Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease.

This work examines the skeletal accumulation of fluorescently tagged zoledronate in an animal model of chronic kidney disease. The results show higher accumulation in 24-h post-dose animals with lower kidney function due to greater amounts of binding at individual surfaces. INTRODUCTION: Chronic kidney disease (CKD) patients suffer from increased rates of skeletal-related mortality from changes driven by biochemical abnormalities. Bisphosphonates are commonly used in reducing fracture risk in a variety of diseases, yet their use is not recommended in advanced stages of CKD. This study aimed to characterize the accumulation of a single dose of fluorescently tagged zoledronate (FAM-ZOL) in the setting of reduced kidney function. METHODS: At 25 weeks of age, FAM-ZOL was administered to normal and CKD rats. Twenty-four hours later, multiple bones were collected and assessed using bulk fluorescence imaging, two-photon imaging, and dynamic histomorphometry. RESULTS: CKD animals had significantly higher levels of FAM-ZOL accumulation in the proximal tibia, radius, and ulna, but not in lumbar vertebral body or mandible, based on multiple measurement modalities. Although a majority of trabecular bone surfaces were covered with FAM-ZOL in both normal and CKD animals, the latter had significantly higher levels of fluorescence per unit bone surface in the proximal tibia. CONCLUSIONS: These results provide new data regarding how reduced kidney function affects drug accumulation in rat bone.

In vitro progression of artificial white spot lesions sealed with an infiltrant resin.

This study assessed the ability of an infiltrant resin (Icon, DMG Chemisch-Pharmazeutische Fabrik GmbH, Hamburg, Germany) to prevent artificial lesion progression in vitro when used to impregnate white spot lesions and also assessed the effect of saliva contamination on resin infiltration. Enamel specimens (n=252) were prepared and covered with nail varnish, leaving a window of sound enamel. After demineralization (pH 5.0; four weeks), specimens were divided into six groups (n=42 per group): group 1, 2% fluoride gel (positive control); group 2, resin infiltrant; group 3, resin infiltrant + fluoride gel; group 4, no treatment (negative control); group 5, resin infiltrant application after saliva contamination; and group 6, resin infiltrant + fluoride gel after saliva contamination. Specimens from each group were cut perpendicular to the surface, and one-half of each specimen was exposed to a demineralizing solution for another four weeks. The other half was set aside as a record of initial lesion depth and was used later in the determination of lesion progression. Lesion progression and infiltrant penetration were measured using confocal laser scanning microscopy (CLSM) and transverse microradiography (TMR). For lesion depth, based on CLSM, groups 2 and 3 showed the least changes when submitted to demineralization challenge, followed by group 1, then groups 5 and 6, and finally group 4. There were no significant differences between groups 2 and 3 or groups 5 and 6 in their ability to inhibit further lesion progression (p<0.05). Based on TMR, groups 2 and 3 also showed the fewest changes when submitted to demineralization challenge, followed by group 5, then groups 1 and 6, and finally group 4. In terms of mineral loss as measured by TMR, all groups that contained fluoride (groups 1, 3, and 6) show less percentage change in mineral loss than the groups that did not contain fluoride (groups 2, 4, and 5). It can be concluded that infiltrant penetration into early enamel lesions inhibited further demineralization in vitro, especially in the presence of fluoride. Saliva contamination decreased the ability of the infiltrant to prevent further demineralization, but the presence of fluoride seemed to counteract this effect.

Effect of immunisation with cancer procoagulant on the growth of Walker 256 carcinosarcoma cells in rats.

The effect of preimmunisation with cancer procoagulant (CP) on the growth of Walker 256 carcinosarcoma cells in Wistar Lew/Han/IMP rats in vivo has been analysed. One group of rats was immunised with CP purified from human amnion-chorion membranes. The rest of the animals (control groups) were injected with 0.9% NaCl in Freund's adjuvant or were not immunised at all. When the presence of polyclonal anti-CP antibody was detected in CP-immunised rats' serum, all (CP-immunised and control) animals were injected i.p. with 4.8 x 10(5) Walker 256 cells per rat. After 5 days ascitic fluid was collected and viable cells were counted. The complete lack of viable Walker 256 carcinosarcoma cells in 24% of the CP-immunised rats was observed. However, the viable neoplastic cells were present in all control (NaCl-injected and nonimmunised) animals. It seems possible that CP plays an important role in tumour progression, so immunisation with CP can reduce the risk of development of malignant disease.