Comparison of Postoperative Analgesic Effects Between Nalbuphine and Fentanyl in Children Undergoing Adenotonsillectomy: A Prospective, Randomized, Double-Blind, Multicenter Study.

Objective: There is no universal agreement on optimal pharmacological regimens for pain management during surgeries. The aim of this study to compare the postoperative analgesic effects of nalbuphine with fentanyl in children undergoing adenotonsillectomy. Design, Setting, Participants: We conducted a prospective, randomized, double-blind, non-inferiority and multicenter trial in 311 patients admitted to four different medical facilities in China from October 2017 to November 2018. Main Outcome Measure: The primary outcome was postoperative pain score. The secondary outcomes were as follows: the numbers of patients who developed moderate or severe pain (FLACC ≥4 points); time to first rescue analgesic top up and the actual number of rescue pain medicine given in pain control in post-anesthesia care unit (PACU), and additional analgesics requirement (received ≥2 rescue analgesics or/and other analgesics except study medications administered in PACU and ward); emergence and extubation time; Waking up time; time of PACU stay, and other side effects (desaturation, nausea/vomiting etc.). Results: A total of 356 children were screened and 322 patients were randomized. The mean age was 5.8 (5.5, 6.1) in the nalbuphine group and 5.6 (5.3, 5.8) in the fentanyl group (p = 0.2132). FLACC score of nalbuphine group was lower than that of fentanyl group upon patients' arrival at PACU (p < 0.05). The time to first required rescue dose of pain drug for nalbuphine group was longer than for the fentanyl group (2.5 vs 1.2 h, p < 0.0001). Only one patient (0.6%) in nalbuphine group presented a slow respiratory rate (RR) at 9/min while 29 patients (18.5%) in fentanyl group developed slow RR ≤10/min in PACU. Meanwhile, SpO2 was lower in the fentanyl group at 10 min after patients' arrival in PACU (p < 0.05). The other profiles observed from these two drug groups were similar. Conclusion: Nalbuphine provided better pain relief with minimal respiration depression than fentanyl in children undergoing Adenotonsillectomy.

Lipoxin A4 ameliorates lipopolysaccharide-induced lung injury through stimulating epithelial proliferation, reducing epithelial cell apoptosis and inhibits epithelial-mesenchymal transition.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by alveolar epithelial disruption. Lipoxins (LXs), as so-called "braking signals" of inflammation, are the first mediators identified to have dual anti-inflammatory and inflammatory pro-resolving properties. METHODS: In vivo, lipoxinA4 was administrated intraperitoneally with 1 µg/per mouse after intra-tracheal LPS administration (10 mg/kg). Apoptosis, proliferation and epithelial-mesenchymal transition of AT II cells were measured by immunofluorescence. In vitro, primary human alveolar type II cells were used to model the effects of lipoxin A4 upon proliferation, apoptosis and epithelial-mesenchymal transition. RESULTS: In vivo, lipoxin A4 markedly promoted alveolar epithelial type II cells (AT II cells) proliferation, inhibited AT II cells apoptosis, reduced cleaved caspase-3 expression and epithelial-mesenchymal transition, with the outcome of attenuated LPS-induced lung injury. In vitro, lipoxin A4 increased primary human alveolar epithelial type II cells (AT II cells) proliferation and reduced LPS induced AT II cells apoptosis. LipoxinA4 also inhibited epithelial mesenchymal transition in response to TGF-ß1, which was lipoxin receptor dependent. In addition, Smad3 inhibitor (Sis3) and PI3K inhibitor (LY294002) treatment abolished the inhibitory effects of lipoxinA4 on the epithelial mesenchymal transition of primary human AT II cells. Lipoxin A4 significantly downregulated the expressions of p-AKT and p-Smad stimulated by TGF-ß1 in primary human AT II cells. CONCLUSION: LipoxinA4 attenuates lung injury via stimulating epithelial cell proliferation, reducing epithelial cell apoptosis and inhibits epithelial-mesenchymal transition.

Pharmacokinetics of Intranasally Administered Dexmedetomidine in Chinese Children.

