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Background Exposure to isoflurane increases apoptosis among postnatally generated hippocampal dentate granule cells. These neurons play important roles in cognition and behavior, so their permanent loss could explain deficits after surgical procedures. Methods To determine whether developmental anesthesia exposure leads to persistent deficits in granule cell numbers, a genetic fate-mapping approach to label a cohort of postnatally generated granule cells in Gli1-CreERT2::GFP bitransgenic mice was utilized. Green fluorescent protein (GFP) expression was induced on postnatal day 7 (P7) to fate map progenitor cells, and mice were exposed to 6 h of 1.5% isoflurane or room air 2 weeks later (P21). Brain structure was assessed immediately after anesthesia exposure (n = 7 controls and 8 anesthesia-treated mice) or after a 60-day recovery (n = 8 controls and 8 anesthesia-treated mice). A final group of C57BL/6 mice was exposed to isoflurane at P21 and examined using neurogenesis and cell death markers after a 14-day recovery (n = 10 controls and 16 anesthesia-treated mice). Results Isoflurane significantly increased apoptosis immediately after exposure, leading to cell death among 11% of GFP-labeled cells. Sixty days after isoflurane exposure, the number of GFP-expressing granule cells in treated animals was indistinguishable from control animals. Rates of neurogenesis were equivalent among groups at both 2 weeks and 2 months after treatment. Conclusions These findings suggest that the dentate gyrus can restore normal neuron numbers after a single, developmental exposure to isoflurane. The authors’ results do not preclude the possibility that the affected population may exhibit more subtle structural or functional deficits. Nonetheless, the dentate appears to exhibit greater resiliency relative to nonneurogenic brain regions, which exhibit permanent neuron loss after isoflurane exposure.

Testicular Leydig cells are the primary source of testosterone in males. Adult Leydig cells have been shown to arise from stem cells present in the neonatal testis. Once established, adult Leydig cells turn over only slowly during adult life, but when these cells are eliminated experimentally from the adult testis, new Leydig cells rapidly reappear. As in the neonatal testis, stem cells in the adult testis are presumed to be the source of the new Leydig cells. As yet, the mechanisms involved in regulating the proliferation and differentiation of these stem cells remain unknown. We developed a unique in vitro system of cultured seminiferous tubules to assess the ability of factors from the seminiferous tubules to regulate the proliferation of the tubule-associated stem cells, and their subsequent entry into the Leydig cell lineage. The proliferation of the stem Leydig cells was stimulated by paracrine factors including Desert hedgehog (DHH), basic fibroblast growth factor (FGF2), platelet-derived growth factor (PDGF), and activin. Suppression of proliferation occurred with transforming growth factor β (TGF-β). The differentiation of the stem cells was regulated positively by DHH, lithium- induced signaling, and activin, and negatively by TGF-β, PDGFBB, and FGF2. DHH functioned as a commitment factor, inducing the transition of stem cells to the progenitor stage and thus into the Leydig cell lineage. Additionally, CD90 (Thy1) was found to be a unique stem cell surface marker that was used to obtain purified stem cells by flow cytometry.

This Statistical Analysis Plan details the statistical procedures to be applied for the analysis of data for the multicenter electroencephalography study. It consists of a basic description of the study in broad terms and separate sections that detail the methods of different aspects of the statistical analysis, summarized under the following headings (a) Background; (b) Definitions of protocol violations; (c) Definitions of objectives and other terms; (d) Variables for analyses; (e) Handling of missing data and study bias; (f) Statistical analysis of the primary and secondary study outcomes; (g) Reporting of study results; and (h) References. It serves as a template for researchers interested in writing a Statistical Analysis Plan.

Advances in neuropsychosis have concluded that addiction is a chronically relapsing brain disorder. Cue-, drug-and (or) stress- primed reinstatement play important parts on the development of drug abuse. Stress is a key factor in the acquisition and persistence to illicit drugs and psychostimulants such as cocaine, heroin, ketamine, alcohol and nicotine. When the access to the drug is prevented, the emergence of a negative emotional state will trigger the crucial neurochemical elements involved in the brain reward and stress systems. In this review, we will first discuss the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in the compulsive drug taking. The prominent components of stress-responsive system including CRH, vasopressin and glucocorticoid will be considered as the dark side drivers in addiction. And then we will reveal the essential mechanisms of propofol abuse as well as its association with HPA axis responsiveness. Propofol is a widely used intravenous anesthetic. However, in recently year’s propofol has been demonstrated as an addictive drug in anesthesiology. Converging evidence suggests the activation of mesocorticolimbic system and the interactions between the reward and stress system can partly illustrate the specific mechanisms of propofol abuse. Future directions in research are identified to increase understandings of the mechanisms by which stress may increase risks of drug addiction.

Propofol has shown abuse potential. The aim of the present study is to investigate the effects of GABA(A) antagonist and GABA(B) agonist on propofol reinforcement.Sprague-Dawley rats were trained to self-administer propofol at a dose of 1.7 mg/kg per infusion under a fixed ratio (FR1) schedule of reinforcement for 14 d. In a separate set of experiments, food-maintained self-administration under a fixed ratio (FR5) schedule and locomotor activities of Sprague-Dawley rats were examined.GABA(A) receptor antagonist bicuculline (0.25 mg/kg, ip) significantly increased the number of injections and active responses. Pretreatment with GABA(B) receptor agonist baclofen (3 mg/kg, ip) significantly decreased the number of active responses and total infusions of propofol during the training session. Moreover, microinjection of baclofen (50 and 100 ng/side) into the ventral tegmental area (VTA) significantly decreased the number of active responses and total infusions of propofol. Neither baclofen (1-3 mg/kg, ip) nor bicuculline (0.25-1 mg/kg, ip) affected food-maintained responses or motor activities.Propofol maintains its reward properties partially through GABA(A) receptor activation. Stimulation of GABA(B) receptors in VTA may counteract the reinforcing properties of propofol.

