Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor

Chronic bone infection, as attends periodontitis, is often complicated by severe osteolysis. While LPS is believed to be central to the pathogenesis of the osteolytic lesion, the mechanisms by which this bacteria-derived molecule promotes bone resorption are unknown. We find that LPS induces bone marrow macrophages (BMMs) to express c-src, a protooncogene product that we demonstrate is a specific marker of commitment to the osteoclast phenotype. We next turned to possible soluble mediators of LPS-induced c-src. Of a number of osteoclastogenic cytokines tested, only TNF-alpha mirrors the c-src-enhancing effect of LPS. Suggesting that LPS augmentation of c-src is TNF-mediated, endotoxin sequentially induces BMM expression of TNF, followed by c-src. TNF and c-src expression, by cultured BMMs derived from LPS-injected mice, reflects duration of exposure to circulating endotoxin, intimating that endotoxin's effect in vivo is also mediated by TNF. Consistent with these findings, thalidomide (which antagonizes TNF action) attenuates c-src induction by LPS. An anti-TNF antibody blocks LPS enhancement of c-src mRNA, validating the cytokine's modulating role in vitro. Using BMMs of TNF receptor-deleted mice, we demonstrate that TNF induction of c-src is transmitted through the cytokine's p55, but not p75, receptor. Most importantly, LPS administered to wild-type mice prompts osteoclast precursor differentiation, manifest by profound osteoclastogenesis in marrow cultured ex vivo, and by a profusion of marrow-residing cells expressing the osteoclast marker tartrate resistant acid phosphatase, in vivo. In contrast, LPS does not substantially enhance osteoclast proliferation in mice lacking the p55TNF receptor, confirming that LPS-induced osteoclastogenesis is mediated by TNF in vivo via this receptor. Thus, therapy targeting TNF and/or its p55 receptor presents itself as a means of preventing the osteolysis of chronic bacterial infection.     

Toward functional magnetic stimulation (FMS) theory and experiment

Examines the use of magnetic fields to functionally stimulate peripheral nerves. All electric fields are induced via a changing magnetic field whose flux is entirely confined within a closed magnetic circuit. Induced electric fields are simulated using a nonlinear boundary element solver. The induced fields are solved using duality theory. The accuracy of these predictions is verified by saline bath experiments. Next, the theory is applied to the stimulation of nerves using small, partially occluded ferrite and laminated vanadium permendur cores. Experiments demonstrate the successful stimulation of peripheral nerves in the African bullfrog with 11 mA, 153 mV excitations. These results offer a new vista of possibilities in the area of functional nerve stimulation. Unlike functional electric stimulation (FES), FMS does not involve any half cell reactions, and thus would not have the commensurate FES restrictions regarding balanced biphasic stimulation, strength duration balances, and oxidation issues, always exercising care that the electrodes remain in the reversible operating regime     

Growth kinetics and treatment response of the intracerebral rat 9L brain tumor model: a quantitative in vivo study using magnetic resonance imaging

We report the use of magnetic resonance imaging (MRI) for in situ tumor growth rate studies of experimental intracranial 9L tumors. T2-weighted spin-echo coronal magnetic resonance images of rat brains with 9L tumors were obtained every 2 days beginning at 8-11 days postimplantation using a 7 tesla MRI system. Tumors were clearly delineated in the images as a hyperintense region with a relatively well-demarcated border and minimal peritumoral edema. Tumor volumes from individual slices were summed together to yield the total tumor volume. The accuracy of this methodology for volumetric determination was verified by MRI phantom studies. Tumor growth rates determined from sequential MRI measurements of tumor volumes were quantitated in terms of volumetric doubling time. Tumor doubling times were found to range from 50 to 81 h, with an average of 66 +/- 8 h (n = 10). Intracranial 9L tumors were found to grow exponentially over the entire life span of the animal, allowing treated animals to serve as their own controls since the volumetric doubling time could be determined from three to four MRI scans before treatment administration. The intracerebral tumor growth delay following a single injection of 1, 3-bis(2-chloroethyl)-1-nitrosourea (13.3 mg/kg i.p.) allowed for noninvasive determination of in vivo log cell kill. A 2.0 +/- 0.2 (n = 3) log cell kill from 1,3-bis(2-chloroethyl)-1-nitrosourea treatment was found from post-treatment MRI volume measurements. These results demonstrate that MRI provides a powerful and sensitive method for assessing the growth and treatment response of intracranial 9L tumors in the rat.     