Background: Intranasal application is a comfortable, effective, nearly non-invasive, and easy route of administration in children. To date, there is, however, only one pharmacokinetic study on intranasal dexmedetomidine in pediatric populations and none in Chinese children available. Therefore, this study aimed to characterize the pharmacokinetics of intranasally administered dexmedetomidine in Chinese children. Methods: Thirteen children aged 4 to 10 years undergoing surgery received 1 µg/kg dexmedetomidine intranasally. Arterial blood samples were drawn at various time points until 180 min after dose. Dexmedetomidine plasma concentrations were measured with high performance liquid chromatography (HPLC) and mass spectrometry. Pharmacokinetic modeling was performed by population analysis using linear compartment models with first-order absorption. Results: An average peak plasma concentration of 748 ± 30 pg/ml was achieved after 49.6 ± 7.2 min. The pharmacokinetics of dexmedetomidine was best described by a two-compartment model with first-order absorption and an allometric scaling with estimates standardized to 70-kg body weight. The population estimates (SE) per 70 kg bodyweight of the apparent pharmacokinetic parameters were clearance CL/F = 0.32 (0.02) L/min, central volume of distribution V1/F = 34.2 (4.9) L, intercompartmental clearance Q2/F = 10.0 (2.2) L/min, and peripheral volume of distribution V2/F = 34.9 (2.3) L. The estimated absorption rate constant was Ka = 0.038 (0.004) min-1. Conclusions: When compared with studies in Caucasians, Chinese children showed a similar time to peak plasma concentration after intranasal administration, but the achieved plasma concentrations were about three times higher. Possible reasons are differences in age, ethnicity, and mode of administration.

Isoflurane anesthesia in aged mice and effects of A1 adenosine receptors on cognitive impairment.

AIMS: Isoflurane may not only accelerate the process of Alzheimer's disease (AD), but increase the risk of incidence of postoperative cognitive dysfunction (POCD). However, the underlying mechanisms remain unknown. This study was designed to investigate whether isoflurane contributed to the POCD occurrence through A1 adenosine receptor (A1AR) in aged mice. METHODS: We assessed cognitive function of mice with Morris water maze (MWM) and then measured expression level of two AD biomarkers (P-tau and Aß) and a subtype of the NMDA receptor (NR2B) in aged wild-type (WT) and homozygous A1 adenosine receptor (A1AR) knockout (KO) mice at baseline and after they were exposed to isoflurane (1.4% for 2 hours). RESULTS: For cognitive test, WT mice with isoflurane exposure performed worse than the WT mice without isoflurane exposure. However, A1AR KO mice with isoflurane exposure performed better than WT mice with isoflurane exposure. WT mice exposed to isoflurane had increased levels of Aß and phosphorylated tau (P-tau). Levels of Aß and P-tau were decreased in A1AR KO mice, whereas no differences were noted between KO mice with and without isoflurane exposure. NR2B expression was inversely related to that of P-tau, with no differences found between KO mice with and without isoflurane exposure. CONCLUSIONS: We found an association between isoflurane exposure, impairment of spatial memory, decreasing level of NR2B, and increasing levels of A-beta and P-tau, presumably via the activation of the A1A receptor.

Bezold-Jarisch reflex occurred in a pediatric patient with giant intra-abdominal teratoma during induction of anesthesia: A case report.

RATIONALE: Bezold-Jarisch reflex (BJR) occurs when the cardioinhibitory receptors in the walls of ventricles are activated by various stimuli, with typical features of bradycardia, vasorelaxation, and hypotension. This reflex usually happens in parturient intrathecal anesthesia, as a result of decreased venous return by compression of inferior vena cava, but it is only rarely reported during general anesthesia. PATIENT CONCERNS: Severe bradycardia and hypotension, indicating BJR, occurred during the induction of general anesthesia in a 3-month-old female child with giant intra-abdominal teratoma. DIAGNOSES: A giant intra-abdominal teratoma was detected by computed tomography scanning. The decreased left ventricular ejection faction along with increased troponin I and N-terminal pro-B-type natriuretic peptide indicated a preoperative mild cardiac dysfunction. BJR was diagnosed on the basis of the severe bradycardia and hypotension observed during the induction of general anesthesia, INTERVENTIONS:: Atropine failed to increase heart rate. Cardiopulmonary resuscitation was initiated immediately and epinephrine was injected intravenously because of sudden circulatory collapse. Soon after the return of spontaneous circulation, a central venous line was placed and invasive blood pressure was monitored. Vital signs and homeostasis were kept stable during teratoma resection. OUTCOMES: The child was extubated after emergence from anesthesia in the operating room. Eleven days later, she had recovered without complications and was discharged. LESSONS: General anesthesia should be induced with great care in patients with giant intra-abdominal masses, and the patient should be kept in the left-lateral table tilt position before induction.

