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PubMed1997

Endotoxin levels in donors and recipients during orthotopic liver transplantation.

BACKGROUND: The hypothesis being tested in this paper is that endotoxin levels in donors and in recipients during liver transplantation influences postoperative outcome. METHODS: Endotoxin levels in systemic venous and portal venous blood were measured using in 46 adult donors and 44 adult recipients (47 liver transplants) during the period 1992-95. Endotoxin was measured using a modification of the Limulus amoebocyte lysate (LAL) assay. RESULTS: In the donor, systemic endotoxin levels were above normal levels at 10.0 +/- 1.3 pg/mL from the start and rose to 15.8 +/- 2.9 pg/mL after dissection of the hilar structures, but fell to 10.6 +/- 0.8 pg/mL just prior to the removal of the liver (control = 7.8 pg/mL). The mean portal venous endotoxin levels were 18.2 +/- 3.4 pg/mL after dissection of the hilar structures and 12.6 +/- 0.9 pg/mL after cannulation of the portal vein. In the recipients, the highest level in the portal venous blood occurred at the end of the anhepatic phase (46.5 +/- 6.7 pg/mL). The systemic venous samples in the recipients were elevated to start with, but fell rapidly to 19.3 +/- 1.5 pg/mL 24 h postoperatively, and to 13.2 +/- 1.0 pg/mL by day 7. The endotoxin concentrations were higher in recipients who developed complications. CONCLUSIONS: Endotoxin is elevated throughout the recipient transplantation procedure and up to 7 days postoperatively. High levels of endotoxin at induction, the anhepatic phase and at certain time points correlated with patients who developed postoperative complications.

Adolescent↗
PubMed1981

Polymyxin B sulphate protects cats against the haemodynamic and metabolic effects of E. coli endotoxin.

1 The intravenous administration of E. coli endotoxin (2 mg/kg) in cats anaesthetized with pentobarbitone resulted in an initial acute increase in right atrial pressure and a transient systemic hypotension. Later (from 1 h onwards) there was a progressive decrease in cardiac output, a reduced right atrial filling pressure, systemic hypotension and a profound metabolic acidosis (lactate of 30 +/- 1 mg/100 ml at 5 h compared with 5.1 +/- 0.5 mg/100 ml pre-endotoxin). Only one of eight animals so treated survived 8 h. 2 Polymyxin B sulphate, given intravenously (1 min before endotoxin) as a bolus injection (5 mg/kg) followed by a continuous intravenous infusion (additional 5 mg/kg given over a 30 min period) prevented the endotoxin-induced pulmonary (right atrial) hypertension but not the acute systemic hypotension. 3 Polymyxin B sulphate reduced the delayed haemodynamic effects of endotoxin (systemic hypotension, decrease in cardiac output); all the eight animals so treated survived 8 h compared with only 1/8 of the controls. 4 Polymyxin B did not prevent the initial (1-3 h) and marked metabolic acidosis following endotoxin; however, after 3 h, arterial lactate levels returned towards control whereas in the endotoxin-alone group they continued to increase until death. 5 The mechanism of this marked protective effect of the antibiotic and the possible clinical repercussions are discussed; the most likely explanation for the protection is in chemical combination with the lipid A moiety of the endotoxin.

Animals↗
PubMed1983

Plasma acid phosphatase levels in endotoxaemia: modification by drugs and chemically detoxified endotoxins.

The ability of chemically detoxified E. coli endotoxins and membrane-active agents to modify the toxicity of native E. coli endotoxin in vivo was examined. The time- and dose-dependent increase in plasma acid phosphatase activity following toxin administration to rats provided a convenient quantitative measure of in vivo toxicity under various experimental conditions. Treatment of endotoxin with either sodium hydroxide or sodium periodate produced substances which, when injected alone, failed to cause an increase in plasma acid phosphatase activity. When given before native endotoxin, periodate-detoxified toxin produced a dose-dependent reduction in the elevation of plasma enzyme activity caused by unmodified toxin. Pretreatment with pranolium, hydrocortisone or (+)-propranolol also reduced the in vivo toxicity of endotoxin. Mortality studies in mice provided further independent support for the effectiveness of periodate-detoxified endotoxin and membrane-active drugs as endotoxin antagonists. Evidence has been found that under certain conditions gentamicin may act synergistically with bacterial endotoxins in vivo.

