Objective To investigate the effects of different doses of intrathecal magnesium on bone cancer pain (BCP) in mice.Methods Two hundred and eighty-eight male C3H/HeJ mice,aged 8-10 weeks,weighing 18-22 g,were randomly divided into 6 groups (n =48 each):control group (group C) ; sham operation group (group S) ; BCP + artificial cerebro-spinal fluid (aCSF) 5 μl group (group BCP) ; BCP + MgSO4 14.4 μg group (group M1 ) ; BCP + MgSO4 43.2 μg group (group M2 ) and BCP + MgSO4 86.4 μg group (group M3 ).BCP was produced by injecting fibrosarcoma cells of bone into the medullary cavity of right femur.Intrathecal catheter was placed in the 4 BCP groups.The aCSF 5 μl or MgSO4 14.4μg/5 μl,43.2 μg/5 μl,or 86.4μg/5 μl was injected intrathecally on 14th day after inoculation of tumor cells.The paw withdrawal threshold to mechanical stimuli (PWMT) and paw withdrawal lateney to thermal stimuli (PWTL) were measured at 0.5 h before administration (T0 ) and at 0.5,2,4 and 8 h after administration (T1-4).Eight animals chosen from each group at T0-4 were sacrificed,and L4-5 segment of the spinal cord was removed for determination of NR2B expression (by immuno-flurorescence) in the spinal cord.Results PWMT and PWTL were significantly decreased at T0-4,and NR2B expression was significantly up-regulated at T0-4 in groups BCP,M1,M2,M3 compared with groups C and S ( P ＜0.05).Compared with group BCP,PWMT and PWTL were significandy increased at T1-3,and NR2B expression was significantly down-regulated at T1-3 in groups M2 and M3 ( P ＜ 0.05).Compared with group M2,PWMT and PWTL were significantly increased at T1-3,and NR2B expression was significantly down-regulated at T1-3 in group M3 ( P ＜ 0.05).Conclusion Intrathecal magnesium can reduce BCP in a dose-dependent manner in mice.

Objective To systematically review the preventive efficacy of N-methyl-D-aspartate (NMDA) receptor antagonists on remifentanil-induced postoperative hyperalgesia.Methods Pubmed,EMBase,Springer and Cochrane Controlled Trials Register were searched to identify all randomized controlled trials(RCTs) about efficacy of NMDA receptor antagonists for preventing remifentanil-induced postoperative hyperalgesia.The quality of the studies was evaluated by the method recommended by Cochrane Collaboration.The data was extracted,including postoperative analgesic consumption,pain scores,time for first analgesic request and the incidence of adverse effects.Meta-analysis was conducted using the Cochrane Collaboration's RevMan 5.0 software.Results Fourteen RCTs involving 623 patients were included in our Meta-analysis.NMDA receptor antagonists significantly decreased pain scores at 4 h after operation ( P ＜ 0.05),and had no effect on postoperative analgesic consumption,time for first analgesic request and the incidence of adverse effects ( P ＞ 0.05).Conclusion NMDA receptor antagonists (ketamine and magnesium)can not prevent the occurrence of postoperative hyperalgesia induced by remifentanil.

Objective In the treatment of acute myeloid leukemia (AML-M2a), the first CCR (continuous complete remission) has been one of the most critical indicators to the prognosis of the patients. Using microarray approaches, gene expression profiles have been studied in patients with different CCR, in order to find out the genes relevant to the progresses of the AML. Methods Bone marrow mononuclear cells were collected and used as different experimental groups respectively. Group A composed of three AML patients with CCR<6 months, while group B composed of three AML patients with CCR>12 months. mRNAs were purified and labeled with Cy3 and Cy5 respectively, which were used to hybridize against the Agilent human 1B 60mer oligonucleotide microarrays. Results In the 20173 genes tested, 21 genes were found expressed differentially between these two groups. Of these differentially expressed genes, 10 genes were up-regulated while 11 genes were down-regulated in group A. Conclusion Through microarray studies, 21 genes including APP were found to be differentially expressed in AML patients whom were treated with standard chemotherapy. Theses genes can be early indicators for the diagnosis as well as prognosis of the refractory AML.

Biopsy ; Child, Preschool ; Female ; Humans ; Infant ; Lung ; pathology ; Lung Diseases, Interstitial ; diagnosis ; pathology ; Male

10.3969/j.issn.1007-3969.2013.05.004

OBJECTIVE: To research the effect of thiochroman-4-one derivatives on acetylcholine esterase activity. METHODS: Substituted thiophenols as the starting materials were transformed into 6-hydroxythiochroman-4-ones by substitution reaction and cycliza-tion reaction with concentrated sulfuric acid, and the resultant compounds were reacted with benzylpiperazins to prepare 3-(4-benzylpiperazine-1-methyl) thiochroman-4-ones hydrochloride, and their bioactivities as AChE inhibitors were measured in vitro. RESULTS: The target compounds had AChE inhibitive activity in micromolar range, and compound 8a was better than rivastigmine with IC50=0.96 μmol · L-1. CONCLUSION: 3-(4-Benzylpiperazine-1-methyl) thiochroman-4-ones show anti-acetylcholinesterase activity in vitro, which are worth further research.

