Comparison of ED of intranasal dexmedetomidine sedation in children with acyanotic congenital heart disease before and after cardiac surgery / 南方医科大学学报

OBJECTIVE@#To compare the median effective dose (ED) of intranasal dexmedetomidine for procedural sedation in uncooperative pediatric patients with acyanotic congenital heart disease before and after cardiac surgery.@*METHODS@#We prospectively recruited 47 children (22 in preoperative group and 25 in postoperative group) who needed sedation for transthoracic echocardiography (TTE). A modified up-and-down sequential study design was employed to determine dexmedetomidine dose for each patient with a starting dose of 2 μg/kg in both groups; dexmedetomidine doses for subsequent subjects were determined according to the responses from the previous subject using the up-and-down method at a 0.25 μg/kg interval. The ED was determined using probit regression. The onset time, examination time, wake-up time and adverse effects were measured, and the safety was evaluated in terms of changes in vital signs every 5 min.@*RESULTS@#The ED value of intranasal dexmedetomidine for sedation was 1.84 μg/kg (95% : 1.68-2.00 μg/kg) in children with congenital heart disease before cardiac surgery, and 3.38 μg/kg (95% : 3.21-3.54 μg/kg) after the surgery. No significant difference was found between the two groups in the demographic variables, onset time, examination time, wake-up time, or adverse effects.@*CONCLUSIONS@#In children with acyanotic congenital heart disease, the ED of intranasal dexmedetomidine for TTE sedation increases to 3.38 μg/ kg after cardiac surgery from the preoperative value of 1.84 μg/kg.

Propofol combined with hypoxia induces cognitive dysfunction in immature rats p38 pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of propofol combined with hypoxia on cognitive function of immature rats and the possible role of p38 pathway and tau protein in mediating such effects.@*METHODS@#Ninety 7-day-old (P7) SD rats were randomized for daily intraperitoneal injection of propofol (50 mg/kg) or lipid emulsion (5.0 mL/kg) for 7 consecutive days. After each injection, the rats were placed in a warm box (38 ℃) with an oxygen concentration of 18% (hypoxia), 21% (normal air), or 50% (oxygen) until full recovery of the righting reflex. Another 90 P7 rats were similarly grouped and received intraperitoneal injections of p-p38 blocker (15 mg/kg) 30 min before the same treaments. The phosphorylated tau protein, total tau protein and p-p38 content in the hippocampus were detected using Western blotting. The spatial learning and memory abilities of the rats were evaluated with Morris water maze test.@*RESULTS@#Compared with lipid emulsion, propofol injection resulted in significantly increased levels of p-p38, phosphorylated tau and total tau proteins in rats with subsequent hypoxic or normal air treatment ( < 0.05), but propofol with oxygen and injections of the blocker before propofol did not cause significant changes in the proteins. Without subsequent oxygenation, the rats receiving injections of propofol, with and without prior blocker injection, all showed significantly prolonged latency time and reduced platform-crossing times and third quadrant residence time compared with the corresponding lipid emulsion groups ( < 0.05). With oxygen treatment, the rats in propofoland blocker-treated groups showed no significant difference in the performance in Morris water maze test from the corresponding lipid emulsion group. The results of Morris water maze test differed significantly between blocker-propofol group and propofol groups irrespective of exposures to different oxygen levels ( < 0.05), but not between the lipid emulsion and blocker group pairs with exposures to different oxygen levels.@*CONCLUSIONS@#Propofol combined with hypoxia can affect the expression of tau protein through p38 pathway to impair the cognitive function of immature rats, in which oxygen plays a protective role.

