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Interleukin-6 is pyrogenic but not somnogenic.

Interleukin-6 (IL6) induces acute phase protein production and is hypothesized to mediate systemic and central effects of IL1. To determine whether IL6 possesses somnogenic properties, rabbits were injected intracerebroventricularly with IL6; sleep-wake activity was determined and brain temperatures recorded for 6 hr. IL6 induced fever in a dose-related manner with no effect on sleep-wake activity. IL6, therefore, is the first cytokine reported to elicit fever without promoting sleep. We conclude that the somnogenic action of IL1 is not mediated through IL6.

Acute-Phase Proteins↗

Enhancement of humoral immune responses against viral vaccines by a non-pyrogenic 6-O-acylmuramyldipeptide and synthetic low toxicity analogues of lipid A.

6-O-Acyl derivatives of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and synthetic, low toxicity lipid-A analogues were examined for their ability to enhance the potency of current viral vaccines. 6-O-(2-Tetradecylhexadecanoyl)-MDP (B30-MDP) in non-irritative vehicles such as physiological saline, phosphate-buffered saline (PBS), squalene-PBS emulsion, Intralipid or liposomes, significantly stimulated the primary and secondary antibody production of guinea-pigs against influenza split or subunit vaccine and inactivated the hepatitis B virus surface (HBs) antigen. Mice seemed less responsive to the adjuvanticity of B30-MDP than guinea-pigs. Two low toxicity lipid A analogues, acylated beta(1-6)-D-glucosamine disaccharide bisphosphates (which do not have amide-bound or ester-bound 3-acyloxyacyl groups unlike fully toxic Escherichia coli-type lipid A), caused significantly enhanced antibody responses, primary or secondary, when administered to mice by incorporation into liposomes with inactivated HBs antigen.

Acetylmuramyl-Alanyl-Isoglutamine↗

Fever produced by intrahypothalamic pyrogen: effect of protein synthesis inhibition by anisomycin.

In the unrestrained cat, the inhibition of protein synthesis by anisomycin, given either subcutaneously (5.0--25.0 mg/kg) or directly into the anterior hypothalamic, preoptic area (1.0--25.0 micrograms) impaired the development of a bacterial fever. S. typhosa infused intravenously (1:10 dilution in 1 ml) or into AH/POA (1.0 microliter) evoked an intense fever which was either significantly delayed or prevented by anisomycin. Conversely, anisomycin failed to affect the typical hyperthermia evoked by 100 ng PGE2 or 1.0--7.0 micrograms 5-HT similarly infused into AH/POA. These data demonstrate that an intermediary humoral factor of unknown nature is required in the hyperthermic effector pathway underlying the febrile response.

Animals↗

Dual infections with Staphylococcus aureus and Streptococcus pyogenes causing toxic shock syndrome. Possible synergistic effects of toxic shock syndrome toxin 1 and streptococcal pyrogenic exotoxin C.

We describe a 35-year-old woman with clinical, microbiologic, and serologic findings suggesting that the patient developed toxic shock syndrome as a result of dual infections caused by toxin-producing strains of Staphylococcus aureus and Streptococcus pyogenes. Certain aspects of the pathogenesis of this toxin-related syndrome are reviewed.

Adult↗

Identification, characterization and quantitation of pyrogenic polycylic aromatic hydrocarbons and other organic compounds in tire fire products.

