OBJECTIVETo research the mechanism of dopamine (DA) controlled memory in mice.

METHODSMice received i.p. injection of scopolamine (0.3 mg/kg, SCOP 0.3, and 3.0mg/kg, SCOP 3.0, respectively, n = 10) and saline (NS, n = 10) for 60 days in experiment 1. Memory of mice was detected by dark avoidance behavior in the 53" d and the 60"' d. Animals were sacrificed after the memory test; brain tissues were processed for Fos-ir and TH-ir by immunohistochemistry. Mice were divided into four groups according results of expri-ment 1, they received i.p. injection of apomorphine (0.1 mg/kg, APO 0.1, 0.5 mg/kg, APO 0.5, and 2.0 mg/kg, APO2.0 respectively, n = 10).

RESULTSMemory was inhibited in mice injected scopolamine 3.0 mg/kg. Latency was significantly less than in NS group, only 1/ 4 that of NS group (P > 0.05). The number of mistake of SCOP 3.0 group increased about four times than that of NS group (P > 0.05). But there was no difference of latency and number of mistake between SCOP 0.3 and NS group in expriment 1. Scopolamine-induced memory deficit was associated with decreased cellular activation, indicated by Fos immunoreactive (ir) staining, in NAcc CA1 and CA3 (P < 0.05), and also associated with decreases in the number of cells labeled for tyrosine hydroxylase (TH-ir), the rate limiting enzyme for dopamine conversion (P < 0.01) and the number of cells co-labeled for TH-ir/Fos-ir (P <0.01) in the ventral tegmental area(VTA), apomorphine lessened scopolamine-induced memory deficit in experiment 2. The number of cells co-labeled for TH-ir/Fos-ir (P <, 0.05) was increased in VTA after apomorphine treatment.

CONCLUSIONApomorphine lessened scopolamine-induced memory deficit in mice by increasing DA activities in VTA.

Animals ; Apomorphine ; pharmacology ; Disease Models, Animal ; Dopamine Agonists ; pharmacology ; Male ; Memory Disorders ; chemically induced ; drug therapy ; Mice ; Scopolamine Hydrobromide ; toxicity

Animals ; Arcuate Nucleus of Hypothalamus ; drug effects ; metabolism ; Body Temperature Regulation ; Cyclic AMP ; metabolism ; Dinoprostone ; metabolism ; Eugenol ; pharmacology ; Fever ; metabolism ; Preoptic Area ; drug effects ; metabolism ; Rabbits

BACKGROUND:Conventional therapies for lumbar spondylolisthesis can result in trauma,bleeding and low back pain.With the vigorous development of spinal biomechanics and novel spinal fixation systems,we have more understanding on the reduction and fusion after spondylolisthesis.OBJECTIVE:To observe the clinical effects of transforaminal lumbar interbody fusionvia the quadrant system on lumbar spondylolisthesis and related biomechanical changes.METHODS:A retrospective analysis was done in 23 patients with lumbar spondylolisthesis undergoing transforaminal lumbar interbody fusionviathe quadrant system admitted from June 2012 to September 2013.Oswestry disability index and visual analog scale score were detected at 3 months and 1 year after treatment,as wel as fusion conditions and internal fixation with or without loosening or breakage.RESULTS AND CONCLUSION:Al patients were successfuly treated,with no cerebrospinal fluid leakage and nerve injury.Incisions were healed wel in al cases except one case suffered from incision infection that wascontroled after 10 days of antibiotic treatment.Al the patients were folowed up.The Oswestry disability indexes and visual analog scale scores were significantly improved at 3 months and 1 year after treatment (P ＜0.05),but there was no difference in these two scores at 3 months and 1 year after treatment (P＞0.05).The improvement rates of Oswestry disability index and visual analog scale score were (65.3±14.8)％and (58.2±12.0)％,respectively.These findings indicate that the transforaminal lumbar interbody fusionvia the quadrant system is safe and effective to correct lumbar spondylolisthesis,maintains the biomechanical stability,improves patient's symptoms,reduces the incidence of low back pain and improves the quality of life.

A new dynamic in vitro intestinal absorption model for screening and evaluating lipid formulations was established by means of the characteristics of the intestinal digestion and absorption of the lipid formulations. This model was composed of two systems, including intestinal digestion and the intestinal tissue culture, which drew the evaluation method of intestinal absorption into the in vitro lipolysis model. The influence of several important model parameters such as Ca2+, D-glucose, K+ on the two systems of this model has been investigated. The results showed that increasing of Ca2+ concentration could be significantly conductive to intestinal digestion. The increasing of D-glucose concentration could stepped significantly down the decay of the intestinal activity. K+ was able to maintain intestinal activity, but the influence of different concentration levels on the decay of the intestinal activity was of no significant difference. Thus the model parameters were set up as follows: Ca2+ for 10 mmol x L(-1), D-glucose for 15 mmol x L(-1) and K+ for 5.5 mmol x L(-1). Type I lipid formulation was evaluated with this model, and there was a significant correlation between the absorption curve in vitro and absorption curve in vivo of rats (r = 0.995 6, P < 0.01). These results demonstrated that this model can be an attractive and great potential method for the screening, evaluating and predicting of the lipid formulations.

