Biological & pharmaceutical bulletin
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Clinical Trial
Estimating the plasma effect-site equilibrium rate constant (Ke₀) of propofol by fitting time of loss and recovery of consciousness.
The present paper proposes a new approach for fitting the plasma effect-site equilibrium rate constant (Ke0) of propofol to satisfy the condition that the effect-site concentration (Ce) is equal at the time of loss of consciousness (LOC) and recovery of consciousness (ROC). Forty patients receiving intravenous anesthesia were divided into 4 groups and injected propofol 1.4, 1.6, 1.8, or 2 mg/kg at 1,200 mL/h. Durations from the start of injection to LOC and to ROC were recorded. ⋯ Only Ke0 adjusted by dose and age achieved the level of accuracy required for clinical applications. We conclude that the Ke0 estimated based on clinical signs and the two-point fitting method significantly improved the ability of CeLOC to predict CeROC. However, only the Ke0 adjusted by dose and age and not a fixed Ke0 value can meet clinical requirements of accuracy.
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Randomized Controlled Trial
Effects of intrathecal dexmedetomidine on low-dose bupivacaine spinal anesthesia in elderly patients undergoing transurethral prostatectomy.
Low-dose bupivacaine can limit the spinal block level with minimal hemodynamic effects and yield a rapid recovery, but sometimes it may not provide adequate anesthesia for surgery. Dexmedetomidine, a selective α2-adrenoreceptor agonist, was shown to be a potent antinociceptive agent when given intrathecally in animals and humans. The purpose of this study was to evaluate the adjuvant effects of intrathecal dexmedetomidine in elderly patients undergoing transurethral prostate surgery with low-dose bupivacaine spinal anesthesia. ⋯ There was less analgesic request and the time to the first analgesic request was longer in the dexmedetomidine group than in the saline group (each 487, 345 min, p<0.05). Dexmedetomidine 3 µg when added to intrathecal bupivacaine 6 mg produced fast onset and a prolonged duration of sensory block and postoperative analgesia in elderly patients for transurethral surgery. However, recovery of motor block could be delayed in dexmedetomidine-added patients.
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Clinical Trial
Method for individualized evaluation of antiemetic effect induced by 5-HT3 receptor antagonist.
5-HT3 receptor antagonists are widely used for prevention of chemotherapy-induced nausea and vomiting, though their antiemetic effects vary among patients. We investigated a method for evaluation of antiemetic effects in individual patients. We used the 5-HT3 receptor occupancy of serotonin for our evaluation, which was estimated based on the plasma concentration of granisetron and concentration of serotonin near the 5-HT3 receptor in the small intestine, obtained by measuring the urinary concentrations of granisetron and 5-hydroxyindoleacetic acid (5-HIAA)/creatinine (Cre). ⋯ Furthermore, the estimated 5-HT3 receptor occupancy of serotonin in the small intestine and actual individual patient condition corresponded well, showing the validity of our method. Our results suggest that it is possible to evaluate individual antiemetic effects by estimating the 5-HT3 receptor occupancy of serotonin in the small intestine based on plasma concentrations of granisetron and serotonin near the 5-HT3 receptor in the small intestine using noninvasive urine samples. This method of individual evaluation is considered to be useful and effective.
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Pirfenidone (PFD) is the first and only clinically used antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). This study evaluated the antifibrotic effects of two metabolites of PFD, 5-hydroxypirfenidone (PFD-OH) and 5-carboxypirfenidone (PFD-COOH), on WI-38 cells in an in vitro lung fibroblast model. ⋯ These results indicate that PFD-OH and PFD-COOH have antifibrotic activities, which inhibit collagen synthesis in fibroblasts. This study suggests that the concentrations of PFD and its metabolites should be considered in clinical therapy for IPF.
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The blood-brain barrier (BBB) is formed by brain endothelial cells. Many immortalized brain endothelial cell lines have been established; these have been used as in vitro BBB models. ⋯ In addition, bEND.3 cells expressed the highest level of claudin-5 among all cells. These results suggest that bEND.3 cells are a convenient and useful model for evaluating BBB function, especially the paracellular barrier.