Objective An investigation was conducted to assess the effects and mechanism of celecoxib [a selective cyclooxygenase(COX) 2 inhibitor] on a rat colitis model induced by trinitrobenzene sulfonic acid (TNBS). Methods The rats were divided into four groups. Group 1 and group 2 were experimental groups. Group 3 and group 4 were control groups. Colitis was induced by intracolonic administration of TNBS (25 mg/ml) in a vehicle of 50% ethanol (0.25 ml) in rats of experiment groups. Three hours before induction of colitis ,the rats were beginning and continuing to treat orally with celecoxib (1.25 mg/kg, group 1) and distilled water (1 ml/0.3 kg, group 2) twice per day for 7 days , respectively. The rats in group 4 were treated orally with celecoxib (1.25 mg/kg) twice per day for 7 days. Group 3 served as healthy control. All rats that survived until the end of the experiment (7 d) were killed and the severity of damage were assessed. The prostaglandin E2 (PGE2) concentrations of colonic mucosa were tested by radioimmunoassay. Results The colonic damage scores were 11.15?3.3 in group 1 and 8.50?2.82 in group 2. Both were significantly higher than that of group 3 (0.62?0.09)( P

AIM: To find whether lipoxin A_4 (LXA_4) inhibits cell proliferation induced by TNF-? in rat mesangial cells, and to explore the molecular mechanisms of signal pathways of LXA_4 actions. METHODS: Cultured rat mesangial cells were growth-arrested and exposed to TNF-? with or without preincubation with LXA_4. Proliferation of mesangial cells was measured by MTT methods. Activities of STAT_3 were analyzed by electrophoretic mobility shift assay. Expression of cyclin E mRNA was assessed by RT-PCR. Cyclin E proteins were determined by Western blotting analysis. RESULTS: TNF-?-induced proliferation and increased mRNA and protein expression of cyclin E in mesangial cells were inhibited by LXA_4 in a dose-dependant manner. TNF-?-stimulation of the STAT_3-binding activities in mesangial cells was down-regulated by lipoxin A_4. CONCLUSION: Inhibitory effect of LXA_4 on TNF-?-induced mesangial cell proliferation is mediated by Jak_1/STAT_3 signal pathway.

AIM: To examine whether lipoxin A_4 (LXA_4) induces apoptosis of rat renal interstitial fibroblasts and explore the mechanisms. METHODS: Rat renal interstitial fibroblasts (NRK-49F cells) were incubated in RPMI-1640 medium supplemented with 5% fetal calf serum and exposed to LXA_4 at the concentration of 10 nmol/L, 100 nmol/L or 1 ?mol/L for 24 hours. Prior to experiment, some cells were transfected with calpain 10 antisense oligodeoxynucleotide. Apoptosis of cells was recognized by double staining using fluorescent dye acridine orange and ethidium bromide, observed under laser scanning confocal microscopy and counted by flow cytometry following propidium iodide and annexin staining. Activity of caspase-3 was measured by colorimetric assay. The expression of calpain 10 mRNA was determined by RT-PCR. RESULTS: LXA_4 at the concentration of 100 nmol/L or 1 ?mol/L induced 9.83% or 33.82% apoptosis of cells, respectively. Treatment of cells with LXA_4 up-regulated the expression of calpain 10 mRNA and increased the activity of caspase-3. The transfection of the cells with calpain 10 antisense oligodeoxynucleotide inhibited the LXA_4-induced apoptosis, activity of caspase-3 and expression of calpain 10. CONCLUSION: LXA_4 at high concentration induceds apoptosis in rat renal interstitial fibroblasts via up-regulating of calpain 10 mRNA expression.