The study is to investigate the potential protective effect of sevoflurane on adriamycin induced myocyte injury. We prepared primary myocyte culture from neonatal rats and subjected the cells to adriamycin treatment. We found that adriamycin treatment induced cell apoptosis, decreased cell vitality, which could be reversed with sevoflurane exposure after the drug treatment, potentially through the regulation of Bcl-2 anti-apoptotic pathway. The study suggested the potential roles of sevoflurane in clinical management of patients after adriamycin chemotherapy.

Deletion of the insulin-like growth factor 1 (Igf1) gene was shown in previous studies to result in reduced numbers of Leydig cells in the testes of 35-day-old mice, and in reduced circulating testosterone levels. In the current study, we asked whether deletion of the Igf1 gene affects the number, proliferation, and/or steroidogenic function of some or all of the precursor cell types in the developmental sequence that leads to the establishment of adult Leydig cells (ALCs). Decreased numbers of cells in the Leydig cell lineage (ie, 3β-hydroxysteroid dehydrogenase-positive cells) were seen in testes of postnatal day (PND) 14-90 Igf1(-/-) mice compared with age-matched Igf1(+/+) controls. The development of ALCs proceeds from stem Leydig cells (SLCs) through progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs). The bromodeoxyuridine labeling index of putative SLCs was similar in the Igf1(-/-) and Igf1(+/+) mice. In contrast, the labeling index of PLCs was reduced in the Igf1(-/-) mice on each day of PND 14 through PND 35, and that of more mature Leydig cells (referred to herein as LCs, a combination of ILCs plus ALCs) was reduced from PND 21 through PND 56. In Igf1(-/-) mice that received recombinant IGF-I, the labeling indices of PLCs and LCs were similar to those of age-matched Igf1(+/+) mice, indicating that the reductions in the labeling indices seen in the PLCs and LCs of the Igf1(-/-) mice were a consequence of reduced IGF-I. On each day of PND 21 through PND 90, testicular testosterone concentrations were significantly reduced in the Igf1(-/-) mice, as were the expressions of testis-specific mRNAs involved in steroidogenesis, including Star, Cyp11a1, and Cyp17a1. The increased expression of the gene for 5α-reductase (Srd5a1) in adult Igf1(-/-) testes suggests that the depletion of Igf1 might suppress or delay Leydig cell maturation. These observations, taken together, indicate that the reduced numbers of Leydig cells in the adult testes of Igf1(-/-) mice result at least in part from altered proliferation and differentiation of ALC precursor cells, but not of the stem cells that give rise to these cells.

The cytochrome P450 2A1 (CYP2A1) is a P450 enzyme that catalyzes the metabolism of testosterone. CYP2A1 has been reported to be present in rat testis. However, its developmental changes and function have not been well characterized. The purpose of this study was to measure the abundance of CYP2A1 (Cyp2a1) mRNA in the developing rat testis and Leydig cells and examine the effects of its product, 7 alpha-hydroxytestosterone (7HT), on an important enzyme, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) that interconverts active corticosterone and inactive 11-dehydrocorticosterone. As detected by real-time PCR, Cyp2a1 was found to be present exclusively in the Leydig cell. CYP2A1 activity in adult Leydig cells was 5-fold higher than those in progenitor or immature Leydig cells. 7HT competitively suppressed 11 beta-HSD1 oxidase and reductase activities in rat testis microsome with inhibitory constant of 1.2 and 2.9 mum, respectively. In intact Leydig cells, 7HT did not inhibit 11 beta-HSD1 reductase activity, but it stimulated its reductase activity. Thus, at 100 nm and higher concentrations, 7HT significantly switched 11 beta-HSD1 oxidoreductase activities toward reductase. The present data shows that 7HT, the product formed by CYP2A1 from testosterone, regulates the direction of 11 beta-HSD1 activity in rat Leydig cells.

Proliferating cells express cyclins, cell cycle regulatory proteins that regulate the activity of cyclin-dependent kinases (CDKs). The actions of CDKs are regulated by specific inhibitors, the CDK inhibitors (CDKIs), which are comprised of the Cip/Kip and INK4 families. Expression of the Cip/Kip CDKI 1B (Cdkn1b, encoding protein CDKN1B, also called p27(kip1)) in developing Leydig cells (LCs) has been reported, but the function of CDKN1B in LCs is unclear. The goal of the present study was to determine the effects of CDKN1B on LC proliferation and steroidogenesis by examining these parameters in Cdkn1b knockout (Cdkn1b(-/-)) mice. LC proliferation was measured by bromodeoxyuridine incorporation. Testicular testosterone levels, mRNA levels, and enzyme activities of steroidogenic enzymes were compared in Cdkn1b(-/-) and Cdkn1b(+/+) mice. The labeling index of LCs in Cdkn1b(-/-) mice was 1.5% +/- 0.2%, almost 7-fold higher than 0.2% +/- 0.08% (P < 0.001) in the Cdkn1b(+/+) control mice. LC number per testis in Cdkn1b(-/-) mice was 2-fold that seen in the Cdkn1b(+/+) control mice. However, testicular testosterone levels, mRNA levels of steroidogenic acute regulatory protein (Star), cholesterol side-chain cleavage enzyme (Cyp11a1), and 3beta-hydroxtsteroid dehydrogenase 6 (Hsd3b6), and their respective proteins, were significantly lower in Cdkn1b(-/-) mice. We conclude that deficiency of CDKN1B increased LC proliferation, but decreased steroidogenesis. Thus, CDKN1B is an important regulator of LC development and function.

