Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay. LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific

Nondifferentiable Dynamic: Two Examples

Some nondifferentiable quantities (for example, the metric signature) can be the independent physical degrees of freedom. It is supposed that in quantum gravity these degrees of freedom can fluctuate. Two examples of such quantum fluctuation are considered: a quantum interchange of the sign of two components of the 5D metric and a quantum fluctuation between Euclidean and Lorentzian metrics. The first case leads to a spin-like structure on the throat of composite wormhole and to a possible inner structure of the string. The second case leads to a quantum birth of the non-singular Euclidean Universe with frozen $5^{th}$ dimension. The probability for such quantum fluctuations is connected with an algorithmical complexity of the Einstein equations.Comment: essential changes: the initial equations in section III are changed, as the consequence the obtained solution describes the quantum birth of the nonsingular Universe with the matter (electromagnetic field=nondiagonal components of the MD metric

Quantum Geometrodynamics I: Quantum-Driven Many-Fingered Time

The classical theory of gravity predicts its own demise -- singularities. We therefore attempt to quantize gravitation, and present here a new approach to the quantization of gravity wherein the concept of time is derived by imposing the constraints as expectation-value equations over the true dynamical degrees of freedom of the gravitational field -- a representation of the underlying anisotropy of space. This self-consistent approach leads to qualitatively different predictions than the Dirac and the ADM quantizations, and in addition, our theory avoids the interpretational conundrums associated with the problem of time in quantum gravity. We briefly describe the structure of our functional equations, and apply our quantization technique to two examples so as to illustrate the basic ideas of our approach.Comment: 11, (No Figures), (Typeset using RevTeX

Putting pharmaceuticals into the wider context of challenges to fish populations in rivers

The natural range of fish species in our rivers is related to flow, elevation, temperature, local habitat and connectivity. For over 2000 years, humans have altered to varying degrees the river habitat. In the past 200 years, we added to the environmental disruption by discharging poorly treated sewage, nutrients and industrial waste into our rivers. For many rivers, the low point arrived during the period of 1950s–1970s, when rapid economic development overrode environmental concerns and dissolved oxygen concentrations dropped to zero. In these more enlightened times, gross river pollution is a thing of the past in the Developed World. However, persistent legacy chemical contaminants can be found in fish long after their discharge ceased. Changes in habitat quality and morphology caused and continue to cause the disappearance of fish species. The range of fish stressors has now increased as temperatures rise, and non-native fish introductions bring new diseases. The threat from pharmaceuticals to fish populations remains hypothetical, and no studies have yet linked change in fish populations to exposure

EPR before EPR: a 1930 Einstein-Bohr thought experiment revisited

In 1930 Einstein argued against consistency of the time-energy uncertainty relation by discussing a thought experiment involving a measurement of mass of the box which emitted a photon. Bohr seemingly triumphed over Einstein by arguing that the Einstein's own general theory of relativity saves the consistency of quantum mechanics. We revisit this thought experiment from a modern point of view at a level suitable for undergraduate readership and find that neither Einstein nor Bohr was right. Instead, this thought experiment should be thought of as an early example of a system demonstrating nonlocal "EPR" quantum correlations, five years before the famous Einstein-Podolsky-Rosen paper.Comment: 11 pages, revised, accepted for publication in Eur. J. Phy

Suppression of nuclear factor-κB activity in macrophages by chylomicron remnants: modulation by the fatty acid composition of the particles

Current evidence indicates that chylomicron remnants (CMR) induce macrophage foam cell formation, an early event in atherosclerosis. Inflammation also plays a part in atherogenesis and the transcription factor nuclear factor-κB (NF-κB) has been implicated. In this study, the influence of CMR on the activity of NF-κB in macrophages and its modulation by the fatty acid composition of the particles were investigated using macrophages derived from the human monocyte cell line THP-1 and CMR-like particles (CRLPs). Incubation of THP-1 macrophages with CRLPs caused decreased NF-κB activation and downregulated the expression of phospho-p65–NF-κB and phospho-IκBα (pIκBα). Secretion of the inflammatory cytokines tumour necrosis factor α, interleukin-6 and monocyte chemoattractant protein-1, which are under NF-κB transcriptional control, was inhibited and mRNA expression for cyclooxygenase-2, an NF-κB target gene, was reduced. CRLPs enriched in polyunsaturated fatty acids compared with saturated or monounsaturated fatty acids had a markedly greater inhibitory effect on NF-κB binding to DNA and the expression of phospho-p65–NF-κB and pIκB. Lipid loading of macrophages with CRLPs enriched in polyunsaturated fatty acids compared with monounsaturated fatty acids or saturated fatty acids also increased the subsequent rate of cholesterol efflux, an effect which may be linked to the inhibition of NF-κB activity. These findings demonstrate that CMR suppress NF-κB activity in macrophages, and that this effect is modulated by their fatty acid composition. This downregulation of inflammatory processes in macrophages may represent a protective effect of CMR which is enhanced by dietary polyunsaturated fatty acids