic blood flow (AoQ)≥10% in beagles. ⋯ Continuous, non-invasive measurement of CO by bioreactance provides data that satisfactorily approximates invasive measurement of aortic blood flow in beagles. In addition, despite a 30s interval between measurements, the NICOM appears to have sufficient fidelity to detect and quantify acute, drug-induced changes in CO. These data suggest that the NICOM may represent an alternative to open chest instrumentation for CO measurement in preclinical drug evaluation studies.
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J Pharmacol Toxicol Methods · May 2011
Simultaneous assessment of cytochrome P450 activity in cultured human hepatocytes for compound-mediated induction of CYP3A4, CYP2B6, and CYP1A2.
The human nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), and aryl hydrocarbon receptor (AhR) are known to regulate gene expression of the cytochrome P450 (CYP) enzymes, 3A4, 2B6, and 1A2, respectively. In conventional CYP induction studies, the activity of each CYP enzyme is assessed in a separate incubation with the appropriate marker substrate. The objective of this study was to assess, simultaneously, the induction of CYP3A4, CYP2B6, and CYP1A2 activity in cultured human hepatocytes treated with various prototypical ligands of PXR, CAR, and AhR by utilizing an optimized substrate cocktail, as well as a rapid, sensitive liquid chromatography-mass spectrometry method. ⋯ The combination of three marker substrates in a single 30-min incubation, in addition to a rapid, sensitive LC-MS/MS method, resulted in an efficient and robust method for assessing cytochrome P450 induction as compared to the conventional methodology.
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J Pharmacol Toxicol Methods · Nov 2009
Comparative StudyProinflammatory tissue response and recovery of adipokines during 4 days of subcutaneous large-pore microdialysis.
Subcutaneous adipose tissue (SAT) is increasingly being recognized as a highly active tissue secreting adipokines involved in many physiological and pathophysiological processes. Microdialysis is a technique used for in vivo sampling of interstitial fluid from e.g. SAT. The technique was originally designed for sampling of small molecules but recently the availability of catheters with large-pore membranes has made it possible to recover larger molecules such as adipokines. The present study investigated tissue response towards large-pore microdialysis catheters inserted into human SAT for 4 days. ⋯ Insertion of a large-pore microdialysis catheter into human SAT results in tissue trauma leading to changes in the interstitial concentrations of IL-1beta, IL-6, IL-8, MCP-1, TNF-alpha and adiponectin.