Effect of hypoxemia factor on hippocampal long-term potentiation in newborn rats undergoing propofol anesthesia / 中华麻醉学杂志

Objective To evaluate the effect of hypoxemia factor on hippocampal long-term potentiation(LTP)in newborn rats undergoing propofol anesthesia. Methods Forty-two pathogen-free healthy Sprague-Dawley rats(21 males,21 females),aged 7 days,weighing 14-18 g,were divided into 3 groups(n=14 each)using a random number table:propofol plus air group(group PA),propofol plus pure oxygen group(group PO)and intralipid plus pure oxygen group(group IO).Propofol 50 mg/kg was injected intraperitoneally once a day for 7 consecutive days in PA and PO groups. Intralipid 5.0 ml/kg was injected intraperitoneally once a day for 7 consecutive days in IO group. The rats were exposed to air or pure oxygen for 6 h after the end of each injection. The arterial oxygen saturation and respiratory rate were determined after administration. The rats were returned to the cage after recovery of righting reflex. Six rats in each group were selected for preparation of hippocampal slices at 24 h after the last injection on 7th day,and the electric stimulation-induced field excitatory post synaptic potential(fEPSP)and success rate of LTP induction were recorded. Morris water maze test was performed in the other rats at 2 weeks after administration to assess the cognitive function. Results Compared with group IO,the respiratory rate,amplitude of fEPSP and success rate of LTP induction were significantly decreased,and the escape latency was prolonged in group PO(P<0.05).Compared with group PO,the arterial oxygen saturation,amplitude of fEPSP and success rate of LTP induction were significantly decreased,the escape latency was prolonged,and the number of crossing the original platform was decreased in group PA(P<0.05).Conclusion Hypoxemia factor increases propofol-induced neurotoxicity in the central nervous system of newborn rats.

Effect of Di-(2-ethylhcxyl) phthalate exposure on blood-testis barrier integrity in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate mechanism of di-(2-ethylhcxyl)phthalate (DEHP) exposure in causing blood-testis barrier (BTB) impairment in rats.</p><p><b>METHODS</b>Two-months-old male SD rats were randomly divided into corn oil control group and DEHP (750 mg/kg) exposure group for daily intragastic treatment for 30 consecutive days. After the treatments the rats were examined for histomorphological changes of the testicle using HE staining and the expressions of the junction proteins N-cadherin β-catenin, occludin and connexin43 of the BTB using Western blot. In the in vitro study, the vitality and ROS generation level in Sertoli cells exposed to different concentrations of DEHP were examined with MTT and ROS assay kits, respectively, and Nrf2 and p-p38 expressions were detected with Western blot.</p><p><b>RESULTS</b>Compared with the control group, the rats with DEHP exposure showed structural damage of the seminiferous tubule and polarity loss of the spermatids. DEHP exposure caused significantly decreased expressions of occludin and connexin43 but increased expressions of N-cadherin and β-catenin in the testicle tissues of the rats (P<0.05). The vitality of Sertoli cells was obviously decreased and ROS level increased significantly after exposure of the cells to increasing concentrations of DEHP, which also resulted in significantly up-regulated Nrf2 and p-p38 expressions (P<0.05).</p><p><b>CONCLUSIONS</b>DEHP exposure causes increased oxidative stress in the Sertoli cells of the testis, activates p38 MAPK signaling pathway, and results eventually in impaired spermatogenesis in rats.</p>

Effect of propofol on apoptosis of PC12 cells under hypoxic condition and the mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism by which propofol exposure causes PC12 cell apoptosis under hypoxic conditions.</p><p><b>METHODS</b>PC12 cells were exposed to room air, 35% oxygen, or 5% oxygen (hypoxia) for 24 h in the presence of either 10 µmol/L lipid emulsion or 10 µmol/L propofol. After the treatments, the cell apoptosis was measured by flow ceytometry, and the level of reactive oxygen species (ROS) and the activity of superoxide dismutase (SOD) were evaluated.</p><p><b>RESULTS</b>In room air, PC12 cells treated with propofol showed increased apoptosis rate and ROS production as compared with the cells treated with the lipid emulsion; propofol treatment of the cells exposed to 35% oxygen showed obvious enhancement of the apoptosis rate, ROS production and SOD activity. Under the hypoxic condition, propofol treatment even further increased the apoptosis rate, ROS production and SOD activity. Lipid emulsion caused no such changes in cells exposed to room air, 35% oxygen or 5% oxygen.</p><p><b>CONCLUSION</b>Under hypoxic conditions, propofol can cause apoptosis in PC12 cells by inducing oxidative stress injury.</p>