[Show abstract][Hide abstract] ABSTRACT: Diisononyl phthalate (DINP) is a synthetic material that has been widely used as a substitute for other plasticizers prohibited due to reproductive toxicity in consumer products. Some phthalates have been associated with testicular dysgenesis syndrome in male fetus when female pregnant dams were exposed to them. The present study investigated effects of DINP on fetal Leydig cell function and testis development. Female pregnant Sprague Dawley rats received control vehicle (corn oil) or DINP (10, 100, 500, and 1000 mg/kg) by oral gavage from gestational day (GD) 12 to 21. At GD 21.5, testicular testosterone production, fetal Leydig cell numbers and distribution, testicular gene and protein expression levels were examined. DINP showed dose-dependent increase of fetal Leydig cell aggregation with the low observed adverse-effect level (LOAEL) of 10 mg/kg and multinucleated gonocyte with LOAEL of 100 mg/kg. At 10 mg/kg, DINP also significantly increased fetal Leydig cell size, but inhibited insulin-like 3 and 3β-hydroxysteroid dehydrogenase gene expression and protein levels. DINP inhibited testicular testosterone levels at 1000 mg/kg. The results indicate that in utero exposure to DINP affects the expression levels of some fetal Leydig cell steroidogenic genes, gonocyte multinucleation and Leydig cell aggregation.
[Show abstract][Hide abstract] ABSTRACT: Drug resistance poses a major challenge to ovarian cancer treatment. Understanding mechanisms of drug resistance is important for finding new therapeutic targets. In the present work, a cisplatin-resistant ovarian cancer cell line A2780-DR was established with a resistance index of 6.64. The cellular accumulation of cisplatin was significantly reduced in A2780-DR cells as compared to A2780 cells consistent with the general character of drug resistance. Quantitative proteomic analysis identified 340 differentially expressed proteins between A2780 and A2780-DR cells, which involve in diverse cellular processes, including metabolic process, cellular component biogenesis, cellular processes and stress responses. Expression levels of Ras-related proteins Rab 5C and Rab 11B in A2780-DR cells were lower than those in A2780 cells as confirmed by real-time quantitative PCR and western blotting. The short hairpin (sh)RNA-mediated knockdown of Rab 5C in A2780 cells resulted in markedly increased resistance to cisplatin whereas overexpression of Rab 5C in A2780-DR cells increases sensitivity to cisplatin, demonstrating that Rab 5C-dependent endocytosis plays an important role in cisplatin resistance. Our results also showed that expressions of glycolytic enzymes PKM, GPI, ALDO, LDH, and PGK were down-regulated in drug resistant cells, indicating drug resistance in ovarian cancer is directly associated with a decrease in glycolysis. Furthermore, it was found that glutathione reductase were up-regulated in A2780-DR, while vimentin, HSP90, and Annexin A1 and A2 were down-regulated. Taken together, our results suggest that drug resistance in ovarian cancer cell line A2780 is caused by multifactorial traits, including the down-regulation of Rab 5C-dependent endocytosis of cisplatin, glycolytic enzymes and vimentin, and up-regulation of antioxidant proteins, suggesting Rab 5C is a potential target for treatment of drug-resistant ovarian cancer. This constitutes a further step towards a comprehensive understanding of drug resistance in ovarian cancer.
[Show abstract][Hide abstract] ABSTRACT: To explore the effect of single-dose dexmedetomidine on recovery period after sevoflurane anesthesia with spontaneous respiration in pediatric patients undergoing cleft lip and palate repair.
[Show abstract][Hide abstract] ABSTRACT: To investigate the ameliorative effect of curcumin pretreatment against impaired spatial working memory on global cerebral ischemia-reperfusion rats and to explore its mechanism.
[Show abstract][Hide abstract] ABSTRACT: In pediatric fluid therapy it would be preferable to describe distribution and elimination a fluid bolus based on repetitive hemoglobin (Hb) according to kinetic principles. Pulse CO-Oximetry is a recent advancement in patient monitoring that allows for the continuous noninvasive measurement of Hb (SpHb). The aim of this study was to describe the distribution and elimination of hydroxyethylstarch (HES) 130/0.4 in combination with crystalloids using a noninvasive Hb monitor in two cohorts of young children undergoing minor surgeries under general anesthesia. Two cohorts, 16 children aged 1-3 years and 12 aged 4-6 years, were investigated during anesthesia and minor surgical procedures. They were given a maintenance solution of lactated Ringer's and a fluid bolus of HES 130/0.4, 6 mL/kg over a period of 20 min. The whole procedure lasted 120 min, and SpHb values were measured every 10 min. The SpHb values were used to calculate plasma dilution, net volume, and mean residence time (MRT) of the infused fluid. A total of 377 measured SpHbs generated individual dilution plots that showed variability, particularly for the older cohort. Distribution and elimination rates of the infused fluid were calculated. Mean dilution plots were generated. There were no significant differences in dilution, net volume or MRT between groups. A non invasive Hb analyzer could be used to calculate fluid distribution. The variability in the data can probably be explained by reactions to anesthetic drugs, variability in measurement technique, variability in generating the complex capillary signals, and individual variability in baseline fluid status. The latter finding is important because this is a prerequisite for perioperative fluid planning for each individual.