Objective To investigate the effects of penehyclidine hydrochloride combined with ulinastatin on postoperative cognitive function in the patients undergoing thoracic surgery.Methods One hundred and twenty patients undergoing lung cancer thoracotomic radical resection were randomly divided into hydrochloride penehyclidine composite ulinastatin group(HU group),hydrochloride penehyclidine group(H group),ulinastatin group(U group)and control group(C group).The arterial blood was collected for detecting OI,TNF-α,IL-6 and IL-8.The serum levels of S-100β and NSE were detected.The MMSE scores were evaluated.Results Compared with the H group and U group,the levels of TNF-α at T3-4 in the HU group were decreased,and the levels of IL-6 and IL-8 at T2-4 were decreased,while OI was increased(P＜0.05).Compared with the H group and U group,the serum levels of S-100β and NSE at T5-8 in the HU group were decreased(P＜0.05);compared with the H group and U group,the MMSE scores at T6-7 in the HU group were increased(P＜0.05).Conclusion Penehyclidine hydrochloride combined with ulinastatin could reduce the inflammation reaction during one lung ventilation in thoractomy and improves the postoperative cognitive function.

A series of novel 2-amino-4-phenylthiazole derivatives were designed and synthesized, furthermore, their inhibition effect on acetylcholinesterase were investigated. 2-Amino-4-phenylthiazoles were prepared from alpha-bromoacetophenones by Hantzsch reaction, acylation reaction and substitution reaction. Moreover, their bioactivities as AChE inhibitors in vitro were measured with Ellman spectrophotometry. The results showed that most of them had a certain inhibition activity on AChE, and the compound 8a was the best of them. The IC50 of 8a to AChE is 3.54 micromol x L(-1), and the value was better than that of rivastigmine. 2-Amino-4-phenylthiazole derivatives showed a certain bioactivity in vitro, which were worth further investigation.
Acetylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Inhibitory Concentration 50 ; Molecular Structure ; Thiazoles ; chemical synthesis ; chemistry ; pharmacology

To investigate the metabolic rate and metabolites of 9-dehydro-17-dehydro-andrographolide, which is the main active ingredient in Xiyanping injection, by using the in vitro rat liver microsome incubation system. 9-dehydro-17-dehydro-andrographolide was incubated together with liver microsome mixed with NADPH. Its metabolic rate was studied by determining its residual concentrations with the UHPLC-MS/MS method; Its metabolites were identified by the UPLC-TOF-MS(E) method. The results showed that 9-dehydro-17-dehydro-andrographolide was metabolized faster than rat liver microsomes mixed with coenzymes, with t½ and CL of (19.7 ± 0.5) min and (35.1 ± 0.8) mL x min(-1) x g(-1) (protein), respectively. Based on the high resolution mass spectrum data and information from literatures, altogether nine metabolites of 9-dehydro-17-dehydro-andrographolide were identified in the incubation system, particularly hydroxylated and dehydrogenized products. The results of identification would provide a basis for screening out more active andrographolide derivatives.
Animals ; Chromatography, High Pressure Liquid ; Diterpenes ; chemistry ; metabolism ; Drugs, Chinese Herbal ; chemistry ; metabolism ; Microsomes, Liver ; chemistry ; metabolism ; Molecular Structure ; Rats ; Tandem Mass Spectrometry

N-Acyl-4-phenylthiazole-2-amines were designed and synthesized, moreover their effects on acetylcholinesterase activities were tested. N-Acyl-4-phenylthiazole-2-amines were prepared from substituted 2-bromo-1-acetophenones by three steps reaction, and their AChE inhibitory activities were measured by Ellman method in vitro. The results showed that the target compounds had a certain inhibitory activity on AChE in vitro. Among them, 8c was the best, and IC50 of 8c was 0.51 micromol x L(-1), better than that of rivastigmine and Huperzine-A. The inhibitory activities of N-acyl-4-phenylthiazole-2-amines on acetylcholinesterase are worth while to be further studied.
Acetylcholinesterase ; metabolism ; Alkaloids ; pharmacology ; Amines ; chemical synthesis ; pharmacology ; Cholinesterase Inhibitors ; chemical synthesis ; pharmacology ; Drug Design ; Rivastigmine ; pharmacology ; Sesquiterpenes ; pharmacology ; Structure-Activity Relationship ; Thiazoles ; pharmacology