bluuebunny/crossref_metadata_2025 huggingface dataset:
A murine model with aspects of clinical relevance for the study of antibiotic-induced endotoxin release in septic hosts
Authors: Neely Alice N. , Holder Ian A.
Published: January 2008

A murine model which utilizes a burn to increase susceptibility to sepsis is presented. The model is inexpensive, highly reproducible, versatile, easy to use, and clinically relevant to many aspects of a Gram-negative sepsis which develops over time from a localized focus of infection. Additionally, studies of LPS-intoxication in mice with the same burn indicate that the animals show increased sensitivity to endotoxin without having to be exposed to exogenous sensitizing chemicals. Hence, this burned mouse model of sepsis might provide a sensitive, clinically relevant model for the study of antibiotic-induced endotoxin release from Gram-negative bacteria in septic hosts.
Contribution of soluble endotoxin released from Gram-negative bacteria by antibiotics to the pathogenesis of experimental sepsis in mice
Authors: Morrison D.C. , Bucklin S.E. , Leeson M.C. , Norimatsu M.
Published: January 2008

The results from our laboratory summarized in this review support the importance of endotoxin release from the Gram-negative microbe as a requirement for the full manifestation of the biological activity of the lipopolysaccharide (LPS) macromolecule. They further suggest that LPS is the most important bacterial component released from Gram-negative microbes treated in vitro with cell-wall active antibiotics in terms of biological activity. The use of several experimental mouse models of infection confirm that mice treated with the reversible hepatotoxin, D-galactosamine, are sensitive to both endotoxin lethality and to infection with Gram-negative microbes. Infected LPS-sensitive animals can be protected if they are treated with antibiotics, but the degree of protection (e.g. 5-10-fold) is significantly less than that observed when infection-sensitive but LPS-insensitive mice are similarly treated (500-fold protection). Additional levels of protection in infected, antibiotic-treated mice can be observed with antiendotoxin agents (e.g. polymyxin B-dextran, monoclonal antibody). Finally, antibiotics with equivalent minimal inhibitory concentrations for Escherichia coli, but differing in their mode of action and endotoxin releasing potential in vitro, also differ in their protective efficacy in vivo to reduce mortality in infected animals. Collectively, these data provide evidence to support a role for microbe-derived endotoxin, released from the microbial surface following treatment with cell-wall active antibiotics, in the pathogenesis of experimental Gram-negative sepsis.
Effects of anti-interleukin 6 on inflammatory responses during murine septic peritonitis
Authors: van der Poll T. , Keogh C.V. , Helfgott D. , Berman L. , Buurman W.A. , Lowry S.F.
Published: January 2008

Interleukin (IL)-6 has a limited role in the pathogenesis of the acute systemic inflammatory response syndrome elicited by bolus administration of bacteria or bacterial products. We sought to determine the role of IL-6 in septic peritonitis induced by cecal ligation and puncture (CLP). CLP led to a rapid and sustained induction of IL-6 in plasma and organ homogenates. Pretreatment (-2 h) with an anti-IL-6 mAb (1 mg) resulted in higher plasma and hepatic levels of tumor necrosis factor (TNF), as well as higher plasma concentrations of soluble TNF receptors and IL-10, while attenuating the acute phase protein response. Administration of anti-IL-6 did not influence survival. These results suggest that IL-6 production during septic peritonitis serves to inhibit the appearance of both agonist and antagonist members of the cytokine network. The importance of IL-6 in mediating the cytokine response to infection may be underestimated in more acute sepsis models.
Oral administration of Escherichia coli in enteric coated microparticles induces serum antibodies against lipopolysaccharide antigens
Authors: Flanagan M.P. , Battisti G. , Michael J.G.
Published: January 2008

Heat-killed Escherichia coli O55:B5 were encapsulated in microcapsules coated with a pH-sensitive enteric coating (methacrylic acid copolymer). Oral immunization of C57BI/6 x DBA/2 (BDF1) mice with encapsulated bacteria resulted in a humoral immune response directed against bacterial lipopolysaccharide (LPS). This response was greatly boosted by a second series of immunization and differed both quantitatively and qualitatively from that induced by intraperitoneal immunization with non-encapsulated heat-killed bacteria. The anti-LPS response following oral immunization was comprised almost exclusively of IgG1 subclass antibodies and was highly specific for the LPS of the immunizing bacteria. The anti-LPS response following intraperitoneal immunization consisted mainly of IgM and IgG2a antibodies which were crossreactive with several bacterial strains. Our results demonstrate that whole killed bacteria, encapsulated by an enteric coating and administered orally, effectively induces an antibody response to LPS in mice which shows a typical memory response following secondary challenge.
Effects of pig hemoglobin binding on some physical and biological properties of Actinobacillus pleuropneumoniae lipopolysaccharides
Authors: Archambault M. , Olivier M. , Foiry B. , Diarra M.S. , Paradis S.-É. , Jacques M.
Published: January 2008