A role of KIT receptor signaling for proliferation and differentiation of rat stem Leydig cells in vitro.

In the testis, KIT ligand (KITL, also called stem cell factor) is expressed by Sertoli cells and its receptor (c-kit, KIT) is expressed by spermatogonia and Leydig cells. Although KITL-KIT signaling is critical for the spermatogenesis, its roles in Leydig cell development during puberty are not clear. In the present study, we investigated effects of KITL on stem Leydig cell proliferation and differentiation. Using an in vitro culture system of seminiferous tubules from Leydig cell-depleted testis, we found that KITL increased the proliferation activity of putative stem Leydig cells at higher concentration (10 and 100 ng/ml). Low concentration (1 ng/ml) of KITL significantly induced the differentiation of stem Leydig cells via increasing the expression level of steroidogenic acute regulatory protein (Star). In contrast, higher concentration (100 ng/ml) of KITL inhibited the differentiation of stem Leydig cells via inhibiting the steroidogenic enzyme (Cyp11a1, Cyp17a1, and Hsd17b3) expression levels. We cultured rat progenitor Leydig cells with KITL for 48 h and did not find any influence of KITL on the proliferation and androgen production of these cells. In conclusion, KITL is a growth factor that regulates the development of the stem Leydig cell.

Population Pharmacokinetics of Dexmedetomidine After Short Intravenous Infusion in Chinese Children.

BACKGROUND AND OBJECTIVE: Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist with sedative and analgesic properties which is also used in pediatric anesthesia. Although the pharmacokinetics of dexmedetomidine have been studied in pediatric patients, there are no data for Chinese children available. As alterations in pharmacokinetics due to ethnicity cannot be ruled out, it was the aim of this study to characterize the pharmacokinetics of dexmedetomidine in Chinese pediatric patients. METHODS: Thirty-nine children aged 1-9 years undergoing surgery were enrolled in the study. Dexmedetomidine was administered as short intravenous infusion of 1-2 µg/kg in 10 min. Venous blood samples were drawn until 480 min after stopping of infusion. Dexmedetomidine plasma concentrations were measured with high-performance liquid chromatography and mass spectrometry. Pharmacokinetic modeling was performed by population analysis using linear compartment models. RESULTS: Data of 36 patients (age 1-9 years, weight 10-27 kg) were analyzed. The pharmacokinetics of dexmedetomidine were best described by a two-compartment model with an allometric power model and estimates standardized to 70 kg body weight. The population estimates (95 % CI) per 70 kg bodyweight were: clearance 36.2 (33.3-41.1) l/h, central volume of distribution 84.3 (70.3-91.4) l, intercompartmental clearance 82.8 (63.6-136.6) l/h, peripheral volume of distribution 114 (95-149) l, and terminal half-life 4.4 (3.6-5.3) h. Age did not show any influence on weight-adjusted parameters. CONCLUSIONS: Chinese children showed a similar clearance, but larger volumes of distribution and longer terminal half-life when compared to studies in Caucasians. TRIAL REGISTRATION: ChiCTR-OPC-14005659.

Structure-activity relationships of phthalates in inhibition of human placental 3ß-hydroxysteroid dehydrogenase 1 and aromatase.

Phthalates are associated with preterm delivery. However, the mechanism is unclear. Progesterone formed by 3ß-hydroxysteroid dehydrogenase 1 (HSD3B1) and estradiol by aromatase (CYP19A1) in placenta are critical for maintaining pregnancy. In this study, we compared structure-activity relationships (SAR) of 14 phthalates varied in carbon atoms in alcohol moiety to inhibit human HSD3B1 in COS1 and CYP19A1 in JEG-3 cells. There were responses in that only diphthalates with 4-7 carbon atoms were competitive HSD3B1 inhibitors and diphthalates with 6 carbon atoms were CYP19A1 inhibitors. IC50s of dipentyl (DPP), bis(2-butoxyethyl) (BBOP), dicyclohexyl (DCHP), dibutyl (DBP), and diheptyl phthalate (DHP) were 50.12, 32.41, 31.42, 9.69, and 4.87µM for HSD3B1, respectively. DCHP and BBOP inhibited CYP19A1, with IC50s of 64.70 and 56.47µM. DPP, BBOP, DCHP, DBP, and DHP inhibited progesterone production in JEG-3 cells. In conclusion, our results indicate that there is clear SAR for phthalates in inhibition of HSD3B1 and CYP19A1.