On 15 August 2001, a tire fire took place at the Pneu Lavoie Facility in Gatineau, Quebec, in which 4000 to 6000 new and recycled tires were stored along with other potentially hazardous materials. Comprehensive gas chromatography-mass spectrometry (GC-MS) analyses were performed on the tire fire samples to facilitate detailed chemical composition characterization of toxic polycyclic aromatic hydrocarbons (PAHs) and other organic compounds in samples. It is found that significant amounts of PAHs, particularly the high-ring-number PAHs, were generated during the fire. In total, 165 PAH compounds including 13 isomers of molecular weight (MW) 302, 10 isomers of MW 278, 10 isomers of MW 276, 7 isomers of MW 252, 7 isomers of MW 228, and 8 isomers of MW 216 PAHs were positively identified in the tire fire wipe samples for the first time. Numerous S-, O-, and N-containing PAH compounds were also detected. The identification and characterization of the PAH isomers was mainly based on: (1) a positive match of mass spectral data of the PAH isomers with the NIST authentic mass spectra database; (2) a positive match of the GC retention indices (I) of PAHs with authentic standards and with those reported in the literature; (3) agreement of the PAH elution order with the NIST (US National Institute of Standards and Technology) Standard Reference Material 1597 for complex mixture of PAHs from coal tar; (4) a positive match of the distribution patterns of PAH isomers in the SIM mode between the tire fire samples and the NIST Standard Reference Materials and well-characterized reference oils. Quantitation of target PAHs was done on the GC-MS in the selected ion monitoring (SIM) mode using the internal standard method. The relative response factors (RRF) for target PAHs were obtained from analyses of authentic PAH standard compounds. Alkylated PAH homologues were quantitated using straight baseline integration of each level of alkylation.

Automobiles↗

Involvement of tyrosine kinase in the pyrogenic fever exerted by NOS pathways in organum vasculosum laminae terminalis.

Nitric oxide synthase (NOS) is an enzyme which has a distinct cytokine-inducible isoform (iNOS). Many cytokine receptors have an intracellular tyrosine kinase domain. Here we have used two tyrosine kinase inhibitors (genistein and lavendustin A) to investigate the potential role of tyrosine kinase activation in the induction on both iNOS and fever caused by lipopolysaccharide (LPS) in rabbits. Direct administration of LPS into the organum vasculosum laminae terminalis (OVLT) increased iNOS expression. These increases paralleled the increase in deep body temperature in unanesthetized rabbits. Pretreatment with genistein or lavendustin A not only reduced the fever but also attenuated the iNOS expression in the OVLT following an intra-OVLT dose of LPS. These results suggest that tyrosine phosphorylation is part of the signal transduction mechanism that mediates the induction of both iNOS and fever elicited by LPS in the OVLT of rabbit brain.

Animals↗

High-resolution record of pyrogenic polycyclic aromatic hydrocarbon deposition during the 20th century.

A high-resolution record of polycyclic aromatic hydrocarbon (PAH) deposition in Rhode Island over the past approximately 180 years was constructed using a sediment core from the anoxic Pettaquamscutt River basin. The record showed significantly more structure than has hitherto been reported and revealed four distinct maxima in PAH flux. The characteristic increase in PAH flux at the turn of the 20th century was captured in detail, leading to an initial maximum prior to the Great Depression. The overall peak in PAH flux in the 1950s was followed by a maximum that immediately preceded the 1973 Organization of Petroleum Exporting Countries (OPEC) oil embargo. During the most recent portion of the record, an abrupt increase in PAH flux between 1996 and 1999 has been found to follow a period of near constant fluxes. Because source-diagnostic ratios indicate that petrogenic inputs are minor throughout the record, these trends are interpreted in terms of past variations in the magnitude and type of combustion processes. For the most recent PAH maximum, energy consumption data suggest that diesel fuel combustion, and hence traffic of heavier vehicles, is the most probable cause for the increase in PAH flux. Systematic variations in the relative abundance of individual PAHs in conjunction with the above changes in flux are interpreted in relation to the evolution of combustion processes. Coronene, retene, and perylene are notable exceptions, exhibiting unique down-core profiles.

Environmental Monitoring↗

Strong sorption of native PAHs to pyrogenic and unburned carbonaceous geosorbents in sediments.

