The homeostasis of extracellular glutamate concentration is critically regulated by glutamate transporters(GTs).Malfunction or decreased expression of GTs has been implicated in the pathogenesis of various nervous system diseases.And among the GTs,glutamate transporter 1(GLT-1)plays a critical role as "glutamate pump".Recent research also finds some GLT-1 variants which alternate C-terminal splicings.Altered expression of proteins encoded by splice variants of GLT-1 has been noted in a number of disease states.Maintaining a physiological range of extracellular glutamate through regulating GTs expression or function may improve some pathological conditions.Many drugs are reported that can regulate GTs.For example,ceftriaxone,phencyclidine,citicoline,riluzole,AKT,thrombosin can up-regulate the expression or function of glutamate transporters;etomidate,clozapine,aspartic acid analogs,endothelin can down-regulate the expression or function of glutamate transporters.In this paper,the drugs which effect GTs will be summarized in order to provide a new insight into the drug design and clinical treatment of neurological diseases.

BACKGROUND:Pasteurization is a perfect method for albumin virus inactivation, which may not be required for virus inactivation validation. However, there are no systematical reports concerning virus inactivation of hemoglobin blood substitutes. OBJECTIVE:To explore the effects of pasteurization on the physicochemical properties and biological function of hemoglobin blood substitutes. METHODS:Appropriate cord blood samples were taken fol owed by centrifugation, washing blood, rupture of membranes, stabilizer treatment. In the control group, the samples were placed in 55℃water bath, and when the temperature of hemoglobin solution reached (55±1)℃, a heat treatment began and lasted for 2 hours. In the pasteurization group, the samples were placed in 60℃water bath, and when the temperature of hemoglobin solution reached (60±1)℃, a heat treatment began and lasted for 10 hours. The heating process was under continues nitrogen protection. Then, the hemoglobin solution was placed in ice bath and cooled to below 4℃fol owed by low-speed centrifugation and filtration via microporous membrane, purification and viral inactivation thereby to obtain cord blood hemoglobin. RESULTS AND CONCLUSION:The products in the pasteurization group were al red clear liquid. There was no significant difference between the two groups in the yield, methemoglobin concentration, and oxygen-carrying capacity. The purification of the two groups was more than 98%. Two kinds of purification methods had no effects on the oxygen-carrying capacity of hemoglobin. Therefore, pasteurization method can replace thermosensitive purification method of 55℃, 2 hours. The pasteurization method wil not only ensure the physicochemical and biological properties of hemoglobin, but also achieve the purpose of virus inactivation.

Objective To compare the resuscitation effect of 6% hydroxyethyl starch (HES) of different molecular weight in normal saline on hemorrhagic shock in rats. Methods Hemorrhagic shock model was established in 50 SD rats by 45% hemorrhage,and then they were equally divided into 5 groups. The rats were administered with HES40/,HES130/,HES200/normal saline,Voluven or Haes. Their mean arterial blood pressure (MAP),left intraventricular systolic pressure (LVSP),the maximal change rate of left intraventricular pressure (?dp/dtmax) of hemorrhagic shock rat were observed. Meanwhile,the artery blood gas,the survival time and 24-hour survival rate were also observed. Results Similar hemodynamic parameters values were obtained in the rats treated with our HES and those with Voluven or Haes. HES130 and HES200 prolonged the survival time of shocked animals in comparison with HES40. Among the 3 types of HES,HES200 had the best effect,which is equivalent to Voluven and Haes. Conclusion HES of 3 molecular weights have beneficial effect on hemorrhagic shock,and HES200 exerts best.

Objective To investigate radio-sensitivity and expression of GRP78 protein in the survival subclones of nasopharyngeal carcinoma (NPC) C666-1 cells.Methods NPC C666-1 cells were first irradiated with X-ray at a large dose of 8Gy.Three survival subclones were selected and named as C666-1-R1, C666-1-R2, and C666-1-R3.The radio-sensitivity was analyzed for the radiated survival subclones and their parent control C666-1 cells with Methyl Thiazolyl Tetrazolium assay(MTT) and Trypan blue dye methods.The expression of GRP78 was analyzed for three survival subclones and control C666-1 with Western blot.Results After 6 Gy irradiation, the cell survival rate of three subclones was higher than that of the control cells, especially a significant difference for C666-1-R2 cells (P ＜ 0.05), which suggested a radioresistance in C666-1-R2 cells.Moreover, GRP78 expression in each subclone was significantly higher than that of parent C666-1 cells (P ＜ 0.05).Conclusions The irradiated-survival subclone C666-1-R2 was radio-resistant.GRP78 was overexpressed in the irradiated-survival subclones.GRP78 might be an ideal target for treatment of a nasopharyngeal carcinoma.