Effects of Etomidate on the Steroidogenesis of Rat Immature Leydig Cells.

BACKGROUND: Etomidate is a rapid hypnotic intravenous anesthetic agent. The major side effect of etomidate is the reduced plasma concentration of corticosteroids, leading to the abnormal reaction of adrenals. Cortisol and testosterone biosynthesis has similar biosynthetic pathway, and shares several common steroidogenic enzymes, such as P450 side chain cleavage enzyme (CYP11A1) and 3ß-hydroxysteroid dehydrogenase 1 (HSD3B1). The effect of etomidate on Leydig cell steroidogenesis during the cell maturation process is not well established. METHODOLOGY: Immature Leydig cells isolated from 35 day-old rats were cultured with 30 µM etomidate for 3 hours in combination with LH, 8Br-cAMP, 25R-OH-cholesterol, pregnenolone, progesterone, androstenedione, testosterone and dihydrotestosterone, respectively. The concentrations of 5α-androstanediol and testosterone in the media were measured by radioimmunoassay. Leydig cells were cultured with various concentrations of etomidate (0.3-30 µM) for 3 hours, and total RNAs were extracted. Q-PCR was used to measure the mRNA levels of following genes: Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Srd5a1, and Akr1c14. The testis mitochondria and microsomes from 35-day-old rat testes were prepared and used to detect the direct action of etomidate on CYP11A1 and HSD3B1 activity. RESULTS AND CONCLUSIONS: In intact Leydig cells, 30 µM etomidate significantly inhibited androgen synthesis. Further studies showed that etomidate also inhibited the LH- stimulated androgen production. On purified testicular mitochondria and ER fractions, etomidate competitively inhibited both CYP11A1 and HSD3B1 activities, with the half maximal inhibitory concentration (IC50) values of 12.62 and 2.75 µM, respectively. In addition, etomidate inhibited steroidogenesis-related gene expression. At about 0.3 µM, etomidate significantly inhibited the expression of Akr1C14. At the higher concentration (30 µM), it also reduced the expression levels of Cyp11a1, Hsd17b3 and Srd5a1. In conclusion, etomidate directly inhibits the activities of CYP11A1 and HSD3B1, and the expression levels of Cyp11a1 and Hsd17b3, leading to the lower production of androgen by Leydig cells.

[Protective effect of curcumin against Aß25-35-induced neurotoxicity in differentiated PC12 cells].

OBJECTIVE: To explore the effects of curcumin on the expression of high mobility group box1 (HMGB1) , cell viability and morphology in a cellular model of Alzheimer's disease (AD). METHODS: Cultured PC12 cells in logarithmic growth phase were divided into 5 groups: normal cell group (A, non-treatment), model control group (B, 20 µmol/L Aß25-35), curcumin treatment group (C, 20 µmol/L Aß25-35+1 µmol/L Cur), Aß25-35+rHMG1 (D, 20 µmol/L Aß25-35+500 ng/ml HMGB1) and solvent control group (E, 20 µmol/L Aß25-35+1 µl/ml DMSO). Cell viability was examined by methyl thiazolyl tetrazolium (MTT). And the cellular expression and distribution of HMGB1 were detected by immunofluorescence and Western blot 24 hours later. RESULTS: Compared with group A, the levels of cell viability in groups B, D and E significantly declined (0.76 ± 0.06, 0.63 ± 0.02, 0.75 ± 0.03 vs 1.22 ± 0.06, P < 0.05) while the expression of HMGB1 increased (1.19 ± 0.14, 1.12 ± 0.16, 1.16 ± 0.09 vs 0.85 ± 0.04, P < 0.05). Compared with group B, cell viability in group C significantly increased by 33% (1.01 ± 0.05, P < 0.05) while the expression of HMGB1 declined by 31% (0.78 ± 0.03, P < 0.05). A larger amount of extracellular HMGB1 was released in group B compared with group A. And the extracellular release of HMGB1 declined less in group C versus group B. CONCLUSION: Curcumin may reduce Aß25-35-induced cytotoxicity through a down-regulated expression of HMGB1 and an inhibition of extracellular release of HMGB1 in PC12 cell.

[Effect of M8046 on expression of COX-2/PGE2 in spinal cord and DRG in rats with neuropathic pain].

