Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Feb 2015
Exercise training protects against atherosclerotic risk factors through vascular NADPH oxidase, extracellular signal-regulated kinase 1/2 and stress-activated protein kinase/c-Jun N-terminal kinase downregulation in obese rats.
Exercise training reverses atherosclerotic risk factors associated with metabolic syndrome and obesity. The aim of the present study was to determine the molecular anti-inflammatory, anti-oxidative and anti-atherogenic effects in aorta from rats with high-fat diet-induced obesity. Male Sprague-Dawley rats were placed on a high-fat (HFD) or control (CD) diet for 12 weeks. ⋯ Exercise training and switching from the HFD to CD reversed almost all these molecular changes. In addition, training increased aortic SOD-1 protein expression and decreased ERK1/2 phosphorylation. These findings suggest that protective effects of exercise training on atherosclerotic risk factors induced by obesity are associated with downregulation of NADPH oxidase, ERK1/2 and SAPK/JNK activity and increased SOD-1 expression.
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Clin. Exp. Pharmacol. Physiol. · Jan 2015
Minocycline can delay the development of morphine tolerance, but cannot reverse existing tolerance in the maintenance period of neuropathic pain in rats.
Neuropathic pain is a challenge for physicians and basic science researchers, because it often does not respond to routine treatment. The administration of morphine has been considered one of the effective recommended treatments, but its wide application is limited because of the development of antinociceptive tolerance. In general, basic science studies focus on neuropathic pain and morphine tolerance separately. ⋯ Fourth, the pre-administration of minocycline can delay the development of morphine tolerance, but repeated minocycline administration cannot reverse existing morphine tolerance. We concluded that microglial activation contributes to the morphine tolerance of SNL rats in the maintenance period of neuropathic pain, and that minocycline delays the development of morphine tolerance, but does not reverse existing morphine tolerance during the maintenance period of neuropathic pain in rats. These findings might be useful for clinical pain management.
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Clin. Exp. Pharmacol. Physiol. · Dec 2014
Alpha attenuation soon after closing the eyes as an objective indicator of sleepiness.
Attenuation of alpha rhythm in occipital derivation serves as a reliable electroencephalographic (EEG) marker of sleep onset. If such attenuation not only coincides with but also anticipates sleep onset, objective evaluation of sleepiness of permanently waking individuals might be facilitated by probing alpha attenuation immediately after closing eyes. We tested whether alpha-based EEG indexes reflect self-scored sleepiness and objectively measured waking ability. ⋯ Alpha attenuation during the first minute with eyes closed was found to be significantly related to the levels of subjective sleepiness and waking ability. The relationship between alpha attenuation and subjective sleepiness was confirmed by analysing 1-min eyes closed EEG recordings obtained with a 3-h interval in the course of 24-h sustained wakefulness of 130 adolescents and adults. We concluded that such 1-min eyes closed EEG recordings might be used for simple and quick measurements of sleepiness and waking ability in experimental and field studies of permanently waking individuals.
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Clin. Exp. Pharmacol. Physiol. · Nov 2014
Randomized Controlled TrialDoes dexmedetomidine have a cardiac protective effect during non-cardiac surgery? A randomised controlled trial.
This study was designed to determine the effects of dexmedetomidine on perioperative myocardial injury by observing peripheral circulatory changes in response to tracheal intubation and extubation, myocardial enzyme levels, myocardial ischaemia improvements, cardiovascular adverse events and cytokines in patients with coronary heart disease (CHD) undergoing non-cardiac surgery. This study was a prospective, randomized, double-blind trial. Eighty patients having CHD were scheduled for elective hip-replacement surgery and randomly allocated to receive a loading dose of 1 μg/kg dexmedetomidine followed by a 0.2 μg/kg per h infusion (Dex group; n = 40) or normal saline (control group; n = 40). ⋯ In addition, the Dex group had lower serum CK-MB, IL-6, cTnI and GP-BB concentrations than the control group (P < 0.05). There was no significance difference in TNF-α between the two groups (P > 0.05). Dexmedetomidine can reduce myocardial injury and cytokine levels in patients with CHD undergoing non-cardiac surgery.
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Clin. Exp. Pharmacol. Physiol. · Oct 2014
Characterization of a double-hit murine model of acute respiratory distress syndrome.
The aim of the present study was to characterize a murine model of acute respiratory distress syndrome (ARDS) abiding by the Berlin definition of human ARDS and guidelines for animal models of ARDS. To this end, C57BL/6NCrl mice were challenged with lipopolysaccharide (LPS; 15 mg/kg, i.p.) followed 18 h later by injection of oleic acid (OA; 0.12 mL/kg, i.v.). Controls received saline injection at both time points. ⋯ The lung wet : dry ratio indicated damage to the alveolar capillary membrane. Cytokine patterns evidenced a severe local and systemic inflammatory state in plasma and lung tissue. In conclusion, the described two-hit model of ARDS shows a pathological picture of ARDS closely mimicking human ARDS according to the Berlin definition and may facilitate interpretation of prospective experimental results.