International Journal of Clinical Monitoring and Computing 02/2014;
[Show abstract][Hide abstract] ABSTRACT: Previous studies have shown that a low dose of propofol IV bolus had a beneficial effect on intrathecal morphine-induced pruritus in humans. However, its exact mechanism has not been fully understood. In this study, we hypothesized that propofol relieved intrathecal morphine-induced pruritus in rats by upregulating the expression of cannabinoid-1 (CB) receptors in anterior cingulate cortex (ACC).
Twenty-four Sprague-Dawley rats were divided into a control group and 20, 40, 80 μg/kg morphine groups to create an intrathecal morphine-induced scratching model. The effects of propofol on intrathecal 40 μg/kg morphine-induced scratching responses were then evaluated. Sixty rats were randomly assigned to control, normal saline, intralipid, and propofol groups, with pruritus behavior observation or killed 8 minutes after venous injection of normal saline, intralipid, or propofol, and brain tissues were then collected for assay. Immunohistochemistry was then performed to identify the expression of CB (1) receptor in ACC, and the concentration of CB(1) receptor in ACC was determined by Western blot analysis.
Compared with the control group, rats in the 20, 40, 80 μg/kg morphine groups had higher mean scratching response rates after intrathecal morphine injection (P =0.020, 0.005, and 0.002, respectively). There was a statistical difference between 20 and 40 μg/kg morphine groups at 10 to 15 and 15 to 20 timepoints after intrathecal morphine injection (P = 0.049 and 0.017, respectively). Propofol almost abolished the scratching response that was induced by 40 μg/kg intrathecal morphine injection (F[2, 15] = 46.87, P < 0.001; F[22, 165] = 2.37, P = 0.001). Compared with the intralipid and normal saline groups, the scratching behavior was significantly attenuated in the propofol group (P < 0.001). Compared with control, normal saline, and intralipid groups, the protein expression of CB(1) receptor in ACC (Western blot) in the propofol group increased (0.86 ± 0.21, 0.94 ± 0.18, 0.86 ± 0.13, and 1.34 ± 0.32, respectively, P < 0.001). There was no significant difference among control, normal saline, and intralipid groups. Compared with the control, normal saline, and intralipid groups, the average number of neurons of CB(1) receptor in the ACC area were higher in the propofol group (21.0 ± 1.4, 19.3 ± 1.8, 24.8 ± 7.7, and 37.2 ± 3.3, respectively, P < 0.001).
Morphine elicits dose-independent scratching responses after intrathecal injection in rats. Morphine 40 μg/kg intrathecal injection-induced scratching responses can be prevented by propofol. Increased protein expression of CB(1) receptors in ACC may contribute to the reversal of intrathecal morphine-induced scratching.
Anesthesia and analgesia 02/2014; 118(2):303-9. · 3.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Resveratrol is a polyphenol produced by several plants. It has been demonstrated that it has anti-inflammatory, antitumor, and anti-diabetic effects in animal models. However, its side effects are generally unclear. In the present study, we reported that resveratrol inhibited luteinizing hormone-stimulated androgen production in rat immature Leydig cells. Further analysis demonstrated that it was a competitive inhibitor of rat and human 3β-hydroxysteroid dehydrogenase with IC50 values of 3.87±0.06 and 8.48±0.04μM, respectively. The inhibition on 3β-hydroxysteroid dehydrogenase was specific since it did not inhibit another hydroxysteroid dehydrogenase 17β-hydroxysteroid dehydrogenase 3 at the highest concentration (100μM) tested. In conclusion, resveratrol potentially interferes with androgen biosynthesis of rat Leydig cells.