OBJECTIVE: To investigate the effects of glucocorticoid receptor antagonist-M8046 on the behavior and the cyclooxygenase-2/prostaglandin E2( COX-2/PGE2) expression in spinal cord dorsal horn and dorsal root ganglia (DRG) in chronic constrictive injury (CCI) rats. METHODS: One hundred and forty-four male SD rats were randomly divided into 4 groups, 36 rats in each group: Sham operation group (Sham), chronic constrictive group (CCI), M8046 treated group (M8046) and solvent controlled group (Sc). M8046 3 mg/(kg x d) intraperitoneal injection was given after operation in group M8046. Paw thennal withdrawal (PTWL) and paw mechanical withdrawal threshold (PMWT) of rats were measured on 2 pre-operative and 1, 3, 7, 10, 14 post-operative days. The spinal cord and L15 DRG of the operated side was removed at 3, 7, 14 days after surgery. The change of COX-2 and PGE2 expression was determined by immunohistochemical staining and ELISA separately. RESULTS: PTWL and PMWT in CCI group were significantly lower than those in Sham group on every post-operative day (P < 0.05). PTWL and PMWT in M8046 group were significantly higher than those in CCI group on 7, 10, 14 post-operative day (P < 0.05). In spinal dorsal horn, the level of COX-2 and PGE2 expression in CCI group was significantly higher than that in Sham group (P < 0.05). M8046 could significantly attenuate the activation of COX-2 and PGE2 induced by CCI (P < 0.05). The expression of COX-2 and PGE2 in DRG was similar to that in spinal dorsal horn. CONCLUSION: The effects of M8046 ameliorate the CCI-induced neuropathic pain may be related to attenuate the expression of COX-2 and PGE2 in spinal cord and DRG.

Contribution of CFTR to alveolar fluid clearance by lipoxin A4 via PI3K/Akt pathway in LPS-induced acute lung injury.

The lipoxins are the first proresolution mediators to be recognized and described as the endogenous "braking signals" for inflammation. We evaluated the anti-inflammatory and proresolution bioactions of lipoxin A4 in our lipopolysaccharide (LPS-)induced lung injury model. We demonstrated that lipoxin A4 significantly improved histology of rat lungs and inhibited IL-6 and TNF- α in LPS-induced lung injury. In addition, lipoxin A4 increased alveolar fluid clearance (AFC) and the effect of lipoxin A4 on AFC was abolished by CFTRinh-172 (a specific inhibitor of CFTR). Moreover, lipoxin A4 could increase cystic fibrosis transmembrane conductance regulator (CFTR) protein expression in vitro and in vivo. In rat primary alveolar type II (ATII) cells, LPS decreased CFTR protein expression via activation of PI3K/Akt, and lipoxin A4 suppressed LPS-stimulated phosphorylation of Akt. These results showed that lipoxin A4 enhanced CFTR protein expression and increased AFC via PI3K/Akt pathway. Thus, lipoxin A4 may provide a potential therapeutic approach for acute lung injury.

Effects of luteinizing hormone and androgen on the development of rat progenitor Leydig cells in vitro and in vivo.

Progenitor Leydig cells are derived from stem cells. The proliferation and differentiation of progenitor Leydig cells significantly contributes to Leydig cell number during puberty. However, the regulation of these processes remains unclear. The objective of the present study was to determine whether luteinizing hormone (LH) or androgen contributes to the proliferation and differentiation of progenitor Leydig cells. Fourteen-day-old male Sprague-Dawley rats were treated for 7 days with NalGlu, which is a gonadotropin-releasing hormone antagonist, to reduce the secretion of LH in the pituitary and thus, androgen in the testis. Rats were co-administered with LH or 7α-methyl-nortestosterone (MENT), which is an androgen resistant to metabolism by 5α-reductase 1 in progenitor Leydig cells, and the subsequent effects of LH or androgen were measured. (3)H-Thymidine was also intravenously injected into rats to study thymidine incorporation in progenitor Leydig cells. Progenitor Leydig cells were examined. NalGlu administration reduced progenitor Leydig cell proliferation by 83%. In addition, LH or MENT treatment restored Leydig cell proliferative capacity to 73% or 50% of control, respectively. The messenger RNA levels of proliferation-related genes were measured using real-time PCR. The expression levels of Igf1, Lifr, Pdgfra, Bcl2, Ccnd3 and Pcna were upregulated by MENT, and those of Pdgfra, Ccnd3 and Pcna were upregulated by LH. Both LH and MENT stimulated the differentiation of progenitor Leydig cells in vitro. We concluded that both LH and MENT were involved in regulating the development of progenitor Leydig cells.