Stress-mediated elevations in circulating glucocorticoid levels lead to corresponding rapid declines in testosterone production by Leydig cells in the testis. In previous studies we have established that glucocorticoids act on Leydig cells directly, through the classic glucocorticoid receptor (GR), and that access to the GR is controlled prior to the GR by a metabolizing pathway mediated by the type 1 isoform of 11beta-hydroxysteroid dehydrogenase (11betaHSD1). This enzyme is bidirectional (with both oxidase and reductase activities) and in the rat testis is exclusively localized in Leydig cells where it is abundantly expressed and may catalyze the oxidative inactivation of glucocorticoids. The predominant reductase direction of 11betaHSD1 activity in liver cells is determined by an enzyme, hexose-6-phosphate dehydrogenase (H6PDH), on the luminal side of the smooth endoplasmic reticulum (SER). Generation of the pyridine nucleotide cofactor NADPH by H6PDH stimulates the reductase direction of 11betaHSD1 resulting in increased levels of active glucocorticoids in liver cells. Unlike liver cells, steroidogenic enzymes including 17beta-hydroxysteroid dehydrogenase 3 (17betaHSD3) forms the coupling with 11betaHSD1. Thus the physiological concentrations of androstenedione serve as a substrate for 17betaHSD3 utilizing NADPH to generate NADP+, which drives 11betaHSD1 in Leydig cells primarily as an oxidase; thus eliminating the adverse effects of glucocorticoids on testosterone production. At the same time 11betaHSD1 generates NADPH which promotes testosterone biosynthesis by stimulating 17betaHSD3 in a cooperative cycle. This enzymatic coupling constitutes a rapid mechanism for modulating glucocorticoid control of testosterone biosynthesis. Under stress conditions, glucocorticoids also have rapid actions to suppress cAMP formation thus to lower testosterone production.

The capacity of Brown Norway rat Leydig cells to produce testosterone (T) decreases with aging. In a previous study, we reported that a new generation of Leydig cells can be restored in both young and old rat testes after a single injection of ethane dimethanesulfonate (EDS), and that the abilities of the new Leydig cells in young and old rats to produce T were equivalent. Our objective herein was to compare the steroidogenic fate of the new Leydig cells over time. Young (3 month-old) and old (18 month-old) rats were injected with EDS to eliminate the existing Leydig cells. Ten weeks after EDS, Leydig cells had been restored and T production by the new Leydig cells isolated from young and old rat testes was equivalent. Thirty weeks after EDS treatment of young rats, the ability of the new Leydig cells to produce T had not diminished from 10 weeks post-EDS. In contrast, at 30 weeks post-EDS, T production by new cells in old rat testes was reduced significantly from the 10-week level. Serum T levels at 10 and 30 weeks were consistent with Leydig cell T production. Serum LH levels did not differ in any group. Thus, although the Leydig cells restored to both young and old rats after EDS initially produced T at high, equivalent levels, the cells in the old testes did not maintain this ability. These results suggest that: 1) the cells from which new populations of Leydig cells are derived may differ depending upon the age of the rat; and/or 2) factors extrinsic to the new Leydig cells in young and old testes differ, and it is these differences that are responsible for reductions in T by the newly formed Leydig cells in the testes of old rats.

The microsomal CYP2C9 alleles involved in the biotransformation of propofol, a widely used anesthetic agent, were investigated in vitro. To examine the enzymatic activity of the CYP2C9 alleles, kinetic parameters for propofol 4-hydroxylation were determined in recombinant human P450s CYP2C9 microsomes from Sf21 insects cells carrying CYP2C9*1 and other variants. Some of the variants showed decreased enzyme activity compared with the wild type, as previously reported. Two variants (CYP2C9*36 and *56) were found substantially to increase intrinsic clearance relative to the wild type variant. Most variants significantly (p0.05) decreased intrinsic clearance of propofol compared with the wild type, except *11, *47, and *54. This study is the first to report these rare alleles for propofol metabolism, providing fundamental data for further clinical studies on CYP2C9 alleles for propofol metabolism in vivo.

Cyclin-dependent kinase inhibitors p21(Cip1) (CDKN1A) and p27(Kip1) (CDKN1B) are expressed in Leydig cells. Previously, we reported that Cdkn1b knockout in the mouse led to increased Leydig cell proliferative capacity and lower steroidogenesis. However, the relative importance of CDKN1A and CDKN1B in these regulations was unclear. In the present study, we examined the relative importance of CDKN1A and CDKN1B in regulation of Leydig cell proliferation and steroidogenesis by whole-body knockout of CDKN1A (Cdkn1a(-/-)) and CDKN1A/CDKN1B double knockout (DBKO). The cell number, 5-bromo-2-deoxyuridine incorporation rate, steroidogenesis, and steroidogenic enzyme mRNA levels and activities of Leydig cells were compared among wild-type (WT), Cdkn1a(-/-), and DBKO mice. Relative to WT mice, Leydig cell number per testis was doubled in the DBKO and unchanged in the Cdkn1a(-/-) mice. Testicular testosterone levels and mRNA levels for luteinizing hormone receptor (Lhcgr), steroidogenic acute regulatory protein (Star), cholesterol side-chain cleavage enzyme (Cyp11a1), 17alpha-hydroxylase/17,20-lyase (Cyp17a1), and 17beta-hydroxysteroid dehydrogenase 3 (Hsd17b3) and their respective proteins were significantly lower in the DBKO mice. However, testicular testosterone level was unchanged in the Cdkn1a(-/-) mice, although Lhcgr mRNA levels were significantly lower relative to those in the WT control. We conclude that Cdkn1a(-/-) did not increase Leydig cell numbers (although a defect of Leydig cell function was noted), whereas DBKO caused a significant increase of Leydig cell numbers but a decrease of steroidogenesis.

