Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Apr 2014
Emulsified isoflurane protects rat heart in situ after regional ischemia and reperfusion.
Volatile anesthetic postconditioning reduces myocardial infarct size against ischemia/reperfusion (I/R) injury. We tested the hypothesis that emulsified isoflurane (EIso) administrated after ischemia exerts cardioprotection in a rat model of myocardial I/R. Male SD rats underwent 30-min coronary occlusion followed by 3-h reperfusion except for sham rats. ⋯ Serum levels of cardiac enzyme leakage were reduced in EIso-treated hearts compared with CON (P < 0.01 or P < 0.05). EIso preserved the ultrastructure of mitochondria, protected against mPTP opening, decreased cytochrome c release and preserved ATP production and ΔΨm. In conclusion, EIso is effective in reducing infarct size and in preserving mitochondrial function after ischemia and reperfusion injury.
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Fundam Clin Pharmacol · Apr 2014
The effects of dexketoprofen on duration of analgesia to a thermal stimulus when compared with a systemic control in a rat sciatic nerve block with levobupivacaine.
This study was designed to investigate whether dexketoprofen added to perineuraly or subcutaneously alters the effects of levobupivacaine in a rat model of sciatic nerve blockade. Thirty-six rats received unilateral sciatic nerve blocks along with a subcutaneous injection by a blinded investigator assigned at random. Combinations were as follows: Group 1 (sham) perineural and subcutaneous saline; Group 2, perineural levobupivacaine alone and subcutaneous saline; Group 3, perineural levobupivacaine plus dexketoprofen and subcutaneous saline; Group 4, perineural levobupivacaine and subcutaneous dexketoprofen; Group 5, perineural dexketoprofen and subcutaneous saline; and Group 6, perineural saline and subcutaneous dexketoprofen. ⋯ Significant differences were not determined between the levobupivacaine alone group and dexketoprofen added groups in operative paw. The effects of dexketoprofen are unknown for perineural administration. There is no significant difference between the analgesic effects of peripheral nerve blocks using levobupivacaine alone and plus subcutaneous or perineural dexketoprofen.
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Fundam Clin Pharmacol · Feb 2014
Randomized Controlled Trial Multicenter StudyComparison of two doses of ketoprofen to treat pain: a double-blind, randomized, noninferiority trial.
The aim of our study was to compare the efficacy and safety of two doses of ketoprofen (200 mg vs. 300 mg/day) in ambulatory emergency patients with pain related to traumatic and nontraumatic bone and joint diseases. We tested the hypothesis that the efficacy of the lower dose was not lower than that of the higher dose in a double-blind, randomized, noninferiority trial. Patients included in the study were aged 18-65 years with closed benign trauma of the motor system or acute noninfectious rheumatologic conditions, with a resting pain intensity ≥3/10 on a numeric pain scale (NPS), requiring ketoprofen for 5 days. ⋯ The mean change in pain intensity at rest (difference between groups: 0.0, 95% CI -0.4 to 0.4; P = 1.00) and in analgesic consumption (difference between groups: -0.6, 95% CI -1.9 to 0.6; P = 0.33) was not significantly different between the two groups, and the differences were lower than the predefined inferiority margins (0.5 and 1.5, respectively), thus demonstrating noninferiority. No significant difference was noted in the incidence of adverse events (21% vs. 20%, P = 0.71). The efficacy of the 200-mg daily dose of ketoprofen in relieving pain in emergency cases was not inferior to that of the 300-mg dose.
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Fundam Clin Pharmacol · Feb 2014
Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice.
Dexmedetomidine (DEX) is a α₂ -adrenoceptor (α₂ -AR) agonist used as an anesthetic adjuvant and as sedative in critical care settings. Typically, α₂ -AR agonists release nitric oxide (NO) and subsequently activate NO-GMPc pathway and have been implicated with antinociception. In this study, we investigate the pharmacological mechanisms involved in the antinociceptive effects of DEX, using an acetic acid-induced writhing assay in mice. ⋯ The rotarod and open-field tests confirmed there is no detectable sedation or even significant motor impairment with DEX at 10 μg/kg dose. Our results suggest that the α₂ -AR and NO-GMPc pathways play important roles in the systemic antinociceptive effect of DEX in a murine model of inflammatory pain. Furthermore, the antinociceptive effect exerted by DEX appears to be dependent on KATP channels, independent of opioid receptor activity.
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Fundam Clin Pharmacol · Dec 2013
Comparative StudySingle and repeated sevoflurane or desflurane exposure does not impair spatial memory performance of young adult mice.
Volatile anesthetics are known to disturb the spatial memory in aged rodents, but there is insufficient information on their effects on young adult rodents. The aim of this study was to compare the effects of single and repeated exposure to desflurane and sevoflurane on spatial learning and memory functions in young adult mice. Balb/c mice (2 months old) were randomly divided into six equal groups (n = 8). ⋯ In the 4-day learning process, there was no significant difference between the groups in terms of mean latency to platform, mean distance traveled and average speed (P > 0.05). During the memory-test phase, all mice exhibited spatial memory, but there was no significant difference between the groups in terms of time spent in the target quadrant (P > 0.05). Sevoflurane and desflurane anesthesia did not impair acquisition learning and retention memory in young adult mice.