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 1,081 records · Page 60Linked to original sources
PubMed2001

Estrogen modulates the hypothalamic-pituitary-adrenal and inflammatory cytokine responses to endotoxin in women.

Endotoxin stimulates the release of the inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha, which are potent activators of the hypothalamic-pituitary-adrenal (HPA) axis. Recent studies in the rodent and in the primate have shown that the HPA responses to endotoxin and IL-1 were enhanced by gonadectomy and attenuated by estradiol (E2) replacement. In addition, there is some evidence, in the rodent, that estrogen modulates inflammatory cytokine responses to endotoxin. To determine whether estrogen has similar effects in humans, we studied the cytokine and HPA responses to a low dose of endotoxin (2--3 ng/kg) in six postmenopausal women with and without transdermal E2 (0.1 mg) replacement. Mean E2 levels were 7.3 +/- 0.8 pg/mL in the unreplaced subjects and increased to 102 +/- 13 pg/mL after estrogen replacement. Blood was sampled every 20 min for 1--2 h before, and for 7 h after, iv endotoxin administration. Endotoxin stimulated ACTH, cortisol, and cytokine release in women with and without E2 replacement. E2 significantly attenuated the release of ACTH (P < 0.0001) and of cortisol (P = 0.02). Mean ACTH levels peaked at 190 +/- 91 pg/mL in the E2-replaced group vs. 411 +/- 144 pg/mL in the unreplaced women, whereas the corresponding mean cortisol levels peaked at 27 +/- 2.9 microg/dL with E2 vs. 31 +/- 3.2 microg/dL without E2. Estrogen also attenuated the endotoxin-induced release of IL-6 (P = 0.02), IL-1 receptor antagonist (P = 0.003), and TNF-alpha (P = 0.04). Mean cytokine levels with and without E2 replacement peaked at 341 +/- 94 pg/mL vs. 936 +/- 620 pg/mL for IL-6, 82 +/- 14 ng/mL vs. 133 +/- 24 ng/mL for IL-1 receptor antagonist, and 77 +/- 46 pg/mL vs. 214 +/- 87 pg/mL for TNF-alpha, respectively. We conclude that inflammatory cytokine and HPA responses to a low dose of endotoxin are attenuated in postmenopausal women receiving E2 replacement. These data show, for the first time in the human, that a physiological dose of estrogen can restrain cytokine and neuroendocrine responses to an inflammatory challenge.

Adrenocorticotropic Hormone↗
PubMed2003

ONO-1714, a nitric oxide synthase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits.

UNLABELLED: Overproduction of nitric oxide by inducible nitric oxide synthase (iNOS) expressed in the lung is thought to play a crucial role in the pathogenesis of endotoxin-induced acute lung injury (ALI). In this two-part study, we determined whether ONO-1714, a new selective iNOS inhibitor, attenuates endotoxin-induced ALI in rabbits. For Part I of the study, a control group received IV saline and ALI was induced by IV infusion of endotoxin 5 mg/kg over 30 min in 4 groups. Three groups received either 0.1, 0.03, or 0.01 mg/kg of ONO-1714 10 min before the start of endotoxin and the fourth group received saline. For Part II of the study, ALI was induced by endotoxin infusion in all 6 groups. One group was treated with saline. The other 5 groups received ONO-1714 0.1 mg/kg at various timings (10 min before or 1, 2, 3, or 4 h after ALI induction). The lungs were mechanically ventilated with 40% oxygen for 6 h after induction of ALI. In Part I, pretreatment with 0.1 mg/kg ONO-1714 mitigated endotoxin-induced ALI. In Part II, early posttreatment (within 2 h after the insult) with ONO-1714 was as effective as pretreatment in improving oxygenation, lung mechanics, lung leukosequestration, pulmonary edema, and histological change. However, lung damage was not improved in rabbits receiving the drug 3 or 4 h after endotoxin. These data suggest that the current study is a basis for future clinical trials to elucidate whether ONO-1714 can be a promising therapeutic approach in patients with acute respiratory distress syndrome induced by endotoxin/sepsis. IMPLICATIONS: An excess of nitric oxide is thought to play a crucial role in the pathogenesis of acute organ injury in endotoxemia. Early posttreatment with ONO-1714, a nitric oxide synthase inhibitor, attenuated physiological, biochemical, and pathological changes in endotoxin-induced acute lung injury in rabbits.

Airway Resistance↗
PubMed2003

The effects of vasopressin on systemic and splanchnic hemodynamics and metabolism in endotoxin shock.

