[Effects of Tongbi capsule on joint lesions in rabbits with rheumatoid arthritis].

The purpose of this experiment is to observe the effects of Tongbi capsule on joint lesions in rabbit with rheumatoid arthritis induced by ovalbumin and explore the mechanism in order to provide reference for clinical application of Tongbi capsule. Rheumatoid arthritis in rabbits was induced by subcutaneous injection of emulsions of ovalbumin and Freund's complete adjuvant and intra articular injection of ovalbumin. After successful modeling, 30 New Zealand rabbits with arthritis were randomly divided into model control group, the high, medium and low dose groups of Tongbi capsule (90, 45, 22.5 mg·kg⁻¹) and prednisone group (5 mg·kg⁻¹). Another six normal rabbits were used as normal control group. After 24 hours of modeling, the rabbits in Tongbi capsule groups received intragastric (i.g.) administrations of Tongbi capsule at 90, 45, 22.5 mg·kg⁻¹·d⁻¹, and the rabbits of prednisone group received i.g. administrations of prednisone at 5 mg·kg⁻¹·d⁻¹ for 2 weeks. The rabbits in normal and model groups received the same volume of distilled water at the same time. The swelling degree of rabbit knee joint and local skin temperature were observed daily. After two weeks of administration, pathological changes of rabbit knee joint were examined by magnetic resonance imaging (MRI); the morphological changes of articular cartilage and synovial membrane were observed by microscope; and the contents of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) in serum were detected by enzyme linked immunosorbent assay (ELISA).The results showed that 24 h after modeling, the knee joints of the rabbits were swollen, with red or dark redlocal skin, and fever, elevated local skin temperature and increased diameters of knee joints. Two weeks after modeling, the swelling of rabbit knee joints was obvious in model group; the joint cavities were filled with purulent fluid; joint synovial membranes were obviously thickened, and even joint cavities were fibrotic and cartilage surfaces showed slight defect; the surface of articular cartilage was obvious fibrosis; synovial epithelial cell proliferation was obvious and accompanied by extensive inflammatory cell infiltration; the levels of IL-1 and TNF-α were significantly higher as compared with those seen in model rabbits (P<0.05, P<0.01). After 1 and 2 weeks of administration, knee joint diameters and local skin temperatures were smaller or lower than thosein model group (P<0.05, P<0.01); The lesions of joint cartilage and synovial of all rabbits in each group were less than those in model group; IL-1 and TNF-α levels in serum were also lower than those in model group (P<0.05, P<0.01). The results reveal that high and medium doses of Tongbi capsule can suppress rheumatoid arthritis induced by ovalbumin in rabbits, reduce joint swelling, inhibit synovial epithelial and fiber hyperplasia and inflammatory cell infiltration, and alleviate articular cartilage damage. The mechanism may be associated with decreasing IL-1 and TNF-α levels in serum.

[Synthesis and animal imaging of 99mTc-hydrazinonicotinamide-folate as a new folate receptor-targeted tumor imaging agent].

OBJECTIVE: The synthesis, biodistribution, and animal imaging of 99mTc- hydrazinonicotinamide-folate (99mTc-HYNIC-Folate) were studied as a folate receptor-targeted tumor imaging agent. METHODS: HYNIC-Folate was synthesized by a muti-step reaction and radiolabeled with 99mTc using tricine and trisodium phenylphosphine-3, 3', 3"-trisulfonate (TPPTS) as coligands. The radiochemical purity and stability of 99mTc HYNIC-Folate was measured. The biodistributions of 99mTc-HYNIC-Folate in normal mice and tumor-bearing mice were detected. Whole-body gamma imaging was performed using an athymic mouse tumor xenograft model. RESULTS: The ligand HYNIC-Folate was successfully synthesized and characterized by hydrogen nuclear magnetic resonance (1HNMR) and mass spectrometry (MS). The radiochemical purity of 99mTc-HYNIC-Folate was 96% under optimal conditions. Data from gamma scintigraphy and the biodistribution in tumor-bearing mice showed that 99mTc-HYNIC-Folate predominantly accumulated in tumor, its uptake rate per gram tissue alpham was 5. 620+/- 0. 753. The uptakes of 99mTc-HYNIC-Folate in the other non-target tissues were very low, except it was high in the kidneys ( am was 41. 959 +/-6. 759) . CONCLUSION: 99mTc-HYNIC-Folate has the potential to be used as a noninvasive radiodiagnostic imaging agent for the detection of folate receptor-positive human cancers.

In-vitro cytotoxicity, in-vivo biodistribution and anti-tumour effect of PEGylated liposomal topotecan.

In attempt to increase the accumulation of topotecan in tumours and improve its anti-cancer activity, PEGylated liposome (H-PEG) containing topotecan was prepared. The in-vitro cytotoxicity, in-vivo biodistribution pattern and anti-tumour effect of H-PEG were studied systemically. Compared with free topotecan or conventional liposome (H-Lip), H-PEG improved the cytotoxic effect of topotecan against human ovarian carcinoma A2780 and human colon carcinoma HCT-8 cells. The IC50 value (concentration leading to 50% cell-killing) of H-PEG decreased 5 fold (P<0.01) and 9 fold (P<0.01) against A2780 and HCT-8 cells compared with H-Lip, respectively. The results of biodistribution studies in sarcoma S(180) tumour-bearing mice showed that liposomal encapsulation increased the concentration of total topotecan and the ratio of lactone form in plasma. H-PEG resulted in a 70-fold and 3.7-fold increase in AUC(0-->24 h) compared with free topotecan and H-Lip, respectively. Moreover, H-PEG increased the accumulation of topotecan in tumours and the relative tumour uptake ratio compared with free topotecan was 5.2, and higher than that of H-Lip. The anti-cancer effect studies in murine heptocarcinoma H(22) tumour-bearing mice showed that H-PEG improved the therapeutic efficiency of topotecan and decreased the toxicity of topotecan to a certain extent compared with H-Lip. These results indicated that PEG-modified liposome might be an efficient carrier of topotecan.