Acid Phosphatase↗
PubMed1989

Endotoxin-induced hyperreactivity of the guinea-pig isolated trachea coincides with decreased prostaglandin E2 production by the epithelial layer.

1. Pretreatment of guinea-pigs with endotoxin (1 mg kg-1 b.w., i.p., 4 days before the experiments) results in respiratory airway hyperreactivity in vitro. Dose-response curves with either arecoline or histamine on isolated tracheae from these animals display increased maximal contractions, and decreased EC50 values. 2. Tracheae denuded of epithelium respond with a similar hyperreactivity to histamine as observed in preparations from endotoxin pretreated animals. Removal of the epithelial layer of tracheae from endotoxin pretreated guinea-pigs did not additionally affect the histamine dose-response curve. 3. The cyclo-oxygenase inhibitor indomethacin (10 microM) induces histamine hyperreactivity which is equal in intact and epithelium-denuded tracheae from saline or endotoxin pretreated guinea-pigs. Similar results are obtained with the combined lipoxygenase/cyclo-oxygenase inhibitor nordihydroguaiaretic acid (10 microM). 4. Histamine (0.1 mM) induces an increase in prostaglandin E2 (PGE2) formation by the tracheal spiral in vitro, which is reduced by 34% by endotoxin pretreatment, and by about 60% following epithelium removal irrespective of endotoxin pretreatment. 5. Arachidonic acid (AA, 22 microM) stimulation of the guinea-pig trachea in vitro induces a relaxation, and an increase in PGE2 production. In preparations lacking the epithelium, AA induces a contraction which coincides with a 60% reduced increase in PGE2 formation. These effects are not altered by endotoxin pretreatment. 6. It is concluded that the endotoxin-induced respiratory airway hyperreactivity may be caused by a disturbed ability of epithelial cells to synthesize PGE2. The decreased formation of this prostaglandin is rather the consequence of a diminished liberation of AA from the phospholipid stores than a dysfunction of the cyclo-oxygenase enzyme.

Airway Resistance↗
PubMed1992

Endotoxin-induced vasodilatation in anaesthetized rat skin involves nitric oxide and prostaglandin synthesis.

1. The effect of intradermally injected endotoxin on skin blood flow was investigated in anaesthetized male Wistar rats in vivo. 2. Local skin blood flow changes were measured hourly for 6 h in the shaved dorsal skin with a laser-Doppler flow probe and compared to changes in control sites which had been injected with 100 microliters of phosphate-buffered saline. By 3 h, skin blood flow increased above basal by 129 +/- 27% and 186 +/- 29% with 1 and 10 micrograms of endotoxin respectively. Blood flow remained significantly elevated at 6 h, the corresponding figures being 129 +/- 24% and 154 +/- 31% (P less than 0.05, n = 6 rats, mean +/- s.e.mean). 3. In further experiments, the response to 3 micrograms of endotoxin was measured at 4 h and treatment with a cyclo-oxygenase inhibitor, nitric oxide synthase inhibitors or a topical steroid all significantly inhibited this response (P less than 0.05 in each case, n = 6 rats in each group with duplicate sites in each animal). 4. Indomethacin 3 x 10(-9) mol per site injected 3.5 h after injection of endotoxin suppressed the mean 4 h response to endotoxin by 78%; NG-nitro-L-arginine methyl ester (L-NAME) 10(-7) mol per site suppressed the response by 95%; NG-monomethyl-L-arginine (L-NMMA) 10(-7) mol per site suppressed the response by 50%; whereas the D-isomer of NG-monomethyl-arginine 10(-7) mol per site had no significant effect.5. Topical application of the corticosteroid, betamethasone 17-valerate (1% solution) 18 h before injection of endotoxin inhibited the mean 4 h response to endotoxin by 66% and the 6 h response by 48%.6. In the same model, the vasodilator response to arachidonic acid was inhibited by both indomethacin and nitric oxide synthase inhibitors (P<0.05 in each case).7. These data suggest that the microcirculatory vasodilator response to endotoxin and arachidonic acid injected locally involves both nitric oxide synthase and cyclo-oxygenase in this in vivo model.

