Atom probe tomography data analysis procedure for precipitate and cluster identification in a Ti-Mo steel.

An atom probe tomography data analysis procedure for identification of particles in a Ti-Mo steel is presented. This procedure has been used to characterise both carbide precipitates (larger particles) and solute clusters (smaller particles), as reported in an accompanying Mater. Sci. Eng. A paper [1]. Particles were identified using the maximum separation method (cluster-finding algorithm) after resolving peak overlaps at several locations in the mass spectrum. The cluster-finding algorithm was applied to the data in a two-stage process to properly identify particles having a bimodal size distribution. Furthermore, possible misidentification of matrix atoms (mainly Fe) due to the local magnification effect (from the difference in field evaporation potential between the matrix and precipitates) has been resolved using an atomic density approach, comparing that measured experimentally using APT to the theoretical density of both the matrix and particles.

Effect of process control agent on the porous structure and mechanical properties of a biomedical Ti-Sn-Nb alloy produced by powder metallurgy.

The influence of different amounts and types of process control agent (PCA), i.e., stearic acid and ethylene bis-stearamide, on the porous structure and mechanical properties of a biomedical Ti-16Sn-4Nb (wt.%) alloy was investigated. Alloy synthesis was performed on elemental metal powders using high-energy ball milling for 5h. Results indicated that varying the PCA content during ball milling led to a drastic change in morphology and particle-size distribution of the ball-milled powders. Porous titanium alloy samples sintered from the powders ball milled with the addition of various amounts of PCA also revealed different pore morphology and porosity. The Vickers hardness of the sintered titanium alloy samples exhibited a considerable increase with increasing PCA content. Moreover, the addition of larger amounts of PCA in the powder mixture resulted in a significant increase in the elastic modulus and peak stress for the sintered porous titanium alloy samples under compression. It should also be mentioned that the addition of PCA introduced contamination (mainly carbon and oxygen) into the sintered porous product.

In vitro bioactivity evaluation of titanium and niobium metals with different surface morphologies.

Current orthopaedic biomaterials research mainly focuses on designing implants that could induce controlled, guided and rapid healing. In the present study, the surface morphologies of titanium (Ti) and niobium (Nb) metals were tailored to form nanoporous, nanoplate and nanofibre-like structures through adjustment of the temperature in the alkali-heat treatment. The in vitro bioactivity of these structures was then evaluated by soaking the treated samples in simulated body fluid (SBF). It was found that the morphology of the modified surface significantly influenced the apatite-inducing ability. The Ti surface with a nanofibre-like structure showed better apatite-inducing ability than the nanoporous or nanoplate surface structures. A thick dense apatite layer formed on the Ti surface with nanofibre-like structure after 1 week of soaking in SBF. It is expected that the nanofibre-like surface could achieve good apatite formation in vivo and subsequently enhance osteoblast cell adhesion and bone formation.

Titanium-nickel shape memory alloy foams for bone tissue engineering.

Titanium-nickel (TiNi) shape memory alloy (SMA) foams with an open-cell porous structure were fabricated by space-holder sintering process and characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. The mechanical properties and shape memory properties of the TiNi foam samples were investigated using compressive test. Results indicate that the plateau stresses and elastic moduli of the foams under compression decrease with the increase of their porosities. The plateau stresses and elastic moduli are measured to be from 1.9 to 38.3 MPa and from 30 to 860 MPa for the TiNi foam samples with porosities ranged from 71% to 87%, respectively. The mechanical properties of the TiNi alloy foams can be tailored to match those of bone. The TiNi alloy foams exhibit shape memory effect (SME), and it is found that the recoverable strain due to SME decreases with the increase of foam porosity.

The 'metacarpal cascade lines'; use in the diagnosis of dislocations of the carpometacarpal joints.

Dislocations of the carpometacarpal joints of the ring and little fingers are common and are frequently missed at presentation. We describe a radiographic observation which assists in the confirmation of the diagnosis.

Hydroxyapatite/titania sol-gel coatings on titanium-zirconium alloy for biomedical applications.