There is a clear link between epilepsy and depression. Clinical data demonstrate a 30-35% lifetime prevalence of depression in patients with epilepsy, and patients diagnosed with depression have a three to sevenfold higher risk of developing epilepsy. Traditional epilepsy models partially replicate the clinical observations, with the demonstration of depressive traits in epileptic animals. Studies assessing pro-epileptogenic changes in models of depression, however, are more limited. Here, we examined whether a traditional rodent depression model--bilateral olfactory bulbectomy--predisposes the animals towards the development of epilepsy. Past studies have demonstrated increased neuronal excitability after bulbectomy, but continuous seizure monitoring had not been conducted. For the present study, we monitored control and bulbectomized animals by video-EEG 24/7 for approximately two weeks following the surgery to determine whether they develop spontaneous seizures. All seven bulbectomized mice exhibited seizures during the monitoring period. Seizures began about one week after surgery, and occurred in clusters with severity increasing over the monitoring period. These results suggest that olfactory bulbectomy could be a useful model of TBI-induced epilepsy, with advantages of relatively rapid seizure onset and a high number of individuals developing the disease. The model may also be useful for investigating the mechanisms underlying the bidirectional relationship between epilepsy and depression.

To compare the efficacy of laryngeal mask airway-Supreme(TM) versus common laryngeal mask airway in children with general anesthesia.With local research ethics committee's approval and written informed parental consent, 100 children were randomly divided into groups L (size 2.0 common laryngeal mask airway) and S (size 2.0 laryngeal mask airway-Supreme(TM)) according to random number (n = 50 each). After anesthesia induction, a common laryngeal mask airway or laryngeal mask airway-Supreme(TM) was inserted and mechanically ventilated. Time and ease for insertion, insertion success rate, airway leak pressure, success rate and ease of disposal sputum collecting tube insertion in group S, quality of airway during anesthetic maintenance, abdominal circumference changes and complications within 24 h post-operation were measured.Compared with group L, abdominal circumference increased less in group S (0.90 ± 0.35 vs 0.43 ± 0.18 cm, n = 46, P0.01). No significant inter-group differences existed for other measurements. Disposal sputum collecting tube was successfully placed in group S(100%).In children with mechanical ventilation, laryngeal mask airway-Supreme(TM) can be effectively applied to maintain a good airway. And the incidence of gastric insufflation is lower. It is particularly useful for those requiring evacuation of gastric contents during general anesthesia.

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).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 Aβ25-35), curcumin treatment group (C, 20 µmol/L Aβ25-35+1 µmol/L Cur), Aβ25-35+rHMG1 (D, 20 µmol/L Aβ25-35+500 ng/ml HMGB1) and solvent control group (E, 20 µmol/L Aβ25-35+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.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, P0.05) while the expression of HMGB1 increased (1.19 ± 0.14, 1.12 ± 0.16, 1.16 ± 0.09 vs 0.85 ± 0.04, P0.05). Compared with group B, cell viability in group C significantly increased by 33% (1.01 ± 0.05, P0.05) while the expression of HMGB1 declined by 31% (0.78 ± 0.03, P0.05). 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.Curcumin may reduce Aβ25-35-induced cytotoxicity through a down-regulated expression of HMGB1 and an inhibition of extracellular release of HMGB1 in PC12 cell.

To explore the protective effect of lipoxin (LX)A4 during myocardial ischemia reperfusion injury (MIRI) and discuss the molecular mechanism of excessive endoplasmic reticulum stress (ERS) in rats.Seventy-two male SD rats were divided into 6 groups, according to random number table, 12 in each group: sham operation group (group sham)1, 2: injected with normal saline (NS) 2 ml/kg before and after coronary artery threading. MIRI group (group I/R)1, 2: injected with NS 2 ml/kg before and after MIRI. Group LX1, LX2: injected with LXA4 100 µg/kg in 2 ml/kg NS before and after MIRI treatment. After the rat MIRI model was established, the serum concentrations of troponin I (cTnI) were measured in each group before open-chest operation (T1) and at the end of the experiment (T2). Besides, expressions of GRP-78, caspase-12 protein and mRNA were test. At the same time, myocardial cell apoptosis, the myeloperoxidase (MPO), superoxide dismutase (SOD) activation and malondialdehyde (MDA) content were detected while the HE and ultrastructural changes of cardiac muscle were observed.The expression levels of GRP-78, caspase-12 protein and mRNA, apoptotic index, serum cTnI concentrations (T2) and MPO, SOD activation, MDA content were all significantly higher in groups I/R and LX than those in group sham 1 and sham 2 (all P0.05). The expression levels of GRP-78, caspase-12 protein in group LX1 (compared with group I/R1) and in group LX2 (compared with group I/R2) were all significantly lower (all P0.05). Besides, the expression of GRP-78, caspase-12 mRNA in group LX1 were significantly less than those in group I/R1 ((0.86 ± 0.06)×10(5) vs (1.95 ± 0.65)×10(5), (12.35 ± 4.15)×10(5) vs (23.76 ± 6.57) ×10(5), both P0.05), so were those in groups LX2 and I/R2 ((0.64 ± 0.05)×10(5) vs (2.36 ± 0.57)×10(5), (7.04 ± 0.81)×10(5) vs (26.49 ± 6.82)×10(5), both P0.05). The apoptotic index, the serum concentrations of cTnI (T2), MPO activation and MDA content were all significantly lower in group LX1 than those in group I/R1 (34.6% ± 5.7% vs 52.5% ± 6.4%, (293 ± 22) vs (581 ± 44) ng/L, (176 ± 47) vs (331 ± 94) U/g tissue, (1549 ± 238) vs (2403 ± 439) nmol/g protein, both P0.05), so were those in groups LX2 and I/R2(26.5% ± 4.6% vs 54.8% ± 6.3%, (207 ± 29) vs (593 ± 61) ng/L, (99 ± 24) vs (329 ± 92) U/g tissue, (1055 ± 237) vs (2422 ± 518) nmol/g protein, all P0.05). In addition, the activity of SOD in groups LX1 and LX2 were both significantly higher respectively than those in groups I/R1 and I/R2 (both P0.05). Moreover, compared with groups I/R1 and I/R2, the neutrophils infiltration were significantly less than those in groups LX1 and LX2 respectively, and the ultrastructure damage were also much milder.Before and after MIRI, application of LXA4 may significantly inhibit neutrophil infiltration and attenuate myocardial oxidative injury. LXA4 play its role in myocardial protection via down-regulating the expression of GRP-78, caspase-12 and the inhibition of excessive ERS.

