Pharmacol Rep
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Clinical Trial
Assessing circadian rhythms during prolonged midazolam infusion in the pediatric intensive care unit (PICU) children.
This study evaluates possible circadian rhythms during prolonged midazolam infusion in 27 pediatric intensive care unit (PICU) children under mechanical ventilation. ⋯ We concluded that the light-dark cycle did not influence midazolam pharmacokinetics in intensive care units children. Also, endogenous rhythms in critically ill and sedated children are severely disturbed and desynchronized. Our results confirmed that it is necessary to adjust the dose of midazolam to the patient's body weight. The low value of midazolam clearances observed in our study was probably caused by mechanical ventilation, which was shown to decrease the cardiac output.
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Comparative Study
Nisoxetine blocks sodium currents and elicits spinal anesthesia in rats.
Although nisoxetine has been shown to elicit infiltrative cutaneous local anesthesia, the inhibition of voltage-gated Na(+) channels by nisoxetine has not been reported. The aim of this study was to evaluate the effect of nisoxetine on Na(+) currents and its efficacy on spinal anesthesia. ⋯ Our results showed that nisoxetine displayed a more potent and prolonged spinal anesthesia with a more sensory/nociceptive-selective action over motor blockade, compared with mepivacaine. The local anesthetic effect of nisoxetine could be probably due to the suppression of Na(+) currents.
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Comparative Study
Can the antiplatelet effects of cangrelor be reliably studied in mice under in vivo and in vitro conditions using flow cytometry?
The effects of blood platelet inhibitors are often not quite equivalent under in vivo and in vitro conditions. Amongst various models of human pathology using laboratory animals, mice offer several benefits that make them convenient tools for studying the putative therapeutic value of various compounds. However, despite its advantages, the mouse model has methodological limitations concerning the small amount of blood available and technical difficulties with its collection. Among the variety of available methods used to study blood platelet activation and/or reactivity, flow cytometry seems an attractive technique that largely minimizes the constraints of using small rodents and enables outcomes of laboratory research to be transferred successfully to clinical practice. In this study we aimed at a critical evaluation of the optimal discriminative flow cytometric protocol, useful for reliable studies of the effect of cangrelor, a P2Y12 receptor antagonist, on mouse platelets under in vitro and in vivo conditions. ⋯ The agreement between the in vivo and in vitro approaches with respect to cangrelor-inhibited hallmarks of blood platelet activation and reactivity supports our proposal that flow cytometry is useful and reliable for determining the effects of antiplatelet agents on the activation of circulating platelets in the mouse model, as well as the in vitro response of platelets to agonists.
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Comparative Study
Influence of chronic stress on brain corticosteroid receptors and HPA axis activity.
Disruption of the glucocorticoid negative feedback system evoked in animals by chronic stress can be induced by downregulation of glucocorticoid receptors (GRs) in several brain regions. In the present study, the dynamics of the changes in GRs, in brain structures involved in stress reactions, prefrontal cortex, hippocampus and hypothalamus was compared with the peripheral hypothalamo-pituitary-adrenocortical (HPA) axis hormones response to chronic stress. ⋯ Comparison of the dynamics of changes in plasma ACTH and corticosterone level with respective alterations in GR and MR in brain structures suggests that the buffering effect of repeated stress depends on the period of habituation to stress and the brain structure involved in regulation of these stress response.
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It has been shown that spinal PKA/CREB signaling pathway is involved in neuropathic and inflammatory pain, but its effects on bone cancer pain have not previously been investigated. The aim of this study was to examine the potential role of the spinal PKA/CREB signaling pathway in the development of bone cancer pain. ⋯ The results suggest that the spinal PKA/CREB signaling pathway may participate in the development of bone cancer pain. The findings of this study may provide an evidence for developing novel analgesics to block bone cancer pain.