Amyloid beta-Peptides ; analysis ; Animals ; Frontal Lobe ; drug effects ; physiology ; Hippocampus ; drug effects ; physiology ; Learning ; drug effects ; Memory ; drug effects ; Rats ; Rats, Wistar ; Sodium Azide ; pharmacology ; Space Perception

Objective To examine the role of noggin on the expression of nestin and glial fibrillary acidic protein (GFAP) in the hippocampus of adult rats. Methods Antisense oligodeoxynucleotide (ASODN) technique was employed to inhibit endogenous noggin expression and immunohistochemistry was used to detect the expressions of Nestin and GFAP in the hippocampus of adult rats. Results It was observed that the number of nestin and GFAP immunoreactive cells in the dentate gyrus (DG) of hippocampus was increased in adult rats treated with antisense oligodeoxynucleotide to noggin. Moreover, the number of GFAP immunoreactive cells was increased in the subventricular zone of the rats treated with antisense oligodeoxynucleotide to noggin. Conclusion The results in the present study indicates that noggin may play a role in the differentiation of neural stem cells in the adult hippocampus, and it promotes the differentiation of neural stem cells in the DG to neuronal fate.

OBJECTIVETo explore the effect of peimine on excision repair cross-complementation 1 (ERCC1) mRNA and lung resistant protein (LRP) expressions in A549/cisplatin (DDP) multidrug resistance (MDR) cell line.

METHODSLung cancer A549/DDP cells were cultured in vitro.Cells at logarithmic growth phase were divided into 4 groups, i.e., the blank control group, the DDP group, the ligustrazine group (DDP+ligustrazine), the peimine group (DDP + peimine). After 48-h drug action, ERCC1 mRNA expression was detected by RT-PCR and LRP expression detected by cell immunofluorescence.

RESULTSThere was no statistical difference in expression levels of ERCC1 mRNA and LRP between the DDP group and the blank control group (P > 0.05). Compared with the DDP group, expression levels of ERCC1 mRNA and LRP obviously decreased in the ligustrazine group and the peimine group (P < 0.05). They were obviously lower in the peimine group than in the ligustrazine group (P < 0.05).

CONCLUSIONSPeimine could reverse MDR of A549/DDP cell line. Its mechanism might be associated with down-regulating ERCC1 mRNA and LRP expression levels.

Cell Line, Tumor ; Cevanes ; pharmacology ; Cisplatin ; DNA-Binding Proteins ; genetics ; Down-Regulation ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; drug effects ; Endonucleases ; genetics ; Humans ; Low Density Lipoprotein Receptor-Related Protein-1 ; genetics ; Lung Neoplasms ; RNA, Messenger ; metabolism

Histocytochemistry ; methods ; Humans ; Pathology, Clinical ; methods ; Specimen Handling ; methods ; Staining and Labeling ; methods

OBJECTIVETo study the protective effect of hyperoxia solution on acute lung injury caused by phosgene poisoning by observing the changes of PaO2 and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity in serum and Glutathione (GSH/GSSG) contents in lung tissues.

METHODSThe rabbits were divided into normal control group, hyperoxia solution (H0) and balance salt (BS) groups. Group HO and Group BS inhaled phosgene and the former was given intravenously hyperoxia solution (which was replaced by balance salt solution in Group BS). The content of MDA and the activity of SOD in serum were observed at different time points, the amount of GSH and GSSG in lung tissue were also measured.

RESULTS(1) The serum MDA contents increased and PaO2, SOD activity decreased significantly in Group HO and Group BS along with time increasing as compared with control group. The contents of GSH in lung tissue decreased in two groups compared with that in control group, however the contents of GSSG ascended instead. (2) At 3 and 8 h of the experiment, PaO2 of Group HO [(9.91 +/- 0.49), (9.15 +/- 0.46) mm Hg respectively] were significantly higher than those of Group BS [(9.03 +/- 0.76), (8.11 +/- 0.57) mm Hg respectively] (P < 0.01). The contents of MDA of Group HO (3.66 +/- 0.35), (5.31 +/- 0.15) micromol/L respectively] were lower than those of Group BS [(4.32 +/- 0.26), (7.4 +/- 0.33) micromol/L respectively] (P < 0.01). SOD activity in Group HO [(237.37 +/- 29.96), (208.10 +/- 18.80) NU/ml respectively] were higher than those of Group BS [(195.02 +/- 21.44), (144.87 +/- 21.26) NU/ml respectively] (P < 0.05 or P < 0.01). The content of GSSG lung tissue in Group HO (423.67 +/- 38.21) micromol/L were lower than those of Group BS (523.85 +/- 43.14) mol/L (P < 0.01). There were no significant differences in the content of GSH in lung tissues between Group HO and group BS.

