Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ENDOTOXINS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,639 records · Page 91Linked to original sources
PubMed1993

Mice treated with a leumedin or antibody to Mac-1 to inhibit leukocyte sequestration survive endotoxin challenge.

Endotoxin challenge causes metabolic dysfunction mediated by TNF, and sequestration of leukocytes. NPC 15669, N-carboxy-L-leucine, N-[2,7-dimethylfluoren-9-yl)methyl] ester, inhibits leukocyte recruitment into inflammatory lesions in animals, and inhibits endotoxin-induced neutropenia and lymphopenia in mice. This study was carried out to determine whether the ability of NPC 15669 to inhibit leukocyte sequestration is sufficient to promote survival after endotoxin challenge. To inhibit leukocyte sequestration directly, mice were treated with anti-CD11a (LFA-1) or anti-CD11b (Mac-1) before endotoxin challenge. Anti-CD11b partly inhibited neutropenia and lymphopenia in response to challenge with LPS, but anti--CD11a had little effect on leukopenia. At doses of 100 and 1000 micrograms/kg, anti-CD11b increased survival to endotoxin challenge from 0 to 20 and 40%, respectively, whereas anti-CD11a was without effect. These observations, coupled with the finding that NPC 15669 does not inhibit endotoxin-induced TNF release suggest that inhibition of leukocyte sequestration can increase survival after endotoxin challenge, and that NPC 15669 or antibodies to Mac-1 may represent effective therapies for gram-negative sepsis and shock.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Effect of alcohol on the endotoxin binding protein produced in the liver.

The Kupffer cell-hepatocyte interaction in the process of endotoxin clearance and the effect of alcohol on it were investigated in a newly developed rat Kupffer cell-hepatocyte culture system. The hepatic production of endotoxin binding protein was increased when the Kupffer cells were preincubated in the medium containing ethanol, and the resultant culture supernatant was added to the hepatocyte culture system. The amount of endotoxin binding protein produced by the hepatocytes was increased as the ethanol concentration in the culture medium of Kupffer cells was increased. This endotoxin binding protein was proved to enhance the uptake of endotoxin and suppressed the production of tumor necrosis factor in the Kupffer cells. When Kupffer cells and hepatocytes were isolated from chronically alcohol-fed rats, further addition of ethanol to the culture medium of Kupffer cells did not affect the hepatic production of endotoxin binding protein. The increase in hepatic production of endotoxin binding protein may serve as a defence mechanism against endotoxicity. There is a possibility that an impairment of the defence mechanism has a pivotal role in the development of endotoxemia and endotoxicity in chronic alcoholics.

Animals↗
PubMed1997

Increased susceptibility to endotoxin shock in complement C3- and C4-deficient mice is corrected by C1 inhibitor replacement.

Endotoxin shock is a life-threatening syndrome associated with a Gram-negative infection and mediated by a systemic inflammatory response. As a major effector of inflammation, the complement system has been implicated in both the pathogenesis and the protection from endotoxin shock. To clarify the role of complement in endotoxin shock, we have used mice totally deficient in either complement component C3 or C4. We found that both the C3- and C4-deficient mice were significantly more sensitive to endotoxin than wild-type controls. The endotoxin-challenged complement-deficient mice failed to clear endotoxin efficiently from the circulation and this led to excess consumption of C1 inhibitor protein (C1 INH), a major regulator of both complement and the contact system of blood coagulation. Replacement of C1 INH rescued the endotoxin-challenged complement-deficient mice from shock and death. These findings suggest a novel therapy for treatment of endotoxemia with C1 INH protein.

Animals↗
PubMed1976

In vivo decomplementation of guinea pigs with cobra venom factor and anti-C3 serum: analysis of the requirement of C3 and C5 for the mediation of endotoxin-induced death.