Amino Acid Oxidoreductases↗
PubMed1995

Endotoxin inhibition of distension-stimulated gastric acid secretion in rat: mediation by NO in the central nervous system.

1. The involvement of nitric oxide in the acute inhibitory effects of low doses of endotoxin, following intracerebroventricular (i.c.v.) or intravenous (i.v.) administration, on gastric acid secretion stimulated by distension or i.v. infusion of pentagastrin has been investigated in the continuously perfused stomach of the anaesthetized rat. 2. The i.c.v. administration of E. coli endotoxin (800 ng kg-1) abolished the acid secretory response induced by gastric distension (20 cm water intragastric pressure) within 30 min of administration. 3. By contrast, submaximal rates of acid secretion induced by i.v. infusion of pentagastrin (8 micrograms kg-1 h-1) were not inhibited by i.c.v. administration of endotoxin (800 ng kg-1). 4. Prior i.c.v. administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 800 micrograms kg-1) restored the acid secretory responses to distension in rats treated with endotoxin (i.c.v.). 5. Likewise, i.v. administration of endotoxin (5 micrograms kg-1) abolished the acid secretory response induced by gastric distension within 30 min of administration. Prior i.c.v. injection of L-NAME (800 micrograms kg-1) or its i.v. administration (10 mg kg-1) restored acid secretory responses in rats receiving i.v. endotoxin. 6. The reversal by L-NAME (i.v.) of the acid inhibitory effects of endotoxin (i.v.) was prevented by L-arginine (12 mg kg-1, i.c.v. or 100 mg kg-1, i.v.), but not by its enantiomer D-arginine. 7. The present results imply the existence of an acute response to endotoxin involving NO synthesis in the brain. NO may act as a neuromodulator or neurotransmitter in a nervous reflex leading to the inhibition of acid secretion stimulated by gastric distension.

Animals↗
PubMed1989

The effects of slow infusion of a low dosage of endotoxin in healthy horses.

The effects of slow intravenous (i.v.) infusion of a very low dosage of endotoxin (a cumulative dosage of 0.03 microgram/kg bodyweight [bwt] infused over 60 mins) were evaluated in six conscious healthy horses. Duodenal, right ventral colon, and caecal contractions were detected with strain gauge force transducers. Lateral caecal arterial blood flow was measured using transit time ultrasonic blood flow probes. Duodenal contractile activity was not significantly altered by infusion of endotoxin. In contrast, the contractile activity of the right ventral colon 90 and 270 mins after infusion of endotoxin was less than after infusion of saline solution (control). The contractile activity of the caecal body 30, 60, 90, 120 and 240 mins after infusion of endotoxin was significantly less than control. The contractile activity of the caecal apex 60, 90, 120, 240 and 270 mins after termination of endotoxin infusion was significantly less than control. Lateral caecal arterial blood flow was significantly less than control at the end of endotoxin infusion and at 30, 45, 60, 90, 105 and 120 mins afterwards. Average carotid arterial pressure was significantly greater than control at 210, 225, 240, 255 and 270 mins after endotoxin infusion. Infusion of endotoxin increased heart rate, respiratory rate and body temperature significantly. The decrease in caecal contractile activity occurred before the increase in body temperature. All horses became depressed and developed injected mucous membranes. Signs of abdominal pain (including stretching, pawing, kicking at abdomen) were seen in four of the six horses.