CONCLUSIONHyperoxia solution can reduce acute lung injury of rabbits following phosgene poisoning.

Acute Lung Injury ; etiology ; metabolism ; pathology ; Animals ; Glutathione Peroxidase ; metabolism ; Hyperoxia ; Lung ; drug effects ; metabolism ; pathology ; Malondialdehyde ; analysis ; Oxygen ; administration & dosage ; pharmacology ; Phosgene ; poisoning ; Rabbits ; Superoxide Dismutase ; metabolism

In the present study, a risperidone loaded microsphere/sucrose acetate isobutyrate (SAIB) in situ forming complex depot was designed to reduce the burst release of SAIB in situ forming depot and to continuously release risperidone for a long-term period without lagime. The model drug risperidone (Ris) was first encapsulated into microspheres and then the Ris-microspheres were embedded into SAIB depot to reduce the amount of dissolved drug in the depot. The effects of different types of microsphere matrix, including chitosan and poly(lactide-coglycolide) (PLGA), matrix/Ris ratios in microspheres and morphology of microspheres on the drug release behavior of complex depot were investigated. In comparison with the Ris-loaded SAIB depot (Ris-SAIB), the complex depot containing chitosan microspheres (in which chitosan/Ris = 1 : 1, w/w) (Ris-Cm-SAIB) decreased the burst release from 12.16% to 5.80%. However, increased drug release rate after 4 days was observed in Ris-Cm-SAIB, which was caused by the high penetration of the medium to Ris-Cm-SAIB due to the hydrophilie of chitosan. By encapsulation of risperidone in PLGA microspheres, most drugs can be prevented from dissolving in the depot and meanwhile the hydrophobic PLGA can reduce the media penetration effect on the depot. The complex depot containing PLGA microspheres (in which PLGA/ drug=4 : 2, w/w) (Ris-Pm-SAIB) showed a significant effectiveness on reducing the burst release both in vitro and in vivo whereby only 0.64% drug was released on the first day in vitro and a low AUC0-4d value [(105.2± 24.4) ng.mL-1.d] was detected over the first 4 days in vivo. In addition, drug release from Ris-Pm-SAIB can be modified by varying the morphology of microspheres. The porous PLGA microspheres could be prepared by adding medium chain triglyceride (MCT) in the organic phase which served as pore agents during the preparation of PLGA microspheres. The complex depot containing porous PLGA microspheres (which were prepared by co-encapsulation of 20% MCT) (Ris-PPm-SAIB) exhibited a slightly increased AUC0-4d of (194.6±15.8) ng.mL-1d and high plasma concentration levels from 4 to 78 days [Cs(4-78d)=(7.8±1.2) ng.mL-1]. The plasma concentration on 78 day C78d was (9.0 2.5) ng.mL-1 which was higher than that of Ris-Pm-SAIB [C78d= (1.6 ± 0.6) ng.mL-1]. In comparison with Ris-Pm-SAIB, the AUC4-78d of Ris-PPm-SAIB increased from (379.0±114.3) ng.mL-1.d to (465.0 ±149.2) ng.mL-1.d, indicating sufficient drug release from the Ris-PPm-SAIB. These results demonstrate that the risperidone loaded porous PLGA microsphere/SAIB in situ forming complex depot could not only efficiently reduce the burst release of SAIB depot both in vitro and in vivo, but also release the drug sufficiently in vivo, and be capable to continuously release the drug for 78 days.
Chitosan ; Drug Carriers ; Lactic Acid ; Microspheres ; Polyglycolic Acid ; Risperidone ; chemistry ; Sucrose ; analogs & derivatives ; Technology, Pharmaceutical

