Effect of sonication on the dispersion state of lipopolysaccharide and its pyrogenicity in rabbits.

Komuro, Takashi; Murai, Toshimi; Kawasaki, Hironoshin

doi:10.1248/cpb.35.4946

Cited by 21 publications

(15 citation statements)

References 8 publications

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“…The most endotoxically active lipid-A monomer structure is conical whereas less active lipid-A is cylindrical. The activity of endotoxin can be increased by sonication [47]. The biological significance of these supra-molecular structures, and the relative importance of LPS aggregates versus LPS monomers towards host recognition, remains unclear.…”

Section: Structure Activitymentioning

confidence: 99%

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

Hurley

2013

Toxins

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Endotoxin is a potent mediator of a broad range of patho-physiological effects in humans. It is present in all Gram negative (GN) bacteria. It would be expected that anti-endotoxin therapies, whether antibody based or not, would have an important adjuvant therapeutic role along with antibiotics and other supportive therapies for GN infections. Indeed there is an extensive literature relating to both pre-clinical and clinical studies of anti-endotoxin antibodies. However, the extent of disconnect between the generally successful pre-clinical studies versus the failures of the numerous large clinical trials of antibody based and other anti-endotoxin therapies is under-appreciated and unexplained. Seeking a reconciliation of this disconnect is not an abstract academic question as clinical trials of interventions to reduce levels of endotoxemia levels are ongoing. The aim of this review is to examine new insights into the complex relationship between endotoxemia and sepsis in an attempt to bridge this disconnect. Several new factors to consider in this reappraisal include the frequency and types of GN bacteremia and the underlying mortality risk in the various study populations. For a range of reasons, endotoxemia can no longer be considered as a single entity. There are old clinical trials which warrant a re-appraisal in light of these recent advances in the understanding of the structure-function relationship of endotoxin. Fundamentally however, the disconnect not only remains, it has enlarged.

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Section: Structure Activitymentioning

confidence: 99%

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

Hurley

2013

Toxins

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“…In particular, the activity of endotoxin is not a uniform gravimetric property for endotoxins of different bacterial origins. Also, the mode of LPS aggregation (60), the interactive effect of plasma (61), and the presence of nonviable bacterial cells and cell fragments that accompany a GN bacteremia (62) influence the relationship. Moreover, differential kinetics of endotoxemia and GN bacteremia are likely each influenced by the presence of virulence factors, which differ for different species of GN bacteria (63).…”

Section: Figmentioning

confidence: 99%

Endotoxemia as a Diagnostic Tool for Patients with Suspected Bacteremia Caused by Gram-Negative Organisms: a Meta-Analysis of 4 Decades of Studies

et al. 2015

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The clinical significance of endotoxin detection in blood has been evaluated for a broad range of patient groups in over 40 studies published over 4 decades. The influences of Gram-negative (GN) bacteremia species type and patient inclusion criteria on endotoxemia detection rates in published studies remain unclear. Studies were identified after a literature search and manual reviews of article bibliographies, together with a direct approach to authors of potentially eligible studies for data clarifications. The concordance between GN bacteremia and endotoxemia expressed as the summary diagnostic odds ratios (DORs) was derived for three GN bacteremia categories across eligible studies by using a hierarchical summary receiver operating characteristic (HSROC) method. Forty-two studies met broad inclusion criteria, with between 2 and 173 GN bacteremias in each study. Among all 42 studies, the DORs (95% confidence interval) were 3.2 (1.7 to 6.0) and 5.8 (2.4 to 13.7) in association with GN bacteremias with Escherichia coli and those with Pseudomonas aeruginosa, respectively. Among 12 studies of patients with sepsis, the proportion of endotoxemia positivity (95% confidence interval) among patients with P. aeruginosa bacteremia (69% [57 to 79%]; P ‫؍‬ 0.004) or with Proteus bacteremia (76% [51 to 91%]; P ‫؍‬ 0.04) was significantly higher than that among patients without GN bacteremia (49% [33 to 64%]), but this was not so for patients bacteremic with E. coli (57% [40 to 73%]; P ‫؍‬ 0.55). Among studies of the sepsis patient group, the concordance of endotoxemia with GN bacteremia was surprisingly weak, especially for E. coli GN bacteremia. The Limulus amebocyte lysis (LAL) assay, which utilizes extracts of blood cells (amebocytes) of the Limulus polyphemus horseshoe crab, is a highly sensitive and specific test available for the detection of endotoxin (lipopolysaccharide [LPS]) (1). This assay is a reliable method for the detection of infection with Gramnegative (GN) bacteria in body fluids other than blood (1). However, the clinical significance of endotoxin detection in blood as both a diagnostic and a prognostic test is unclear, despite over 100 studies published over 4 decades for a broad range of patient groups (2-45). The interpretation of the literature is confounded by a 100-fold increase in assay sensitivity (3) and substantial differences in patient inclusion criteria among the studies in the literature over this period.Moreover, in the evaluations of endotoxemia therapies over this time period, there has been a substantial and unexplained disconnect between the results of animal models of sepsis and the results of subsequent clinical trials of the same therapies (46).Five factors have prompted a reappraisal of this question of the clinical significance of endotoxin detection. First, new studies and new data from older studies relating to endotoxemia detection have appeared and need to be incorporated (5-7, 15, 24, 32, 37, 43, 44). Second, the relevance of recently defined structural differences in lipid A,...

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“…At least twelve animals were used in each experiment. Fever responses were measured rectally and recorded continuously for 4 h. Maximum rectal temperature increase (ATm~ x) and fever index (FI-4) representing the area under the fever curve for 4 h, were determined [19]. Pyrogenicity was also expressed using the MPD-3 value, representing a minimal pyrogenic dose raising the rectal temperature by 0.6 ° C, 3 h after injection.…”

Section: Pyrogen Test Of Lps In Rabbitsmentioning

confidence: 99%

Comparison of R- and S-form lipopolysaccharides fractionated from Escherichia coli UKT-B lipopolysaccharide in pyrogen and Limulus tests

Komuro¹

1989

FEMS Microbiology Letters

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Different LPS was shown to have a relatively different proportion of O-specific chain-less (R-form) LPS by polyacrylamide gel electrophoresis (PAGE) with sodium deoxycholate (DOC). By using DOC-PAGE, S-form LPS having O-chain with approximately 11 repeating units on average (S-Fr) and O-chain-less LPS (R-Fr) were separated from Escherichia coli UKT-B S-form LPS. Significantly stronger pyrogenicity was observed in R-Fr than in S-Fr when measured on the weight basis. Similar result was observed in Limulus test. Comparing biological activities of different S-form LPS, attention should be given to the amounts of co-existing R-form LPS.

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Effect of sonication on the dispersion state of lipopolysaccharide and its pyrogenicity in rabbits.

Cited by 21 publications

References 8 publications

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

Endotoxemia as a Diagnostic Tool for Patients with Suspected Bacteremia Caused by Gram-Negative Organisms: a Meta-Analysis of 4 Decades of Studies

Comparison of R- and S-form lipopolysaccharides fractionated from Escherichia coli UKT-B lipopolysaccharide in pyrogen and Limulus tests

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