Guinea pigs were decomplemented by administration of cobra venom factor and goat anti-C3 serum in order to determine whether endotoxin-induced death could be prevented. The combined use of both reagents resulted in the complete elimination of all serum C3 and C5 hemolytic activity. This yielded, however, a shortened rather than extended longevity following endotoxin challenge. The mixing of endotoxin in vitro or in vivo with serum of animals already partially depleted of C3 resulted in no further activation of this component, further suggesting that the interaction of complement with endotoxins does not relate to mortality in animals following endotoxin challenge. Thus, although it has been demonstrated that complement components aid in the detoxification of endotoxin, the present data show that the C3 and C5 components are not mediators of endotoxin-induced death.

Animals↗
PubMed1963

Characterization of a Cr51-labeled endotoxin and its identification in plasma and urine after parenteral administration.

The incubation of endotoxin with Na(2)Cr(51)O(4) yielded a product which was well labeled. That the label was fixed on the endotoxin itself was shown by autoradiography on specific lines of precipitation formed in agar. Ultracentrifugation at 40,000 RPM sedimented 80 per cent of the total weight of the starting Boivin preparation. Agar diffusion patterns with subsequent autoradiographs demonstrated that the chromium tag was associated only with the heavy fractions of the pellet. The supernatant contained precipitable, but unlabeled endotoxin. Toxicity measurements showed that more than 99 per cent of the total toxicity resided in the pellet fractions. The chromate-tagged endotoxin was specifically identified in plasma samples taken up to 6 hours after intravenous administration of LD(50) or sublethal doses. The endotoxin was not totally detoxified in vivo since plasma collected 6 hours after the injection of even the sublethal dose was toxic when assayed in adrenalectomized mice. The endotoxin was specifically identified in urine specimens but it was no longer toxic or radioactive. Agar diffusion experiments indicated that only degraded material was present.

Animals↗
PubMed1962

Physicochemical changes in endotoxin associated with loss of biological potency.

Ribi, Edgar (National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratory, Hamilton, Mont.), Willard T. Haskins, Kelsey C. Milner, Robert L. Anacker, Daniel B. Ritter, Granville Goode, Robert-John Trapani, and Maurice Landy. Physicochemical changes in endotoxin associated with loss of biological potency. J. Bacteriol. 84:803-814. 1962.-The preparation of endotoxins whose gross chemical composition approached that of refined polysaccharide haptenes raised anew the question of which features of composition and structure are essential for their characteristic host reactivity. Alterations in the physicochemical, immunochemical, and biological properties of Salmonella enteritidis endotoxin subjected to hydrolysis with 0.1 n acetic acid were therefore investigated to relate physical characteristics to biological attributes. As hydrolysis proceeded, the decline in biological potency was paralleled by dissociation of endotoxin into particles of the size of haptenic polysaccharide. The potency still present at various stages of hydrolysis could be accounted for by residual undissociated endotoxin. These findings are consistent with the hypothesis that a macromolecular complex of critical size is one of the major requirements for endotoxin to elicit its characteristic effects in the mammalian host.

Animals↗
PubMed1991

Endotoxin concentrations in cerebrospinal fluid correlate with clinical severity and neurologic outcome of Haemophilus influenzae type B meningitis.

Endotoxin concentrations were measured in paired samples of cerebrospinal fluid from 38 patients with Haemophilus influenzae type b meningitis. On admission, the median concentration of endotoxin in cerebrospinal fluid was 104 ng/mL and decreased rapidly in follow-up samples. From 17 to 48 hours after admission, 50% of the patients had concentrations of less than 1 ng/mL. Endotoxin concentrations correlated significantly with concentrations of interleukin 1 beta, protein, and glucose in cerebrospinal fluid, duration of secondary fever, and neurologic abnormalities during hospitalization and on follow-up examinations. Twenty-eight percent of patients with endotoxin concentrations of 100 ng/mL or more on admission had long-term complications, compared with none of those with lower endotoxin concentrations (relative risk, 2.31; 95% confidence interval, 1.53 to 3.48). These results indicate that quantitation of endotoxin in cerebrospinal fluid could be a valuable aid in identifying those children at increased risk of complications during Haemophilus influenzae type b meningitis and provide additional evidence that the Haemophilus influenzae type b meningitis lipo-oligosaccharide is important in the pathogenesis of meningitis.