Binding of pig hemoglobin (Hb) to Actinobacillus pleuropneumoniae lipopolysaccharide (LPS), either extracted or present at the surface of whole cells, was studied. After a short incubation period, pig Hb seemed to cover the bacterial cell surface and enhanced the cells' contrast when examined by transmission electron microscopy (TEM). Energy-dispersive X-ray spectroscopy analysis showed that the amount of elemental iron detected was increased when cells of A. pleuropneumoniae were incubated with pig Hb. Coating with pig Hb, however, did not interfere with the accessibility of O- and capsular antigens to antibodies on the bacterial cell surface. Binding of pig Hb and polymyxin B to lipid A of A. pleuropneumoniae was confirmed with a fluorescent probe (dansylcadaverine) displacement assay. The binding of pig Hb to extracted LPS resulted in a disaggregation of LPS as observed by TEM after negative staining. Additional evidence for a direct physical interaction between pig Hb and A. pleuropneumoniae LPS was demonstrated by a shift in the sedimentation velocity of LPS-Hb complexes determined by sucrose gradient centrifugation. Pig Hb binding to extracted LPS or to bacterial cells resulted in a significant decrease of chromogenic Limulus amebocyte lysate activation. Finally, the capacity of extracted LPS to induce NO2- in the presence of pig Hb was tested by using cell line J774 and determined by the Greiss' reaction. LPS alone induced, as expected, NO2- production, whereas the presence of pig Hb significantly reduced NO2- production by murine macrophages. Taken together, our results indicate that binding of pig Hb affected some physical and biological properties of A. pleuropneumoniae LPS.
Rhodobacter sphaeroides diphosphoryl lipid A inhibits interleukin-6 production in CD14-negative murine marrow stromal ST2 cells stimulated with lipopolysaccharide or paclitaxel (taxol)
Authors: Kirikae T. , Kirikae F. , Tominaga K. , Qureshi N. , YamaMoto S. , Nakano M.
Published: January 2008

Paclitaxel (taxol), a microtubule stabilizer with anticancer activity, mimics the actions of lipopolysaccharide (LPS) on murine macrophages in vitro. Recent studies have shown that the Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) inhibits both LPS- and paclitaxel-induced activation of murine macrophages, and have suggested that LPS, RsDPLA, and paclitaxel share the same receptor site on murine macrophages. To analyze this receptor site, the present study focused on the interactions between LPS, RsDPLA and paclitaxel in the activation of ST2 cells derived from murine bone marrow stroma. The ST2 cells did not express CD14 mRNA. The cells produced IL-6 molecules and expressed IL-6 mRNA in response to LPS, but did not produce TNF and nitric oxide. Paclitaxel induced IL-6 mRNA expression in ST2 cells. RsDPLA inhibited both LPS- and paclitaxel-induced IL-6 mRNA expression in a dose-dependent manner. These results suggest that LPS, RsDPLA, and paclitaxel are recognized by the same receptor complex on ST2 cells, and that the receptor functions without membrane CD14.
Interleukin-10 is downregulated in mononuclear cells from endotoxin tolerant humans
Authors: Flach R. , Flohé S. , Laschinski M. , Hofmann K. , Kreuzfelder E. , Schade F.U.
Published: January 2008

It has been shown that induction of endotoxin tolerance results in a decreased potential to produce pro-inflammatory cytokines such as TNF or IL-1. The present study was carried out to examine the capacity of peripheral blood mononuclear cells (PBMC) from endotoxin tolerant humans to synthesize the anti-inflammatory cytokines IL-10 and TGFβ in response to endotoxin. Four individuals were rendered endotoxin tolerant by daily i.v. injections of endotoxin. PBMC were isolated before tolerance induction and on day 4 after the last endotoxin treatment. The cells were stimulated with endotoxin ex vivo and cytokines in culture supernatants were determined. PBMC isolated on day 4 of all of the volunteers showed decreased TNFα, IL-6 and IL-10 synthesis upon endotoxin treatment in vitro compared to pretolerant cells, while no differences occurred with regard to the amount of TGFβ formed by PBMC before and after tolerance induction. Furthermore, no changes were found in the expression of HLA-DR on PBMC after tolerance induction.
Peritoneal macrophages from endotoxin-tolerant mice produce an inhibitor of tumor necrosis factor α synthesis and protect against endotoxin shock
Authors: Flach R. , Schade F.U.
Published: January 2008

In the present study it was found that development of early endotoxin-tolerance is associated with the capacity of mouse peritoneal macrophages (MPM) to produce an activity interfering with the synthesis of tumor necrosis factor α. Peritoneal macrophages from LPS-tolerant mice (tMPM), treated with LPS in vitro produced less TNFα, IL-10 and TGFβ than LPS-treated macrophages from normal mice (nMPM). The supernatants of LPS-activated tMPM contained activities which suppressed formation of TNF in nMPM and RAW 264.7 cells as determined by bioassay, ELISA and PCR. Supernatants of nMPM and unstimulated tMPM were devoid of the inhibitory activity. The inhibitor did not interfere with the bioactivity of TNFα in WEHI cells. It also suppressed PMA/IFN-γ induced TNF synthesis in macrophage cultures. The transfer of macrophages isolated from endotoxin-tolerant mice into normal mice protected against endotoxin shock, whereas macrophages from normal mice increased susceptibility to endotoxin.
Modulation of interleukin 1β production in macrophages stimulated with lipopolysaccharide by the protein kinase inhibitor staurosporine
Authors: Schilling D. , Brauburger J. , Ruiner W. , Nixdorff K.
Published: January 2008