[Show abstract][Hide abstract] ABSTRACT: Volatile anesthetics are widely used in pediatric anesthesia but their potential neurotoxicity raise significant concerns regarding sequelae after anesthesia. However, whether physiological disturbance during anesthetic exposure contributes to such side effects remains unknown. The aim of the current study is to compare the neurotoxic effects of isoflurane and sevoflurane in 14 day old rat pups under spontaneous breathing or ventilated conditions.
Postnatal 14 day rats were assigned to one of five groups: 1) spontaneous breathing (SB) + room air (control, n = 17); 2) SB + isoflurane (n = 35); 3) SB + sevoflurane (n = 37); 4) mechanical ventilation (MV) + isoflurane (n = 29); 5) MV + sevoflurane (n = 32). Anesthetized animal received either 1.7% isoflurane or 2.4% seveoflurane for 4 hours. Arterial blood gases and blood pressure were monitored in the anesthetized groups. Neurodegeneration in the CA3 region of hippocampus was assessed with terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling immediately after exposure. Spatial learning and memory were evaluated with the Morris water maze in other cohorts 14 days after experiments.
Most rats in the SB groups developed physiological disturbance whereas ventilated rats did not but become hyperglycemic. Mortality from anesthesia in the SB groups was significantly higher than that in the MV groups. Cell death in the SB but not MV groups was significantly higher than controls. SB + anesthesia groups performed worse on the Morris water maze behavioral test, but no deficits were found in the MV group compared with the controls.
These findings could suggest that physiological disturbance induced by isoflurane or sevoflurane anesthesia may also contribute to their neurotoxicity.
PLoS ONE 01/2014; 9(1):e84622. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ovarian cancer is a major cause for death of gynecological cancer patients. The efficacy of traditional surgery and chemotherapy is rather compromised and platinum-resistant cancer recurs. Finding new therapeutic targets is urgently needed to increase the survival rate and to improve life quality of patients with ovarian cancer. In the present work, phosphoproteomic analysis was carried out on untreated and gossypol-treated ovarian cancer cell line, HOC1a. We identified approximately 9750 phosphopeptides from 3030 phosphoproteins, which are involved in diverse cellular processes including cytoskeletal organization, RNA and nucleotide binding, and cell cycle regulation. Upon gossypol treatment, changes in phosphorylation of twenty-nine proteins including YAP1 and AKAP12 were characterized. Western blotting and qPCR analysis were used to determine expression levels of proteins in YAP1-related Hippo pathway showing that gossypol induced upregulation of LATS1, which phosphorylates YAP1 at Ser 61. Furthermore, our data showed that gossypol targets the actin cytoskeletal organization through mediating phosphorylation states of actin-binding proteins. Taken together, our data provide valuable information to understand effects of gossypol on protein phosphorylation and apoptosis of ovarian cancer cells.
BioMed Research International 01/2014; 2014:123482. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the present work, metabolomic and redox proteomic analyses were carried out on an untreated- and gossypol-treated ovarian cancer cell line, SKOV3. Gossypol treatment resulted in cell death through oxidative stress. Metabolite analysis showed that gossypol induces a decrease of the cellular levels of GSH, aspartic acid, and FAD. Using a combination of double labeling and LC-MS-MS, we identified changes in thiol-redox states of 545 cysteine-containing peptides from 356 proteins. The frequently occurring amino acid residue immediately before or after the cysteine in these peptides is the non-polar and neutral leucine, valine, or alanine. These redox sensitive proteins participate in a variety of cellular processes. We have characterized the redox-sensitive cysteine residues in PKM2, HSP60, malate dehydrogenase and other proteins that play important roles in metabolism homeostasis and stress responses. The three cysteine residues of HSP60 exhibit different responses to gossypol treatment: an increase of thiol/disulfide ratio for the Cys447 residue due to a decrease of the cellular GSH level, and a decrease of thiol/disulfide ratios for Cys442 and Cys237 residues due to oxidation and sulfation. This study suggests that thiol/disulfide ratios are dependent on the level of cellular GSH. Our data provide a valuable resource for deciphering the redox regulation of proteins and for understanding gossypol-induced apoptosis in ovarian cancer cells.
