Production of platelet-derived growth factor in aseptic loosening of total hip replacement

Aseptic loosening is the predominant cause of total hip implant failure. It has been assumed that a layer or membrane, containing macrophages, fibroblasts and vascular endothelial cells, of synovial-like tissue develops at the implant-to-bone interface almost invariably and, with time, somehow leads to loosening of the components from the surrounding bone. These cells produce a variety of cytokines and proteolytic enzymes which stimulate bone resorption. Platelet derived growth factor (PDGF) may be one of the cytokines which stimulate bone resorption and contribute to aseptic loosening in total hip replacement (THR). Synovial-like membrane from the implant or cement-to-bone interface (n = 10) and pseudocapsule (n = 10) were obtained from ten patients operated on for aseptic loosening of THR. As a control, nine samples of connective tissues were obtained from patients who had mandibular or maxillary fractures fixed with bone implant. The avidin-biotin-peroxidase complex (ABC) method with polyclonal rabbit anti-human IgG against the A-chain and B-chain of PDGF was used for staining. ABC-alkaline phosphatase-anti-alkaline-phosphatase double staining with monoclonal mouse anti-human fibroblast IgG1 and CD68 antibodies was used to ascertain the cellular origin of PDGF. Results of the PDGF staining were quantitated by a semi-automatic VIDAS image analysis system. The PDGF-A and PDGF-B chain containing cells were found in all periprosthetic tissues, in particular in macrophages with phagocytosed particulate debris, but to some extent also in fibroblasts and in endothelial cells. The numbers of PDGF-A and PDGF-B chain positive cells per mm 2 in synovial-like interface membrane (1881 +/- 486 and 1877 +/- 214) and pseudocapsule (1786 +/- 236 and 1676 +/- 152) were higher (P < 0.01) around loose THR than in control tissue (821 +/- 112 and 467 +/- 150), respectively. The results of the present study suggest that PDGF is preferably expressed by macrophages, which to an increased extent produce it in the synovial-like interface membrane and pseudocapsular synovial-like membrane. Because of its role in bone resorption, it may well play a role in periprosthetic bone loss and aseptic loosening and deserves more detailed study as a mediator and potential target in the modulation or prevention of loosening of THR.     

Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes

The glycoxidation products Nepsilon-(carboxymethyl)lysine and pentosidine increase in skin collagen with age and at an accelerated rate in diabetes. Their age-adjusted concentrations in skin collagen are correlated with the severity of diabetic complications. To determine the relative roles of increased glycation and/or oxidation in the accelerated formation of glycoxidation products in diabetes, we measured levels of amino acid oxidation products, distinct from glycoxidative modifications of amino acids, as independent indicators of oxidative stress and damage to collagen in aging and diabetes. We show that ortho-tyrosine and methionine sulfoxide are formed in concert with Nepsilon-(carboxymethyl)lysine and pentosidine during glycoxidation of collagen in vitro, and that they also increase with age in human skin collagen. The age-adjusted levels of these oxidized amino acids in collagen was the same in diabetic and nondiabetic subjects, arguing that diabetes per se does not cause an increase in oxidative stress or damage to extracellular matrix proteins. These results provide evidence for an age-dependent increase in oxidative damage to collagen and support previous conclusions that the increase in glycoxidation products in skin collagen in diabetes can be explained by the increase in glycemia alone, without invoking a generalized, diabetes-dependent increase in oxidative stress.     

Altered visual field asymmetry for lexical decision as a result of concurrent presentation of music fragments of different emotional valences

OBJECTIVES: To investigate the effect of membrane lipid composition on the susceptibility to bile salt damage and protection. DESIGN: Artificial model cholesterol/phospholipid (c/p) membranes (vesicles) with a varying cholesterol (0-15 mM) and phospholipid content (3-30 mM), and with a c/p ratio ranging up to 1.70, were prepared by sonication. We examined the effect of incubation with increasing concentrations of either tauroursodeoxycholate (TUDC), taurocholate (TC) or taurodeoxycholate (TDC) alone, or with proportionally varying mixtures of TUDC and TDC. METHOD: Vesicle integrity was assessed by the change in optical absorbance at 340 nm. RESULTS: Absorption of the bile salt-vesicle mixture decreased, with increasing bile salt concentration and hydrophobicity: TUDC less than TC less than TDC. Moreover, bile salt-induced damage also depended on membrane composition: vesicles containing more than 5 mM cholesterol and with a c/p ratio greater than 0.8 were less likely to be solubilized by 30 mM bile salt. Similarly, only in cholesterol-rich vesicles (c/p > 0.5) was a protective effect of TUDC against membrane disruption by TDC revealed upon incubation with various TUDC/TDC mixtures. CONCLUSION: Apart from the bile salt concentration and hydrophobicity, the cholesterol content of vesicles is pivotal, both in the bile salt-induced solubilization of cholesterol/phospholipid vesicles and in the potency of TUDC to prevent this.     

