No abstract

Abstract:Dextran-based hydrogels were obtained by polymerization of aqueous solutions of methacrylated dextran (dex-MA) or lactate-hydroxyethyl methacrylate-derivatized dextran (dex-lactate-HEMA). Both nondegradable dex-MA and degradable dex-lactate-HEMA disk-shaped hydrogels, varying in initial water content and degree of substitution (DS, the number of methacrylate groups per 100 glucose units), were implanted subcutaneously in rats. The tissue reaction was evaluated over a period of 6 weeks. The initial foreign-body reaction to the dex-MA hydrogels was characterized by infiltration of granulocytes and macrophages and the formation of fibrin, and exudate, as well as new blood vessels. This reaction depended on the initial water content as well as on the DS of the hydrogel and decreased within 10 days. The mildest tissue response was observed for the gel with the highest water content and intermediate DS. At day 21 all dex-MA hydrogels were surrounded by a fibrous capsule and no toxic effects on the surrounding tissue were found. No signs of degradation were observed. The initial foreign-body reaction to the degradable dex-lactate-HEMA hydrogels was less severe compared with the dex-MA gels. In general, the size of the dex-lactate-HEMA hydrogels increased progressively with time and finally the gels completely dissolved. Degradation of the dex-lactate-HEMA hydrogels was associated with infiltration of macrophages and the formation of giant cells, both of which phagocytosed pieces of the hydrogel. A good correlation between the in vitro and the in vivo degradation time was found. This suggests that extra-cellular degradation is not caused by enzymes but depends only on hydrolysis of the ester and/or carbonate bonds present in the crosslinks of the hydrogels. After 21 days, the degradable hydrogels, as such, could not be retrieved, but accumulation of macrophages and giant cells was observed, both of which contained particles of the gels intracellularly. As for the dex-MA hydrogels, no toxic effects on the surrounding tissue were found. The results presented in this study demonstrate that dextran-based hydrogels can be considered as biocompatible materials, making these hydrogels attractive systems for drug delivery purposes.

Phospholipids from malignant, benign and noninvolved human breast tissues were extracted by chloroform-methanol (2:1) and analysed by 31P MR spectroscopy at 202.4 MHz. Thirteen phospholipids were identified as constituents of the profiles obtained among the 55 tissue specimens analysed. Observed patterns in phospholipid tissues profiles were distinct, allowing qualitative characterisation of the three tissue groups. Multivariate analysis of lysophosphatidylcholine (LPC) and an uncharacterised phospholipid were shown to be independently significant in predicting benign tissue histology as either fibrocystic disease or fibroadenoma in 92% of cases. Univariate analysis of relative mole-percentage of phosphorus concentrations of individual phospholipids using the Scheffé comparison procedure revealed that in malignant tissues, phosphatidylethanolamine was significantly elevated compared to benign (+ 32%) and noninvolved tissues (+ 22%). Phosphatidylinositol (+ 33%) and phosphatidylcholine plasmalogen (PC plas) (+ 25%) were increased in malignant compared to benign and LPC was decreased (-44%) in malignant compared to noninvolved. LPC was significantly depressed (-39%) in benign tissue compared to normal. Phospholipid indices computed to further characterise the three tissue groups showed PC plas/PC elevated in malignant tissue compared to benign and PE plas/PE depressed in malignant tissue compared to noninvolved. These findings support previous investigations reporting that the alkyl-phospholipid analogues of phosphatidylcholine are released by malignant tissues and that levels of ethanolamine are elevated in malignant tissues. Indices describing the choline-containing phospholipids showed that these lipids are depressed significantly in malignant tissue relative to healthy tissue.

Cartilage from normal controls, patients with osteoarthritis, and patients with rheumatoid arthritis produced no interleukin-6 (IL-6) in culture. However, IL-1 induced massive production of IL-6 (up to 135 nglml) in cartilage from all 3 sources, in a dosedependent manner (in some cases, a peak value was reached). The levels of induced IL-6 were similar to those found in rheumatoid arthritis synovial fluid. At IL-1 concentrations that induced almost complete inhibition of proteoglycan (PG) synthesis, IL-6 production could still be increased considerably. Exogenous IL-6 inhibited PG synthesis by up to 25%. IL-1-induced inhibition of PG synthesis was reversed by antibodies against recombinant human IL-6. These results suggest that IL-6 is required for the IL-1-induced inhibition of PG synthesis.