[Effect of sustained release of recombinant rat insulin-like growth factor-1 from poly (lactide-CO-glycolide ) microspheres on bone formation in the peri-implant areas in Goto-Kakizaki rats with type 2 diabetes].

OBJECTIVE: To evaluate the effect of sustained release of recombinant rat insulin-like growth factor-1(rrIGF-1) from poly (lactide-CO-glycolide) (PLGA) microspheres on bone formation in the peri-implant areas in Goto-Kakizaki rats with type 2 diabetes. METHODS: Type 2 diabetes models were successfully established in 20 male Goto-Kakizaki rats, which were then randomly divided into treatment group (sustained release of rrIGF-1 from PLGA microspheres were loaded on the peri-implant areas, n=10) and diabetic group (loaded with isodose placebo from PLGA microspheres, n=10). Another ten male SD rats served as control group (did not sustain any loading). Titanium implants were inserted into the tibias of 30 diabetic and normal animals. Four, 5, and 8 weeks after implantation, local blood samples around the implants were obtained for the determination of serum osteocalcin (OCN), serum bone specific alkaline phosphatase (B-ALP), and serum procollagen I carboxyterminal propeptide (PICP) with enzyme linked immunosorbent assays. RESULTS: Four weeks after implantation, OCN, B-ALP, and PICP were significantly lower in both treatment group and diabetic group than in control group(both P<0.05). Five weeks after implantation, serum OCN and B-ALP levels of the diabetic group were significantly lower than those of the other two groups (all P<0.05). Serum PICP levels of both diabetic group and treatment group were significantly lower than that of control group(both P<0.05). The OCN level in the trealment group was significantly higher in the post-operative 5th week than in the post-operative 4th week, while the PICP levels in the diabetic group were significantly lower than those in the treatment group and control group in the post-operative 8th week (both P<0.05). CONCLUSION: Sustained release of rrIGF-1 from PLGA microspheres loaded on the local peri-implant areas can promote bone formation in the peri-implant areas in Goto-Kakizaki rats with type 2 diabetes.

[Expressions of MMP-2 and COX-2 mRNA in bladder transitional cell carcinoma and their correlation].

OBJECTIVE: To determine the levels of MMP-2 and COX-2 mRNA in bladder transitional cell carcinoma tissues and explore their relationship. METHODS: We enrolled in this study 42 patients with bladder transitional cell carcinoma, including Ta-T1 (n = 18), T2-T4 (n = 24), G1 (n = 12), G2 (n = 19), G3 (n = 11), metastasis (n =26) and non-metastasis (n = 16). Another 5 cases of normal bladder tissues were taken as controls, and the levels of MMP-2 and COX-2 mRNA were detected by RT-PCR. RESULTS: The relative expressions of COX-2 mRNA were 1.038 +/- 0. 484 in Ta-T1, 1.489 +/- 0.584 in T2-T4, 0.920 +/- 0.442 in G1, 1.338 +/- 0.584 in G2 and 1.632 +/- 0.515 in G3, all significantly higher than that of the controls (0.460 +/- 0.224, P < 0.05). And the corresponding relative levels of MMP-2 mRNA were 1.107 +/- 0.384, 1.604 +/- 0.425, 0.971 +/- 0.370, 1.445 +/- 0.378 and 1.755 +/- 0.387, also significantly higher than that of the latter group (0.423 +/- 0.227, P < 0.05). The COX-2 and MMP-2 mRNA levels in the tumor tissues with and without metastasis were 1.591 +/- 0.455 vs 0.815 +/- 0.430 and 1.676 +/- 0.339 vs 0.927 +/- 0.228, (P < 0.01), respectively, with a positive correlation between the mRNA level of COX-2 and that of MMP-2 (r = 0. 703, P < 0.01). CONCLUSION: MMP-2 and COX-2 mRNA are highly expressed in bladder transitional cell carcinoma tissues and their expressions are positively correlated with the degree of malignancy. MMP-2 and COX-2 might play a synergetic role in the pathogenesis and progression of bladder transitional cell carcinoma.

[Apoptosis and expression of caspase-3 protein in germ cells of varicocele rats].

OBJECTIVE: To explore the relationship between the expression of caspase-3 in testicular germ cells of rats with experimental left varicocele (ELV) and apoptosis of germ cells. METHODS: Twenty-four male SD rats were randomly divided into three groups with eight animals each: sham-operation group (SOG), 30-day post-operation group (PG1) and 60-day psot-operation group (PG2). ELV model was established by the partial ligation of the left renal vein. To detect apoptosis of germ cells and expression of caspase-3, TUNEL assay and immunohistochemistry (SABC) were used respectively. RESULTS: The number of caspase-3 positive germ cells per tubular cross section in left and right testes of rats in SOG, PG1, PG2 were 0.1175 +/- 0.0129, 0.2463 +/- 0.0421, 0.2938 +/- 0.0511 and 0.1650 +/- 0.0192, 0.2538 +/- 0.0219, 0.2775 +/- 0.0343, respectively. Compared with SOG, the expression of caspase-3 in bilateral testes of rats in PG1 and PG2 were increased, and the differences were statistically significant(P = 0.0115 and P = 0.0144). CONCLUSION: Expression of caspase-3 protein increased in germ cells of rats with ELV, which may be one of the molecular mechanisms related to excessive testicular germ cell apoptosis.

Sustained release of insulin-like growth factor-1 from poly(lactide-co-glycolide) microspheres improves osseointegration of dental implants in type 2 diabetic rats.

Dental implantation is an effective and predictable treatment modality for replacing missing teeth and repairing maxillofacial defects. However, implants in patients with type 2 diabetes mellitus are likely to have a high failure rate and poor initial osseointegration. In the current study, we established an effective drug delivery system designed to improve osseointegration of dental implants in an animal model of type 2 diabetes. Twenty type 2 diabetic rats were divided into two groups: a group receiving recombinant rat Insulin-like Growth Factor 1 (rrIGF-1) Microsphere Therapy (MST) (10 rats) and a control group (10 rats). The rrIGF-1 was encapsulated into poly(lactide-co-glycolide) (PLGA) microspheres to produce a sustained-release effect around titanium (Ti) dental implants in the rrIGF-1 MST group. Scanning electron microscopy, confocal laser scanning microscopy, and cumulative-release studies were conducted to verify the release effect of the microspheres as well as rrIGF-1 bioactivity. Five rats from each group were sacrificed at weeks 4 and 8 post surgery, and a histological analysis was performed on the rats from both groups. Compared to the control group, rats that received rrIGF-1 by PLGA microsphere treatment were observed to have a higher bone-implant contact percentage around the Ti implants at week 4 or week 8 post surgery (P<0.05). This result clearly indicates that sustained release of rrIGF-1 through encapsulation by PLGA microspheres positively affects osseointegration of dental implants in type 2 diabetic rats.