To investigate the role of P2Y12 receptor in rat bone cancer pain model and its influence on p38MAPK (Mitogen-activated protein kinase).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.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 (P0.01), and the expression of p-p38MAPK in spinal cord was increased on day 12 (P0.01). 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) (P0.05); 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) (P0.01); 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) (P0.01). Immunofluorescent showed that p-p38MAPK was colocalized with microglia in spinal dorsal horn, but not with neurons and astrocytes.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.

To evaluate the efficacy of ultrasound guidance for ilioinguinal or iliohypogastric nerve block in pediatric outpatients undergoing inguinal surgery.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.HR at skin incision and sac traction in Group U was significantly lower than those in Group T (P0.05). Six children (12%) needed to increase inhaled sevoflurane concentration during operation in Group U versus 17 (34%) in Group T (P0.05). The pain score at recovery time, 2 and 4 h postoperation in Group U was significantly lower than those in T group (P0.05). Only 4 children (8%) needed postoperative rectal acetaminophen in Group U versus 13 (26%) in Group T (P0.05). The degree of parental satisfaction at 2 h postoperation was significantly higher in Group U than that in Group T (P0.05). One case in Group T had needle puncturing into blood vessels. No other adverse event was observed in two groups.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.

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.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.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.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.

The 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) are involved in the reactions that culminate in androgen biosynthesis in Leydig cells. Human and rat testis microsomes were used to investigate the inhibitory potencies on 3β-HSD and 17β-HSD3 activities of 14 different phthalates with various carbon numbers in the ethanol moiety. The results demonstrated that the half-maximal inhibitory concentrations (IC(50)s) of dipropyl (DPrP), dibutyl (DBP), dipentyl (DPP), bis(2-butoxyethyl) (BBOP) and dicyclohexyl (DCHP) phthalate were 123.0, 24.1, 25.5, 50.3 and 25.5μM for human 3β-HSD activity, and 62.7, 30.3, 33.8, 82.6 and 24.7μM for rat 3β-HSD activity, respectively. However, only BBOP and DCHP potently inhibited human (IC(50)s, 23.3 and 8.2μM) and rat (IC(50)s, 30.24 and 9.1μM) 17β-HSD3 activity. Phthalates with 1-2 or 7-8 carbon atoms in ethanol moieties had no effects on both enzyme activities even at concentrations up to 1mM. The mode of action of DCHP on 3β-HSD activity was competitive with the substrate pregnenolone but noncompetitive with the cofactor NAD+. The mode of action of DCHP on 17β-HSD3 activity was competitive with the substrate androstenedione but noncompetitive with the cofactor NADPH. In summary, our results showed that there are clear structure-activity responses for phthalates in the inhibition of both 3β-HSD and 17β-HSD3 activities. The length of carbon chains in the ethanol moieties of phthalates may determine the potency to inhibit these two enzymes.

To explore the effects of curcumin on the expression of high mobility group box 1 (HMGB1) and apoptotic neurons in hippocampus after global cerebral ischemia/reperfusion in SD rats.A total of 192 male SD rats were randomly divided into 4 groups: sham group (SH), ischemia-reperfusion group (IR), curcumin group (Cur) and solvent control group (SC). Bilateral vertebrate arteries were electrocauterized and bilateral common carotid arteries liberated in 3 ischemic groups. Isasteric curcumin solutions (200 mg/kg) or menstruum were injected intraperitoneally at 1 hour pre-ischemia in Cur and SC groups. The rats in each group were ligated for 15 minutes and then decapitated at 1, 3, 5 and 7 d post-reperfusion respectively. Cell morphology was observed on hematoxylineosin-stained slides. Apoptotic neurons were detected in CA1 region by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Western blot was used to make a semi-determination of HMGB1 expression.At each time point, the number of apoptotic neurons was much more in IR and SC groups than that in SH group (P0.05). And the number of apoptotic neurons at 1, 3, 5, 7 d post-reperfusion was only 41%, 57%, 65% and 70% in Cur group respectively (P0.05). The expressional level of HMGB1 in IR and SC groups was significantly lower at 1d post-reperfusion (0.685 ± 0.050; 0.695 ± 0.053 vs 0.977 ± 0.063, P0.05). And it was significantly higher at 3, 5, 7 d post-reperfusion in IR and SC groups than that in SH groups (1.360 ± 0.045/1.353 ± 0.045; 1.342 ± 0.046/1.338 ± 0.047; 1.319 ± 0.052/1.322 ± 0.035 vs 0.992 ± 0.031; 0.978 ± 0.090; 0.992 ± 0.075, P0.05). The level at 1 d post-reperfusion (0.842 ± 0.063) in Cur group was significantly higher than that in IR and SC groups but lower than that in SH group. And it was lower at 3, 5, 7 d post-reperfusion (1.125 ± 0.023, 1.098 ± 0.073, 1.087 ± 0.089) than those in IR and SC groups (P0.05). There was no significant difference of HMGB1expression level between IR and SC groups.The expression level of HMGB1 in hippocampus is significantly reduced at 1 d post-reperfusion. Then it significantly increases and a high level is maintained until 7 d after global cerebral ischemia/reperfusion. Curcumin can reduce hippocampal neuronal apoptosis and injury. Such an effect may be due to an inhibition of the synthesis and release of HMGB1.

