Journal of pharmacological and toxicological methods
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J Pharmacol Toxicol Methods · Sep 2013
A new biomarker--index of cardiac electrophysiological balance (iCEB)--plays an important role in drug-induced cardiac arrhythmias: beyond QT-prolongation and Torsades de Pointes (TdPs).
In the present study, we investigated whether a new biomarker - index of cardiac electrophysiological balance (iCEB=QT/QRS) - could predict drug-induced cardiac arrhythmias (CAs), including ventricular tachycardia/ventricular fibrillation (VT/VF) and Torsades de Pointes (TdPs). ⋯ Our data from 7 reference drugs of known pro-arrhythmic effects suggests that 1) this non-invasive iCEB predicts potential risk of drug-induced CAs beyond long QT and TdP; 2) iCEB is more useful than the current biomarkers (i.e. transmural dispersion and instability) in predicting potential risks for drug-induced non-TdP-like VT/VF.
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J Pharmacol Toxicol Methods · May 2013
Reducing suffering in experimental autoimmune encephalomyelitis (EAE).
This report is based on discussions and submissions from an expert working group consisting of veterinarians, animal care staff and scientists with expert knowledge relevant to the field. It aims to facilitate the implementation of the Three Rs (replacement, reduction and refinement) in the use of animal models or procedures involving experimental autoimmune encephalomyelitis (EAE), an experimental model used in multiple sclerosis research. ⋯ Specific welfare issues are identified and discussed, and practical measures are proposed to reduce animal use and suffering. Some general issues for refinement are summarised to help achieve this, with more detail provided on a range of specific measures to reduce suffering.
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J Pharmacol Toxicol Methods · Mar 2013
Troubleshooting the rat model of cardiopulmonary bypass: effects of avoiding blood transfusion on long-term survival, inflammation and organ damage.
Rat models of cardiopulmonary bypass (CPB) have been used to examine the mechanisms of associated organ damage and to test intervention strategies. However, these models only partly mimic the clinical situation, because of the use of blood transfusion and arterial inflow via the tail artery. Thus a model using arterial inflow in the aorta and a miniaturized CPB circuit without need of transfusion was validated by examining intra-procedure characteristics, mortality and the effects of CPB on biomarkers of inflammation and cerebral injury during 5days follow-up. ⋯ Our rat model of CPB without homologous blood transfusion produces a reproducible and reliable systemic inflammatory response, with low mortality rates on long term follow up. The model more closely mimics the human situation in respect to arterial inflow site and avoidance of blood transfusion. Thus, our CPB model is suitable to study its influence on systemic inflammation, ischemia-reperfusion injury, microcirculation and vascular dysfunction in vivo, and to evaluate potential therapeutic interventions.
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J Pharmacol Toxicol Methods · Jan 2013
ReviewReducing suffering in animal models and procedures involving seizures, convulsions and epilepsy.
This report is based on discussions and submissions from an expert working group consisting of veterinarians, animal care staff and scientists with expert knowledge relevant to the field and aims to facilitate the implementation of the Three Rs (replacement, reduction and refinement) in the use of animal models or procedures involving seizures, convulsions and epilepsy. Each of these conditions will be considered, the specific welfare issues discussed, and practical measures to reduce animal use and suffering suggested. The emphasis is on refinement since this has the greatest potential for immediate implementation, and some general issues for refinement are summarised to help achieve this, with more detail provided on a range of specific refinements.
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J Pharmacol Toxicol Methods · Jul 2012
Comparative StudyComparison of manual and automated filaments for evaluation of neuropathic pain behavior in rats.
The most commonly used Von Frey filaments are productive in evaluating behavioral responses of neuropathic pain in preclinical and clinical research. To reduce the potential experimenter bias, automated instruments are being developed for behavioral assessment. In preclinical research, neuropathic pain models of nerve injury with varied etiology like partial sciatic nerve ligation (PNL), chronic constricted injury (CCI) and spinal nerve ligation (SNL) are employed to screen the analgesic drugs to treat symptoms like allodynia and hyperalgesia. The current study was aimed to validate and compare conventionally used Von Frey monofilaments and automated dynamic plantar aesthesiometer using three different pain models. ⋯ Manually used Von Frey filaments can be used in assessment of mechanical allodynia in all the three models, whereas dynamic plantar aesthesiometer is suitable for assessing mechanical allodynia in SNL but not in PNL and CCI models. The reason for variable paw withdrawal thresholds during assessment of mechanical allodynia in PNL and CCI models with dynamic plantar aesthesiometer may be due to the paw deformity and change in foot posture.