Animals↗
PubMed1998

Is Fas ligand or endotoxin responsible for mucosal lymphocyte apoptosis in sepsis?

BACKGROUND: Apoptosis (Ao) is a normal constitutive process that seems to have pathological effects in diseases of immune deficiency and autoimmune disorders, as well as in certain lymphoid tissues during sepsis. Little is known about this process in mucosal lymphoid tissue, such as intestinal intraepithelial lymphocytes (IELs). OBJECTIVES: To determine whether sepsis induces increased Ao in small intestinal IEL, whether this was associated with functional changes in cytokine gene expression in the IEL, and which mediators control this process and their impact on the survival of the mouse with sepsis. DESIGN: Male C3H/HeN (endotoxin-sensitive), C3H/HeJ (endotoxin-tolerant), and C3H/HeJ-FasLgld (endotoxin-tolerant/Fas ligand [FasL]-deficient) mice were subjected to sepsis (cecal ligation and puncture [CLP]) and IELs were harvested at 4 (early) or 24 hours (late sepsis). Alterations in the cell phenotype and Ao (TUNEL [terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling] assay) were determined by 3-color flow cytometry. Cytokine gene expression was assessed by multiprobe RNase protection assay. RESULTS: At 4 hours after CLP, only the frequency of IEL which was CD8+ decreased markedly. By 24 hours after CLP, the number of CD8+ and CD4+ cells decreased while the proportion of double-negative cells showed a marked increase when compared with sham-controls. The percentage of Ao positive in CD8+ and CD4+ double-positive and double-negative cells increased markedly 24 hours after CLP concomitant with a significant (P<.05 vs sham-controls, Mann-Whitney U test) increase in expression of the IL-2, IL-10, and IL-15 gene. These data collectively suggest that sepsis causes lymphocyte activation-induced Ao that may be mediated by FasL. Additional studies were done to determine if the increased Ao was due to either endotoxin or FasL. The results of studies with endotoxin-tolerant C3H/HeJ or FasL-deficient C3H/HeJ-FasLgld mice showed an increase in A,, in CD4+ and CD8+ cells from septic C3H/HeJ but not C3H/HeJ-FasLgld mice. With regard to septic mortality, our results indicated that there was a marked reduction in mortality in C3H/HeJ-FasLgld vs C3H/HeJ mice. CONCLUSIONS: We conclude that the phenotypic changes associated with increased Ao may be a reflection of localized immune cell activation due to a FasL-mediated process and not endotoxin. Thus, FasL directly and/or indirectly contributes to higher septic mortality.

Animals↗
PubMed1991

Endotoxin and renal glutamine metabolism.

The effect of endotoxin on renal glutamine metabolism and ammoniagenesis was investigated in vivo in the rat to gain further insight into the altered glutamine flow that characterizes critical illness. Studies were done 15 hours following a single dose of Escherichia coli lipopolysaccharide (10 mg/kg). Renal blood flow and arterial glutamine concentration were similar in control and study rats, but the kidney switched from an organ of slight glutamine uptake in controls (129 +/- 52 nmol/100 g of body weight per minute) to net release in the endotoxin-treated animals (-273 +/- 170 nmol/100 g of body weight per minute). Simultaneously, the specific activity of renal glutamine synthetase increased by almost 50% (374 +/- 40 nmol/mg of protein per hour in rats given endotoxin vs 253 +/- 12 nmol/mg of protein per hour in controls), while glutaminase was unchanged. Urinary ammonia excretion was reduced by 35% in the endotoxin-treated animals (47 +/- 6 mumol/12 h in endotoxin-treated animals vs 70 +/- 8 mumol/12 h in controls) despite a 10% fall in the arterial bicarbonate value. Endotoxin alters the net flux of glutamine across the kidney which appears to be partially regulated enzymatically. This may impair the kidneys' ability to maintain acid/base homeostasis.

