Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit

OBJECTIVE: The initially well-fixed implants of total hip replacement (THR) are in the long-term subject to aseptic loosening. Many cytokines can contribute to osteolysis due to osteoclast recruitment and/or activation. However, in this respect tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role, because it upregulates interleukin-1 and 6 and granulocyte-macrophage colony stimulating factor. The aim of this study was to assess the eventual presence, cellular localization and extent of expression of TNF-alpha in the synovial-like membrane at the implant or at the cement to bone interface compared to control synovial membrane. METHODS: Twenty samples from the synovial-like membrane of the periprosthetic tissues were compared to control samples. TNF-alpha containing cells were visualized using an avidin-biotin-peroxidase complex (ABC) method and analyzed by light microscopy, double labelling and image analysis. RESULTS: TNF-alpha was found in the periprosthetic tissues in fibroblasts and vascular endothelial cells, but mainly in the macrophages was it found to coincide with areas containing implant-derived debris. TNF-alpha containing cells were more numerous in the synovial-like membrane in the interface tissue from the proximal stem area (2816 +/- 318 cells) than in the control synovial membrane (565 +/- 93 cells, p < 0.01). Interestingly, similarly high TNF-alpha expression (3452 +/- 582 cells) was also seen in the synovial-like membrane of the pseudocapsule. CONCLUSION: These findings suggest that the foreign body-type host reaction caused by THR is characterized by the high expression of TNF-alpha. Because such expression occurred in the interface tissue between the implant and surrounding bone, TNF-alpha, due to its pivotal direct and indirect role in the activation and recruitment of osteoclasts, may contribute to periprosthetic osteolysis and to the loosening of THR.     

Binding properties of bovine colostral anti-dinitrophenyl (dnp) immunoglobulins g2 (igg2)

The number of combining sites per mole of bovine colostral anti-DNP IgG2 was found to be 2 and the total affinity constant was 0.81 X 10(4) M-1. Unlike bovine colostral IgG1, the nonspecific binding of H3-epsilon-DNP-1-lysine by IgG2 as a function of increased concentrations, did not show a negative, cooperative slope. Spectral measurements made with anti-DNP IgG2 in the reference cell vs. anti-DNP IgG2 plus hapten in the experimental cell revealed a hypochromic, red shift from 363 to 365 nm. If the reference cell contained hapten, a red shift from 280 to 283 nm and an enhancement in the extinction coefficient of IgG2 was observed. These spectral changes were not observed if nonspecific IgG2 was substituted for anti-DNP IgG2 in the experimental cell. The enhancement in the extinction coefficient was interpreted to be due to a possible exposure of previously buried tryosine and tryptophan residues.     

Theoretical analysis of the binding of salicylate by human serum albumin: the relationship between free and bound drug and therapeutic levels

The binding of salicylates by human serum albumin was analyzed by use of a computer program using previously published association constants and binding capacities for the two sets of binding sites on the protein. The analysis consisted of computing free and bound salicylates for a range of therapeutic and toxic concentration from 181 to 7246 mumole/L (25 to 1000 mg/L). At low and therapeutic levels the total amount of bound drug would exceed the amount of free drug. At higher levels, which included therapeutic and toxic ranges, the amount of free drug plasma, up to 2000 mumole/L the high affinity sites (Site 1), would bind most of the drug, but as the concentration of drug increased this site would approach saturation and the low affinity Site 2 would bind increasing amounts of salicylate. At high salicylate levels the amount of drug bound by the low affinity sites. Computation also showed that when the total amount of protein in the analysis was reduced, from 5, 4, 3, to 2 gm%, as in hypoalbuminemia, the total amount of drug bound by the protein would decrease and the quantity of free drug would increase. The amount of drug bound by each of the two sets of sites also fell as the concentration of protein decreased. Some of the possible clinical implications of these findings are discussed.     

Cancer, emotions and mental illness: the present state of understanding

The authors review recent and current literature on the relationship between psychological factors and cancer. They discuss the roles of predisposing personality patterns and emotional stress in the development, site, and course of cancer; the influence of awareness of terminal illness on the behavior of cancer patients; and the management of psychiatric symptoms in these patients.