It has recently been shown that the presence of carbonaceous geosorbents (CG, including black carbon (BC), unburned coal, and kerogen) can cause strong sorption of polycyclic aromatic hydrocarbons (PAHs) in sediments. We studied sorption of native PAHs in four Norwegian harbor sediments of which high fractions (21-56%) of the total organic carbon (TOC) consisted of CG carbon (CGC), as shown by organic petrography. PAH sorption coefficients were 1-2 orders of magnitude above predictions based on amorphous organic carbon partitioning alone. In recent studies, such strong sorption was attributed solely to BC sorption under the implicit assumption that sorption is linear for coal and kerogen. The most important result of the present study is that total sorption is better explained by considering all three nonlinearly sorbing CGC materials than by only considering BC. In addition, it was evaluated whether activated carbon (AC) amendments could be effective in reducing the freely dissolved pore-water concentrations (CW) and thus the environmental risks of the PAHs in such strongly sorbing sediments. The results indicated that an addition of 2 weight % AC reduced the Cw by factors of 21-153 for the four sediments (average values for all PAHs). Itwas shown that phenanthrene sorption to AC was, on average, reduced by a factor of 6 in sediment-AC mixtures compared to pure AC.

Adsorption↗

Pyrogenic iron(III)-doped TiO2 nanopowders synthesized in RF thermal plasma: phase formation, defect structure, band gap, and magnetic properties.

Iron(III)-doped TiO(2) nanopowders, with controlled iron to titanium atomic ratios (R(Fe/Ti)) ranging from nominal 0 to 20%, were synthesized using oxidative pyrolysis of liquid-feed metallorganic precursors in a radiation-frequency (RF) thermal plasma. The valence of iron doped in the TiO(2), phase formation, defect structures, band gaps, and magnetic properties of the resultant nanopowders were systematically investigated using Mössbauer spectroscopy, XRD, Raman spectroscopy, TEM/HRTEM, UV-vis spectroscopy, and measurements of magnetic properties. The iron doped in TiO(2) was trivalent (3+) in a high-spin state as determined by the isomer shift and quadrupole splitting from the Mössbauer spectra. No other phases except anatase and rutile TiO(2) were identified in the resultant nanopowders. Interestingly, thermodynamically metastable anatase predominated in the undoped TiO(2) nanopowders, which can be explained from a kinetic point of view based on classical homogeneous nucleation theory. With iron doping, the formation of rutile was strongly promoted because rutile is more tolerant than anatase to the defects such as oxygen vacancies resulting from the substitution of Fe(3+) for Ti(4+) in TiO(2). The concentration of oxygen vacancies reached a maximum at R(Fe/Ti) = 2% above which excessive oxygen vacancies tended to concentrate. As a result of this concentration, an extended defect like crystallographic shear (CS) structure was established. With iron doping, red shift of the absorption edges occurred in addition to the d-d electron transition of iron in the visible light region. The as-prepared iron-doped TiO(2) nanopowders were paramagnetic in nature at room temperature.

Journal Article↗

Pyrogenic cytokines injected into the rat cerebral ventricle induce cyclooxygenase-2 in brain endothelial cells and also upregulate their receptors.

Peripheral immunological insults induce interleukin (IL)-1 beta and IL-6 in the brain. To elucidate the mechanism(s) of fever evoked by these brain-derived cytokines, and possible interactions between them, we examined in rats: (i) whether cyclooxygenase-2 is responsible for fever evoked by central injection of these cytokines; (ii) if so, where in the brain cyclooxygenase-2 is induced; (iii) where the receptors for these cytokines are located; and (iv) how the expression of these receptors is influenced by the cytokines. Intracerebroventricular injection of these cytokines evoked fever that was suppressed by a cyclooxygenase-2 inhibitor. Brain endothelium was the site of cyclooxygenase-2 induction by these cytokines. IL-1 receptor (IL-1R) was constitutively expressed in brain endothelium, and its mRNA was further upregulated by either cytokine. IL-6R mRNA was constitutively expressed in the cerebral cortex, and was newly induced in as yet unidentified cells in brain blood vessels by either cytokine. Messenger RNAs for cyclooxygenase-2, IL-1R, and IL-6R were often observed in the same blood vessels. These results suggest that COX-2 induced in brain endothelium is, at least in part, involved in the fever evoked by these cytokines, and that one possible interaction between these two cytokines is mutual upregulation of their receptors in the endothelium or perivascular cells, resulting in augmentation of their actions.

Animals↗