[Show abstract][Hide abstract] ABSTRACT: Post-operative cognitive dysfunction has been widely observed, especially in older patients. An association of post-operative cognitive dysfunction with the neurodegenerative diseases, such as Alzheimer's disease, has been suggested. Neuroinflammation contributes to Alzheimer pathology, through elevated pro-inflammatory cytokines and microglial activation in the CNS leading to neuronal damage, synaptic disruption and ultimately cognitive dysfunction. We compare the effects of three different, clinically-used, anesthetics on microglial activation with, and without, the prototypical inflammatory trigger, lipopolysaccharide (LPS). Microglial BV-2 cell cultures were first exposed to isoflurane, sevoflurane (each at 2 concentrations) or propofol for 6 h, and cytokine levels measured in lysates and media. The same experiments were repeated after 1 h LPS pre-treatment. We found; 1) anesthetics alone have either no or only a small effect on cytokine expression; 2) LPS provoked a large increase in microglia cytokine expression; 3) the inhaled anesthetics either had no effect on LPS-evoked responses or enhanced it; 4) propofol nearly eliminated the LPS pro-inflammatory cytokine response and improved cell survival as reflected by lactate dehydrogenase release. These data suggest that propofol may be a preferred anesthetic when it is desirable to minimize neuroinflammation.
PLoS ONE 01/2013; 8(1):e52887. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As a widely used intravenous short-acting anesthetic, propofol is recently indicated by clinical and animal studies for its abuse potential, but the mechanism underlying propofol abuse is largely unknown. This study examined the contribution of dopamine receptor subtype (D1 and D2 receptors) and neuroanatomical locus (i.e. nuclear accumbens) in maintenance of propofol self-administration in rats. After the acquisition and maintenance of self-administration of propofol (1.7 mg/kg/infusion) under a fixed ratio (FR1) schedule of reinforcement over 14 days, rats were treated by either intraperitoneal injection or intra-nucleus accumbens (NAc) injection of D1 receptor antagonist (SCH23390) or D2 receptor antagonists (spiperone and eticlopride) 10 minutes prior to the subsequent propofol self-administration. We demonstrated i) systemic administration of SCH23390 (10, 30, 100 g/kg, i.p.) dose-dependently decreased the rate of propofol-maintained self-administration, suggesting a critical role of D1 receptor in mediating propofol self-adminstration; ii) the blockade of the propofol self-administration by SCH23390 was specific since spiperone and eticlopride did not affect propofol self-administration and SCH23390 at these doses did not affect food-maintained responding under an FR5 schedule; iii) intra-accumbenal injection of SCH23390 (2.5ug/site) but not eticopride (3.0ug/site) attenuated the propofol self-administration, localizing nuclear accumbal D1 receptors as a critical locus in the reinforcement of propofol. Together, these findings provide the first direct evidence that D1 receptors in nuclear accumbens play an important role in the maintenance of propofol self-administration.
[Show abstract][Hide abstract] ABSTRACT: To investigate the effects of curcumin on the behavior of chronic constrictive injury (CCI) rats and the CX3CR1 expression in spinal cord dorsal horn and dorsal root ganglia (DRG).
Seventy-two male SD rats were randomly divided into 4 groups: 1) Sham operation group (Sham); 2) Chronic constrictive injury group (CCI); 3) Curcumin treated group (Cur), administrated with curcumin 100 mg x kg(-1) x d(-1) ip for 14 days after CCI; 4) Solvent contrast group (SC), administrated with an equal volume of solvent for 14 days after CCI. Paw thermal withdrawal (PTWL) and paw mechanical withdrawal threshold (PMWT) were measured on 2 pre-operative and 1, 3, 5, 7, 10, 14 post-operative days respectively. The lumbar segments L4-5 of the spinal cord and the L4, L5 DRG were removed at 3, 7, 14 days after surgery. The expression of CX3CR1 was determined by immunohistochemical staining.
Compared with Sham group, PTWL and PMWT in CCI group were significantly lower on each post-operative day (P<0.01), which reached a nadir on the 3rd day after CCI (PTWL was 6.5 +/- 1.1, PMWT was 22.6 +/- 5.1), and the expression of CX3CR1 were markedly increased in spinal cord dorsal horn and DRG. In Cur group, PTWL were higher than in CCI group on 7, 10, 14 post-operative day (P<0.05), and PMWT were higher than those in CCI group on 10 and 14 post-operative day (P<0.05). The administration of curcumin could significantly attenuate the activation of CX3CR1 induced by CCI.
The study suggests that curcumin ameliorates the CCI-induced neuropathic pain, probably by attenuating the expression of CX3CR1 in spinal cord dorsal horn and dorsal root ganglia.
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 09/2011; 36(18):2552-6.