Inhibitors of key components of intracellular signaling pathways were used to detect differences in the regulation of the production of interleukin 1β (IL-1β) and tumor necrosis factor α (TNFα) in macrophages activated with lipopolysaccharide (LPS). The protein kinase inhibitor staurosporine caused an increase in the level of IL-1β in supernatants of macrophages stimulated with LPS. Calphostin C and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) dihydrochloride, specific inhibitors of protein kinase C (PKC), also promoted enhancement of IL-1β secretion, but the effect was not as pronounced as that of staurosporine. In contrast, all three substances inhibited TNFα production. Measurement of IL-1β in lysates and supernatants of macrophage cultures indicated that staurosporine effected enhancement of the production of the cytokine in the cellular fraction, the greater portion of which was not secreted. Kinetics of accumulation of IL-1β mRNA and production of the cytokine during a 24 h period showed that enhanced production of IL-1β obtained 24 h after LPS stimulation of macrophages in the presence of staurosporine paralleled the increased levels in mRNA specific for the cytokine.
A model of Neisseria meningitidis vaccine based on LPS micelles detoxified by synthetic antiendotoxin peptides
Authors: Velucchi M. , Rustici A. , Meazza C. , Villa P. , Ghezzi P. , Tsai C-M. , Porro M.
Published: January 2008

We describe a model of vaccine based on detoxified endotoxin (LPS) conserving the supramolecular structure of micelles. Detoxification of LPS from Neisseria meningitidis group A, strain A1 (LPS A1), has been achieved by complex formation with a synthetic anti-endotoxin peptide (SAEP 2) binding to the lipid A moiety of LPS A1 with high affinity. Following subcutaneous injection in SW mice, LPS A1/SAEP 2 complex induced high titers of boostable IgG antibodies against the immunotype determinants of LPS A1, cross-reactive with group B LPS in either purified or cell-associated form. These antibodies were able to functionally fix and activate homologous and heterologous species of complement after binding to LPS A1-coated sheep erythrocytes. None of the IgG antibodies induced were specific for lipid A or SAEP 2 and none of the IgG antibodies cross-reacted with heterologous LPS. The purified IgG polyclonal antibodies significantly inhibited serum TNF production in CD1 mice intravenously challenged by homologous but not heterologous LPS. The immunogenic properties of LPS A1/SAEP 2 complex, investigated by the kinetic, magnitude and sub-isotype composition of the polyclonal antibodies induced, were comparable to those of a glycoconjugate obtained by covalent binding of LPS A1, detoxified by SAEP 2, to BSA working as a T-cell dependent carrier protein. The results obtained suggest that LPS behaves in vivo as a T-cell dependent antigen. The strategy of properly delivering to the immune system of mammalians, non-toxic LPS fully expressing its supramolecular antigenic structure, represents a novel approach for development of a new generation of R- and S-LPS/SAEP complex-based vaccines for prophylaxis of specific Gram-negative infections leading to sepsis and endotoxemia.
Delayed therapy with a polymyxin B-dextran conjugate (PMX-622) improves survival in rabbits with Gram-negative peritonitis
Authors: Camerota A.J. , Lögdberg L. , Lake P. , Larkin V.A. , Fink M.P.
Published: January 2008

Polymyxin B (PMB) is an amphipathic nephrotoxic antibiotic, which has been shown to neutralize the effects of endotoxin both in vitro and in vivo. PMB-D70 (PMX-622), a covalent conjugate of PMB with dextran 70 (D70), is less nephrotoxic than the parent compound. We sought to determine whether therapy with PMB-D70, in addition to conventional antimicrobial chemotherapy, could improve survival in a model of Gram-negative peritonitis. At T = 0 h, New Zealand white rabbits were implanted intraperitoneally with 10 ml of a suspension containing hemoglobin (40 μg/ml), mucin (150 μg/ml), and 1.0 ± 0.2 x 104 cfu/kg of viable Escherichia coli (O18:K1). Beginning at T = 4 h, the rabbits were treated with gentamicin (5 mg/kg every 12 h) for five doses or until death, and infused for 24 h or until death with either D70 or PMB-D70. Two pairs of groups were studied (doses indicate cumulative amounts infused over 24 h). The PMB-D70 (low dose) group received PMB-D70 (5 mg/kg of the PMB component) and the D70 (low dose) group received an equivalent dose of D70. The PMB-D70 (high dose) group received PMB-D70 (10 mg/kg of the PMB component) and the D70 (high dose) group received an equivalent dose of D70. Results for the two PMB-D70 groups, on the one hand, and the two D70 group, on the other hand, were statistically indistiguishable and, accordingly, were pooled for all analyses. Survival at 7 days was 11/25 (44%) for rabbits treated with PMB-D70 as compared to 2/23 (9%) for animals treated with D70 ( P = 0.007). We conclude that adjuvant treatment with PMB-D70 improves survival in a clinically relevant model of Gram-negative sepsis.
Antibiotic-induced endotoxin release is organism-dependent in experimental Gram-negative sepsis
Authors: Healy D.P. , Clendening C.E. , Neely A.N. , Holder I.A.
Published: January 2008