UNLABELLED: We compared the effects of vasopressin and norepinephrine on systemic and splanchnic circulation and metabolism in endotoxin shock in pigs. Twenty-one pigs were randomized to endotoxin shock (Escherichia coli endotoxin infusion) (n = 6), endotoxin and vasopressin (VASO; n = 6), endotoxin and norepinephrine (NE; n = 6), and controls (n = 3). Endotoxin infusion was increased to induce hypotension, after which vasopressin or norepinephrine was started to keep systemic mean arterial blood pressure >70 mm Hg. Regional blood flows and arterial and regional lactate concentrations were measured. Tonometers with microdialysis capillaries were inserted into the stomach, jejunum, and colon. Systemic mean arterial blood pressure >70 mm Hg was achieved in the VASO and NE groups. Vasopressin decreased cardiac output, superior mesenteric artery, and portal vein blood flow, whereas hepatic arterial blood flow increased. Arterial lactate concentration increased from 2.0 mM (1.6-2.1 mM) to 4.7 mM (4.7-4.9 mM) (P = 0.007). Systemic and mesenteric oxygen delivery and consumption decreased and oxygen extraction increased in the VASO group. Vasopressin increased mucosal-arterial PCO(2) gradients in all three locations, whereas luminal lactate release occurred only in the jejunum. Animals in the NE group remained stable. Vasopressin reversed hypotension but decreased systemic and gut blood flow. This was associated with hyperlactatemia, signs of visceral dysoxia, and jejunal luminal lactate release. IMPLICATIONS: Although vasopressin induces vasoconstriction in visceral region, its effects on splanchnic circulation and metabolism during septic-endotoxin shock are still poorly characterized. We evaluated the metabolic and hemodynamic effects of vasopressin and norepinephrine within the splanchnic area in porcine endotoxin shock.

Animals↗
PubMed2001

Adherent endotoxin on orthopedic wear particles stimulates cytokine production and osteoclast differentiation.

Aseptic loosening of orthopedic implants is thought to be caused primarily by osteoclast differentiation induced by bone resorptive cytokines produced in response to phagocytosis of implant-derived wear particles. This study examined whether adherent endotoxin on the wear particles is responsible for inducing osteoclast differentiation as well as production of interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor a (TNF-alpha). Removal of adherent endotoxin almost completely inhibited the responses to titanium (Ti) particles by both murine marrow cells and human peripheral blood monocytes. In vivo experiments showed that endotoxin removal reduced particle-induced osteolysis by 50-70%. Addition of lipopolysaccharide (LPS) to the "endotoxin-free" particles restored their ability to induce cytokine production and osteoclast differentiation in vitro. Moreover, marrow cells from mice that are hyporesponsive to endotoxin because of mutation of Toll-like receptor 4 induced significantly less cytokine production and osteoclast differentiation in response to Ti particles with adherent endotoxin than did marrow cells from normoresponsive mice. This mutation also resulted in significantly less particle-induced osteolysis in vivo. Taken together, these results show that adherent endotoxin is involved in many of the biological responses induced by orthopedic wear particles and should stimulate development of new approaches designed to reduce the activity of adherent endotoxin in patients with orthopedic implants.

Adhesiveness↗
PubMed1991

Endotoxin-refractory liver macrophages secrete tumor necrosis factor-alpha upon viral infection.

Rat liver macrophages (Kupffer cells) secrete tumor necrosis factor-alpha (cachectin) after exposure to Newcastle disease virus or bacterial endotoxin. Macrophages treated with endotoxin become refractory and fail to release tumor necrosis factor-alpha to a secondary challenge with endotoxin. The acquisition of the refractory state is dose-dependent, requires the continuous presence of endotoxin for a minimum of 8 h, is transient, and reversible. Endotoxin, however, renders Kupffer cells unresponsive only to itself. When endotoxin-refractory macrophages are activated by Newcastle disease virus, they still secrete tumor necrosis factor-alpha in amounts expected with this stimulus. Immunoprecipitation studies show that the precursor of tumor necrosis factor-alpha is found only in lysates of endotoxin-sensitive, but not in refractory macrophages, thus arguing against a post-translational regulatory process. Whereas prostaglandin E2 inhibits the production of tumor necrosis factor-alpha in response to endotoxin and viruses, it does not appear to mediate the refractory state.

Animals↗
PubMed1994

Assay of endotoxin in human plasma using immobilized histidine, Limulus amoebocyte lysate and chromogenic substrate.

