Macrophages overexpressing tartrate-resistant acid phosphatase show altered profile of free radical production and enhanced capacity of bacterial killing

Activated macrophages and osteoclasts express high amounts of tartrate-resistant acid phosphatase (TRACP, acp5). TRACP has a binuclear iron center with a redox-active iron that has been shown to catalyze the formation of reactive oxygen species (ROS) by Fenton's reaction. Previous Studies Suggest that ROS generated by TRACP may participate in degradation of endocytosed bone matrix products in resorbing osteoclasts and degradation of foreign Compounds during. antigen presentation in activated macrophages. Here we have compared free radical production in macrophages of TRACP overexpressing (TRACP +) and wild-type (WT) mice. TRACP overexpression increased both ROS levels and Superoxide production. Nitric oxide production was increased in activated macrophages or WT mice, but not in TRACP+ mice, Macrophages from TRACP+ mice showed increased capacity or bacterial killing. Recombinant TRACP enzyme was capable of bacterial killing in the presence of hydrogen peroxide. These results suggest that TRACP has an important biological function in immune defense systern.

Rifampicin and sodium fusidate reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) isolation in adults with cystic fibrosis and chronic MRSA infection

Nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) to patients with cystic fibrosis (CF) frequently results in chronic respiratory tract carriage. This is an increasing problem, adds to the burden of glycopeptide antibiotic use in hospitals, and represents a relative contraindication to lung transplantation. The aim of this study was to determine whether it is possible to eradicate MRSA with prolonged oral combination antibiotics, and whether this treatment is associated with improved clinical status. Adult CF patients (six mate, one female) with chronic MRSA infection were treated for six months with rifampicin and sodium fusidate. Outcome data were examined for six months before treatment, on treatment and after treatment. The patients had a mean age of 29.3 (standard deviation = 6.3) years and FEV1 of 36.1% (standard deviation = 12.7) predicted. The mean duration of MRSA isolation was 31 months. MRSA isolates identified in these patients was of the same lineage as the known endemic strain at the hospital when assessed by pulsed-field get electrophoresis. Five of the seven had no evidence of MRSA during and for at [east six months after rifampicin and sodium fusidate. The proportion of sputum samples positive for MRSA was lower during the six months of treatment (0.13) and after treatment (0.19) compared with before treatment (0.85) (P < 0.0001). There was a reduction in the number of days of intravenous antibiotics per six months with 20.3 +/- 17.6 on treatment compared with 50.7 before treatment and 33.0 after treatment (P = 0.02). There was no change in lung function. Gastrointestinal side effects occurred in three, but led to therapy cessation in only one patient. Despite the use of antibiotics with anti-staphylococcal activity for treatment of respiratory exacerbation, MRSA infection persists. MRSA can be eradicated from the sputum of patients with CF and chronic MRSA carriage by using rifampicin and sodium fusidate for six months. This finding was associated with a significant reduction in the duration of intravenous antibiotic treatment during therapy. (C) 2003 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

S100A8 chemotactic protein is abundantly increased, but only a minor contributor to LPS-induced, steroid resistant neutrophilic lung inflammation in vivo

Neutrophilic lung inflammation is an essential component of host defense against diverse eukaryotic and prokaryotic pathogens, but in chronic inflammatory lung diseases, such as chronic obstructive lung disease (COPD), severe asthma, cystic fibrosis, and bronchiolitis, it may damage the host. Glucocorticosteroids are widely used in these conditions and in their infectious exacerbations; however, the clinical efficacy of steroids is disputed. In this study, we used a proteomic approach to identify molecules contributing to neutrophilic inflammation induced by transnasal administration of lipopolysaccharide (LPS) that were also resistant to the potent glucocorticosteroid dexamethasone (Dex). We confirmed that Dex was biologically active at both the transcript (suppression of GM-CSF and TNFalpha transcripts) and protein levels (induction of lipocortin) and used 2D-PAGE/MALDI-TOF to generate global expression profiles, identifying six LPS-induced proteins that were Dex resistant. Of these, S100A8, a candidate neutrophil chemotactic factor, was profiled in detail. Steroid refractory S100A8 expression was highly abundant, transcriptionally regulated, secreted into lung lavage fluid and immunohistochemically localized to tissue infiltrating neutrophils. However, in marked contrast to other vascular beds, neutralizing antibodies to S100A8 had only a weak anti-neutrophil recruitment effect and antibodies against the related S100A9 were ineffective. These data highlight the need for extensive in vivo profiling of proteomically identified candidate molecules and demonstrates that S100A8, despite its abundance, resistance to steroids and known chemotactic activity, is unlikely to be an important determinant of LPS-induced neutrophilic lung inflammation in vivo.