The majority of in vitro and animal experiments that have been performed to assess antibiotic-induced endotoxin release (AIER) have employed a single test isolate, usually Escherichia coli. To determine the influence of microorganism type on AIER and interleukin-6 (IL-6) response, CF-1 mice were made septic following a 12-15% total body surface area nonlethal burn and subeschar challenge (LD90) with Klebsiella pneumoniae K2 (∼103 cfu), Proteus mirabilis 4552 (∼101 cfu) and Pseudomonas aeruginosa SBI-N (∼102 cfu). Three intraperitoneal (i.p.) doses, given every 4 h, of ceftazidime (TAZ, 200 mg/kg), imipenem (IMI, 100 mg/kg), ciprofloxacin (CIP, 25 mg/kg) and gentamicin (GEN, 25 mg/kg) were administered post burn and infection beginning when mice were septic with organ dysfunction. Free endotoxin concentrations were significantly ( P < 0.001) higher following all antibiotics for treatment of K. pneumoniae as compared to Ps. aeruginosa (intermediate) and P. mirabilis infections. Differential AIER was highest for TAZ and IMI, intermediate for CIP and lowest for GEN, for the treatment of K. pneumoniae and Ps. aeruginosa infections. There was a strong positive correlation between endotoxin release and IL-6 production for K. pneumoniae-treated animals, however increased endotoxin levels for Pseudomonas were accompanied by decreases in IL-6 levels. For P. mirabilis infection endotoxin levels were comparatively low, but highest for GEN and IMI. However, corresponding IL-6 levels increased only 3.2-fold for IMI and actually decreased by 50% for GEN following the first dose. Interestingly, CIP resulted in only modest endotoxin release and TAZ caused no appreciable release, however IL-6 concentrations dramatically increased 39.9-fold (TAZ) and 32.6-fold (CIP). This suggests that other pro-inflammatory mediators released from the bacterium, and not endotoxin, were more important determinants in the overall host response to antibiotic exposure. In conclusion, these data provide supportive evidence that absolute and differential AIER and production of IL-6 is organism-dependent in experimental Gram-negative sepsis. As a result, general conclusions concerning differential AIER for infection caused by E. coli or K. pneumoniae cannot necessarily be extrapolated to other species of Gram-negative bacilli. Furthermore, these study results strongly indicate that the microorganism and other pertinent pro-inflammatory factors (i.e. exotoxins, proteases), must be taken into account in the study design and data analysis of any experimental or clinical trial that is conducted to determine the significance of differential AIER.
Synthesis of deoxy analogues of (2→8)-linked 3-deoxy-α-D-manno-oct-2-ulopyranosylonic acid (Kdo) disaccharides for binding studies with Chlamydia specific monoclonal antibodies
Authors: Müller R. , Brade H. , Kosma P.
Published: January 2008

Deoxy analogues of the Chlamydia-specific, α-(2→8)-linked Kdo disaccharide epitope modified at the pyranose ring of the terminal Kdo unit have been prepared. Utilizing the 3,5-dideoxy-D-arabino-oct-2-ulosonate bromide donor [1] and the acceptor [2] under Helferich conditions, the 5-deoxy-α-Kdo-(2→8)-α-Kdo disaccharide [3] was obtained as the minor product together with unsaturated, α-(2→8)-glycosidically and (4→8)-ether-linked derivatives [5] and [7] as the major components. Deprotection afforded the disaccharide allyl glycosides [4], [6], and [8]. Further transformation of protected intermediates by hydrogenation followed by deblocking gave the propyl glycosides [12], [14] and [17]. The compounds may be used for binding studies with Chlamydia-specific and cross-reactive, Kdospecific monoclonal antibodies.
A strict requirement for LBP in the TNFα hyper-response of Propionibacterium acnes-sensitized mice to LPS
Authors: Freudenberg M.A. , Gumenscheimer M. , Jack R. , Merlin T. , Schütt C. , Galanos C.
Published: January 2008

One important feature of the Propionibacterium acnes-induced hypersensitivity to LPS is the enhanced production of TNFα induced in the sensitized mice upon LPS challenge [Katschinski T., Galanos G., Coumbos A., Freudenberg M.A. Gamma interferon mediates Propionibacterium acnes-induced hypersensitivity to lipopolysaccharide in mice. Infect Immun 1992; 60: 1994-2001]. We investigated the role of LPS binding protein (LBP) in the TNFα response of normal and P. acnes-sensitized mice to LPS in LBP+/+ and LBP-/- mice. Treatment of LBP+/+ (BalbC and 129 Sv) mice with P. acnes enhanced their TNFα response to LPS by 75-200-fold compared to the non-treated controls. Unsensitized LBP-/- (129 Sv x BalbC) mice were also stimulated by LPS to produce low amounts of TNFα. These were enhanced by prior P. acnes treatment, however, only by a factor of 4. The characteristic TNFα hyper-response was absent suggesting that the enhanced activity of LPS in sensitized mice is expressed only in the presence of LBP. Evidence for this was obtained by showing that administration of exogenous LBP restored fully the inducibility of the TNFα hyper-response in P. acnes-sensitized LBP-/- mice. Their response to LPS was 1000-fold higher then that of sensitized controls without LBP. A similar LBP treatment of unsensitized LBP-/- mice increased the TNFα response by a factor of only 5. In an analogous experiment, also IFN-γ-sensitized LBP-/- mice exhibited a TNFα overproduction in response to LPS only in the presence of exogenous LBP.
IFN-γR -/- mice show an enhanced liver and brain metallothionein I+II response to endotoxin but not to immobilization stress
Authors: Hernandez J. , Carrasco J. , Arbonés M.L. , Hidalgo J.
Published: January 2008