Ammonia↗
PubMed1991

Alterations in host defense associated with anesthesia and blood transfusions. II. Effect on response to endotoxin.

The effect of blood transfusions and anesthesia on host response to endotoxin was evaluated in multiple Lewis rat models. The rats were randomized to receive A'Sogaloff Cancer Institute rat blood, pentobarbital sodium, or lactated Ringer's solution and, at either 2 or 7 days following administration of these agents, were challenged with intravenous endotoxin. Neither blood transfusions nor anesthesia altered mortality when administered 2 days before endotoxin challenge. However, blood transfusions administered 7 days before endotoxin challenge were found to prolong survival, to prevent endotoxin-induced alterations in T-lymphocyte subsets, and to decrease plasma tumor necrosis factor levels. In conclusion, blood transfusions appear to depress immune function in a beneficial manner in endotoxin shock.

Anesthesia, General↗
PubMed1991

Tumor necrosis factor and endotoxin can cause neutrophil activation through separate pathways.

We investigated the possibility that tumor necrosis factor (TNF) mediates neutrophil activation by endotoxin. The number of C3b receptors on the neutrophil cell-surface was used as the indicator of activation, as assessed by indirect immunofluorescence. Incubation of buffy-coat neutrophils with TNF-alpha for 30 minutes at 37 degrees C caused neutrophil activation, increasing C3b receptor-dependent fluorescence from 340 with buffer alone to 580 with TNF (250 pg/mL). Increasing amounts of anti-TNF IgG progressively inhibited neutrophil activation by TNF (250 pg/mL). Addition of the active dose range of anti-TNF to neutrophils incubating in endotoxin (10 ng/mL) did not affect the degree of endotoxin-mediated neutrophil activation. Mixtures of neutrophils with the 50% suppressive dose of anti-TNF and varying endotoxin concentrations showed the same degree of neutrophil activation as mixtures without the antibody. Thus, an antibody that can inhibit TNF-mediated neutrophil activation does not inhibit endotoxin-mediated neutrophil activation. We conclude that endotoxin and TNF can activate neutrophils through separate pathways.

Antibodies↗
PubMed1994

Endotoxin disrupts beta-adrenergic signal transduction in the heart.

BACKGROUND: Nonsurvivors of septic shock demonstrate impaired myocardial function refractory to the administration of beta-agonists. METHODS: Using the isolated rat heart preparation, the integrity of the beta-adrenergic transduction pathway was tested (rate pressure product, rate of contraction, rate of relaxation, and cyclic adenosine monophosphate content) using isoproterenol hydrochloride (beta-receptor agonist) or colforsin (forskolin) (adenylyl cyclase activator) stimulation following intracoronary endotoxin infusion. RESULTS: Basal rate pressure product, rate of contraction, rate of relaxation, and cyclic adenosine monophosphate concentrations were unaffected by endotoxin infusion. Endotoxin impaired, increases in rate pressure product, rates of contraction and relaxation, and cyclic adenosine monophosphate to isoproterenol (P < .05), but the response to colforsin was unaffected by endotoxin. CONCLUSIONS: Endotoxin disrupts the myocardial response to direct beta-receptor stimulation but not to adenylyl cyclase stimulation in the isolated rat heart. CLINICAL RELEVANCE: Alteration of the proximal beta-adrenoreceptor complex by endotoxin suggests that therapy of the failing heart during refractory septic shock may be directed to intact sites distal in the beta-adrenergic pathway.

Adenylyl Cyclases↗
PubMed1994

Translocation of bacteria and endotoxin in organ donors.