Lipoxin A(4) activates alveolar epithelial sodium channel, Na,K-ATPase, and increases alveolar fluid clearance.

Edema fluid resorption is critical for gas exchange, and both alveolar epithelial sodium channel (ENaC) and Na,K-ATPase are accredited with key roles in the resolution of pulmonary edema. Alveolar fluid clearance (AFC) was measured in in situ ventilated lungs by instilling isosmolar 5% BSA solution with Evans Blue-labeled albumin tracer (5 ml/kg) and measuring the change in Evans Blue-labeled albumin concentration over time. Treatment with lipoxin A4 and lipoxin receptor agonist (5(S), 6(R)-7-trihydroxymethyl 17 heptanoate) significantly stimulated AFC in oleic acid (OA)-induced lung injury, with the outcome of decreased pulmonary edema. Lipoxin A4 and 5(S), 6(R)-7-trihydroxymethyl 17 heptanoate not only up-regulated the ENaC α and ENaC γ subunits protein expression, but also increased Na,K-ATPase α1 subunit protein expression and Na,K-ATPase activity in lung tissues. There was no significant difference of intracellular cAMP level between the lipoxin A4 treatment and OA group. However, the intracellular cGMP level was significantly decreased after lipoxin A4 treatment. The beneficial effects of lipoxin A4 were abrogated by butoxycarbonyl-Phe-Leu-Phe-Leu-Ph (lipoxin A4 receptor antagonist) in OA-induced lung injury. In primary rat alveolar type II epithelial cells stimulated with LPS, lipoxin A4 increased ENaC α and ENaC γ subunits protein expression and Na,K-ATPase activity. Lipoxin A4 stimulated AFC through activation of alveolar epithelial ENaC and Na,K-ATPase.

[Application of ultrasound guidance for ilioinguinal or iliohypogastric nerve block in pediatric inguinal surgery].

OBJECTIVE: To evaluate the efficacy of ultrasound guidance for ilioinguinal or iliohypogastric nerve block in pediatric outpatients undergoing inguinal surgery. METHODS: The present study was approved by the ethics committee of our hospital. One hundred children with ASA status I, aged 4 - 8 years old, scheduled for unilateral inguinal surgery were randomly divided into ultrasound group (Group U) and traditional group (Group T) (n = 50 each). Upon entering operation room, they were monitored by electrocardiography (ECG), heart rate (HR) and oxygen saturation (SpO(2)). After an induction of general anesthesia, intravenous access was established and laryngeal mask inserted with spontaneous breathing. Intraoperative anesthesia was maintained with 2% sevoflurane in 50% nitrous oxide with 50% oxygen. Children in Group U received an ilioinguinal or iliohypogastric block under ultrasonic guidance with a mixture of 0.8% lidocaine and 0.25% levobupivacaine at 0.2 ml/kg while those in Group T performed according to the traditional method of anatomical localization with the same local anesthetic at 0.3 ml/kg. During surgery, the vital signs of HR, respiratory rate (RR), SpO(2), partial pressure of end-tidal carbon dioxide (P(ET)CO(2)) and exhaled sevoflurane concentration were recorded. Additional intraoperative analgesic requirements were recorded. Face legs activity cry consolability (FLACC) score was used to assess the pain score postoperatively at recovery time, 2 and 4 h postoperation respectively. If the pain score was above 3, the child received acetaminophen rectally. The number of postoperative rectal acetaminophen was recorded. The degrees of parental satisfaction were investigated at 2 and 4 h postoperation. Intra-or postoperative adverse events were also recorded. RESULTS: HR at skin incision and sac traction in Group U was significantly lower than those in Group T (P < 0.05). Six children (12%) needed to increase inhaled sevoflurane concentration during operation in Group U versus 17 (34%) in Group T (P < 0.05). The pain score at recovery time, 2 and 4 h postoperation in Group U was significantly lower than those in T group (P < 0.05). Only 4 children (8%) needed postoperative rectal acetaminophen in Group U versus 13 (26%) in Group T (P < 0.05). The degree of parental satisfaction at 2 h postoperation was significantly higher in Group U than that in Group T (P < 0.05). One case in Group T had needle puncturing into blood vessels. No other adverse event was observed in two groups. CONCLUSION: The method of ultrasonic guidance for ilioinguinal or iliohypogastric nerve block is both feasible and effective. It can not only enhance the effect of nerve block, reduce the occurrences of complications, lower the quantity of local anesthetic and alleviate the medicinal toxicity.