Acute promyelocytic leukemia (APL) was considered to be the most rapidly fatal leukemia,because of serve clinical manifestation,high rate of early death and the low cure rate.APL has achieved great success due to the application of ATRA and ATO.Although the complete remission rate is about 90％,the relapse rate has been reported to be as high as 15％-30％.So reducing the recurrence and improving long-time survival have become the focus of the study.Choosing the reasonable treatment after remission is very important.The post remission therapy usually include consolidation therapy and maintenance therapy,but the optimal strategy has been controversy.Therefore,this artical will review the literature of APL in consolidation therapy.

Objective To investigate the mechanical properties of carbon-fiber-reinforced polyether-ether-ketone (CF/PEEK)composite materials and to evaluate the biocompatibility and bioactivity of CF/PEEK after implanted into mandibula.Methods 27 adult Japanese white rabbits were randomly divided into experimental group (n=9) and control group (n=18),CF/PEEK was implanted into bilateral mandibula of the rabbits in experimental group, autologous bone was implanted into left mandibula of the rabbits in positive control group (n=9 )while the right sides were taken as blank control group (n=9 )without implants. The materials-bone interface of samples were collected to make the observation of gross,imaging and histology and to analyze the histological score after 8,12, and 16 weeks.Results All the animals and no infection had secondary fractures.Obviously callus formation was observed on the edge of the defect in both experimental group and positive control group in the imaging observation, while the rabbits in blank control group had no obvious change.Compared with 8 weeks after operation, the score evaluation of local cellular immune response showed significant decreasing in 12 weeks after operation(P<0.01), the data was the minimum in 16 weeks(P<0.05).At the same time,the score evaluation of local cellular immune response in three groups showed no significant difference (P> 0.05).Trabecular bone and osteoblasts could be observed in the bone defect of both experimental group and positive control group after 16 weeks,and blank control group was filled with fibrous connective tissue.The osteogenesis rates in experimental group and positive control group were increased with the prolongation of time, and they were better than that in blank control group (P<0.01).Conclusion CF/PEEK material has good mechanical property,biocompatibility and bioactivity;and it has light immune response after implantation.

Five influencing factors of the polymerization process of glutaraldehyde with hemoglobin were studied in cluding the approach of feeding glutaraldehyde, hemoglobin concentration, the molar ratio of glutaraldehyde and hemoglobin, reaction time and temperature, in order to reduce the average molecular weight and to improve the effective polymerization ratio. The results showed that the optimal process reduced the average molecular weight of hemoglobin based oxygen carriers (HBOCs) from (350.20 +/- 35.45)kD to (158.60 +/- 8.70)kD and improved the effective polymerization ratio from 53.27% +/- 4.95% to 69.50% +/- 3.70%. When the experiments expanded 30 folds, the results of the effective polymerization ratio and the average molecular weight mentioned above could be achieved.
Female ; Glutaral ; chemistry ; Hemoglobins ; chemistry ; Humans ; Molecular Weight ; Oxygen ; chemistry ; Placenta ; Polymerization ; Pregnancy

Objective To investigate the anti-inflammatory effect of C1q/ tumor necrosis factor (TNF)-related protein 9 (CTRP9) in RAW264.7 mouse macrophage cells treated with oxidized low density lipoprotein (oxLDL),and to explore its mechanism.Methods RAW264.7 mouse macrophage cells were divided into three groups:the control group,the oxLDL group (treated with oxLDl) and the gCTRP9-oxLDL group (pretreated with recombinant globular domain of CTRP9 and stimulated by oxLDL).Foam cells were detected by oil red O staining.Western blot was used to detect the expressions of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1).In addition,the expression levels of NF-κB p65 in cytoplasm and nucleus proteins extraction were both determined.Results The relative levels of MCP-1 and NF-κB were increased in the oxLDL group as compared with the control group (1.66±0.09 vs.1.03±0.10,0.52±0.11 vs.1.03±0.06,both P＜0.05).The expression levels of TNF-α and MCP-1 were decreased in gCTRP9+oxLDL group as compared with the oxLDL group (both P＜0.05).The expression level of NF κB p65 in nucleus 2 and 8 h after treatment was lower in the gCTRP9+oxLDL group than in the oxLDL group (1.03±0.06 vs.0.17±0.10,0.31±0.03,both P＜0.05).Conclusions oxLDL may induce the expressions of inflammatory cytokines of TNF α and MCP-1 in macrophage ceils.gCTRP9 pretreatment could reduce the oxLDL-induced pro inflammatory effect and nuclear factor κB translocation may be involved in this process,which suggests that gCTRP9 may play a protective role in anti inflammatory and anti-atherosclerosis.

