Relapse is the reinstatement of drug-seeking and drug-taking behaviors following a period of abstinence.It is one of the main characteristics of drug addiction and is also the major problem requiring immediate action for the treatment of drug addiction.In this review,in order to offer new ideas to eventually treat drug addiction,efforts are made to describe the establishment of two animal models of relapse-the drug self-administration (SA) and extinctionreinstatement procedure,and the drug-conditioned place preference(CPP) and extinction-reactivation procedure.Then attention is given to assess the criterion validity of the animal models of relapse and to explore the neurobiological mechanisms involved in relapse.

Recent discoveries about the effects of drugs of abuse on the brain and the mechanisms of their addictions, and new actions of available medications are offering many opportunities for the discovery and development of novel medications to treat addictive disorders.This article reviews the current medications that have shown promising results for treating opioid, cocaine, methamphetamine, cannabis, alcohol and nicotine addictions.

Objective　To study the effect of glucagon-like peptide 2 (GLP-2) on mitogen-activated protein kinase (MAPK) activity in small intestinal epithelia in mice after radiation injury and its relation with the change of small intestinal epithelial proliferation. Methods　Mice were given a single dose of 8 Gy of total body 60Co gamma irradiation and then divided into GLP-2 and control groups. The activity of MAPK and proliferation rate in small intestinal epithelia were measured. Results　The activity of MAPK in small intestinal epithelia was higher in GLP-2-treated mice than in irradiated mice, and the proliferation rate in small intestinal epithelia significantly increased in GLP-2-treated mice. These two indices were of significantly positive correlated. Conclusion　GLP-2 can promote small intestinal epithelial proliferation in irradiated mice, and this may be related to activation of MAPK in small intestinal epithelia.

Objective　To investigate the effects of glucagon-like peptide 2 (GLP-2) on recovery of small intestinal epithelia from radiation injury in mice. Methods　Mice received a single 8 Gy dose of total body irradiation from 60Co gamma ray followed by treatment with GLP-2 or vehicle. DNA and protein content in small intestinal mucosa were measured, and small intestine was processed for histological examination with light microscope and scanning electron microscope. Results　Small intestinal mucosal DNA and protein content, villus height, and villus number significantly decreased in irradiated mice, partial villus tips were ulcerated. GLP-2 administration caused increase in DNA and protein content, villus height, and villus number as compared with irradiated control group. Meanwhile, the villus tips were lack of ulceration. Conclusion　GLP-2 can promote recovery of small intestinal epithelia from radiation injury in mice.

[Objective] To evaluate the efficacy and safety of drainage blood autotransfusion after total knee or hip arthroplasty.[Methods]Drainage blood in the first 6 hours postoperation was collected and reinfused using the ContavacTM CBCⅡ system in 30 patients taken total knee or hip arthroplasty.The efficacy was evaluated basing on the amount of the allogenic transfusion,the decreasing of the hemoglobin level and the morphology of the red blood cells in the drainage blood.The safety was evaluated basing on whether the patients had autotransfusion complications including fever,hemolytic reaction,coagulation disorders,pulmonary embolism and systemic infection.[Results]The volumes of total blood drainage,autotransfusion and allogenic transfusion were(946?433)ml,(622?313)ml and(233?348)ml,respectively.The average hemoglobin level of drainage blood was 99.67g/L and no apparente haemolysis happened.However,the hemoglobin level significantly decreased after operation in the peripheral blood.Only one rheumatoid arthritis patient had an abnormal fever during autotransfusion process,no other complication was observed.[Conclusion]Drainage blood in the first 6 hours postoperation is valid blood content.Drainage blood autotransfusion is an effective and safe way to slow down the hemoglobin reduction and reduce allogenic blood transfusion in patients being treated with total knee or hip arthroplasty.

