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.     

Characteristics of mammary mitochondria in lines of mice genetically divergent for milk production

The purpose of this study was to determine the relationship of mitochondrial proliferation and ATP production to milk production in two lines of mice that were genetically divergent for milk production. Milk production differed between high production and low production lines by .8 phenotypic standard deviations as determined by cross-fostered litter weight gain from 1 to 12 d postpartum. Mammary weight, mammary total DNA, and RNA:DNA ratio were greater in glands of high line mice. Mammary DNA and protein, expressed per gram mammary tissue, were similar between lines. Mammary mitochondrial mass per gland differed after six generations of divergent selection. Rates of succinate-supported ATP production and ADP:O of isolated mitochondria differed, but the rate of pyruvate-supported ATP production did not differ between lines. Differences between selection lines in mitochondrial mass and in the efficiency of succinate use for support of ATP production were probable consequences of selection for divergent milk production.     

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.     

Diphosphonate treatment of Paget's disease

Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered in a dose of 20 mg/kg/d to 21 patients with symptomatic Paget's disease. All patients were treated for 6 months and then followed for an additional 6 months. There was a striking decline in serum alkaline phosphatase and urinary hydroxy-proline excretion observed after 3 months of therapy which was not significantly improved in the succeeding 3 months. Concomitantly there was marked improvement in clinical symptoms and bone scans. Following cessation of therapy, continued biochemical and clinical evidence of remission persisted. Several patients on repeat treatment with EHDP appeared to respond promptly. Side effects were minimal except for a possibly related osteomalacia and increased incidence of pathologic fractures.