OBJECTIVE To study whether immunosuppressant(IS,cyclophosphamide,CPA) have the function of prevention and treatment of congenitalautoimmune sensorineural hearing loss or not.METHODS The female guinea pigs were immunized by crude conspecific inner ear antigens(CIEAgs),and took orally IS or not at the same time during gestation.Then the pregnant guinea pig's and their offspring's hearing function were measured and inner ear histopathologic changes were observed.Some of offspring borne by the female guinea pigs which immunized with CIEAgs and not treated with IS showed hearing loss and were treated by IS,and their hearing functions were measured and inner ear histopathologic changes were observed with same techniques.RESULTS After immunizing with CIEAgs,some of female guinea pigs which immunized with CIEAgs and not treated with IS showed different degrees of hearing loss(the thresholds of acoustic nerve compound active potential and cochlear microphonic potentials elevated) and immune inflammations in inner ear tissues.All females guinea pigs in experimental group which immunized with CIEAgs and treated with IS at same time,and their offspring have no any hearing loss and inner ear histopathologic changes.After IS therapy,the hearing function improved(mainly at the low-frequency region) in some offspring guinea pigs,which borne by the female guinea pigs which immunized with CIEAgs and not treated with IS.CONCLUSION IS could effectively prevent offspring's congenital sensorineural hearing loss induced by their mother's special antibodies against inner ear tissues antigens.IS showed effective result for treatment of congenitalautoimmune sensorineural hearing loss,but the curative effect was limited.

Objective To examine whether lipoxin A4(LXA4) has an antagonistic effect on interleukin (IL)-1?-induced synthesis of IL-6 in glomerular mesangial cells, and to explore its mechanism. Methods Cultured glomerular mesangial cells (GMCs) of rat were treated with IL-1?, with or without preincubation with LXA4. Protein secretion of IL-6 in supernatants was examined analyzed by enzyme-linked immunosorbent assay (ELISA). Expression of IL-6 mRNA was determined by RT-PCR. The expression of Src homology 2 (SH2) containing protein-tyrosine phosphatase 2 (SHP-2) was assessed by immunoblotting. Activities of DNA-binding of nuclear factor-kappa B (NF-?B) were measured by electrophoretic mobility shift assay (EMSA). Results The secretion of protein and expression of mRNA of IL-6 in GMCs stimulated by IL-1? were inhibited by LXA4 in a dose-dependent manner. LXA4 reduced the phosphorylation of SHP-2 and activities of NF-?B. Pretreatmnet of GMCs with NF-?B inhibitor pyrrolidine dithio-carbamate (PDTC) blocked both the secretion of IL-6 protein and activation of NF-?B induced by IL-13- Conclusion LXA4 antagonists IL-1?-induced synthesis of IL-6 in GMCs through the pathway of SHP-2/NF-?B signal transduction.

Objective To examine whether lipoxin A4(LXA4) induces apoptosis of rat renal interstitial fibroblasts and explore the mechanism concerned.Methods Rat renal interstitial fibroblasts (NRK 49F cells)were incubated in RPMI 1640 medium supplemented with 5%fetal calf serum and exposed to LXA4 at the concentration of 10 nmol/L, 100 nmol/L or 1 ?mol/L for 24 hours. Prior to experiment,some NRK 49F cells were transfected with Smac antisense oligodeoxynucleotide. Apoptosis of NRK 49F cells was recognized by double staining using fluorescent dye acridine orange and ethidium bromide,and observed under laser scanning confocal microscopy and counted by flow cytometry following propidium iodide and annexin staining. Activity of caspase 3 was measured by colorimetric assay. The expression of Smac was determined by Western blotting analysis.Results LXA4 at the concentration of 100 nmol/L or 1 ?mol/L induced apoptosis of 9 83%or 33 82%of NRK 49F cells respectively, and reduced the cells of S and G2～M phase and increased the cells of G0～G1 phase in a dose dependent manner. Treatment of NRK 49F cells with LXA4 up regulated the expression of Smac protein and increased the activity of caspase 3. The transfection with Smac antisense oligodeoxynucleotide inhibited the LXA4 induced apoptosis and expression of Smac in NRK 49F cells. Conclusion LXA4 at high concentration can induce apoptosis of rat renal interstitial fibroblasts via the up regulation of Smac expression.

Objective To develop a new methodology of prenatal sonography scoring to assess and dignose clubfoot.Methods Thirty-one fetuses suspected clubfoot(50 foots) and 62 normal fetuses(124 foots) were scanned with both 2D and 3D sonography,and were divided into normal feet group and clubfeet group.Our scoring system was made according to the Pirani-scoring for children,while considering the morphology of mid-foot and hind-foot of infants.The doctors would give final diagnosis for all fetuses after delivery or induced labor,and analyse the correlations among the abnormal signs,sonographic score and the clinical outcomes.Results The curve lat border,the medial crease,the empty heel and the post crease can be observed in the 3D reconstruction images.These four abnormal signs had close correlations with the clinical results.Conclusions The new prenatal clubfeet scoring system by 3D sonography is a promising methodology with clinical values.