Abdominal Pain↗
PubMed1974

Fever produced by endotoxin injected into the hypothalamus of the monkey and its antagonism by salicylate.

1. A suspension of the killed cell bodies of either E. coli, S. dysenteriae or S. typhosa was micro-injected through cannulae implanted chronically at specific sites within the diencephalon and mid-brain of the unanaesthetized monkey. A biphasic, monophasic or an undifferentiated fever could be induced by each type of micro-organism, but the type of response depended solely upon the locus of injection.2. Although little difference in the potency of the three pyrogens was found, the rise in body temperature was in each instance dependent upon the concentration of the endotoxin. A more intense fever was accompanied by shivering, vasoconstriction of the ear vessels, piloerection and huddling behaviour. Tolerance to the pyrexic effect of repeated injections of endotoxin did not develop.3. The febrile response having the shortest latency, greatest maximum rise in temperature and largest 10-hr fever index was evoked by micro-injections into the anterior hypothalamic, preoptic area. The incidence of biphasic fevers was also greater after endotoxin was injected into this same region. Endotoxin given similarly in the posterior hypothalamus or in the mesencephalon had either no effect or produced a smaller elevation in temperature after a longer latency. The distance of an injection site from the coronal plane formed by the optic chiasm and anterior commissure correlated significantly with the latency and magnitude of the temperature change as well as the fever index.4. When given intravenously, endotoxin in a quantity at least 100 times greater was required to evoke a fever similar to that produced when the pyrogen was micro-injected into the anterior hypothalamic, preoptic region. However, a biphasic fever was evoked with a latency of from 3 to 15 min when a larger amount of endotoxin was injected intravenously. Tolerance developed rapidly to the febrile effect of endotoxin administered by this route although toxic reactions were not observed.5. After the fever evoked by the hypothalamic injection of endotoxin had reached a plateau, 300-1200 mg sodium salicylate administered intragastrically produced a dose-dependent fall in temperature, but had no effect on the body temperature of an afebrile monkey.6. It is concluded that in the rhesus monkey, a bacterial pyrogen can evoke a fever which is mediated entirely by an action on the central nervous system, the principal site being the anterior hypothalamic, preoptic area. The first phase of a biphasic fever caused by bacteria acting either by the central or peripheral route seems to be due either to a direct action of the pyrogen on the cells of the anterior hypothalamus, or to the secondary release within this region of an intermediary thermogenic substance such as 5-hydroxytryptamine or prostaglandin. The finding that sodium salicylate counteracts a centrally evoked fever is not compatible with the hypothesis that an antipyretic exerts its action by preventing a pyrogen that is circulating in the blood stream from entering the central nervous system.

Animals↗
PubMed1986

Autoradiography of tobramycin uptake by the proximal and distal tubules of normal and endotoxin-treated rats.

Multiple factors may modify the pharmacokinetics of aminoglycosides and increase their nephrotoxic potential. In the present study, the influence of Escherichia coli endotoxin on the renal handling of [3H]tobramycin was investigated. The accumulation of [3H]tobramycin in proximal tubules, distal tubules, and collecting ducts was compared in both normal and endotoxin-injected (0.25 mg/kg) rats. Histological observations were also made. Blood pressure and cardiac frequency were recorded, and renal function was evaluated with labeled inulin and p-aminohippuric acid. Following administration of endotoxin, disturbed intrarenal localization of the drug was noted. Grain counts were affected in both proximal and distal tubules. Increased labeling was observed at all time intervals in the proximal tubules. In the distal tubules of endotoxemic animals we could detect higher amounts of drug at 10 and 60 min in the medulla and at 10 min in the cortex. Not all of the tubules were labeled to the same extent. No histological lesion was noted on light microscopy in animals receiving either normal saline or endotoxin. The dose of endotoxin used resulted in very fine physiological disturbance. Both blood pressure and cardiac frequency were minimally affected by endotoxin. Decreases in glomerular filtration rate and renal plasma flow were observed. However, none of these changes was statistically significant. The present study has shown that low doses of endotoxin alter the renal handling of aminoglycosides in the absence of any major physiological disturbance or histological changes. By increasing the total amount of drug within the kidney, endotoxin might increase the nephrotoxic potential of aminoglycosides.