OBJECTIVE: To determine if bacterial translocation and endotoxin absorption occur in organ donors with an anatomically intact gastrointestinal tract. DESIGN: Case series. SETTING: Intensive care units in general and university hospitals. PATIENTS: Twenty-one (multiple) organ donors. INTERVENTION: None. MAIN OUTCOME MEASURES: Occurrence of factors that may promote bacterial translocation and/or endotoxin absorption. Bacterial concentration in mesenteric lymph nodes, abdominal fluid, blood, liver, lung, and spleen. Endotoxin level in abdominal fluid, peripheral blood, and portal blood. Anatomical integrity of the bowel wall. RESULTS: Factors that may promote bacterial translocation and/or endotoxin absorption were present in all organ donors. Culture specimens revealed bacteria in 14 organ donors (67%). In 210 (81%) of 260 culture specimens, the bacteria isolated were identical to those isolated from the bowel content, demonstrating bacterial translocation. Endotoxin was found in nine (53%) of 17 abdominal fluid samples, in four (19%) of 21 peripheral blood samples, and in two (10%) of 21 portal blood samples. Light- and electron-microscopic examination of the bowel wall showed no anatomical abnormalities. CONCLUSION: Bacterial translocation and endotoxin absorption are frequent among organ donors and may adversely influence organ function in transplant recipients and other critically ill patients.

Ascitic Fluid↗
PubMed1998

Acute lung function changes and low endotoxin exposures in the potato processing industry.

Work-related respiratory symptoms, acute lung function changes and personal endotoxin exposure were studied in 61 workers from a potato processing plant. According to their job title mean endotoxin exposure level, workers were divided into low (AM = 21 EU/m3) and high (AM = 56 EU/m3) exposure categories. Shortness of breath and chest tightness during work were reported by 18% and 16% of the workers, respectively, mainly in the low endotoxin exposure category. A total of 148 across-shift lung function changes were measured during three consecutive afternoon shifts. The mean FEV1 and MMEF showed a decrease over the work shift, being largest on the first working day after a 3-day absence from work. Workers exposed to high endotoxin levels showed a larger across-shift decrease in lung function than workers exposed to low endotoxin exposures, the effect being most pronounced on the first day after a 3-day absence from work. At the start of the second work shift, FVC, FEV1 and MMEF were lower than at the start of the first work shift. This difference was larger for high exposed workers. High exposed workers with work-related respiratory symptoms showed an 8-10% across-shift change in FVC, FEV1 and MMEF We conclude that significant across-shift decreases in lung function of potato processing workers is related to endotoxin exposure levels above 53 EU/m3 over 8 hr.

Acute Disease↗
PubMed1999

Activities of conjugating and antioxidant enzymes following endotoxin exposure.

Endotoxin exposure elicits various responses in mammals including the acute phase response that has been shown to cause changes in the activity of several forms of cytochrome P450s and other enzymes. Therefore, the hepatic conjugating enzyme, glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT), the antioxidant enzymes, glutathione peroxidase (GSHPx), catalase, and superoxide dismutase (SOD), as well as lipid peroxidation were investigated following the administration of endotoxin to male Sprague-Dawley rats (8 mg/kg body weight). Rats were euthanized at various times following endotoxin administration and the livers removed and processed to assess various enzyme activities. Glutathione S-transferase, UDPGT, and GSHPx activity showed statistically significant decreases after 24 hours and remained lower than controls for the duration of the study. Decreases in total SOD and catalase activities were seen at 24, 48, and 72 hours following endotoxin administration; however, only catalase activity showed statistically significant differences between control and treated samples at those time points, and total SOD activity showed a statistically significant decrease at 24 hours. No statistically significant changes were seen in the level of lipid peroxidation in the liver microsomes from endotoxin-treated animals. Changes in the conjugative enzymes and the free-radical scavenging enzymes following endotoxin exposure may alter the host's metabolism and response to free radicals.

Animals↗
PubMed1998

Fine structural changes in the ileum of mice fed on delta-endotoxin-treated potatoes and transgenic potatoes.