OBJECTIVE:To investigate the effect of total saponins of Man medicine Thladiantha dubia root(TSTR)on the ex-pressions of CD3+,CD4+and CD8+ in spleen tissue of rats with type Ⅱ collagen-induced arthritis (CIA),and explore its mecha-nism in the treatment of rheumatoid arthritis(RA). METHODS:8 rats were taken as normal control group(NC group),the others 72 rats were injected mixture of bovine type Ⅱ collagen and Freund's complete adjuvant in tail and back to induce CIA model. The 50 modeled rats were randomly divided into model group(MC group),tripterygium polyglycoside(TG)group(12 mg/kg,posi-tive control),TSTR low-dose,medium-dose,high-dose groups (20,40,80 mg/kg),10 in each group. Rats in medicine groups were intragastrically administrated for 35 d,once a day;rats in NC group and MC group were intragastrically administrated equal volume of distilled water. Ankle swelling degree of rats was determined,arthritis indexes were calculated,HE staining was used to observe the lesions in synovial tissue,and immunohistochemistry was used to detect the expressions of CD3+,CD4+,CD8+ in spleen tissue of rats. RESULTS:After 35 d of administration,ankle swelling degree,arthritis indexes,CD4+ expression in spleen tissue,and CD4+/CD8+ ratio in MC group were significantly higher than NC group (P<0.05 or P<0.01),expressions of CD3+, CD8+were significantly lower than NC group(P<0.05);and there was congestion and massive inflammatory cell infiltration in sy-novial tissue. The ankle swelling degree,arthritis indexes,expression of CD4+ in spleen tissue,and CD4+/CD8+ ratio in administra-tion groups were significantly lower than MC group(P<0.05);the expressions of CD3+,CD8+ in spleen tissue in administration groups were significantly higher than MC group (P<0.05);TG group,TSTR medium-dose and high-dose groups showed mild congestion and a small amount of inflammatory cell infiltration in synovial tissue of rats,and TSTR low-dose group showed no ob-vious congestion or inflammatory cell infiltration. CONCLUSIONS:Up-regulating the expressions of CD3+,CD8+ and down-regu-lating the expression of CD4+ may be one of the mechanisms of TSTR in the treatment of RA;and with best efficacy when the TSTR dose of 20 mg/kg.

Objective To elucidate whether down-regulation of homo sapiens eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) expression induces apoptosis in pancreatic cancer cells and its possible mechanisms. Methods Two siRNAs targeting human EEF1A2 were synthesized and the siRNA/liposome complexes were transfected into the pancreatic cancer cell line BxPC-3. RTPCR and Western blot were used to analyze the change of EEF1A2 expression and the apoptosis rate of BxPC-3 cells was studied using Annexin-V/PI assay. To identify the mechanisms involved, the apoptosis associated proteins such as caspase-3, caspase-8, caspase-9, PARP, cytochrome C and Bid were detected by Western blotting. Results Both EEF1A2-targeting siRNAs reduced the EEF1A2expression, and the No. 2 siRNA inhibited EEF1A2 expression to less than 25 % in mRNA and protein levels. Down-regulation of EEF1A2 expression in BxPC-3 cells enhanced cell apoptosis (15.28% ±3.65%) at a greater level than negative siRNA-expressing cells (10. 11% ± 3. 05%) or mock cells (9.41 % ±4.14 %). Furthermore, reduction of EEF1A2 activated the pro-caspase-8, pro-caspase-3,pro-caspase-9,PARP and Bid to their active forms, and increased the expression of cytochrome C.Conclusions These data suggest that EEF1A2 down-regulation could significantly induce apoptosis of pancreatic cancer cell line BxPC-3, which is likely mediated by the death receptor and mitochondrial apoptotic pathways.