[Show abstract][Hide abstract] ABSTRACT: Perfluorinated compounds (PFCs) are persistent organic pollutants ubiquitously distributed in the environment and human populations. Here we report PFC concentrations in the residents of Wenzhou City, which is characterized as the 'Footwear Capital' of China. Specifically, fifty serum samples collected from workers in a leather factory, fifty-five umbilical cord serum samples and fifteen serum samples from infertile men were analyzed. PFOS was one of the most frequently detected PFCs and showed the highest level. The mean serum levels of PFOS and PFOA of workers and infertile males were higher than the cord serum. PFOS concentration in cord serum increased with increase in age of the mother. Gender differences were significant both in worker serum samples and umbilical cord samples with higher levels found in males/male fetuses. Our findings suggested that PFOS, PFOA and PFHxS were widely distributed in Wenzhou residents, but occupational exposure was not the main source for workers.
Ecotoxicology and Environmental Safety 05/2011; 74(6):1787-93. · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 11β-Hydroxysteroid dehydrogenase 2 (11β-HSD2) regulates active glucocorticoid access to glucocorticoid and mineralocorticoid receptors by metabolizing it to an inactive form. Perfluoroalkylated substances (PFASs) are man-made polyfluorinated compounds that are widely used and persistent in the environment. We tested the inhibitory potencies of four PFASs including perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexanesulfonate (PFHxS) and perfluorobutane sulfonate (PFBS) on human and rat 11β-HSD2. PFOS was a potent inhibitor of both human (IC(50)=48 nM) and rat (IC(50)=293 nM) 11β-HSD2 activities. The potencies for the inhibition of human and rat 11β-HSD2 activities were PFOS>PFOA>PFHxS>PFBS. PFASs showed competitive inhibition of both human and rat 11β-HSD2 activities. This observation indicates that PFOS is a potent endocrine disruptor for glucocorticoid metabolism. Article from the Special issue on Targeted Inhibitors.
The Journal of steroid biochemistry and molecular biology 01/2011; 125(1-2):143-7. · 3.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fibroblasts are important to host defence and immunity, can also as initiators of inflammation as well. As the endogenous "braking signal", Lipoxins can regulate anti-inflammation and the resolution of inflammation. We investigated the effect of lipoxinA(4) on the expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts. We demonstrated that the expression of cyclooxygenase-2 protein was significantly increased and peaked initially at 6 hours, with a second increase, with maximal levels occurring 24 hours after lipopolysaccharide challenge. ProstaglandinE(2) levels also peaked at 6 hours, and prostaglandinD(2) levels were increased at both 6 and 24 hours. Exogenous lipoxinA(4) inhibited the first peak of cyclooxygenase-2 expression as well as the production of prostaglandinE(2) induced by lipopolysaccharide in a dose-dependent manner. In contrast, exogenous lipoxinA(4) increased the second peak of cyclooxygenase-2 expression as well as the production of prostaglandinD(2) induced by lipopolysaccharide in a dose-dependent manner. LipoxinA(4) receptor mRNA expression was markedly stimulated by lipopolysaccharide but inhibited by lipoxinA(4). We present evidence for a novel biphasic role of lipoxinA(4) on the expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts, whereby LXA(4) has an anti-inflammatory and proresolving activity in lung fibroblasts following LPS stimulation.
Mediators of Inflammation 01/2011; 2011:745340. · 3.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two isoforms of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1 and 11beta-HSD2) play an important role in regulation of glucocorticoid corticosterone (CORT, the active form in rodents) by the interconversion between CORT and 11-dehydrocorticosterone (11DHC, the biologically inert form). 11beta-HSD1 is an NADP+/NADPH-dependent oxidoreductase which is mainly expressed in liver and kidney, while 11beta-HSD2 is an NAD+-dependent oxidase which is predominantly expressed in kidney. The regulation of 11beta-HSD1 and 11beta-HSD2 mRNA (Hsd11b1 and Hsd11b2) levels and their activities by IGF-1 was performed in liver, kidney, and testis of IGF-1 knockout male mice. Real-time PCR showed that Hsd11b1 in liver was decreased while Hsd11b2 mRNA level was decreased in kidney of IGF-1 null mice. 11beta-HSD1 and 11beta-HSD2 activities fluctuated with the changes of their respective Hsd11b1 or Hsd11b2 mRNA levels. In conclusion, IGF-I tissue-specifically regulates Hsd11b1 and Hsd11b2 expression.
Biochemical and Biophysical Research Communications 01/2010; 391(4):1752-6. · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To describe, in pediatric patients, the effects of three doses of cisatracurium during nitrous oxide-propofol anesthesia and to determine if larger doses result in faster onset time.