Objective To assess the long-term effects of pacing in patients with hypertrophic obstructive eardiomyopathy(HOCM),and explore the most specific echocardiographic indexes.MethodsA total of 37 consecutive HOCM patients implanted dual-chamber pacemakers were enrolled and followed up.Thirty-seven cases were followed up for 1 year,26 cases were followed up for 2 years,and 10 cases were followed up for 3 years.After 1,2 and 3 years pacemaker implantation,pacing frequency,pacing threshold,impedance,atrioventricular delay and cumulative percent atrial and ventricular pacing were respectively tested,and left atrial dimension (LAD),left ventricular end-diastolic dimension (LVEDd),left ventricular posterior wall thickness (LVPW),interventricular septum thickness (IVS),left ventricular outflow tract diameter(LVOTd),left ventricular outflow tract pressure gradient (LVOTPG),left ventricular ejection fraction(LVEF),pulmonary artery systolic pressure (PASP) were measured and mitral valve systolic anterior motion(SAM) was observed.Pacing parameters and echocardiography indexes were dynamically compared before and after pacemaker implantation.ResultsPacing frequency was adjusted 60～70 bpm,atrioventricular delay was adjusted 90～ 180 ms,in order to achieve more than 95％ ventricular pacing,pacing threshold,pacing impedance were normal.The difference of various pacing parameters were no statistically significant within 3 years ( P ＞ 0.05).Compared with before pacing,after 1,2 and 3 years pacemaker implantation,IVS and LVOTPG declined significantly (P ＜ 0.01 ),LVOTd widened significantly ( P ＜0.01),SAM phenomenon improved obviously ( P ＜0.01 ),but the difference of LAD,LVEDd,LVPW,LVEF,PASP were no statistically significant ( P ＞ 0.05 ).Conclusions The heart structure reconstruction of patients with HOCM can been chronically improved by dual-chamber pacing treatment.IVS,LVOTd and LVOTPG can be used as the sensitive and specific indexes to evaluate pacing treatment.

Objective To investigate the serum and placental expressions of asymmetric dimethylarginine (ADMA) and nitric oxide(NO) in fetal growth restriction (FGR),and explore the biological role and mechanisms of ADMA in FGR.Methods Fifty patients with FGR (FGR group)and 50 normal term pregnant women (control group) were detected for the levels of ADMA in maternal sera and placentas with enzyme linked immunosorbent assay (ELISA).The level of NO in maternal sera was analyzed with nitrate reductase method,and the placental tissue sections were analyzed with pathological morphologly.Results For FGR group,the main pathological changes were growth retardation of villi,increased syncytiotrophoblast nodules,and the lack terminal villi;and the incidence rate of pathological change of placental tissue was significantly higher than that in control group [64.0％ (32/50) vs 12.0％ (6/50),x2 =7.90,P ＜ 0.01].For the placental pathological change group,the concentrations of ADMA in the placentas and sera were significantly higher than the normal group [placenta ADMA:(2.21 ± 0.72) μmol/L vs (1.69 ± 0.77) μmol/L,t =3.33,P ＜ 0.01;serum ADMA:(2.01 ± 0.70) μmoL/L vs (1.18 ± 0.54) μmol/L,t =6.66,P ＜0.01].The expression of ADMA was up-regulated in maternal sera and placentas from FGR group compared to normal pregnancy [placenta ADMA (2.24 ± 0.81) μmol/L vs (1.53 ± 0.59) μmol/L,t =5.00,P ＜0.01;serum ADMA (1.89 ±0.75) μmol/L vs (1.10 ±0.43) μ mol/L,t =6.45,P ＜ 0.O1].The NO was extremely lower expressed in maternal sera with FGR than normal pregnancy [(39.59 ± 9.15) μmol/L vs (58.02 ± 15.45) μmol/L t =-7.26,P ＜ 0.01)].For FGR group,a significant negative correlation was observed between ADMA and NO expressions in sera (r =-0.693,P ＜ 0.01).Conelusions ADMA was associated with the occurrence and development of the FGR,and its mechanism maybe inhibits NO synthesis to result in placental malperfusion.