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.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).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 (P0.05). There were significantly differences of T1-T5 values of HR, MAP and BIS in AR and CR subgroups (P0.05), 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 (P0.05).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.

To observe the dynamic changes of CD3+, CD4+, and CD8+ T lymphocytes in the peripheral blood of patients with sepsis and discuss the clinical significance.Sixty-four patients admitted in the Emergency Center and Emergency Intensive Care Unit of the Second Hospital of Wenzhou Medical University between August, 2007 and July, 2009 were enrolled in this study. CD3+, CD4+, and CD8+ T lymphocytes in the peripheral blood were detected by flow cytometry on days 1, 7 and 14 after admission, and the results were compared between the patients with improvement of the condition and those without improvement, with 20 healthy subjects as the control group.On day 1 after admission, CD3+ and CD4+ T lymphocytes and CD4+/CD8+ T cell ratio were obviously lower in the 2 groups of patients with sepsis than in the control group (P0.05), but no significant difference was found in CD8+ T lymphocytes. The sepsis patients with clinical improvement showed significant higher CD3+ and CD4+ T lymphocyte percentages and CD4+/CD8+ T cell ratio than those without improvement on day 1. In the patients with clinical improvement, CD3+ and CD4+T lymphocytes and CD4+/CD8+ T cell ratio increased gradually with time and till day 14, they were comparable with the control levels; in the patients without improvement, CD3+ and CD4+ T lymphocytes and CD4+/CD8+ T cell ratio showed no obvious alterations in the course of observation.Immune imbalance occurs in patients with sepsis represented by lowered CD3+ and CD4+T lymphocyte percentages and CD4+/CD8+ T cell ratio in relation to the severity of the condition. CD3+ and CD4+ T lymphocytes and CD4+/CD8+ T cell ratio can be used as the indicators for assessing the severity of sepsis.

To discuss the effect of the new target controlled infusion (TCI) system in Chinese children undergoing minor operation and compared with TCI system with Marsh parameters.Ninety ASA I, aged 3 - 5 yrs children undergoing elective unilateral high ligation of hernial sac under general anesthesia were randomly divided into group L (n = 45) and group M (n = 45) 2 groups. All subjects were unpremedicated. Systolic blood pressure (SBP), diastolic blood pressure (DBP), ECG, SpO2 and BIS were monitored. Patients of Group L and group M were anesthetized with propofol by Lian propofol TCI system and Marsh system respectively, combined with regional block. The target plasma concentration of TCI system was set at 6 microg/ml initially and up-regulated 1 microg/ml gradually if obvious body movement occurred while skin incision. If the target plasma concentration up to 8 microg/ml but there still had body movement, the TCI venous anesthesia was replaced by inhaled anesthesia. HR, RR, SBP, DBP and BIS were recorded in time points of baseline (T(0)), after the induction (T(1)), skin incision (T(2)), 3, 5 min after skin incision (T(3), T(4)), the end of operation (T(5)). Complications, the awakening time and the number of cases which anesthetized with different propofol plasma concentrations or inhaled anesthesia were recorded respectively as well.The number of cases which completed the operation under TCI plasma concentration 6 microg/ml in group L were significantly more than those in group M (P0.01). There were significantly different of T(1)-T(4) values of HR, RR, SBP, DBP and BIS in group M (P0.05), but not in group L. Compared with group L, T(2)-T(4) values of HR, RR, SBP, DBP and BIS were higher in group M (P0.05 or 0.01). Complications were lower in group L than those in group M.Compared with Marsh system, propofol 6 microg/ml plasma concentration with the new target controlled infusion system applied in Chinese children undergoing unilateral high ligation of hernial sac could maintain stable hemodynamics, less stress reaction and complications.

The cytochrome P450 2A1 (CYP2A1) is a P450 enzyme that catalyzes the metabolism of testosterone. CYP2A1 has been reported to be present in rat testis. However, its developmental changes and function have not been well characterized. The purpose of this study was to measure the abundance of CYP2A1 (Cyp2a1) mRNA in the developing rat testis and Leydig cells and examine the effects of its product, 7 alpha-hydroxytestosterone (7HT), on an important enzyme, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) that interconverts active corticosterone and inactive 11-dehydrocorticosterone. As detected by real-time PCR, Cyp2a1 was found to be present exclusively in the Leydig cell. CYP2A1 activity in adult Leydig cells was 5-fold higher than those in progenitor or immature Leydig cells. 7HT competitively suppressed 11 beta-HSD1 oxidase and reductase activities in rat testis microsome with inhibitory constant of 1.2 and 2.9 mum, respectively. In intact Leydig cells, 7HT did not inhibit 11 beta-HSD1 reductase activity, but it stimulated its reductase activity. Thus, at 100 nm and higher concentrations, 7HT significantly switched 11 beta-HSD1 oxidoreductase activities toward reductase. The present data shows that 7HT, the product formed by CYP2A1 from testosterone, regulates the direction of 11 beta-HSD1 activity in rat Leydig cells.