The Limulus amoebocyte lysate test for endotoxin is inhibited or enhanced by many substances. It is particularly difficult to determine endotoxin in plasma. In order to overcome this problem, we have modified the specific endotoxin assay method by using a membrane filter unit, a chromogenic Limulus amoebocyte lysate reagent, and immobilized histidine (which is a specific adsorbent for endotoxins). This immobilized histidine method consists of the endotoxin adsorption step on immobilized histidine, the separation step, in which Limulus amoebocyte lysate-interfering substances are removed, and the Limulus amoebocyte lysate test. Preheating of plasma samples (40-fold dilution with distilled water, at 100 degrees C for 7.5 min) was necessary, and it was necessary to dilute the sample more than 100-fold for the adsorption step. Under these conditions, the fraction of endotoxin recovered from plasma by the immobilized histidine method was almost 1. Moreover, by increasing the sample volume and extending the Limulus amoebocyte lysate reaction time, the sensitivity could be increased. By using the immobilized histidine method, 50-200 units/l of endotoxin in plasma samples can be accurately assayed. The method was used for the determination of plasma endotoxin in rabbits.

Animals↗
PubMed1981

Effect of conjugated estrogen on disseminated intravascular coagulation induced by endotoxin infusion in rabbits.

Since conjugated estrogen has activities of inhibiting capillary permeability and of blocking alpha-adrenergic action, this study was undertaken to evaluate the effect of conjugated estrogen on experimentally induced disseminated intravascular coagulation (DIC) by endotoxin infusion in rabbits. Endotoxin from E. coli alone was infused into 17 rabbits in a rate of 90 micrograms/kg/hr for 10 hr, the other 17 were given endotoxin with 20 mg of conjugated estrogen, and 6 were infused 20 mg of conjugated estrogen alone. The results obtained were as follows: (1) Decreases in platelet, fibrinogen and plasminogen, prolonged prothrombin time and partial thromboplastin time were noted in animals receiving intravenous drip infusion of endotoxin. All these laboratory findings were typical of consumption coagulopathy. Histologically, fibrin thrombi were demonstrated in the glomeruli, which also indicated the presence of DIC. (2) These changes were almost equally demonstrable in the rabbits given endotoxin alone and in those with endotoxin plus conjugated estrogen. (3) The group of rabbits receiving endotoxin and estrogen, however, showed a significantly low mortality during the study, compared with the group receiving endotoxin alone.

Animals↗
PubMed1997

Dibutyryl cAMP inhibits endotoxin-induced increases in pulmonary vascular resistance and fluid filtration coefficient in the perfused rat lung.

We investigated the effects of pre-treatment with dibutyryl cAMP (db-cAMP) or cGMP on endotoxin-induced hemodynamic changes and pulmonary vascular permeability in isolated perfused rat lungs. Intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) caused increases in pulmonary arterial resistance (Ra) after venous reservoir elevation, in pulmonary filtration coefficient (Kf) and in lung wet-to-dry (W/D) weight ratio. Pre-treatment with db-cAMP blocked endotoxin-induced increases in Ra, Kf and W/D weight ratio. Pre-treatment with cGMP attenuated only the increase in Ra caused by endotoxin. Moreover, administration of db-cAMP 2 hours after endotoxin injection attenuated the increase in Ra induced by endotoxin treatment. The increases in Kf and W/D weight ratio caused by endotoxin were not affected by post-treatment with db-cAMP. Since the increases in Ra, Kf and W/D weight ratio caused by endotoxin were blocked by pre-treatment with db-cAMP, agents that increase intracellular cAMP level may be useful to prevent acute pulmonary vascular injury.

Animals↗
PubMed2003

The lipolytic responsiveness to endotoxin in subcutaneous adipose tissue is greater than mesenteric adipose tissue.

In sepsis and endotoxemia, metabolism is characterized by accelerated catabolism. In the present study, lipolytic responsiveness of subcutaneous and mesenteric adipose tissue to the sub-lethal dose of endotoxin injection (5 mg/kg) was evaluated using microdialysis techniques in rats. All rats were urethane-anesthetized and implanted with microdialysis probes in their subcutaneous and mesenteric adipose tissue. Lipolysis in each adipose tissue was assessed by measuring the glycerol concentration (an index of lipolysis) in the dialysate from the microdialysis probe. Lipolysis was continuously monitored for 7-hours, prior to and following the injection of endotoxin. The control animals were injected with only saline. Lipolysis in subcutaneous adipose tissue began to increase by 1-hours after endotoxin injection, and reached a peak 60% higher than the basal level by 2-hours after injection. This activated lipolysis after endotoxin was markedly greater than that in the control animals and maintained for 5 hours. In mesenteric adipose tissue, lipolysis after endotoxin injection was greater than in the control animals, but not significant. The endotoxin-induced lipolysis in the subcutaneous adipose tissue was significantly greater than that in the mesenteric adipose tissue. We conclude that the sub-lethal dose of endotoxin injection cause active lipolysis in adipose tissues, and that the lipolytic responsiveness to endotoxin in subcutaneous adipose tissue is greater than in mesenteric adipose tissue.