Regulation of hippocampal synaptic plasticity by the tyrosine kinase receptor, REK7/EphA5, and its ligand, AL-1/Ephrin-A5

The Eph-related tyrosine kinase receptor, REK7/EphA5, mediates the effects of AL-1/Ephrin-A5 and related ligands and is involved in the guidance of retinal, cortical, and hippocampal axons during development. The continued expression of REK7/EphA5 in the adult brain, in particular in areas associated with a high degree of synaptic plasticity such as the hippocampus, raises the question of its function in the mature nervous system. In this report we examined the role of REK7/EphA5 in synaptic remodeling by asking if agents that either block or activate REK7/EphA5 affect synaptic strength in hippocampal slices from adult mouse brain. We show that a REK7/EphA5 antagonist, soluble REK7/EphA5-IgG, impairs the induction of long-term potentiation (LTP) without affecting other synaptic parameters such as normal synaptic transmission or paired-pulse facilitation. In contrast, perfusion with AL-1/Ephrin-A5-IgG, an activator of REK7/EphA5, induces a sustained increase in normal synaptic transmission that partially mimics LTP. The sustained elevation of normal synaptic transmission could be attributable to a long-lasting binding of the AL-1/Ephrin-A5-IgG to the endogenous REK7/EphA5 receptor, as revealed by immunohistochemistry. Furthermore, maximal electrical induction of LTP occludes the potentiating effects of subsequent treatment with AL-1/Ephrin-A5-IgG. Taken together these results implicate REK7/EphA5 in the regulation of synaptic plasticity in the mature hippocampus and suggest that REK7/EphA5 activation is recruited in the LTP induced by tetanization.     

The evolution of a successful liver transplant program in 1996: the clinical and administrative role of the anesthesiologist

The establishment of a new liver transplant program requires enormous planning and resources. Extensive negotiations must take place to ensure institutional and departmental commitments to obtain the proper equipment, personnel, and other resources. The formation of a well-trained multidisciplinary team of physicians and nurses becomes the next step. Finally, ample time must be provided to adequately deploy resources, lobby referring physicians, recruit patients, and troubleshoot problems as they arise.     

Altered passive eruption: an etiology of short clinical crowns

The gingival complex plays a vital role in the overall beauty of a smile. To predictably achieve a successful esthetic and functional result, the dentist must be able to precisely predict the treatment outcome based on biologic determinants. In this article, the biologic requirements for gingival health are discussed. In addition, a differential diagnosis for excess gingival display and treatment options for this condition are discussed.     

Severe prepartum ketosis in an obese beef cow

A beef cow was examined to find the cause of decreasing appetite of 2 weeks' duration. The cow was obese (body condition score, 8 of 9), and multiple fetuses were identified on palpation per rectum. Urinalysis revealed > 160 mg of ketones/dl. Abnormal serum biochemical data included high concentrations of bilirubin, creatinine, sodium, and chloride; low concentrations of total CO2 and calcium; and high activity of aspartate transaminase. Treatment included administration of dextrose solution, i.v.; propylene glycol, PO; and insulin, i.v. and SC. The cow's appetite improved gradually over 8 days of treatment. Concentration of ketone bodies in urine decreased to trace amounts by day 4. The cow was discharged on day 10 and gave birth to twins 4 days after discharge (duration of gestation, 279 days). The clinical history of this cow differed from the history of other cattle with ketosis, but mimicked pregnancy toxemia in ewes. Multiple fetuses have not been implicated as a predisposing factor in severe prepartum ketosis of cows.