The present work has been designed to study the effect of feeding on transgenic potatoes, which carry the CryI gene of Bacillus thuringiensis var. kurstaki strain HD1, on the light and electron microscopic structure of the mice ileum, in comparison with feeding on potatoes treated with the 'delta-endotoxin' isolated from the same bacterial strain. The microscopic architecture of the enterocytes of the ileum of both groups of mice revealed certain common features such as the appearance of mitochondria with signs of degeneration and disrupted short microvilli at the luminal surface. However, in the group of mice fed on the 'delta-endotoxin', several villi appeared with an abnormally large number of enterocytes (151.8 in control group versus 197 and 155.8 in endotoxin and transgenic-treated groups, respectively). Fifty percent of these cells were hypertrophied and multinucleated. The mean area of enterocyte was significantly increased (105.3 microm(2) in control group versus 165.4 microm(2) and 116.5 microm(2) in endotoxin and transgenic-treated groups, respectively). Several forms of secondary lysosomes or auotophagic vacuoles were recognized in these cells. These changes were confirmed with the scanning electron microscope which revealed a remarkable increase in the topographic contour of enterocytes (23 microm in control group versus 44 microm and 28 microm in endotoxin and transgenic-treated groups, respectively) at the divulged surface of the villi. The basal lamina along the base of the enterocytes was damaged at several foci. Several disrupted microvilli appeared in association with variable-shaped cytoplasmic fragments. Some of these fragments contained endoplasmic reticulum, as well as ring-shaped annulate lamellae. In addition, the Paneth cells were highly activated and contained a large number of secretory granules. These changes may suggest that delta-endotoxin-treated potatoes resulted in the development of hyperplastic cells in the mice ileum. Although mild changes are reported in the structural configuration of the ileum of mice fed on transgenic potatoes, nevertheless, thorough tests of these new types of genetically engineered crops must be made to avoid the risks before marketing.

Animals↗
PubMed2000

Worker exposures to airborne dust, endotoxin and beta(1,3)-glucan in two New Zealand sawmills.

BACKGROUND: Sawmill workers have an increased risk of developing occupational asthma and other respiratory symptoms. Wood dust and microorganisms have both been suggested to play a role, but few studies have measured microbial exposure levels in sawmills. METHODS: The preliminary study reported in this paper assessed airborne dust, bacterial endotoxin and beta(1,3)-glucan levels in 37 samples from two New Zealand sawmills. RESULTS: Nearly one-third of the measured dust levels exceeded 1 mg/m(3) and only one sample exceeded the legal limit of 5 mg/m(3). Endotoxin levels were clearly elevated with 50% of all measured exposures above 50 EU/m(3) (range: 7-588 EU/m(3)). beta(1,3)-glucan levels were comparable with levels measured in other industries where workers are exposed to organic dust. Workers in the planing department had the highest mean exposures to dust, endotoxin and beta(1,3)-glucan. Dust levels were only weakly correlated with endotoxin and beta(1,3)-glucan levels. CONCLUSIONS: Endotoxin exposures in sawmill workers are at levels sufficient to potentially contribute to the development of respiratory symptoms. Moreover, measurement of dust exposure is a poor proxy for beta(1,3)-glucan and endotoxin exposure in sawmill workers.

Dust↗
PubMed2004

Inter-laboratory analysis of endotoxin in cotton dust samples.

BACKGROUND: Currently there are no mandated exposure limits for endotoxin, but recommended limits have been proposed and interest expressed in developing quantitative standards for endotoxin. A limitation for developing a quantitative standard for endotoxin is the measurement variability between laboratories. Inter-laboratory variability of up to four orders of magnitude has been reported for replicate samples. To evaluate both the intra- and inter-laboratory variability, Round-Robin studies were conducted using replicate samples of cotton dust. METHODS: Replicate samples of cotton dust were collected using vertical elutriators (VE) in a model cardroom. Each participating laboratory evaluated the samples for endotoxin using: their normal extraction procedure; a common extraction procedure; and a common extraction procedure and the same type and lot of a commercially available endotoxin kit. RESULTS: These studies demonstrated that both intra- and inter-laboratory variability is reduced by using a common extraction protocol and a common assay kit; however, significant differences remained between the laboratories. CONCLUSIONS: The data suggest that intra-laboratory assays can be used to assess the relative differences between endotoxin samples, however, the inter-laboratory variability suggests that limitations remain for developing a reliable exposure assessment assay that could be used for a quantitative exposure standard.

Air Pollutants, Occupational↗