Electrooxidation of CO and CO/H2 mixtures on a Pt-Sn catalyst prepared by an implantation method

A new type of ion implantation technique is used to create a non-equilibrium Pt-Sn(IMP) near-surface alloy with ca. 8.6 at% Sn. The surface composition was determined by low-energy ion-scattering (LEIS). The kinetics of the electrooxidation of CO and 2% CO/H₂ mixtures on Pt-Sn(IMP) is essentially identical to that of Pt₃Sn(110). The fact that any non-equilibrium composition can be easily prepared by this implantation method opens an interesting practical opportunity to create a new Pt-Sn alloy fuel cell catalyst having an otherwise unobtainable surface composition of Sn. This method also appears to have general utility in alloy catalysis as a means of exploring compositions in thermodynamically unfavorable regions of the bulk phase diagram. This revised version was published online in July 2006 with corrections to the Cover Date.     

A kinetic and surface study of the thermal decomposition of cellulose powder in inert and oxidizing atmospheres

The thermal decomposition of fibrous cellulose powder from 275° to 340°C has been studied by thermogravimetry, scanning electron microscopy, krypton adsorption, and gas-chromatographic analysis of the gaseous products arising from pyrolysis in various oxidizing and inert atmospheres. The reaction kinetics fit a phase boundary model where the rate is controlled by the movement of an interface through a cylindrical particle and the principal kinetic parameters fit a compensation curve described previously for the decomposition of wood products. An explanation of the physical mechanism of pyrolysis is proposed which is consistent with the observed rate data and the structural changes observed by scanning electron microscopy.     

Reactive Laser Ablation Synthesis of Nanosize Alumina Powder

An aluminum (Al) target was laser ablated in an oxygen (O₂) atmosphere, producing nanosize alumina (Al₂O₃) powder. The powder surface area decreased (and the particle size increased) with both increasing oxygen pressure and laser fluence. All powders produced had surface areas between 135 and 250 m²/g, corresponding to primary particle sizes ranging from 7 to 3 nm in radius. Phase evolution with temperature was studied via X-ray diffraction. These powders showed a direct transformation from γ- to α-alumina at approximately 1200°C, bypassing other transition alumina phases, while still maintaining small particle size ( 30 nm). Despite the nanosize particles, green densities equal to 54% of the skeletal density (i.e., true density of the solid phase) were obtained by uniaxial pressing at 40 MPa.     

A model of ammonia volatilisation from a dairy farm: an examination of abatement strategies

A model (MAST) to calculate the mass flow of NH₃ through amodel dairy farm has been developed. Updated emission factors for UKagriculturewere used to examine different abatement strategies available for a typicaldairy farm. A range of annual NH₃ emissions was calculated for bothslurry and FYM based dairy systems. Emission for the slurry based system ranged between 27 kg NH₃-N ha^–1 yr^–1, achieved using a combination of abatementstrategies, and 107 kg NH₃-N ha^–1 yr^–1, calculated for a worst casescenario. For FYM, this range was between 33 and 86 kg NH₃-Nha^–1 yr^–1. The greatest reductionswereachieved by manipulating options linked to fertiliser usage and manureapplication.     

Reactive Laser Ablation Synthesis of Nanosize Aluminum Nitride

An aluminum (Al) target was laser ablated in a nitrogen (N₂) atmosphere, producing aluminum nitride (AlN) powder. These powders were calcined at 900°C for 2 h. Powders were produced at various nitrogen pressures, and the calcined powders were tested for unreacted aluminum content, using differential thermal analysis (DTA). The AlN powder, produced at a laser fluence of 12 J/cm² and a nitrogen pressure of 10.0 kPa (75 torr), showed no evidence of unreacted aluminum by DTA and was phase-pure AlN by X-ray diffraction (XRD). The surface area of this powder is 82 m²/g, corresponding to a particle size of ∼11 nm, which is in good agreement with TEM observations.