A transgenic mouse containing 70 copies (ND4) of the transgene encoding DM20, a myelin proteolipid protein, appeared clinically normal up to 3 months of age. By 8-10 months, it showed tremors, unsteady gait, and died shortly thereafter. We concluded that the clinical symptoms correlated with demyelination based on the following criteria: 1) at 10 months of age only 17% of the amount of myelin obtained from normal mice was isolated from the ND4 mice; 2) astrogliosis, a prominent feature of demyelinating disease was minimal at 3 months of age but prominent by 10 months; 3) at the electron microscopic level disrupted myelin was seen at 8 months of age in the ND4 mice and ingested myelin debris was found in astrocytes; 4) lymphocytic infiltration in association with endothelial cells was observed routinely in the ND4 mice; 5) sections through optic nerves showed denuded and thinly myelinated axons in the 8 month old ND4 mice. Although the mechanism by which demyelination takes place is not fully understood, measurements of the amounts of PLP suggest it is down-regulated by the large amount of DM20. Since DM20 is a major proteolipid in the young but a minor one in the adult, the persistence of high levels in the adult results in improperly assembled myelin which is prone to disruption. Therefore demyelination in the ND4 mouse appears to result from the persistence of immature myelin into the adult.

Poly(epsilon-caprolactone) (PCL) microspheres containing taxol were prepared by the solvent evaporation method and tested for angiogenesis inhibition using the chick chorioallantoic membrane (CAM) model. Very high encapsulation efficiencies (95%) for taxol in PCL microspheres were obtained. In vitro release studies showed about 25% of the loaded drug was released in 6 weeks from microspheres containing 5% taxol. Studies with the CAM showed that taxol released from the microspheres induced vascular regression and inhibited angiogenesis.

Background Two strains of guinea pig develop spontaneous osteoarthritis of the knee. Although the disease evolves at different rates in the two strains, it is not known whether these differences are reflected in the structure of the cartilage and cancellous bone. Questions/purposes We determined whether the threedimensional structure of the tibial-plateau cartilage and femoral cancellous bone differed between the two strains. Methods Six Dunkin-Hartley and six GOHI/SPF guinea pigs were evaluated. The animals were sacrificed at 11 months of age. The 24 proximal tibias were used for a stereologic histomorphometric analysis of the tibial-plateau cartilage. The 24 femurs were used for a site-specific, three-dimensional quantitative analysis of the cancellous bone by micro-CT. Results Compared to the GOHI/SPF guinea pigs, the tibial-plateau cartilage of the Dunkin-Hartley strain had a larger lesion volume (3.8% versus 1.5%) and a thicker uncalcified cartilage layer (0.042 versus 0.035 mm), but a thinner calcified cartilage zone (0.008 versus 0.01 mm) and a thinner subchondral cortical bone plate (0.035 versus 0.039 mm). The femoral cancellous bone in the DunkinHartley strain had a lower bone mineral density (477 versus 509 mg/cm 3 ). However, the trabeculae were thicker (3.91 versus 3.53 pixels) and farther apart (7.8 versus 5.6 pixels). The osteoarthritic changes in the cartilage were topographically mirrored in the subchondral bone. They were most severe on the medial side of the joint, particularly in the anterior region. Conclusions Spontaneous osteoarthritis in the guinea pig is associated with site-specific changes in the articular cartilage layer, which are topographically mirrored in the underlying subchondral bone. Clinical Relevance Three-dimensional structural information not revealed by two-dimensional radiography may help characterize the stages of osteoarthritis.

Summary Using vanadyl sulphate, sodium orthovanadate or bis(maltolato)oxovanadium (BMOV), Cruz TF, Morgan A, Min W (1995, Mol Cell Biochem 153: 161-166) have recently demonstrated the antineoplastic effects of vanadium in mice. In this study, the antineoplastic effects of BMOV against human tumour cell lines was confirmed, and this effect was shown to depend on the prolonged exposure of the cells to the drug. We have investigated a polymeric drug delivery system for the sustained delivery of BMOV as an antineoplastic agent in mice. The objective was to design and evaluate an injectable polymer-BMOV paste that would act as a drug implant for the slow but sustained release of BMOV in the mice. In vitro studies showed that the biodegradable polymer poly (Ghlr epsilon E-caprolactone) (PCL) released BMOV in a sustained manner with rates of drug release increasing with increased loading of the drug in the polymer. In vivo studies showed that PCL-BMOV paste implants produced a concentration-dependent inhibition of MDAY-D2 tumour growth via systemic drug delivery. Further in vivo studies showed that 5% BMOV-loaded PCL (containing 20% methoxypolyethylene glycol) was effective in preventing tumour regrowth of resected RIF tumour masses in mice when the PCL-BMOV paste was applied to the resected site for localized drug delivery. The results confirm the potential of vanadium as an antineoplastic agent and show that the injectable PCL-BMOV formulation releases a chemotheraputic dose of vanadium for the systemic treatment of whole tumours as well as the localized treatment of resected RIF tumours.

Poly(epsilon-caprolactone) (PCL) microspheres containing taxol were prepared by the solvent evaporation method and tested for angiogenesis inhibition using the chick chorioallantoic membrane (CAM) model. Very high encapsulation efficiencies (95%) for taxol in PCL microspheres were obtained. In vitro release studies showed about 25% of the loaded drug was released in 6 weeks from microspheres containing 5% taxol. Studies with the CAM showed that taxol released from the microspheres induced vascular regression and inhibited angiogenesis.

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