Objective To investigate whether a novel long-acting tumor necrotic factor (TNF) antagonist (soluble TNF receptor:IgG Fc [sTNFR:IgG-Fc]) can protect hepatocyte damage against liver failure caused by drugs in immunity-induced cirrhotic rats.Methods Wistar rats were repeatedly sensitized by human serum albumin (HSA) emulsified in complete freud adjuvant.The blood was collected at day 10 after the final sensitization.If anti-albumin antibody was positive,the rats were intravenously injected with HSA twice a week.After six weeks,liver cirrhosis was induced by immunity.All the model rats were divided into three groups with 15 each.Liver failure was induced with D-galactosamine/ lipopolysaccharide (LPS) intraperitoneal injection in the rats with liver cirrhosis in model group.The rats in pretreatment group were intraperitoneally injected with long-acting soluble TNF receptor p55 18 h before D-galactosamine/LPS injection.The control group were injected with 0.9％ sodium chloride.General condition,survival rate,liver function and pathological changes were all examined.Serum levels of interleukin (IL)-6,IL-22 and intrahepatic level of IL-6 were detected by enzyme linked immunosorbent assay (ELISA).The activity of Caspase 3 in hepatocyte lysis solution was measured by spectrophotography.Real-time polymerase chain reaction (PCR) was used to detect mRNA expressions of proliferating cell nuclear antigen (PCNA),bcl-2,bax and IL-22 receptor.Data were analyzed by variance analysis among groups.Results Rats in model group were dispirited with poor response after 12 hours and only 3 survived,compared with soluble TNF receptor p55 pre-treated group rats,in which all survived (P=0.029 8) with flexible response.Serum alanine aminotransferase levels in these two groups were (6 533± 360) and (105 ± 7) U/L,respectively.Hepatic regenerative nodule developed massive or submassive necrosis with septal fibrosis in model group,whereas soluble TNF receptor p55 alleviated the inflammatory and necrosis reaction of hepatic tissue.Serum IL-6 levels in model group and pretreatment group were (842.0±12.9) and (91.9±1.6) pg/mL,respectively (F=380.30,P＜0.01).Intrahepatic levels of IL-6 in these two groups were (26.2±1.2) and (11.1±0.8) pg/mL,respectively (F=176.90,P＜0.01),and serum IL-22 levels were (167.0±27.8) and (988.0±109.6) pg/mL,respectively (F=37.91,P＜0.01).Hepatic Caspase-3 activity was reduced by almost 60％ by soluble TNF receptor p55 pretreatment (F=303.70,P＜0.01) and bax expression reduced by 22％ (F=108.80,P＜0.01),while bcl-2 and PCNA expressions were up-regulated by 3.6-folds and 23.0-folds,respectively (F=115.60,P＜0.01; F=594.20,P＜0.01).Conclusions Long acting soluble TNF receptor p55 could improve survival rate,liver function and reduce inflammatory reaction of rats with liver failure induced by drugs on the basis of liver cirrhosis caused by immunity,which indicates that this drug may process a potential therapeutic value.

AlM: To explore the different ages of congenital nasolacrimal duct obstruction in infants, take different treatment methods at different times.
METHODS:The 87 cases of 102 children were divided into three different age groups: the first group of 25d-3mo of age 21 cases 26 eyes; The second group >3mo-7mo 31 cases 36 eyes;The third group >7-24mo of age 35 cases 40 eyes. For the first group of infants, the implementation of the lacrimal sac nasolacrimal duct massage + eye drops; for the second group of infants, carry lacrimal pressure washing treatment; for the third group of infants, the implementation of the nasolacrimal duct probing treatment.
RESULTS: The first group of children through the nasolacrimal duct sac massage + drops tobramycin eye drops treatment unobstructed 12, the cure rate was 46. 2%;The second group of children through pressurized irrigation treatment lacrimal patency by 33, the cure rate was 91. 7%; The third group of children through the nasolacrimal duct probing unobstructed 36 treatment, the cure rate was 90. 0%. The second and third group were better than the first group (χ2=15. 71, P<0. 01;χ2=15. 27, P<0. 01);the treatment effect of the second and third groups was no significant difference (χ2=0. 02, P>0. 05).
CONCLUSlON:lnfants with congenital nasolacrimal duct obstruction should distinguish between ages, taking different treatments, in order to obtain a better therapeutic effect, and lacrimal pressure washing is the preferred way of treating infants with congenital nasolacrimal duct obstruction.

Objective To study the changes of phosphatidylcholine-specific phospholipase D (PC-PLD) enzyme activity of glomerular mesangial cells (GMCs) in high glucose and the effect of PLD on cytoskeleton. Methods Rats GMCs were cultured in high glucose(30 mmol/L) for 48 hours. PLD enzyme activity was measured by enzyme coupled colorimetry. PKC activity was measured by substrate phosphorylation, and fluorescence intensity of F-actin was observed by FITC-labeled antibody and laser scan cofocal microscopy (LSCM) . Results In high glucose, PLD and PKC activities were obviously elevated, but fluorescence intensity of F-actin was decreased and its cytoskeletal pattern was disassembly. After treatment with inhibtor of PLD, PKC activity was significantly decreased, and intensity and organization of F-actin were recovered. Conclusion Elevation of PLD activity induced by high glucose may influence the cytoskeleton and contraction of CMC through PKC pathway.

To investigate the feasibility to produce crocetin in tobacco plants.The coding region of zeaxanthin cleavage dioxygenase (CSzCD) gene from Crocus sativus L. was inserted into the downstream of the cauliflower mosaic virus (CaMV) 35S promoter of a binary vector pBI121, and integrated into the genome of Nicotiana tabacum L. Twenty-one transgenic lines were identified by genomic southern blotting analysis. Western blotting and HPLC analysis of the leaf extracts of transgenic tobacco showed that crocetin was produced in CSzCD gene-transformed plants, while no crocetin was found in the untransformed tobacco.