Interferon-γ (IFN-γ) is known for its important antiviral activity and other immunomodulatory actions. In in vitro studies, this cytokine has also been involved in the control of metallothionein (MT) synthesis. MT is a low molecular weight protein comprised of several isoforms called MT-I to MT-IV; of these, MT-1+11 are widely expressed, whereas MT-III and MT-IV are rather tissue specific. In the present report, we have studied in vivo the role of IFN-γ for a normal liver and brain MT-I+II response to immobilization stress and to an inflammatory process caused by bacterial lipopolysaccharide (LPS, endotoxin), using mice carrying a null mutation in the IFN-γ receptor gene (IFN-γR-/-). Liver MT-I mRNA and MT-(I+II) protein levels during stress of IFN-γR-/- mice were similar to those of the two parental mouse strains used to generate them, namely C57BU6 and 129/Sv mice, and that of the F1 C57BU6 x 129/Sv offspring mice. In contrast, liver MT response to LPS was significantly higher in the IFN-γR-/- mice than in the other strains. MT-I+II response to LPS was also higher in IFN-γR-/- mice in medulla plus pons and tended to in hypothalamus, hippocampus, and cerebellum, but not in the remaining brain. These results suggest that a role of IFN-γ on liver and brain MT-I+II response to stress is unlikely, but that this cytokine exerts an inhibitory effect on the signaling pathways activated by LPS involved in MT-I+II regulation. In situ hybridization analysis for MT-I and MT-III mRNAs of control mice revealed significant effects of the functional IFN-γ deficiency on MT-I but not MT-III mRNA levels in the dentate gyrus and the habenula, while no effects were observed in the remaining brain areas studied.
The dense low-density lipoprotein (LDL) subfractions are more potent than buoyant LDL for binding and neutralization of lipopolysaccharide
Authors: Netea Mihai G. , Demacker Pierre N.M. , Verver-Jansen Trees , Jacobs Liesbeth , Jan Kullberg Bart , Stalenhoef Anton F.H. , Van der Meer Jos W.M.
Published: January 2008

Lipoproteins are able to bind the lipopolysaccharide (LPS) component of Gram-negative bacteria, leading to formation of lipoprotein-LPS complexes and inhibition of endotoxin-stimulated cytokines. The differential capacity of the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions to bind and neutralize LPS has been studied in 11 healthy volunteers. The dense LDL2 and LDL3 subfractions were 20-25% more potent for the inhibition of endotoxin-induced production of tumor necrosis factor (TNF) than the buoyant LDL1 subfraction ( P < 0.01). This may have important consequences for the LPS-responsiveness of patients with different LDL subfraction phenotypes, and for the formation of atherogenic LDL-LPS complexes in vivo. No differences in the capacity to neutralize LPS has been detected between the various HDL subfractions.
Effect of acute endotoxin tolerance on NO production by isolated hepatic parenchymal and nonparenchymal cells and alveolar macrophages in rats
Authors: Robert René , Spitzer Judy A.
Published: January 2008

The changes in NO production induced by endotoxin (LPS) tolerance are controversial. The aim of this study was to explore modulation of NO production by LPS tolerance in different liver cell types and alveolar macrophages. Such cells were studied in three groups of male Sprague Dawley rats: non-tolerant rats (sal-LPS) received saline or no treatment 48 h before a 3 mg/kg LPS injection, tolerant rats received low dose LPS (0.5 mg/kg) 48 h before a second injection of saline (LPS-sal) or LPS 3 mg/kg (LPS-LPS). All injections were delivered i.v. Animals were studied 1 and 6 h after the second injection. NO production (assessed by nitrite release) by hepatocytes, Kupffer cells, endothelial cells and alveolar macrophages was simultaneously determined after 20 h of culture in the presence or in the absence of LPS, interferon-y (IFN) or both. Basal NO production by hepatocytes of tolerant and nontolerant LPS injected rats was high 1 h after the second injection, and was dramatically reduced 6 h after the second injection. Hepatocytes of tolerized LPSinjected (LPS-LPS) rats were significantly less sensitive to in vitro stimulation by LPS and IFN at 1 h than hepatocytes of tolerized saline-injected rats and this difference disappeared by 6 h. In Kupffer cells of tolerant rats 6 h after the second LPS injection, basal NO generation was significantly less than in nontolerant rats. In both cell types of tolerant LPS-LPS rats, in vitro stimulated NO production was moderately upregulated at 1 h and then highly upregulated at 6 h, whereas in nontolerant (sal-LPS) animals, stimulated NO production was only slightly upregulated or not at all. Sensitivity to LPS and IFN stimulation of Kupper cells of LPS-LPS rats was not different from Kupffer cells of LPS-sal rats at 1 h, but became significantly higher at 6 h relative to both LPS-sal and sal-LPS animals. In endothelial cells of tolerant saline-injected (LPS-sal) rats, basal NO production was significantly less than in the sal-LPS group both at 1 and 6 h after the second injection. In endothelial cells of tolerant LPS-LPS animals, a significant upregulation of stimulated NO production higher than in the other groups was observed only at 1 h. No difference was evident in basal or stimulated NO production by alveolar macrophages of the different treatment groups, except for a significant increase in basal NO production in tolerant rats (LPS-LPS) at 6 h relative to 1 h after the second LPS injection.
Use of mass spectrometry to compare three O-chain-linked and free lipopolysaccharide cores: differences found in Bordetella parapertussis
Authors: Zarrouk H. , Karibian D. , Godard I. , Perry M.B. , Caroff M.
Published: January 2008