75 ASA physical status I and II children, aged 15 to 60 months, undergoing surgery for hypospadias or undescendent testis.
Patients were randomly assigned to one of three groups according to the dose of cisatracurium: Group A = 0.1 mg/kg (two x effective dose), Group B = 0.15 mg/kg (three x effective dose), and Group C = 0.2 mg/kg (4 x effective dose).
Neuromuscular block was assessed with TOF-Guard (Biometer International, Odense, Denmark) accelerometry. Onset time (from cisatracurium injection to maximal depression of time to first twitch), duration of peak effect (time from cisatracurium injection to 5% recovery of time to first twitch), duration of clinical action (time from cisatracurium injection to 25% recovery of time to first twitch), and recovery index (recovery of time to first twitch from 25% to 75%) were recorded.
Cisatracurium had no effect on heart rate or blood pressure at any dose. Compared with Group A, onset times in Groups B and C were shorter; and durations of peak effect and clinical action in Groups B and C were longer (P < 0.01) than those in Group A. There was no difference in recovery index among the three groups. There was no difference in onset times between Groups B and C. Compared with Group B, durations of peak effect and clinical action in Group C were longer (P < 0.05 or P < 0.01).
Four times the effective dose of cisatracurium did not significantly shorten onset time beyond that produced with three times the effective dose in young children.
Journal of Clinical Anesthesia 09/2008; 20(6):411-4. · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is no information about the pharmacokinetic profile of propofol in Chinese children younger than 3 yr. This study was designed to determine a complete pharmacokinetic profile of a single dose of propofol in Chinese children of different ages.
Arterial blood samples were obtained from 35 children with an American Society of Anesthesiologist physical status of I or II at 2, 4, 6, 8, 10, 20, 30, 45, 60, 90, 120, and 180 min after a single bolus intravenous injection of propofol (3 mg/kg). The plasma concentrations of propofol were measured using high-performance liquid chromatography with an ultraviolet detector. A population model was used to estimate the pharmacokinetics of propofol.
A three-compartment pharmacokinetic model best described the pharmacokinetics of propofol. Clearance was 0.185 l/min, the volume of distribution of the central compartment was 7.41 l, the peripheral volumes of distribution were 54.6 and 7.2 l, and the intercompartmental clearances were 0.614 and 0.692 l/min for a child of the average weight of 13.7 kg. The half-lives were 2.67, 14.89, and 310.60 min. Covariate models were applied, and weight was found to be significant covariate for the clearance and volume of distribution parameters. No significant age effect could be demonstrated on clearance or volume of distribution parameters after weight was taken into account.
This study supports the case that the pharmacokinetic properties of propofol do not differ substantially across Chinese children of different ages after weight has been accounted for.
[Show abstract][Hide abstract] ABSTRACT: To investigate the protective effect of curcumin on endotoxin-induced acute lung injury in rats, and explore the underlying mechanisms, 24 male Wistar rats were randomly divided into 4 experimental groups: sham-vehicle (S), sham-curcumin (C), lipopolysaccharide (LPS)-vehicle (L), and curcumin-lipopolysaccharide (C-L) groups. The wet/dry (W/D) weight ratio of the lung and bronchoalveolar lavage (BAL) fluid protein content were used as measures of lung injury. Neutrophil recruitment and activation were evaluated by BAL fluid cellularity and myeloperoxidase (MPO) activity in cell-free BAL and lung tissue. The levels of cytokine-induced neutrophil chemoattractant-I (CINC-1) in lung tissues were measured by ELISA. The histopathological changes of lung tissues were observed by using the HE staining. Our results showed that lung injury parameters, including the wet/dry weight ratio and protein content in BALF, were significantly higher in the L group than in the S group (P<0.01). In the L group, higher numbers of neutrophils and greater MPO activity in cell-free BAL and lung homogenates were observed when compared with the S group (P<0.01). There was a marked increase in CINC-1 levels in lung tissues in response to LPS challenge (P<0.01, L group vs S group). Curcumin pretreatment significantly attenuated LPS-induced changes in these indices. LPS caused extensive morphological lung damage, which was also lessened after curcumin pretreatment. All the above-mentioned parameters in the C group were not significantly different from those of the S group. It is concluded that curcumin pretreatment attenuates LPS-induced lung injury in rats. This beneficial effect of curcumin may involves, in part, inhibition of neutrophilic recruitment and activity, possibly through inhibition of lung CINC-1 expression.
Journal of Huazhong University of Science and Technology 01/2006; 26(6):678-81. · 0.58 Impact Factor