To investigate the effects of multimodal analgesia on analgesia and sedation during emergence of general anesthesia for cleft lip and/or palate surgery pediatric patients.Fifty-four pediatric patients with ASA I and II cleft lip and/or palate, aged 2-7, undergoing prosthesis were randomly allocated into 2 groups: control group (Group C, n=28) inhaling nitrous oxide/oxygen (50%:50%) and sevoflurane(5%) for general anesthesia, and multimodal group (Group M, n=26), injected intravenously with fentanyl and atracurium in addition to inhalation of nitrous oxide/oxygen (50%:50%) and sevoflurane (5%). Ventilation was controlled with PCV modal to maintain end-tidal CO2 to 35-45 mmHg. Local anesthesia at the surgical site was facilitated by the surgeon before the beginning of surgery. After intubation, rectal paracetamol was used for Group M (120 mg for 2-4 year-olds and 325 mg for 5-7 year-olds) and fentanyl 0.5 microg/kg was injected for postoperative analgesia 10 min before the end of surgery. An observer who was blinded to the protocol recorded the time from the discontinuation of sevoflurane and nitrous oxide to tracheal extubation, accessed the sedation and pain scale, recorded the time ready for discharge from post-anesthesia care unit (PACU) and the incidence of adverse effects.The time ready for discharge from PACU of Group M was (25+/-4) min, significantly shorter than that of Group C [(32+/-3) min, t=7.426, P0.01]. The analgesia satisfaction rate of Group M was 69.2% (18/26), significantly higher than that of Group C [25.0%, 7/28, P0.05]. The severe pain rate of Group M was 7.7%, significantly lower than that of Group C (35.7%, F=5.333, P=0.021). The agitation rate of Group M was 11.5%, significantly lower than that of Group C (39.3%, F=4.571, P=0.033).Multimodal analgesic regimen of infiltration of local anesthetic at surgical site and rectal paracetamol and intravenous fentanyl provides sufficient analgesia, minimizes the incidence of agitation after general anesthesia in cleft lip and/or palate surgery for children, increases the speed of referring patients in PACU, and ensures the safety of the postanaesthetic patients.

To investigate the optimal concentrations of sevoflurane and propofol for laryngeal mask airway (LMA) insertion in Chinese boys of different ages.200 boys with ASA status I weighting 7 - 53 kg undergoing inguinal operation were divided into 4 groups (n = 50) according to age: Group A (aged 7 m-1 yr), Group B (1 - 3 yrs), Group C (4 - 6 yrs), and Group D (7 - 11 yrs). No premedication was given. General anesthesia was induced with propofol intravenous infusion at target effect-site concentration by target controlled infusion (TCI) using children Marsh model (Subgroups As, Bs, Cs, and Ds, 25 cases for each subgroup) or sevoflurane inhalation combined with 50% N2O (Subgroups Ap, Bp, Cp, and Dp, 25 cases for each subgroup) the optimal concentration was predetermined according to the modification of Dixon's up-and-down method. The size of LMA was determined according to the boy's weight and reverse technique was used to place LMA. The insertion conditions were noted as satisfactory when the jaw was relaxed, lash reflex disappeared, no coughing, gagging, swallowing, and laryngospasm was seen, and limb movement was minimal.The levels of ED(50) of P(ET)-sevoflurane for LMA insertion in Subgroups As, Bs, Cs, and Ds were 2.96% (95% CI 2.58% - 3.44%), 2.62% (95% CI 2.31% - 2.90%), 2.16% (95% CI 1.97% - 2.33%), and 1.89% (95% CI 1.66% - 2.24%) respectively. The levels of ED(50) of target effect site concentration with propofol for LMA insertion in Subgroups Ap, Bp, Cp, and Dp were 4.74 microg/ml (95% CI 4.49 - 5.13 microg/ml), 4.33 microg/ml (95% CI 4.07 - 4.62 microg/ml), 4.10 microg/ml (95% CI 3.90 - 4.31 microg/ml), and 3.65 microg/ml (95% CI 3.24 - 3.98 microg/ml) respectively.The ED(50) level of P(ET)-sevoflurane or target effect site concentration with propofol for LMA insertion in Chinese boys decreases gradually along with the increase of age.

Proliferating cells express cyclins, cell cycle regulatory proteins that regulate the activity of cyclin-dependent kinases (CDKs). The actions of CDKs are regulated by specific inhibitors, the CDK inhibitors (CDKIs), which are comprised of the Cip/Kip and INK4 families. Expression of the Cip/Kip CDKI 1B (Cdkn1b, encoding protein CDKN1B, also called p27(kip1)) in developing Leydig cells (LCs) has been reported, but the function of CDKN1B in LCs is unclear. The goal of the present study was to determine the effects of CDKN1B on LC proliferation and steroidogenesis by examining these parameters in Cdkn1b knockout (Cdkn1b(-/-)) mice. LC proliferation was measured by bromodeoxyuridine incorporation. Testicular testosterone levels, mRNA levels, and enzyme activities of steroidogenic enzymes were compared in Cdkn1b(-/-) and Cdkn1b(+/+) mice. The labeling index of LCs in Cdkn1b(-/-) mice was 1.5% +/- 0.2%, almost 7-fold higher than 0.2% +/- 0.08% (P0.001) in the Cdkn1b(+/+) control mice. LC number per testis in Cdkn1b(-/-) mice was 2-fold that seen in the Cdkn1b(+/+) control mice. However, testicular testosterone levels, mRNA levels of steroidogenic acute regulatory protein (Star), cholesterol side-chain cleavage enzyme (Cyp11a1), and 3beta-hydroxtsteroid dehydrogenase 6 (Hsd3b6), and their respective proteins, were significantly lower in Cdkn1b(-/-) mice. We conclude that deficiency of CDKN1B increased LC proliferation, but decreased steroidogenesis. Thus, CDKN1B is an important regulator of LC development and function.