Animals↗
PubMed1980

Movement of endotoxin through soil columns.

Land treatment of wastewater is an attractive alternative to conventional sewage treatment systems and is gaining widespread acceptance. Although land application systems prevent surface water pollution and augment the available water supplies, the potential dangers to human health should be evaluated. Since sewage may contain high amounts of bacterial endotoxin, the removal of endotoxin from sewage by percolation through soil was investigated. It was found that 90 to 99% of the endotoxin was removed after travel of sewage through 100 to 250 cm of loamy sand soil. When distilled water was allowed to infiltrate into the soil to simulate rainfall, the endotoxin was mobilized and moved in a concentrated band through the soil column. On testing samples from actual land treatment sites, as much as 480 ng of endotoxin per milliliter was found in some groundwater samples. The presence of endotoxin in potable water is known to be a potential problem under some circumstances, but the importance of endotoxin in water supplies has not been fully assessed. Therefore, the design, operation, and management of land application systems should take into account the fate of endotoxin in groundwater beneath the sites.

Endotoxins↗
PubMed1984

Automation of chromogenic substrate Limulus amebocyte lysate assay method for endotoxin by robotic system.

The chromogenic substrate Limulus amebocyte lysate (LAL) assay method for the detection of endotoxin was automated by a Zymate robotic system. The software developed enables the robot to automatically dilute a stock reference endotoxin standard (20,000 endotoxin units per ml) for the construction of a five-point standard curve, make sample dilutions to the proper testing concentration, and perform chromogenic substrate LAL assays in duplicate. The linearity of the standard curve and the endotoxin concentration in each sample are calculated and results are printed automatically. In 48 min the automated system assays three samples and a reference standard in duplicate along with a water blank. Sensitivity of the assay is a function of incubation time. The assay is linear (r greater than 0.99) in the region of 0 to 1.0 endotoxin units per ml or 0 to 0.2 endotoxin units per ml with incubation times of 10 or 16 min, respectively. The method can be made very sensitive, detecting as low as 0.003 endotoxin units per ml with 30 min of incubation. The precision of the assay method, determined by assaying an endotoxin reference solution eight times, is ca. 6%. The LAL reagent designed for gel-clot assay was modified for the chromogenic substrate assay. We describe the optimum conditions for the performance of the chromogenic substrate LAL assay and stability of the LAL reagent.

Automation↗
PubMed1999

Removal of endotoxin during purification of poly(3-hydroxybutyrate) from gram-negative bacteria.

Poly(3-hydroxybutyrate) (PHB) was produced by cultivating several gram-negative bacteria, including Ralstonia eutropha, Alcaligenes latus, and recombinant Escherichia coli. PHB was recovered from these bacteria by two different methods, and the endotoxin levels were determined. When PHB was recovered by the chloroform extraction method, the endotoxin level was less than 10 endotoxin units (EU) per g of PHB irrespective of the bacterial strains employed and the PHB content in the cell. The NaOH digestion method, which was particularly effective for the recovery of PHB from recombinant E. coli, was also examined for endotoxin removal. The endotoxin level present in PHB recovered by 0.2 N NaOH digestion for 1 h at 30 degrees C was higher than 10(4) EU/g of PHB. Increasing the digestion time or NaOH concentration reduced the endotoxin level to less than 1 EU/g of PHB. It was concluded that PHB with a low endotoxin level, which can be used for various biomedical applications, could be produced by chloroform extraction. Furthermore, PHB with a much lower endotoxin level could be produced from recombinant E. coli by simple NaOH digestion.