Differential expression of the NMDA NR2B receptor subunit in motoneuron populations susceptible and resistant to amyotrophic lateral sclerosis

We have compared the expression pattern of NMDA receptor subunits (NR1 and NR2A-D)and NRI splice variants (NR1-1a/1b,-2a/2b,-3a/3b,4a/4b) in motor neuron populations from adult Wistar rats that are vulnerable (hypoglossal, XII) or resistant (oculomotor, III) to death in amyotrophic lateral sclerosis (ALS). The major finding was higher levels of expression of the NR2B subunit in the hypoglossal nucleus. Quantitative real-time PCR showed that NR1 was expressed at a greater level than any of the NR2 subunits (> 15 fold greater, P

Experiments to assess the transport of fibrous insulation debris

Loss of coolant accidents (LOCA) in the primary cooling circuit of a nuclear reactor may result in damage to insulation materials that are located near to the leak. The insulation materials released may compromise the operation of the emergency core cooling system (ECCS). Insulation material in the form of mineral wool fibre agglomerates (MWFA) maybe transported to the containment sump strainers mounted at the inlet of the emergency cooling pumps, where the insulation fibres may block or penetrate the strainers. In addition to the impact of MWFA on the pressure drop across the strainers, corrosion products formed over time may also accumulate in the fibre cakes on the strainers, which can lead to a significant increase in the strainer pressure drop and result in cavitation in the ECCS. Thus, knowledge of transport characteristics of the damaged insulation materials in various scenarios is required to help plan for the long-term operability of nuclear reactors, which undergo LOCA. An experimental and theoretical study performed by the Helmholtz-Zentrum Dresden-Rossendorf and the Hochschule Zittau/Görlitz1 is investigating the phenomena that maybe observed in the containment vessel during a LOCA. The study entails the generation of fibre agglomerates, the determination of their transport properties in single and multi-effect experiments and the long-term effect that corrosion of the containment internals by the coolant has on the strainer pressure drop. The focus of this presentation is on the experiments performed that characterize the horizontal transport of MWFA, whereas the corresponding CFD simulations are described in an accompanying contribution (see abstract of Cartland Glover et al.). The experiments were performed a racetrack type channel that provided a near uniform horizontal flow. The channel is 0.1 wide by 1.2 m high with a straight length of 5 m and two bends of 0.5 m. The measurement techniques include particle imaging (both wide-angle and macro lens), concurrent particle image velocimetry, ultravelocimetry, laser detection sensors to sense the presence of absence of MWFA and pertinent measurements of the MWFA concentration and quiescent settling characteristics. The transport of the MWFA was observed at velocities of 0.1 and 0.25 m s-1 to verify numerical model behaviour in and just beyond expected velocities in the containment sump of a nuclear reactor.

UK epidemic strains of meticillin-resistant Staphylococcus aureus in clinical samples from Malta

Since 1999, the European Antimicrobial Resistance Surveillance System (EARSS) has monitored the rise in infection due to a number of organisms, including meticillin-resistant Staphylococcus aureus (MRSA). The EARSS reported that MRSA infections within intensive care units account for 25-50% of infections in many central and southern European countries, these included France, Spain, Great Britain, Malta, Greece and Italy. Each country has defined epidemic MRSA (EMRSA) strains; however, the method of spread of these strains from one country to another is unknown. In this current study, DNA profiles of 473 isolates of MRSA collected from the UK and Malta were determined by PFGE. Analysis of the data showed that two countries separated by a large geographical distance had a similar DNA profile pattern. Additionally it was demonstrated that strains of EMRSA normally found in the UK were also found in the Maltese cohort (EMRSA 15 and 16). A distinct DNA profile was found in the Maltese cohort, which may be a local EMRSA, and accounted for 14.4% of all Maltese isolates. The appearance of the same MRSA and EMRSA profiles in two separate countries suggests that MRSA can be transferred out of their country of origin and potentially establish in a new locality or country.