Effects of breviscapine on pulmonary inflammatory response and lung injury in children undergoing open heart surgery.

This study examined the effects of breviscapine (1) on pulmonary inflammatory response and lung function in pediatric patients undergoing open heart surgery. Forty-five children (ASA II or III, aged 2-72 months) were randomly assigned to control group (saline, Group C), low dose 1 group (0.5 mg/kg, Group Bre0.5), and high dose 1 group (1.0 mg/kg, Group Bre1.0), 15 cases each group. Plasma concentrations of procalcitonin (PCT) and neutrophil elastase (NE) were measured and compared at different time points. Plasma concentrations of PCT and NE were increased after cardiopulmonary bypass (CPB) induction, and the concentrations were lower in 1-treated groups. The present results indicated that continuous infusion of 1 before the CPB suppressed the production of PCT and NE attenuated systemic inflammatory response, which could result in lung protective effect in children undergoing open heart surgery.

[Influence of P2Y12 receptor inhibitor on pain threshold and spinal p38MAPK in rat bone cancer pain model].

OBJECTIVE: To investigate the role of P2Y12 receptor in rat bone cancer pain model and its influence on p38MAPK (Mitogen-activated protein kinase). METHOD: A total of forty female SD rats, weighting 200 - 250 g, were randomly divided into 5 groups (n = 8): normal group (group N), sham group (group S), vehicle group (group DA), cancer group (group A), and analgesia group (group MA). Rats in group N were untreated, rats in group S were injected with Hank's solution 10 µl into the left tibial metaphysis; rats in group DA, group A and group MA were injected with Walker 256 cancer cells (10 µl, 2×107 cells/ml) into the left tibial metaphysic to establish the model of bone cancer pain. Catheterization was simultaneously made in four groups between L3 and L4 vertebra except group N. Saline (0.9%, 15 µl) was injected in group S and group A, DMSO (5%, 15 µl) was injected in group DA, and MRS2395 (400 pmol/µl, 15 µl) was injected in group MA on day 9 to 12 post-inoculation. Mechanical withdrawal thresholds were measured on left hind paw before and every 10 min after intrathecal injection. Rats were euthanized after measuring mechanical withdrawal threshold at day 12 post-inoculation. L4-6 sections of spinal cord were collected to determine the expression of p-p38MAPK by immunohistochemistry and immunofluorescent. RESULT: Compared to that in group N (36.1 g ± 4.0 g) and group S (38.9 g ± 5.2 g), mechanical withdrawal thresholds in group MA (19.8 g ± 5.0 g) were decreased on day 9 post-inoculation (P < 0.01), and the expression of p-p38MAPK in spinal cord was increased on day 12 (P < 0.01). Compared to that in group DA (17.7 g ± 3.0 g) and group A (19.1 g ± 2.5 g), mechanical withdrawal threshold in group MA was obviously increased after intrathecal injection, peaked at (26.5 g ± 4.7 g) (P < 0.05); compared with group DA (number 43.4 ± 3.8, IOD 569 ± 27) and group A(number 45.0 ± 2.6, IOD 594 ± 22), the expression level of p-p38MAPK in spinal cord in group MA at day 12 was significantly decreased (number 20.9 ± 2.2, IOD 246 ± 25) (P < 0.01); Mechanical withdrawal threshold in group MA was still lower than group N and group S, while the expression of p-p38MAPK was higher than group N (number 9.9 ± 2.4, IOD 82 ± 28) and group S (number 10.9 ± 2.2, IOD 109 ± 25) (P < 0.01). Immunofluorescent showed that p-p38MAPK was colocalized with microglia in spinal dorsal horn, but not with neurons and astrocytes. CONCLUSIONS: These results demonstrate rat bone cancer pain could partially relieved after intrathecal injection of P2Y12 receptor inhibitor MRS2395 through inhibiting the phosphorylation of p38MAPK in spinal dorsal horn.

Contraceptives with novel benefits.