The purpose of this study is to explore the feasibility of wheat germ agglutinin (WGA) modified liposome as a vehicle for ophthalmic administration. Liposome loaded with 5-carboxyfluorescein (FAM) was prepared by lipid film hydration method. WGA was thiolated and then conjugated to the surface of the liposome via polyethylene glycol linker to constitute the WGA-modified and FAM-loaded liposome (WGA-LS/FAM). The amount of thiol groups on each WGA molecule was determined, and the bioactivity of WGA was estimated after it was modified to the surface of liposome. The physical and chemical features of the WGA-modified liposome were characterized and the ocular bioadhesive performance was evaluated in rats. The result showed that each thiolated WGA molecule was conjugated with 1.32 thiol groups. WGA-LS/FAM had a mean size of (97.40 +/- 1.39) nm, with a polydispersity index of 0.23 +/- 0.01. The entrapment efficacy of FAM was about (2.95 +/- 0.21)%, and only 4% of FAM leaked out of the liposome in 24 h. Erythrocyte agglutination test indicated that after modification WGA preserved the binding activity to glycoprotein. The in vivo ocular elimination of WGA-LS/FAM fitted first-order kinetics, and the elimination rate was significantly slower than that of the unmodified liposome, demonstrating WGA-modified liposome is bioadhesive and suitable for ophthalmic administration.
Absorption, Physicochemical ; Adhesiveness ; Administration, Ophthalmic ; Animals ; Drug Carriers ; Eye ; metabolism ; Fluoresceins ; chemistry ; Liposomes ; administration & dosage ; chemistry ; pharmacokinetics ; Male ; Particle Size ; Polyethylene Glycols ; chemistry ; Rats ; Rats, Sprague-Dawley ; Wheat Germ Agglutinins ; administration & dosage ; chemistry ; pharmacokinetics

Objective To research the significanec of genes bel-2 and bax in chondrocyte apoptosis in experimental osteoarthritis in rabbits.Method Twelve New Zealand rabbits divided into two groups at random:model group and control group.Model group with osteoarthritis was duplicated by immobilizing with gypsum at extension position in right hind limb of rabbits.Rabbits of model group were executed after 6 weeks and chondrocytes were taken.Positive expression rate of bcl-2 and bax mRNA was measured by immunohisto- chemistry and Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL).Results Positive expression rate of mRNA in bel-2 and bax of model group was obviously more than control group(P＜0.05).According to immunohistochemistry,and grey grade of positive expression of protein in bcl-2 and bax of chondrocytes in model group was lower and positive expression rate was gigher compared with control group (P＜0.05,P＜0.01).bcl-2 and bax of model group were lower than control group(P＜0.05).Conclusion Genes bcl-2 and bax participate and thus accelerate chondrocyte apoptosis of osteoarthritis together.

Objective:To investigate the effects of 125I radioactive particle implantation in the treatment of maxillofacial malignancy. Methods:43 patients with maxillofacial malignancy were treated with 125I radioactive particle implantation.The procedure was carried out according to the treatment planning system(TPS),with the particles spaced uniformly at 1 cm intervals and with the activity of 0.7 m Ciby 41 particles per case on a verage.All patients were followed up for 6-60 months.Results:The whole treatment procedurewas successful,and no particle displaced.The follow-up rate was 93.02% and treatment effective rate(CR+PR) was 90.70%.Norecur-rence was foundinall target areas.The mortality due to tumor was 9.30%and total survival rate was 74.43%.The cumulative survival rate of the patients in 0.5,1,2,3 and 5 years was 93.0%,85.7%,79.3,69.8% and 56.9% respectively.Survival periodon aver-age was 36.06-50.04 months,with the median of 43.05 months.The longest tumor-free survival period was 60 months.Radiation in-jury rate was 20.93% and only level 1 radiation injury was observedinall the cases.Facial nerve dys function was found in 2 cases and recovered after treatment.Conclusion:Treatment of maxillofacial malignancy by implantation of 125I particles is convenient and mini-mally invasive.The treatment canincrease survival rate of the patients and guaran tee the oropharynxes' function.