The steam reforming of hydrocarbons with special reference to methane

From an examination of the literature relating to the catalytic steam reforming of hydrocarbons, it is concluded that the kinetics of high pressure reforming, particularly steam-methane reforming, has received relatively little attention. Therefore because of the increasing availability of natural gas in the U.K., this system was considered worthy of investigation. An examination of the thermodynamics relating to the equilibria of steam-hydrocarbon reforming is described. The reactions most likely to have influence over the process are established and from these a computer program was written to calculate equilibrium compositions. A means of presenting such data in a graphica1 form for ranges of the operating variables is given, and also an operating chart which may be used to quickly check feed ratios employed on a working naphtha reforming plant is presented. For the experimental kinetic study of the steam-methane system, cylindrical pellets of ICI 46-1 nickel catalyst were used in the form of a rod catalyst. The reactor was of the integral type and a description is given with the operating procedures and analytical method used. The experimental work was divided into two parts, qualitative and quantitative. In the qualitative study the various reaction steps are examined in order to establish which one is rate controlling. It is concluded that the effects of film diffusion resistance within the conditions employed are negligible. In the quantitative study it was found that at 250 psig and 6500C the steam-methane reaction is much slower than the CO shift reaction and is rate controlling. Two rate mechanisms and accompanying kinetic rate equations are derived, both of which represent 'chemical' steps in the reaction and are considered of equal merit. However the possibility of a dual control involving 'chemical' and pore diffusion resistances is also expressed.

Verification and validation of numerical models of the transport of insulation debris

Damage to insulation materials located near to a primary circuit coolant leak may compromise the operation of the emergency core cooling system (ECCS). Insulation material in the form of mineral wool fiber agglomerates (MWFA) maybe transported to the containment sump strainers, where they may block or penetrate the strainers. Though the impact of MWFA on the pressure drop across the strainers is minimal, corrosion products formed over time may also accumulate in the fiber cakes on the strainers, which can lead to a significant increase in the strainer pressure drop and result in cavitation in the ECCS. An experimental and theoretical study performed by the Helmholtz-Zentrum Dresden-Rossendorf and the Hochschule Zittau/Görlitz is investigating the phenomena that maybe observed in the containment vessel during a primary circuit coolant leak. The study entails the generation of fiber agglomerates, the determination of their transport properties in single and multi-effect experiments and the long-term effect that corrosion and erosion of the containment internals by the coolant has on the strainer pressure drop. The focus of this paper is on the verification and validation of numerical models that can predict the transport of MWFA. A number of pseudo-continuous dispersed phases of spherical wetted agglomerates represent the MWFA. The size, density, the relative viscosity of the fluid-fiber agglomerate mixture and the turbulent dispersion all affect how the fiber agglomerates are transported. In the cases described here, the size is kept constant while the density is modified. This definition affects both the terminal velocity and volume fraction of the dispersed phases. Note that the relative viscosity is only significant at high concentrations. Three single effect experiments were used to provide validation data on the transport of the fiber agglomerates under conditions of sedimentation in quiescent fluid, sedimentation in a horizontal flow and suspension in a horizontal flow. The experiments were performed in a rectangular column for the quiescent fluid and a racetrack type channel that provided a near uniform horizontal flow. The numerical models of sedimentation in the column and the racetrack channel found that the sedimentation characteristics are consistent with the experiments. For channel suspension, the heavier fibers tend to accumulate at the channel base even at high velocities, while lighter phases are more likely to be transported around the channel.