Canadian journal of physiology and pharmacology
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Can. J. Physiol. Pharmacol. · Apr 2008
Inflammatory cytokines and malnutrition as related to risk for cardiovascular disease in hemodialysis patients.
Malnutrition and inflammation are associated with end-stage renal disease (ESRD). Interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) powerfully predict death from cardiovascular disease. The aim of our study was to establish an association between markers of inflammation and parameters of malnutrition in patients on hemodialysis. ⋯ In summary, this cross-sectional study in hemodialysis patients found a high prevalence of malnutrition, inflammation, carotid plaques, and cardiovascular disease. Malnourished dialysis patients are more often found with cardiovascular disease and carotid plaques. In addition, these patients have higher levels of inflammatory cytokines, which may partly explain the elevated risk for atherosclerotic vascular disease.
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Can. J. Physiol. Pharmacol. · Dec 2007
Biography Historical ArticleAdventures in drug disposition: pas seulement pâté de foie.
Interindividual variability in drug disposition and effect has served to confound the optimization of drug therapy. Over my career, I have focused on delineating mechanisms that contribute to this variability, with the goal of improving the benefit : risk ratio when drug therapy is chosen as an intervention strategy. In this manuscript, I present some of our experimental findings that I believe have contributed to an increased understanding of variability in drug disposition and efficacy.
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Can. J. Physiol. Pharmacol. · Dec 2007
Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion injury by opening K ATP channels.
The present study was undertaken to investigate the protective effect of H2S against myocardial ischemia-reperfusion (I/R) injury and its possible mechanism by using isolated heart perfusion and patch clamp recordings. Rat isolated hearts were Langendorff-perfused and subjected to a 30-minute ischemia insult followed by a 30-minute reperfusion. The heart function was assessed by measuring the LVDP, +/-dP/dt max, and the arrhythmia score. ⋯ The cardioprotective effect of NaHS during reperfusion could be blocked by an ATP-sensitive potassium channel (K ATP) blocker (10 micromol/L glibenclamide). In single cardiac myocytes, NaHS increased the open probability of K ATP channels from 0.07 +/- 0.03 to 0.15 +/- 0.08 after application of 40 mumol/L NaHS and from 0.07 +/- 0.03 to 0.36 +/- 0.15 after application of 100 mumol/L NaHS. These findings provide the first evidence that H2S increases the open probability of K ATP in cardiac myocytes, which may be responsible for cardioprotection against I/R injury during reperfusion.
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Can. J. Physiol. Pharmacol. · Aug 2007
Onset-potency relationship of nondepolarizing muscle relaxants: a reexamination using simulations.
Nondepolarizing muscle relaxants (MRs) display an inverse onset-potency relationship, that is, less potent MRs display a more rapid onset. We have conducted the current investigation to estimate the impact of variable pharmacokinetic or pharmacodynamic properties of the MRs on potency and onset time, and on the onset-potency relationship. Using a model of neuromuscular transmission, we changed either the affinity of MRs for the postsynaptic receptors or the pharmacokinetic properties of the MRs. ⋯ In a double logarithmic plot, the onset-potency relationship was linear. Lesser affinities produce a nearly parallel rightward shift of the regression lines. The inverse onset-potency relationship may be explained by the pharmacokinetic factors producing changes in both the potency and onset times.
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Can. J. Physiol. Pharmacol. · Jun 2007
The time course of inflammatory cytokine secretion in a rat model of postoperative pain does not coincide with the onset of mechanical hyperalgesia.
We characterized the time course of inflammatory cytokine release at the site of injury and in plasma after surgery on the rat tail. Anesthetized Sprague-Dawley rats had a 20 mm long incision made through the skin and fascia of their tails. Control rats were anesthetized, but no incision was made. ⋯ Thereafter, cytokine concentrations remained elevated for 4 (IL-1beta and IL-6) to 8 days (CINC-1, TNF-alpha) after surgery. Control animals did not develop hyperalgesia and no changes in cytokines concentrations were detected. Thus, in our model of postoperative pain, secretion of inflammatory cytokines IL-1beta, IL-6, TNF-alpha, and CINC-1 was not essential for the initiation of postoperative hyperalgesia.