This paper report the development of a new dosage form - self-microemulsifying mouth dissolving films, which can improve the oral bioavailability of water insoluble drugs and have good compliance. A three factor, three-level Box-Behnken design was used for optimizing formulation, investigated the effect of amounts of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hypromellose on the weight, disintegration time, cumulative release of indomethacin after 2 min, microemulsified particle size and stretchability. Optimized self-microemulsifying mouth dissolving films could fast disintegrate in (17.09 +/- 0.72) s; obtain microemulsified particle size at (28.81 +/- 3.26) nm; and release in vitro at 2 min to (66.18 +/- 1.94)%. Self-microemulsifying mouth dissolving films with broad application prospects have good compliance, strong tensile and can be released rapidly in the mouth through fast self-microemulsifying.

Solid carriers had important effects on the properties of solid self-microemulsifying drug delivery systems (S-SMEDDS). In order to make the basis for further development of S-SMEDDS, the influences of silica on the absorption of S-SMEDDS were investigated. An in vitro lipolysis model was used to evaluate the influence of silica on self-microemulsifying drug delivery system digestion from intestinal tract. S-SMEDDS containing silica were prepared by extrusion/spheronization. The drug release and absorption were investigated. The results showed that lipolysis rate and drug concentration in aqueous phase after intestinal lipolysis both increased by adding silica, which was benefit to drug absorption. And silica was not benefit to absorption for slowing drug release. Consistently, there was no significant influence of silica on intestinal absorption. This study implied that the influences of silica on lipolysis rate and drug release were both amount dependent and it is suggested that silica could be used as the solid carrier but the proportion needs to be optimized.

The distribution fate and solubilization behavior of indomethacin through the intestinal tract were investigated with in vitro lipolysis model, by comparing the Capmul MCM and Labrafil M 1944 CS type I lipid formulations. The results showed that the more favorable solubilization was in the aqueous digestion phase from each lipid formulations for indomethacin. The lipolysis rate and extent were decided with chemical constitution of the lipid excipients, which meant that less indomethacin was transferred from the long chain polar oil lipid solution into the aqueous digestion phase. Increasing the concentration of indomethacin in the lipid formualitons from a solution to a suspension led to a linear increase in the concentration of indomethacin attained in the aqueous digestion phase from lipid formulations. This study also implied that adverse effects of the lipolysis rate and extent on drug absorption were could be taken into consideration when screening lipid formulations. Lipid suspensions likely had better enhancement of drug absorption. Last, this study demonstrated that a potential basis for optimizing and assessing type I lipid formulations and also researching in vivo-in vitro correlations of lipid formulations were provided by an in vitro lipolysis model.

Objective To assess the association between interleukin-10-1082 (IL-10-1082) gene polymorphisms and susceptibility of gastric cancer in the Chinese population.Methods Cochrane systematic evaluation was adopted for the analysis.Articles published in Medline,Embase,Cochrane library,CBM,CJFD and CSJD from 1966 to 2012 were retrieved.Case control studies on the correlation between the 1L-10-1082 polymorphism and gastric cancer in Chinese population were collected.Gastric cancer patients were in the gastric cancer group,and healthy individuals were in the control group.Two researchers extracted data and evaluated the quality of literatures independently.Meta analysis was performed to detect whether there were differences between the gastric cancer group and the control group about the distribution of genotypes of IL-10-1082 gene (GG,AA,AG,AA,alleles G and A).The heterogeneity was analyzed using the Q test or I2 test.Fixed effect model or random effect model was adopted,and the results of the meta analysis were presented with odds ratio (OR) and 95％ confidence interval (95％ CI).Results Thirteen literatures including 5252 patients were included in the analysis.There were 2077 patients in the gastric cancer group and 3175 patients in the control group.The results of meta analysis showed that population with the genotypes GG and AG have higher risk of having gastric cancer when compared with population with the genotype AA (OR =1.76,95％ CI 1.33-2.33 ; OR =2.08,95％ CI 1.62-2.66,P ＜0.05).Population with the allele G have higher risk of having gastric cancer when compared with population with allele A (OR =1.67,95％ CI 1.31-2.13,P ＜ 0.05).Conclusion The genotypes GG,AG and the allele G of IL-10-1082 gcne of the Chincse population are significantly associated with the increased risk of gastric cancer.

OBJECTIVETo clone and construct a eukaryotic expression vector of human bone morphogenetic protein (BMP) 2 and histidine in vitro and synthesize chitosan (CS)/pIRES2-EGFP-hBMP2-His nanoparticles.