Bacterial Toxins↗
PubMed1979

Endotoxin lethality and tolerance in mice: analysis with the B-lymphocyte-defective CBA/N strain.

Immune-defective and immunologically normal F1 mice derived from the CBA/N strain were used to study the influence of anti-endotoxin antibody on the lethal effects of endotoxin. Immune-defective F1 male mice were unable to make specific responses to purified preparations of E. coli O111:B4 endotoxin, whereas their immunologically normal F1 female littermates made excellent responses. The ability to form antibody to lipopolysaccharide (LPS) in these F1 mice did not influence either their natural resistance to endotoxin challenge or the effects of pretreatment with sublethal amounts of endotoxin on subsequent challenge with higher normally lethal doses. Furthermore, transfer of sera with high titers of anti-LPS antibody to mice prior to challenge with LPS failed to protect. Thus, anti-LPS antibody does not appear to play a critical role in protection of immune-defective (CBA/N X DBA/2) F1 male mice to the lethal effects of endotoxin or to the protective effects of a single sublethal dose of endotoxin on subsequent endotoxin challenge.

Animals↗
PubMed1979

Effect of cyclic adenosine 3',5'-monophosphate antagonists on endotoxin-induced inhibition of human neutrophil chemotaxis.

We reported previously that Escherichia coli endotoxin inhibited human neutrophil chemotaxis toward C5a. This effect of endotoxin was antagonized by anti-inflammatory steroids. We now report that dibutyryl cyclic adenosine 3',5'-monophosphate, prostaglandin E1, isoproterenol, and cholera toxin also antagonize the suppression of chemotaxis by endotoxin. Each compound inhibited the effect of endotoxin in a dose-dependent fashion. To be effective, each compound except cholera toxin had to be present at the time of endotoxin challenge. Furthermore, propranolol blocked the protective effect of isoproterenol against endotoxin but not the protective effect of dibutyrl cyclic adenosine 3',5'-monophosphate or prostaglandin E1. Dibutyryl cyclic guanosine 3',5'-monophosphate, adenosine 5'-monophosphate, phenylephrine, prostaglandin F2 alpha, and carbachol did not modify the suppression of chemotaxis by endotoxin. Anti-inflammatory steroids and dibutyryl cyclic adenosine 3',5'-monophosphate are thought to stabilize phospholipids in certain cell membranes. This phospholipid-stabilizing action may contribute, at least in part, to the protective effect against endotoxin-mediated suppression of neutrophil chemotaxis.

Bucladesine↗
PubMed1982

Enhancement of host susceptibility to lethal endotoxin shock by staphylococcal pyrogenic exotoxin type C.

Staphylococcal pyrogenic exotoxin (PE) ty pe C enhanced the susceptibility of rabbits to lethal shock by endotoxin by as much as 50,000-fold. A graph of log PE type C dose used for pretreatment versus log 50% lethal dose of endotoxin gave a straight line with a slope of approximately -1. Rabbits that received PE type C alone showed fevers only, but those given both PE ty pe C and endotoxin showed initial fever followed by hypothermia, labored breathing, diarrhea, evidence of vascular collapse, and finally death. When a PE type C dose of 3 micrograms/kg was used, pretreatment of the animals with PE for 2 h before giving the endotoxin was required to obtain maximal susceptibility. However, when 15 micrograms of PE type C per kg was utilized, the endotoxin could be given before, concurrently, or after PE type C. The capacity of PE type C to prepare rabbits for enhanced susceptibility to endotoxin was lost after 24 to 48 h. Animals could be protected from enhanced susceptibility to endotoxin by prior immunization with either PE type C or endotoxin. However, 30% of the rabbits which were immunized with PE type C failed to develop immunity, and after three injections of PE type C, these animals developed gram-negative bacteremia and succumbed. In addition, rabbits with diarrhea initially, possibly caused by Pasteurella infection, died less than 24 h after a single injection of PE type C.