Plasma desorption mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry methods were used to investigate the molecular differences between lipopolysaccharide free core molecules and core molecules substituted by O-chains in Bordetella parapertussis, Salmonella ohio, and Escherichia coli 0119. The B. parapertussis analysis indicated a difference in mass of 569 amu corresponding to 3 distal sugars comprising terminal residues of heptose, galactosaminuronic acid, and, N-acetyl-N-methylfucosamine, a result supported by evidence from NMR and serology. No differences were evident in the analyses of cores in either S. ohio or E. coli O119, although the first O-chain unit carried by S. ohio core lacked a terminal glucose present in the residual O-chain repeating units.
Uridine protection against D-galactosamine-sensitized LPS lethality in mice is complete
Authors: Silverstein R.
Published: January 2008

These studies show that uridine supplementation can quantitatively prevent D-galactosamine sensitization to lethal endotoxin shock. This observation serves to discount the possibility that mechanisms which do not involve uridine nucleotide depletion may contribute even marginally to the basic biochemical mechanism of D-galactosamine sensitization.
Act on Appropriateness and Mutual Seff-interest: Early T'ang Diplomatic Thinking, A.D. 618-649
Authors: Wang zhenping
Published: January 2008

Te and i are terms of multiple connotations. Although they have been conventionally translated as 'virtue' and 'righteousness' respectively, neither of them signifies excellence in personal moral cultivation and conduct in the context of T'ang diplomacy. Te is employed to mean 'getting proper arrangement for things', and i to indicate 'appropriateness' of the intended foreign policy. T'ang foreign policy rested mainly on consideration of efficacy, appropriateness, expedience and mutual self-interest, not on any abstract moral principles such as virtue and righteousness.
Foreign Direct Investment and 'Less Favoured Regions': Greek FDI in Bulgaria and Romania
Authors: Iammarino Simona , Pitelis Christos
Published: January 2008

During the process of industrialization and afterwards (1960-80), Greek outward investment to Western and developing countries had been marginal, and government policy had only emphasized inward investment. But since the beginning of the nineties the opportunities arising from new investment in Eastern European Countries (EECs) have completely changed the scene.

The aim of this article is to shed some light on the foreign direcf investment (FD1) flows from a peripheral European Union (EU) economy such as Greece, to two Less Favoured Regions of Eastern Europe, namely Bulgaria and Romania. In particular, on the basis of the empirical results gathered from a survey carried out in 1995-96, the objective is to analyze key criteria underlying investment choices by Greek firms, in order to help identify their role in the restructuring process and the impact that outward flows might have on the Greek economy.
Negative Political Advertising: Some Effects from the 13th Indian General Election 1999
Authors: Gupta Mukul P.
Published: January 2008

How does negative political advertising work and how effective is it ? This is a question that does not have mambiguous answers. Most research studies in the past have looked at negative political advertising just as a post-facto phenomenon. The results have been inconsistent.

This study looks at the political advertising, some negative, others not too much, used by the two leading political parties in their run up to the 13th general elections in India. Confined to main line English press advertising during 8-9 weeks prior to the date of polling, the study is restricted to the respondents in the seven parliamentary constituencies in Delhi.

Using a survey of voters, the study uses the theoretical basis of Hierarchy of Effects model, Cognitive Response model and the Expeclancy theory to look at the effectiveness of such advertising. Proceeding from simple questions, this study is able to articulate the way such advertising works. It also attempts to classify people in terms of their dispositions towards negative advertising.
The Politics of Labour Reforms in India
Authors: Venkata Ratnam C.S.
Published: January 2008

Labour policies and labour laws in India are focused rather narrowly on the 8 per cent organized labour. In the pre-liberalization era labour was protected in labour markets and capital in product markets. In the post-liberalization era both remain less protected, if not altogether unprotected. The shift in focus from labour markets to product markets in the context of liberalization is viewed with concern by organized labour. For over three decades comprehensive labour reforms have eluded India. The need for aligning labour laws with industrial policies is recognized, but the government is hesitant to take political risks. Unions want more protection, while employers want greater freedom and flexibility in dealing with labour. This paper exposes six myths, identifies key concerns and presents an agenda for labour reform.
Reforming the State: Government Initiatives and People's Movements
Authors: Paul Samuel
Published: January 2008

India's economic reforms of the early nineties were concerned chiefly with macro-economic management and liberalization. Broader reforms of the functioning of the state began to receive attention only at a later stage and that too only on a modest scale. This paper examines the recent developments in reforming the state in India. Both government initiatives for reform and citizen movements for better governance are presented and assessed. Legislation on the 'right to information' and introduction of citizen's charters are examples of government initiatives. Among civil society movements are initiatives that demanded access to information from the state, greater transparency in the electoral processes and enhanced accountability for public services. The paper also examines potentials and constraints in these initiatives and movements, and summarizes the lessons to be learned from them.
The Geography of Post-1991 Indian Economy
Authors: Bhandari Laveesh , Khare Aarti
Published: January 2008