Diethylhexylphthalate (DEHP) has been classified as an antiandrogen. However, whether in utero and lactational exposures of DEHP affect Leydig cells has not been well established. In the present study, the effects of DEHP exposures on fetal Leydig cells (FLCs) and adult Leydig cells (ALCs) were assessed. Pregnant dams of Long-Evans rats were treated with 0, 10, and 750 mg/kg body weight DEHP from Gestational Day 12.5 to Postnatal Day (PND) 21.5. Fetal Leydig cell clustering and FLC-specific gene expression were examined. Anogenital distances (AGDs) of male pups were assessed at PND 2. Serum testosterone levels of male pups and mRNA levels of ALC-specific genes were measured at PNDs 21 and 49. The AGDs of male pups were significantly shorter in the group treated with 750 mg/kg DEHP (mean +/- SEM, 3.68 +/- 0.16 mm) compared with control (4.62 +/- 0.13 mm). The FLCs were aggregated after 10 and 750 mg/kg DEHP exposures. Several FLC-specific genes, including luteinizing hormone receptor (Lhcgr) and steroidogenic enzyme genes, were downregulated at both doses. Serum testosterone levels were significantly lower compared with control at PND 21 after treatment of 10 or 750 mg/kg DEHP, and continued to be lower even up to 49 days postpartum at the higher dose. The mRNA levels for Lhcgr and steroidogenic enzyme genes were significantly lower at both doses of DEHP at PND 21, whereas there were no significant differences for these genes at PND 49. In conclusion, in utero and continued lactational exposures to DEHP exert long-term disruption of steroidogenesis of ALCs.

To investigate the therapeutic effects of alprostadil (Lipo-PGE1) and Ulinastatin on inflammatory response and lung injury after cardiopulmonary bypass (CPB) in pediatric patients with congenital heart diseases.58 children with congenital heart diseases, including atrial septal defect, ventricular septal defect, and atrioventricular septal defect, scheduled to undergo CPB, aged 4 - 72 months, were randomly divided into 4 groups: alprostadil Group P (n = 15) receiving alprostadil 10 ng/ml added into the prime solution and continuous pump infusion of alprostadil 10 ngxkg(-1)xmin(-1) via central vein until the end of operation, Group U (n = 15) receiving ulinastatin 20 000 U/kg divided into several doses to be added into the prime solution, Group PU (n = 14) receiving alprostadil and ulinastatin according to the above protocols, and Group C (control group, n = 14) receiving normal saline of the equal volume. Electrocardiogram (ECG), heart rate (HR), pulse oxygen saturation (SpO(2)), and mean arterial pressure (MAP) were continuously monitored during operation. Duration of mechanical ventilation and staying in ICU were also recorded. Plasma neutrophil (PMN), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha and matrix metalloproteinase (MMP-9) levels in the radial arterial blood samples were measured after induction of anesthesia before CPB (T(1)), 30 minutes and (T(2)), 2 hours (T(3)), 6 hours (T(4)), and 24 hours (T(5)) after the declamping of aorta. Inhaled oxygen concentration and arterial blood gas analysis were recorded at T(1), T(2), and T(3) for calculation of oxygenation index (OI).There were no significant differences in the MAP and HR among these four groups at any time points (all P0.05). The umbers of PMN and the levels of IL-6, IL-8, and TNF-alpha at T(2) and T(3) of Groups P, U, and PU were all significantly lower than that of Group C (all P0.05), with those of Group PU being the lowest. The IL-10 levels at T(2) and T(3) of Groups U and PU were significantly higher than that of Group C (both P0.05), the level of MMP-9 at T(2) and T(3) of Groups U and PU were significantly lower than that of Group C (all P0.05), however, there was not significant difference between Group P and Group C (P0.05). The OIs at T(2) of Groups P, U, and PU were significantly higher than that of Group C (all P0.05). The mechanical ventilation time of Groups P, U, and PU were all significantly shorter than that of Group C, and that of Group PU was significantly shorter than that of group C (P0.05).Decreasing the inflammatory response after CPB, alprostadil and ulinastatin used during CPB effectively reduce the pulmonary injury via inhibition of the neutrophil activation and cytokines release.

Phthalates, the most abundantly produced plasticizers, leach out from polyvinyl chloride plastics and disrupt androgen action. Male rats that are exposed to phthalates in utero develop symptoms characteristic of the human condition referred to as testicular dysgenesis syndrome (TDS). Environmental influences have been suspected to contribute to the increasing incidence of TDS in humans (i.e. cryptorchidism and hypospadias in newborn boys and testicular cancer and reduced sperm quality in adult males). In this review, we discuss the recent findings that prenatal exposure to phthalates affects Leydig cell function in the postnatal testis. This review also focuses on the recent progress in our understanding of how Leydig cell factors contribute to phthalate-mediated TDS.