Objective To discuss repairing effects of articular cartilage defects by nitric oxide synthase inhibitor (S-methylisothiourea, SMT), and explore the role of nitric oxide in cartilage repair. Methods Full-thickness defects of cartilage were created in the intercondylar trochlear groove of femur of thirty-six adult New Zealand white rabbits, and were divided into three groups. Twenty-four defects were untreated as the control, twenty-four were filled with fibrin glue and impregnated with rhBMP as rhBMP group, the rest twenty-four were filled with fibrin glue and impregnated with rhBMP, and hypodermic injection with SMT as SMT group. The animals were sacrified at sixteen weeks postoperatively, and the gross appearance of the defect was estimated. The repair tissue was examined histologically and was evaluated according to the grading scale of histology. The amount of released NO and the activities of nitric oxide synthase (NOS) were examined by chemical colorimetry. The distribution of type-Ⅰ,Ⅱcollagen were examined by Sirius-Red. The proteoglycan synthesis was assessed by incorporation of radio-labelled sodium sulphate Na35SO42-. RT-PCR examined the expression of iNOSmRNA and MMP9mRNA. Results The filled extent of the defect in SMT group and rhBMP group had no significant difference from the control group, and the marginal integration, cellular morphology, architecture within the defect and subchondral plate repair were better than the untreated defects (P

Objective To study the effect of nitric oxide synthase inhibitors S methylisothiorurea (SMT) on cartilage metabolism after intraarticular injection of interleukin 1? (IL 1?) and lipopolysaccharides (LPS) in rabbits.Methods The experiments were performed in three groups:normal group,control group and SMT group.The effects of SMT on IL 1? and LPS induced iNOS mRNA expression ,NO production and NOS activity in synovium,synovial fluid and cartilage were detected after 8 h.Proteoglycan synthesis was measured by ex vivo incorporation of Na 2 35 SO 4 into cartilage after 48 h.Results IL 1? and LPS induced iNOS mRNA expression and increased NO release;SMT could reduce NO release and inhibit iNOS mRNA expression in synovium,synovial fluid and cartilage,and partly restore proteoglycan synthesis of cartilage.Conclusion iNOS inhibitor SMT can protect IL 1? and LPS induced cartilage damage in high concentration.

Objective To investigate the effects of nitric-oxide synthase inhibitor on matrix metalloproteinases (MMPs) expression in osteoarthritis (OA) cartilage by Luminex analysis,and to explore the mechanism of nitric-oxide synthase inhibitor on modification of the metabolism of OA cartilage.Methods Fifteen specimens of articular cartilage taken from the patients with OA were cultured and divided in two groups.The control group was those with no intervention.L-NIL group was co-cultured with NOS inhibitor L-NIL.After 72 h cultivation,the release of NO and the activity of NOS on OA cartilage were measured by Griess reaction and spectrophotometric methods.MMPs (MMP-1,MMP-2,MMP-3,MMP-9,MMP-13) expression was measured by Luminex analysis.Comparisons between groups were performed with paired sampies t test.Results After cultured for 72 h,spectrophotometric analysis showed high concentration of NO release[(216±47) μmol/L ] and high level of active NOS [(5.7±1.3)U/ml]in supernatants of the control,1 mmol/L concentration L-NIL could evidently reduce NO release [(55±20)μmol/L,P<0.01] and NOS activity [(1.7±0.7)U/ml,P<0.01 ].Luminex analysis demonstrated high MMP-1,MMP-2,MMP-3,MMP-9,MMP-13 expression in cartilages of the control group [respectively for (10.8±5.4)ng/ml,(9.2±3.3) ng/ml,[11.6±4.2 )ng/ml,(1.27±1.07)ng/ml,(3.6±1.3)ng/ml] and 1 mmol/L concentration L-NIL could evidently inhibit MMP-1,MMP-2,MMP-3,MMP-9,MMP-13 expression [respectively for (3.6±1.8)ng/ml,(2.3±1.2)ng/ml,(3.6±1.4)ng/ml,(0.65±0.21)ng/ml,(1.8+0.5)ng/ml,P<0.05 ].Conclusion Luminex analvsis has shown that NOS inhibitor can reduce NO release and NOS activity and modify metabolism of articular cartilage by inhibiting the over-expression of MMPs.

Objective To explore the relationship of serum level of Cystatin C and suPAR with tumor infiltration, metastasis, and treatment of patients with malignant tumor. Methods: The serum levels of Cystatin C was detected by particle enhanced nephelometic immunoassay (PENIA) by 7600-010 full-automatic biochemical analyzer made in Japan. The level of suPAR was detected by ELISA. The serum levels of Cystatin C and suPARof 82 normal adults and 172 patients with malignant tumor were measured and compared. Results: The serum level of Cystatin C and suPAR in patients with malignant tumor was significantly increased compared with that of normal adults (P＜0.01 and P＜0.01). The level of Cystatin C and suPAR in terminally ill patients or patients with metastasis was significantly higher than that in the control group. The levels of the two indices in postoperative patients were lower than those in preoperative patients. No significant difference was found in the levels of the two indicies before chemotherapy or radiotherapy and after therapy. Conclusion: The serum levels of Cystatin C and suPARin patients with malignant tumor are correlated with tumor invasion, metastasis and surgical intervention. Detection of Cystatin C and suPAR levels in patients with malignant tumor is valuable for disease monitoring and treatment evaluation.

OBJECTIVE: To explore the pathogenesis of two fetuses from one family affected with Joubert syndrome (JS). METHODS: Whole exome sequencing was employed to screen potential mutations in both fetuses. Suspected mutations were verified by Sanger sequencing. Impact of intronic mutations on DNA transcription was validated by cDNA analysis. RESULTS: Two novel TCTN1 mutations, c.342-8A>G and c.1494+1G>A, were identified in exons 2 and 12, respectively.cDNA analysis confirmed the pathogenic nature of both mutations with interference of normal splicing resulting in production of truncated proteins. CONCLUSION The genetic etiology of the family affected with JS has been identified.Above findings have enriched the mutation spectrum of TCTN1gene and facilitated understanding of the genotype-phenotype correlation of JS.
Abnormalities, Multiple ; diagnosis ; genetics ; Cerebellum ; abnormalities ; Eye Abnormalities ; diagnosis ; genetics ; Humans ; Kidney Diseases, Cystic ; diagnosis ; genetics ; Membrane Proteins ; genetics ; Mutation ; Pedigree ; Retina ; abnormalities ; Whole Exome Sequencing