The economic geography of India has been changing in line with a changing economy in the post-reform period. This paper uses sub-state-level (regional) data to study economic growth in the post-reform period. Using the latest available data (for the late nineties) at the sub-state level we find that a very clear break is observable between the eastern and western parts of India. That is, the western part of India has had an increase in its share in the economy as against the eastern part which has lost out during this period. Unlike others, this study covers all the 78 regions in 35 states of India. The smaller states that are generally left out in state-level studies are covered here. This allows us to generate a comprehensive picture of the geographical profile of India and how it is changing. We find some evidence that regions that have a predominantly natural resource-based economy are not growing as fast. We also find some evidence that regions that contain important river systems have not performed as well. Other issues are identified as well. This study finds that much more work is required and is possible with available data. It concludes by identifying a research agenda on the geographical profile of the post-reform Indian economy.
Reforms and Small Scale Industries in India
Authors: Bhardwaj Anil
Published: January 2008

Small scale industries (SSIs) have grown and improved their share in international trade during the reform period. This paper documents the reform agenda and its implications for SSIs. Despite the recommendations of the Abid Hussain Committee for complete dereservation of items reserved for SSIs and a grand or Rs 5 billion of assistance to the sector, piecemeal approach to the suggested changes meant that while quantitative restrictions were removed facilitating liberal import, due to continuation of reservation non-SSI units still cannot produce the reserved items. In actual practice it amounts to, paradoxically, SSIs enjoying protection from domestic non-SSI units, but facing competition from MNCs from abroad. SSIs hold the key to future employment growth. Governments cannot be expected to tackle small enterprise development properly. It requires a radically different mindset. Apart from legal and institutional reforms, the paper calls for rigorous exposure to international trade through trade fairs and trade delegations, and a collective voice and strategic partnering among SSIs.
Small Scale Industries in the Liberalized Era Beg for Attention
Authors: Yerram Raju B.
Published: January 2008

This paper begins by revisiting the Seoul and Bologna Charters on the SMEs and clarifies that the SME definition centres round the small scale industries in the absence of a clearly defined medium industry sector in India. A review of the policy, laws and the regulatory and institutional framework has been done in sufficient detail with a view to highlighting the fact that the SSIS in India require globally compatible facilitation in order to be competitive both domestically and internationally. The author maintains that easy and adequate institutional finance support is a necessary but not sufficient condition for the growth of this dynamic and vibrant sector. He envisages a clear role for the Small Industry Associations recognized on the basis of well-defined criteria. He argues for a quick enactment of a comprehensive enabling law for the sector and for restructuring the office of the DC-SSI, to attain the envisaged competitiveness.
Strategic Management of Bio-Pharmaceutical Knowledge for Improved R&D Productivity
Authors: Nimmagadda Mohan R.K. , Prasad B.V.L.S.
Published: January 2008

The strategic mapping of research knowledge through corporate intranets and knowledge management informatics initiatives is gaining importance in the bio-pharmaceutical industry. The silent merger of biotechnology and pharmaceutical industries, which are driven by the high-end research and development activities, is playing a pivotal role towards bio-pharmaceutical sectoral growth and development. Further, there is an enhancement in performance-based expectations and demand towards improving medication related to different genetic and non-genetic diseases in the post-human genomic era through personalized medicines. Synchronization through mapping of systems and processes within the available organizational human resources and intellectual capital networks (ICN) would collectively bring out the best knowledge sharing practices, which are of prime importance for the industry's sustenance. Long-term sustainability for this industry is in terms of the strategic knowledge management practices through cross-functional human resources and their ability to contribute and leap ahead of the market competition through sustainable innovation and economics. With most of the biotechnology and pharmaceutical companies looking towards mergers and alliances for their survival, organizational structures that protect the critical creativity are essential for their future survival. Post-human genomics stands to revolutionize and fragment further the industry and the very nature of practising science.
Peer Evaluation of Student Interaction in Organizational Behavior and Other Courses
Authors: Ferris William P. , Hess Peter W.
Published: January 2008

This article summarizes various efforts by instructors to grade and evaluate student interaction in management courses. Obstacles to effective evaluation are discussed. Four criteria are proposed for systems involving peer evaluation. The development of a highly effective system which utilizes behaviorally anchored rating scale (BARS) performance appraisal tech niques is described.
Peer Performance Evaluation: when Peers do it They do it Better
Authors: Murrell Kenneth L.
Published: January 2008

This article discusses the use of a peer evaluation process that involves students in the development of instruments and procedures as well as the evaluations themselves. The article also describes a procedure through which a group member can be terminated (or resign) from a group and pro vides insights about why a combination of these two procedures result in ef fective and realistic peer evaluations.
Marketing Majors' Satisfaction With Their College Experience: Implications for Strategic Planning in Marketing Departments
Authors: Schmidt Sandra L. , Debevec Kathleen , Comm Clare L.
Published: January 2008

This study examines the criteria marketing majors used in selecting a college, their evaluation of and satisfaction with their chosen college, and the extent to which marketing majors differ from other business majors on these issues. Results indicate that marketing majors are satisfied with their college experience overall, but that they are less satisfied than other business majors on some dimensions. Recommendations are offered to enhance strategic planning in marketing departments.
The Diffusion of Marketing Research Techniques in Business: Implications for Marketing Education
Authors: Bellenger Danny N. , Howell Roy D. , Wilcox Jim , Greenberg Barnett A.
Published: January 2008

The use of more sophisticated research techniques, particularly multivariate statistical procedures, has increased dramatically over the past decade. Graduate education appears to be a significant change agent in this diffusion process. Marketing educators must prepare future managers to effectively use information developed with increasingly complex procedures.
A Customer Satisfaction Approach to Introducing Physical Distribution in the Principles of Marketing Course
Authors: Sherwood Charles S. , Nordstrom Richard D.
Published: January 2008

