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.     

Regeneration of active receptor recognition domains on the B subunit of cholera toxin by formation of hybrids from chemically inactivated derivatives

In order to test the hypothesis that binding sites of cholera toxin for its receptor, the monosialoganglioside GM1, are shared between adjacent beta-polypeptide chains, two inactive chemical derivatives of the B subunit of cholera toxin (CTB) were prepared and were subsequently used for the construction of hybrid CTB pentamers. One inactive derivative consisted of CTB specifically modified in the single essential Trp-88 residue of each beta-chain. This residue was modified by formylation, a treatment preserving the structural integrity of CTB. The other inactive derivative consisted of CTB specifically succinylated in three amino groups located in or near the receptor binding site. Using [1,4-14C]succinic anhydride for the site-specific succinylation and analysis of radiolabeled tryptic fragments of S-carboxymethylated [14C]sssCTB revealed that the amino groups specifically modified were the alpha-amino group of Thr-1 and the epsilon-amino groups of respectively Lys-34 and Lys-91. Upon submitting equal amounts of formylated CTB and site-specific succinylated CTB to a denaturation-renaturation cycle, hybrid pentamers were formed which in contrast to the parental compounds were able to bind GM1. The affinity of hybrid CTB for GM1, as estimated by a competitive solid-phase radiobinding assay was unexpectedly high and only 2.5-fold lower than that of its native counterpart. The number of active binding sites on hybrid CTB was determined from: (i) titration with the oligosaccharide moiety of GM1 (oligo-GM1) and monitoring the reversal of the Trp fluorescence quenching by iodide ions and (ii) rapid gel filtration over a superdex HR column of a mixture of hybrid CTB and an excess of 3H-labeled oligo-GM1. The data are in agreement with the formation of one active binding per four reconstituted binding sites in hybrid CTB, which is consistent with a random association of CTB monomers during the denaturation-renaturation cycle.     

Transluminal balloon angioplasty, stents, and atherectomy

Arterial bypass grafting for occlusive disease is still considered the gold standard in the treatment of arterial occlusive disease. However, less invasive methods are available for select patients. Percutaneous balloon angioplasty has been shown to be effective in focal iliac artery stenosis, with patency rates of 50% to 90% at 5 years. Patency rates for femoropopliteal lesions are generally less than 50% at 2 years. Complications seen with balloon angioplasty often can be treated with arterial stents. Stents can be categorized into balloon-expandable, which provide a rigid scaffold to support the artery, self-expanding, which exert radial force to resist external compression, and thermal expanding stents, which allow for the use of a smaller introducer sheath. Another treatment option is atherectomy, in which the offending lesion is removed instead of fracturing and dilating the lumen. Although overall initial results of atherectomy have not been favorable, short lesions with eccentric atheroma or intimal hyperplasia, such as those seen in dialysis access fistulas or vein graft stenoses, may respond well.     

Acquisition of the mental state verb know by 2- to 5-year-old children

The production of the cognitive internal state word know by four 2- to 5-year-old children and their parents was examined. The levels of meaning of cognitive words can be categorized hierarchically along the dimensions of conceptual difficulty and abstractness (see Booth & Hall, 1995). The present study found that children and their parents expressed low levels of meaning less frequently, whereas they expressed high levels of meaning more frequently as a function of age. The children's use of know was also correlated positively with (1) their number of different words produced suggesting that cognitive words are related to more general semantic processes, and (2) with parental use of those same cognitive words suggesting that parental linguistic input may be an important mechanism in cognitive word acquisition. Finally, young children tended to use know more to refer to themselves than to refer to others, whereas their parents tended to use know equally to refer to self and others. The importance of cognitive words in a theory of language acquisition is discussed.     

Post-traumatic stress disorder and functioning and quality of life outcomes in female Vietnam veterans

OBJECTIVE: This investigation assessed whether current post-traumatic stress disorder (PTSD) was associated with impaired functioning in a nationally representative sample of female Vietnam veterans. METHODS: Logistic models were used to determine the association between PTSD and outcome while adjusting for demographic characteristics and medical and psychiatric co-morbidities. RESULTS: PTSD was associated with significantly elevated odds of poorer functioning in five of the six outcome domains; only the association between perpetration of violence in the past year and PTSD did not achieve statistical significance. After adjusting for demographics and medical and psychiatric co-morbidities, PTSD remained associated with significantly elevated odds of bed days, poorer physical health, and currently not working. CONCLUSIONS: Among female Vietnam veterans PTSD is associated with a broad profile of functional impairment. The significantly increased odds of impaired functioning and diminished quality of life suggest that PTSD may be the core problem of the set of problems afflicting female Vietnam veterans.     

The zebrafish Pax3 and Pax7 homologues are highly conserved, encode multiple isoforms and show dynamic segment-like expression in the developing brain

This study describes the isolation and characterization of zebrafish homologues of the mammalian Pax3 and Pax7 genes. The proteins encoded by both zebrafish genes are highly conserved (>83%) relative to the known mammalian sequences. Also the neural expression patterns during embryogenesis are very similar to the murine homologues. However, observed differences in neural crest and mesodermal expression relative to mammals could reflect some functional divergence in the development of these tissues. For the zebrafish Pax7 protein we report the first full-length amino acid sequences in vertebrates and show the existence of three additional isoforms which have truncations in the homeodomain and/or the C-terminal region. These novel variants provide evidence for additional isoform diversity of vertebrate Pax proteins.     

Thermodynamic assessment of the Al deoxidation reaction in liquid iron

The deoxidation reaction of aluminum in liquid iron has been investigated thermodynamically using Al₂O₃ crucible at 1873 K under Ar atmosphere as a fundamental study for the accurate control of inclusions in the ladle refining process. In addition to the equilibrium constant log K_A1 for the aluminum deoxidation reaction, the first-order and second-order interaction parameters between aluminum and oxygen were experimentally determined in the concentration range of aluminum up to 1 %. The temperature dependence of the equilibrium constant and the first-order interaction parameter e^A1 was also obtained: log K_A1 = 12.32 - 47400/T, e^A1 = 15.57 - 36500/T. The equilibrium relation between aluminum and oxygen contents in the aluminum deoxidized iron by applying interaction parameters and the equilibrium constant determined in this work satisfies fairly well the equilibrium data over the whole concentration range of aluminum considered.     

Risk factors for new coronary events in older African-American men and women

Independent risk factors for new coronary events in older African-American men were (1) age (risk ratio = 1.037), (2) cigarette smoking (risk ratio = 2.231), (3) hypertension (risk ratio = 2.531), (4) serum total cholesterol (risk ratio = 1.012), (5) serum high-density lipoprotein (HDL) cholesterol (inverse association) (risk ratio = 0.948), and (6) prior coronary artery disease (CAD) (risk ratio = 2.288). Independent risk factors for new coronary events in older African-American women were (1) cigarette smoking (risk ratio = 2.202), (2) hypertension (risk ratio = 2.344), (3) diabetes mellitus (risk ratio = 1.632), (4) serum total cholesterol (risk ratio = 1.008), (5) serum HDL cholesterol (inverse association) (risk ratio = 0.936), (6) age (risk ratio = 1.026), and (7) prior CAD (risk ratio = 2.368).