INTRODUCTION: Progesterone receptor (PR) agonists (progestins) and antagonists are developed for female contraceptives. However, non-contraceptive applications of newer progestins and PR modulators are being given more attention. AREAS COVERED: The newer PR agonists including drospirenone, nomegestrol, trimegestone, dienogest and nestorone are being evaluated as contraceptives with health benefits because of their unique pharmacological properties. The selective PR modulators (SPRM; PR antagonists with PR agonistic properties) are under development not only for emergency contraception but also for other health benefits such as the treatment of endometritis and leiomyoma. After searching the literature from PubMed, clinicaltrials.gov and patent database, this review focuses on the effects and mechanisms of these progestins, and SPRMs as contraceptives with other health benefits. EXPERT OPINION: PR agonists and antagonists that have novel properties may generate better contraceptive effects with other health benefits.

[Effect of pediatric TCI system for propofol plus remifentanil in pediatric short-duration surgery with laryngeal mask airway anesthesia].

OBJECTIVE: To study the effect of a pediatric TCI patent system for propofol plus remifentanil in pediatric short-duration surgery with laryngeal mask airway (LMA) anesthesia. METHODS: A total of 120 pediatric patients underwent short-duration elective surgery, aged 3 - 9 years old, weighted 13 - 26 kg, ASAI grade, were randomly divided into 3 groups (n = 40 each). The propofol concentrations of effect compartment were set at 2 µg/ml in Group A, 3 µg/ml in Group B and 4 µg/ml in Group C. The remifentanil initial concentration of plasma compartment was 2 ng/ml and increased stepwise by 0.5 ng/ml until a successful insertion of LMA. The remifentanil concentration was recorded when LMA was successfully inserted and the cases were numerated at the each remifentanil concentration. Heart rate (HR), mean arterial pressure (MAP), BIS (bispectral index) values and postoperative adverse events were also recorded at the time points of pre-induction (T0), 2 min post-remifentanil TCI (T1), LMA insertion (T2), skin incision (T3), 5 min post-skin incision (T4), 10 min post-skin incision, (T5) and beginning surgery (T6). RESULTS: The satisfactory ratios of a successful insertion of LMA were highest in remifentanil 3.0 ng/ml (AR subgroup), 2.5 ng/ml (BR subgroup) and 2.0 ng/ml (CR subgroup) respectively. The laryngeal mask satisfactory ratio was high in BR subgroup (P < 0.05). There were significantly differences of T1-T5 values of HR, MAP and BIS in AR and CR subgroups (P < 0.05), but not in BR subgroup. The above-mentioned monitoring indices at T2 in AR subgroup and T3 in CR subgroup were significantly higher than those in BR subgroup. There were more adverse reactions in CR and AR subgroups versus BR subgroup (P < 0.05). CONCLUSION: The patented system for propofol 3 µg/ml effect compartment concentration plus remifentanil 2.5 ng/ml plasma concentration TCI displays stable hemodynamics, less stress, fewer complications and better clinical outcomes in pediatric short-duration surgery with LMA anesthesia.

Sufentanil reduces emergence agitation in children receiving sevoflurane anesthesia for adenotonsillectomy compared with fentanyl.

BACKGROUND: Emergence agitation is a common problem in pediatric anesthesia, especially after sevoflurane induction and maintenance anesthesia. The purpose of this study was to investigate the effect of sufentanil to reduce emergence agitation after sevoflurane anesthesia in children undergoing adenotonsillectomy compared with fentanyl. METHODS: One hundred and five children, aged 3 - 11 years, were randomly allocated to receive normal saline (control group), sufentanil 0.2 µg/kg (S2) or fentanyl 2 µg/kg (F2) 1 minute after loss of the eyelash reflex. Anesthesia was induced and maintained with sevoflurane. Time to tracheal extubation, recovery time, Paediatric Anesthesia Emergence Delirium (PAED) scale, and emergence behavior were assessed. RESULTS: The incidence of severe agitation was significantly lower in S2 and F2 groups vs. the control group, 4/32 and 15/34 vs. 24/34 respectively, (P = 0.002, 0.009, respectively). PAED scales were significantly different among three groups (P = 0.007), and lower in the S2 and F2 groups than in the control group (P = 0.007 and P = 0.025, respectively). And the incidence of severe agitation and the PAED scale score was significantly different between the S2 and F2 groups (P = 0.007, P = 0.019, respectively). Time to tracheal extubation and recovery time were similar in all three groups. CONCLUSIONS: Administration of sufentanil at 0.2 µg/kg after induction of anesthesia reduced emergence agitation in children receiving sevoflurane anesthesia for adenotonsillectomy compared with fentanyl. This was without delaying the recovery time or causing significant hypotension.