A simple sol-gel method was developed for hydroxyapatite/titania (HA/TiO(2)) coatings on non-toxic titanium-zirconium (TiZr) alloy for biomedical applications. The HA/TiO(2)-coated TiZr alloy displayed excellent bioactivity when soaked in a simulated body fluid (SBF) for an appropriate period. Differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction and scanning electron microscopy-energy dispersive spectrometry were used to characterize the phase transformations and the surface structures and to assess the in vitro tests. The HA/TiO(2) layers were spin-coated on the surface of TiZr alloy at a speed of 3000rpm for 15s, followed by a heat treatment at 600 degrees C for 20min in an argon atmosphere sequentially. The TiO(2) layer exhibited a cracked surface and an anatase structure and the HA layer displayed a uniform dense structure. Both the TiO(2) and HA layers were 25microm thick, and the total thickness of the HA/TiO(2) coatings was 50microm. The TiZr alloy after the above HA/TiO(2) coatings displayed excellent bone-like apatite-forming ability when soaked in SBF and can be anticipated to be a promising load-bearing implant material.

Effect of stress on viral-bacterial synergy in bovine respiratory disease: novel mechanisms to regulate inflammation.

The severity of bovine respiratory infections has been linked to a variety of factors, including environmental and nutritional changes, transportation, and social reorganization of weaned calves. Fatal respiratory infections, however, usually occur when a primary viral infection compromises host defences and enhances the severity of a secondary bacterial infection. This viral-bacterial synergy can occur by a number of different mechanisms and disease challenge models have been developed to analyse host responses during these respiratory infections. A primary bovine herpesvirus-1 (BHV-1) respiratory infection followed by a secondary challenge with Mannheimia haemolytica results in fatal bovine respiratory disease (BRD) and host responses to these two pathogens have been studied extensively. We used this disease model to demonstrate that stress significantly altered the viral-bacterial synergy resulting in fatal BRD. Functional genomic analysis revealed that BHV-1 infection enhanced toll-like receptors (TLR) expression and increased pro-inflammatory responses which contribute to the severity of a Mannheimia haemolytica infection. TLRs play a critical role in detecting bacterial infections and inducing pro-inflammatory responses. It is difficult to understand, however, how stress-induced corticosteroids could enhance this form of viral-bacterial synergy. Nuclear translocation of the glucocorticoid receptor activates cell signalling pathways which inhibit both TLR signalling and pro-inflammatory responses. The apparent conundrum between stress-induced corticosteroids and enhanced BRD susceptibility is discussed in terms of present data and previous investigations of stress and respiratory disease.

Augmented hepatic interferon gamma expression and T-cell influx characterize acute hepatitis progressing to recovery and residual lifelong virus persistence in experimental adult woodchuck hepatitis virus infection.

Woodchucks infected with woodchuck hepatitis virus (WHV) have profiles of liver disease and age-dependent rates of progression to chronic hepatitis (CH) comparable with those seen in human hepatitis B. The mechanism of recovery from acute hepadnaviral infection or its evolution to chronicity remains unknown, although the liver immune responses are expected to play an important role. To determine the dynamics of intrahepatic cytokine expression and T-cell involvement, and to assess their value in predicting the outcome of acute hepatitis (AH) in the adult onset of WHV infection, we evaluated liver transcription of interferon gamma (IFN-gamma); tumor necrosis factor alpha (TNF-alpha); interleukins (IL)-2, -4, and -6; and the T-cell influx in relation to disease histologic severity and virus load in serial liver biopsies collected during the life span of experimentally infected woodchucks. Our results show that recovery from viral AH in adulthood is preceded by a significantly greater hepatic expression of IFN-gamma and CD3, an increased TNF-alpha transcription, lower hepatic WHV load, and a greater degree of liver inflammation than those in acute infection with CH outcome. Furthermore, we have learned that the elevated IFN-gamma, TNF-alpha, and CD3 expression in the liver endures for years not only in CH, but also, although to a lesser extent, in apparently completely resolved infection. This is consistent with our previous findings that residual WHV replication and remnant liver inflammation continue for life after recovery from AH. This study indicates that antiviral cytokines, in particular IFN-gamma, may play a central role in the long-term control of occult hepadnavirus persistence in the liver.

Posttranscriptional inhibition of class I major histocompatibility complex presentation on hepatocytes and lymphoid cells in chronic woodchuck hepatitis virus infection.