Animals↗
PubMed1982

Role for endotoxin in the leukocyte infiltration accompanying Escherichia coli inflammation.

Escherichia coli organisms induce polymorphonuclear leukocyte (PMNL) infiltration during clinical infection and also in a rabbit dermal model of inflammation. We investigated the factors which may mediate this host response to E. coli. In vitro incubation of Formalin-killed E. coli in heat-inactivated rabbit plasma or balanced salt solution generated in the supernatant factors which induced in vivo PMNL infiltration upon intradermal injection into rabbits. However, these supernatants, in the presence or absence of plasma, did not induce PMNL migration in vitro. The in vivo activity was stable at 100 degrees C and of high molecular weight (30,000). Antiserum to O antigen or to core glycolipid, but not to K or H antigen, as well as polymyxin B inhibited the release or activity of these E. coli-derived factors. The intradermal injection of 0.02 to 0.2 mug of four different endotoxin preparations or lipid A also induced marked PMNL infiltration in vivo. However, these preparations did not stimulate PMNL migration in vitro and failed to generate chemotactic activity in plasma except at very high concentrations (500 mug/ml). Anti-O serum inhibited PMNL infiltration induced by endotoxins with the corresponding O antigen and anti-core glycolipid serum inhibited all four endotoxins tested, whereas polymyxin B inhibited the activity of the endotoxins as well as that of lipid A. Base hydrolysis of endotoxin abolished PMNL infiltration. It is concluded that (i) endotoxin shed from E. coli (killed or live) may be one factor mediating the PMNL infiltration induced by this organism, (ii) endotoxin probably acts independent of in vivo complement activation, (iii) the activity is dependent on the lipid A moiety, and (iv) antibody binding to O or core glycolipid antigens can modify endotoxin so as to diminish its capacity to induce PMNL infiltration in vivo.

Animals↗
PubMed1983

Induction of nonspecific tolerance to endotoxins reduces the alveolar bone resorption in ligature-treated rats.

Previous experimental data from various laboratories indicate that endotoxin of gram-negative oral microorganisms might be one of the most important bacterial products involved in bone resorption during periodontitis. Immunologically nonspecific tolerance to endotoxins in rats was induced by repeated application of Serratia marcescens trichloroacetic acid-extracted endotoxin. Silk ligature was placed on the second maxillary molar of the endotoxin-tolerant rats as well as of control rats in which tolerance to endotoxin had not been induced. The animals were sacrificed 8 days later. The rats showed no specific immune response to the tolerance-inducing endotoxin as measured by passive hemagglutination and by the lymphoblast assays, but we found that bone resorption was significantly reduced in the endotoxin-tolerant rats as compared with ligature-treated animals in which tolerance to endotoxin had not been induced.

Alveolar Process↗
PubMed1983

Physical and biological properties of U.S. standard endotoxin EC after exposure to ionizing radiation.

Techniques that reduce the toxicity of bacterial endotoxins are useful for studying the relationship between structure and biological activity. We used ionizing radiation to detoxify a highly refined endotoxin preparation. U.S. standard endotoxin EC. Dose-dependent changes occurred by exposure to 60Co-radiation in the physical properties and biological activities of the endotoxin. Sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis showed gradual loss of the polysaccharide components (O-side chain and R-core) from the endotoxin molecules. In contrast, although endotoxin revealed a complex absorption pattern in the UV range, radiation treatment failed to modify that pattern. Dose-related destruction of the primary toxic component, lipid A, was suggested by the results of activity tests: both the pyrogenicity and limulus reactivity of the endotoxin were destroyed by increasing doses of radiation. The results indicate that the detoxification is probably due to multiple effects of the ionizing radiation on bacterial lipopolysaccharides, and the action involves (i) the destruction of polysaccharide moieties and possibly (ii) the alteration of lipid A component of the endotoxin molecule.

Animals↗