Traditional presentations ofphysical distribution in a principles of marketing course commonly focus on the activities of distribution without effectively integrating them into the marketing mix. This article offers instructors an integrative framework for presenting physical distribution activities as a means of achiev ing desired levels of customer service and ultimately customer satisfaction.
Student Journal Writing in Marketing Courses
Authors: Fisher Caroline M.
Published: January 2008

Student journal writing was tested in marketing courses. Journal writing is similar to writing a diary except that personal experiences are related to course concepts. The goals were to increase (1) communication skills, (2) integration of concepts into the "real world," and (3) participation and sharing in the classroom.
A "Real-World" Approach to Coursework in Sales Management
Authors: Kimball Bob
Published: January 2008

Educators and practitioners agree that coursework should help students understand the actual business environment. This article describes an innovative approach to teaching business courses which addresses the functions of a position and also how to be effective, gain power and recognition, play the corporate "game," and move up the ladder.
Bartholow, Sciamanna, Alberti: Pioneers in the Electrical Stimulation of the Exposed Human Cerebral Cortex
Authors: Zago Stefano , Ferrucci Roberta , Fregni Felipe , Priori Alberto
Published: January 2008

Although the past 25 years have witnessed increasing interest in human brain stimulation, its historical development is marked by phases of fascination and obscurity. Its history dates back to the 19th century when the first reports describing application of an electric current to an isolated point on the exposed brain made brain stimulation a major neuroscientific novelty of the time. In this article, the authors present and discuss a number of early experiments involving electrical stimulation of the exposed human brain. In this important, albeit unexplored, historical chapter of brain stimulation, the 3 investigators, Bartholow, Sciamanna, and Alberti, were the first to reproduce findings in animals with electrical brain stimulation in humans. NEUROSCIENTIST 14(5):521—528, 2008. DOI: 10.1177/1073858407311101
A Reporting System for Nutrient Adequacy12
Authors: Johnson Nancy E. , Nitzke Susan , VandeBerg Dina L.
Published: January 2008

Dietary intakes of specified nutrients can be estimated easily and relatively accurately by using techniques proposed in this paper. Foods that contain these nutrients and that are most frequently consumed by a target population group can be used as the basis for development of a quantified food record form. Placing foods of similar nutrient content into groups, evaluating the variance of the foods within each group in respect to nutrient standards used, and estimating nutritional adequacy of diets by using mean nutrient contributions from each group result in a reasonably accurate assessment of nutrient adequacy of diets of groups of people. A simple computer program was written to process the data and to provide nutrient profiles that could be used to develop and monitor nutrition education programs.
Characterization of water soluble pentosans of enzyme supplemented dough and breads/ Caracterización de las pentosanas solubles en agua extraídas de masa y pan conteniendo enzimas comerciales
Authors: Jimenez T. , Martinez-Anaya M.A.
Published: January 2008

Water soluble pentosans (WSP) from doughs and breads made with different enzyme preparations are characterized according to extraction yield, sugar composition, xylose/arabinose ratio and molecular weight (MW) distribution. Extraction yield was greater for dough than for bread samples, ranging from 0.94 to 1.64%, but bread extracts had a higher purity. Percent of pentoses in purified WSP was greater in pentosanase supplemented samples (28-55%) than in control and amylase containing samples (23-32%). Major sugars were xylose and arabinose, but glucose and mannose also appeared in the extracts. The xylose/arabinose (Xyl/Ara) ratio was 1.3-1.6 and underwent small changes during processing. Enzyme addition caused an increase in Xyl/Ara ratio, attributable to a debranching of arabinoxylans (AX) with higher degree of Ara substitution by arabinofuranosidase. Addition of pentosanases had a significant effect in increasing WSP with MW over 39 000, whereas those of low MW changed only slightly. MW distribution depended on enzyme source, and whereas some enzymes showed activity during fermentation others increased their activity during baking. No synergistic effects were observed in studied variables due to the combination of amylases with pentosanases. Protein in WSP extracts eluted together with ferulic acid suggesting they were linked, but not associated with a determined carbohydrate fraction.
Perfil sensorial de diferentes muestras de nuez (Juglans regia L.)/Sensory profiles of different walnuts (Juglans regia L.)
Authors: Guerrero L. , Romero A. , Gou P. , Aleta N. , Arnau J.
Published: January 2008

The nutritional and sensory properties of walnuts (Juglans regia L.) are well known and appreciated by consumers. Despite this, few studies about their basic sensory characteristics or about the effect of agronomic and technological factors on them have been carried out. In this study six different types of walnut were sensorially described, using expert and non-expert assessors, in order to obtain a simple sensory profile which would enable discrimination between the samples studied. The final sensory profile was made up of 18 descriptors. This profile was useful for differentiating and describing samples from several varieties of fruit, two different geographical origins and two different post-harvest treatments. Using only 10 of these descriptors and through discriminant analysis it was possible to classify correctly 100% of the samples into their respective groups. The use of non-expert assessors in the generation of descriptors pointed out the simplicity of the profile, probably allowing for interpretation by non-technical individuals. Selection and interpretation of descriptors was easier and faster than usual as a result of asking the assessors, especially the consumers, to add their own description of the attributes chosen. This also seemed to have affected, in an important way, the number of attributes generated by non-expert assessors.