METHODSpMD18T-hBMP2-His was digested by EcoR I and BamH I to obtain the hBMP2-His gene, which was inserted into pIRES2-EGFP to form pIRES2-EGFP-hBMP2-His. Afterward, CS, which exhibited five different molecular weights and deacetylation degrees, was complexed with pIRES2-EGFP-hBMP2-His to form CS/pIRES2-EGFP-hBMP2-His nanoparticles; in this procedure, a desolvent method was used at different N/P ratios (amino in CS to phospho in plasmid DNA). The gene-encapsulating ability of CS was evaluated by agarose gel electrophoresis and fluorescence spectrophotometry; size, distribution, and potential were analyzed using a ZetaPALS analyzer. The shape of the nanoparticles was observed under an atomic force microscope.

RESULTS1) pIRES2-EGFP-hBMP2-His was constructed after the cloned hBMP2-His gene was confirmed by sequencing. 2) CS/pIRES2-EGFP-hBMP2-His nanoparticles were synthesized and pIRES2-EGFP-hBMP2-His was packaged by CS. 3) CS/pIRES2-EGFP-hBMP2-His nanoparticles were globular with an average size of 111.7 nm to 3,214.2 nm and an average zeta-potential of 4.93 mV to 16.79 mV.

CONCLUSIONCS/pIRES2-EGFP-hBMP2-His nanospheres are successfully synthesized.

Bone Morphogenetic Protein 2 ; Chitosan ; Genetic Vectors ; Green Fluorescent Proteins ; Histidine ; Humans ; Nanoparticles ; Plasmids

Objective To investigate the difference of CCAAT/enhancer-binding protein α (C/EBP-α) gene induced apoptosis between hepatocytes and hepatic stellate cells (HSC) in mice with liver fibrosis.Methods Sixty BALB/c mice were evenly divided into normal group,model group,treatment group,blank control group and negative control group,12 mice in each group.Except the mice of normal control group,the mice of other groups were treated with intraperitoneal injection of CCl4 to establish liver fibrosis mice model.Mice of treatment group,blank control group and negative control group were administrated with C/EBP-α carried adenovirus (Ad-C/EBP-α),phosphate buffered solution and empty vector of adenovirus (Ad-EGFP) respectively through tail vein for the first week.The expression of C/EBP-α and α-smooth muscle actin (α-SMA) was detected by immunohistochemistry method.Sinusoidal endothelial structure of peri-portal regions and far from portal regions was observed by transmission electron microscope (TEM).Terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was applied to detect apoptosis of cells in liver tissue.The degree of liver fibrosis in mice was determined with sirius red staining and hydroxyproline content measurement.Single factor variance analysis was performed for comparison among multiple groups,and t test was used for comparison between two groups.Results C/EBP-α was expressed in nucleus of hepatocyte in normal control group mice.The expression decreased in model group,blank control group and negative control group.However,the expression of C/EBP-α of treatment group increased,and mainly expressed in cells located in perisinusoidal and perivascular.Hepatic sinusoids was distorted,blood vessel wall thickened.Hepatocyte degeneration and lots of lipid droplets was found in model group,blank control group and negative control group.The thicken degree of endothelial layer of blood vessel of treatment group was lower than that of model group.The percentage of sirius red positive cells of normal group,model group,treatment group,blank control group and negative control group was (0.10±0.03)％,(5.81±0.32)％,(2.32±0.45)％,(6.34± 0.81)％ and (6.10± 0.92)％,respectively; content of hydroxyproline was (0.07±0.00) μg/mg,(0.69 ± 0.10) μg/mg,(0.19±0.06) μg/mg,(0.56±0.03) μg/mg and (0.64±0.08) μg/mg,respectively; the percentage of α-SMA positive cells was (0.50 ±0.03)％,(5.30 ± 0.52)％,(2.15 ± 0.29)％,(5.53 ± 0.43) ％ and (5.42 ± 0.25) ％,respectively; the number of TUNEL positive cells was (0.25 ± 0.08),(0.15±0.02),(7.10±1.53),(0.13±0.03) and (0.18±0.07),respectively.The differences between the groups were statistically significant (F=113.74,148.29,292.43 and 140.25,all P＜0.05).The difference between normal group and model group,between model group and treatment group,between treatment group and blank control group,between treatment group and negative control group were statistically significant (tarirus positive cell =-52.54,-16.20,-10.60 and-7.99,thydroxyproline content =-168.00,11.53,11.07 and 12.54,ta SMA pusitive cells-24.77,-13.82,15.94 and 18.37,tTUNEL positive cells =3.26,-11.91,-11.95 and-11.88,all P＜ 0.05),there was no statistically significant difference between model group and blank control group,between model group and negative control group (both P＞0.05).TUNEL positive cells mainly located in perisinusoidal and perivascular of liver in mice,which was consistent with the distribution of α-SMA-positive cells.Conclusion C/EBP-α could effectively relieve CCl4 induced liver fibrosis in mice mainly through inducing HSC apoptosis,however no apoptosis effect on hepatocytes.