Woodchuck hepatitis virus (WHV), similar to human hepatitis B virus, causes acute liver inflammation that can progress to chronic hepatitis and hepatocellular carcinoma. WHV also invades cells of the host lymphatic system, where it persists for life. We report here that acute and chronic hepadnavirus hepatitis is characterized by a profound difference in the expression of class I major histocompatibility complex (MHC) molecules on the surface of infected hepatocytes and, notably, lymphoid cells. While acute WHV infection is accompanied by the enhanced hepatocyte surface presentation of class I MHC antigen and upregulated transcription of the relevant hepatic genes, inhibition of class I antigen display on liver cells is a uniform hallmark of chronic WHV infection. This inhibition in chronic hepatitis occurs despite augmented (as in acute infection) expression of hepatic genes for class I MHC heavy chain, beta(2)-microglobulin, and transporters associated with antigen processing (TAP1 and TAP2). Further, the class I antigen inhibition is not related to the histological severity of hepatocellular injury, the extent of lymphocytic infiltrations, the level of intrahepatic gamma interferon induction, or the hepatic WHV load. Importantly, the antigen expression is also inhibited on organ lymphoid cells of chronically infected hosts. The results obtained in this study demonstrate that the defective presentation of class I MHC molecules on cells supporting persistent WHV replication is due to viral posttranscriptional interference. This event may diminish the susceptibility of infected hepatocytes to virus-specific T-cell-mediated elimination, hinder virus clearance, and deregulate the class I MHC-dependent functions of the host immune system. This multifarious effect could be critical for perpetuation of liver damage and evasion of the antiviral immunological surveillance in chronic infection and therefore could be supportive of hepadnavirus persistence.

Perforin and Fas/Fas ligand-mediated cytotoxicity in acute and chronic woodchuck viral hepatitis.

The Fas ligand (FasL)/Fas and the perforin-granzyme cytotoxic pathways presumably play a central role in the development of hepatocellular injury in viral hepatitis. To recognize the potential contribution of FasL and perforin-based cell killing in hepadnaviral infection, we adopted a cytotoxic assay using murine Fas+ P815 and human Fas- K562 cells as targets. Freshly isolated peripheral blood mononuclear cells (PBMC) from woodchucks with newly acquired woodchuck hepatitis virus (WHV) infection (n = 6), with chronic WHV hepatitis (n = 9), and from healthy animals (n = 11) were used as effector cells. We have found that woodchuck lymphoid cells kill cell targets via both the FasL/Fas and the perforin death pathways. The contribution of Fas-dependent cytolysis was ascertained in blocking experiments with anti-Fas antibody and by incubation of PBMC with cyclohexamide to prevent de novo synthesis of FasL. The involvement of the perforin pathway was confirmed by treatment of K562 cells with colchicine to inhibit the microtubule-dependent perforin release. Comparative analysis showed that peripheral lymphoid cells from acute WHV hepatitis, but not those from chronic WHV infection, are more cytotoxic and that this increase seems to be entirely due to activation of perforin-mediated killing. The data indicate that acute infection in woodchucks is associated with the augmented capacity of lymphoid cells to elicit perforin-dependent killing, but in chronic infection, independent of the severity of liver disease and duration of chronicity, these cells have the same or lower cytotoxic potential as PBMC from healthy controls. These findings suggest a role for non-specific cellular immunity, presumably natural killer (NK) cells, in the control of early WHV infection and in the progression of chronic hepatitis.

The role of nitric oxide generation in interferon-evoked cytochrome P450 down-regulation.

The down-regulation of cytochrome P450 during host defence involves one or more mediators of unknown source and identity. Owing to striking similarities in the features that are involved in the production of NO and the features involved in the down-regulation of cytochrome P450 we hypothesized that NO could be a mediator in the interferon-evoked loss of cytochrome P450. In these experiments the nitric oxide synthase inhibitor L-nitroarginine (5 mg/kg) failed to protect mice from the down-regulation of cytochrome P450, ethoxyresorufin dealkylase and para-nitrophenol hydroxylase in the liver following administration of the interferon inducer polyinosinic.polycytidylic acid. A higher dose of L-nitroarginine (30 mg/kg) given every 12 h for 3 days also did not protect against cytochrome P450 losses. In addition, no down-regulation of the enzyme was observed in animals treated with multiple doses of the NO-generating drugs glyceryl trinitrate (16 and 80 mg/kg given every 4 h for 16 h) and nitroprusside (20 and 100 mg/kg given every 4 h for 16 h). These results indicate that the down-regulation of cytochrome P450 by interferon or its inducers probably does not involve NO as a required intermediary.