BACKGROUND: Pterygium is associated with local chronic inflammatory responses and chronic stimulation from external factors such as. sunlight and wind dust. Presently. there are various theories concerning the onset mechanism of pterygium, but these theories are not generally accepted.OBJECTIVE: To investigate histopathological chractefistics of pterygium and analyze the mulfipotent stem cell effects on the onset of pterygium DESIGN: An open experiment.SETTING: Zhongshan Ophthalmic Center of Sun Yat-sen University.MATERIALS: Experiments were performed at the State Key Laboratory of Ophthalmology, Sun Yat-sen University from September 2006 to January 2007. 218 pterygial paraffin specimens following clinical and pathological diagnosis were obtained from Pathology Lab of Zhongshan Ophthalmic Center, Sun Yat-sea University.METHODS: Pterygial specimens harvested from clinical operations received morphology, immunohistochemistry and immunofluorescence under a confocal microscope.MAIN OUTCOME MEASURES: Morphology of ptorygium and expressions of CD34, vimentin (VIM), smooth muscle acfin (SMA), S- 100 in pterygium.RESULTS: Changes in morphology: Fibroplasia and neovascularization were the main changes in pterygium. Fibroplasia wasdiverse in different regions, and two main phenomena were observed. First, the tissues arranged tightly like the scleral fiber.Secondly, in some loose region, some of spindle-shape, polygonal, asteroid fibroblast-like cells, arranging loosely, could be seen only. No apparent collagen fibers were identified between them. Immunohistochemistry were positive for CD34 in some region where the fibroblast actively proliferated, whereas fibrocytes in mature fibrous tissue were negatively stained.Immunohistochemisu'y was positive for VIM in a large fraction of fibrocytes, vascular endothelial cells, vessel wall and perithelial cells. SMA staining was positive in basophilous small blocks, spindle or irregular cell cluster. Of the 218 cases, 56 cases had smooth muscle. S-100 staining demonstrated that neurofilament protein and adipocytes were positive. Of the 218 cases, 44 cases had adipose tissue, Immunofluorescence showed that proliferative active cells were positive and stained green under a confocal microscope.CONCLUSION: The fibrous tissues in pterygium originate from mesenchymal stem cells, and can differentiate into smooth muscle and adipose tissue.

The paper is to report the pharmacokinetics of sulfamethoxazole in healthy Han volunteers living at plain (PH) and native Han and Tibetan healthy volunteers living at high altitude (HNH and HNT). After healthy volunteers were administrated orally cotrimoxazole tablets, plasma concentration of sulfamethoxazole and metabolite N4-acetylsulfamethoxazole was determined by RP-HPLC, and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters. The main pharmacokinetic parameters t(1/2) of sulfamethoxazole in PH, HNH and HNT were, respectively, 9.30 +/- 1.11, 10.99 +/- 1.23 and 10.44 +/- 1.05 h; tmax were 1.4 +/- 0.3, 2.0 +/- 1.1 and 1.8 +/- 0.4 h; Cmax were 94.42 +/- 15.26, 89.33 +/- 7.67 and 87.43 +/- 11.61 micro x mL(-1); AUC(0-t) were 1202.5 +/- 238.3, 1 434.7 +/- 193.9 and 1302.8 +/- 103.0 microg x h x mL(-1); AUC(0-infinity) were 1240.7 +/- 255.3, 1511.5 +/- 211.9 and 1363.9 +/- 116.5 microg x h x mL(-1); CL were 1.01 +/- 0.22, 0.81 +/- 0.12 and 0.89 +/- 0.08 L x h(-1) x kg(-1); V were 13.27 +/- 1.73, 12.81 +/- 2.15 and 13.28 +/- 1.20 L x kg(-1). Sulfamethoxazole pharmacokinetic parameters of HNH and HNT were significantly different from that of PH. The t(1/2) was significantly higher and the CL was significantly lower in HNH and HNT than that in PH, and the AUC(0-infinity) was significantly lower in HNT compared with HNH. This study found significant changes in the disposition of sulfamethoxazole under the special environment of high altitude hypoxia. This finding may provide some references for clinical rational application of sulfamethoxazole in HNH and HNT.