Adipose Tissue↗
PubMed1987

Growth inhibitory effects of endotoxins from Bacteroides gingivalis and intermedius on human gingival fibroblasts in vitro.

Purified endotoxin or lipopolysaccharide from Bacteroides gingivalis and Bacteroides intermedius caused a similar dose-dependent inhibition of growth of cultured human gingival fibroblasts as determined by 3H-thymidine incorporation and direct cell count. Approximately 200 micrograms/ml endotoxin caused a 50% reduction in 3H-thymidine uptake of logarithmically growing cells. Inhibition of growth was similar in cultures of fibroblasts derived from either healthy or diseased human gingiva. When examining the change in cell number with time of exposure in culture, the rate of proliferation was significantly suppressed during the logarithmic phase of growth. However, the cells recovered so that the rate of proliferation, although reduced, was sufficient to produce a cell density similar to the control cells with prolonged culture. The endotoxins were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The profiles of the Bacteroides endotoxins were different. B. gingivalis endotoxin showed a wide range of distinct bands indicating a heterogeneous distribution of molecular species. Endotoxin from B. intermedius exhibited a few discrete low molecular weight bands, but the majority of the lipopolysaccharides electrophoresed as a diffuse band of high molecular weight material. The apparent heterogeneity of the two Bacteroides endotoxins and the similarity in growth inhibitory capacity suggest that growth inhibitory effects of these substances cannot be attributed to any polysaccharide species of endotoxin.

Bacteroides↗
PubMed2004

Endotoxin neutralizing peptides.

Neutralization and sequestration of bacterial lipopolysaccharide which plays a key role in gram-negative sepsis is required to block the progression of sepsis at early stages in addition to destroying bacteria. Many of the host defense peptides which have antimicrobial activity are also able to bind to and neutralize LPS, however, these two activities do not necessarily correlate. Due to its toxicity application of polymyxin B as the prototype of LPS neutralizing peptide is limited to topical applications and extracorporeal removal of endotoxin. Development of novel endotoxin neutralizing peptides without the toxicity of polymyxin B have been based on the natural host defense peptides, fragments of LPS binding proteins and engineered peptides. Neutralization of LPS can be achieved through several different peptide fold motifs, which are reviewed in this article. Endogenous host defense peptides, fragments of endotoxin-binding proteins and synthetic anti-endotoxin peptides fold into alpha-helical, beta-hairpin, extended and compact conformations without regular secondary structure. In animal models many of the peptides have demonstrated good in vitro and in vivo endotoxin neutralizing activity but up to now none of the peptides has been approved for clinical application with an anti-endotoxin indication. Recent developments include preparation of novel types of endotoxin neutralizing compounds such as peptides modified by lipophilic moieties and non-peptidic molecules, particularly lipopolyamines and on the other hand additional medical applications such as extracorporeal endotoxin removal, targeting to inflammation sites or endotoxoid based vaccines.

Amino Acid Sequence↗
PubMed1989

[Effects of endotoxins from periodontopathic bacteria on the collagen metabolism of cultured normal human gingival fibroblasts].

The present study was performed to investigate the effects of endotoxins from periodontopathic bacteria on collagen metabolism. Endotoxins were extracted from Bacteroides gingivalis 381 and Bacteroides intermedius ATCC 25611 using the hot-phenol method. A commercially available endotoxin from Escherichia coli 0111: B4 was also used as a control. Human gingival fibroblasts (Gin-1, ATCC CRL 1292) were maintained with DMEM containing 10% FBS. When the fibroblasts became confluent they were exposed to each of the endotoxins in various concentrations (0, 5, 10, 15, 20 micrograms/ml). The effects of these endotoxins on the collagen metabolism of the fibroblasts were assessed on the basis of collagen synthesis and collagenase activity. The former was assessed by 3H-proline incorporation and bacterial collagenase digestable protein. The latter was assessed by fibril assay. The results were as follows: There was no change in glucose consumption, cell viability or morphology under the light microscope when the concentration of endotoxin was 20 micrograms/ml or less. 3H-proline incorporation into protein and collagen synthesis were inclined to decrease. Endotoxin from B. gingivalis resulted in an acceleration of collagenase activity. There findings indicate that the endotoxins from these bacteria might affect collagen metabolism early in gingivitis in vivo.

Bacteroides↗
PubMed2002

Apoptosis of bovine neutrophils during mastitis experimentally induced with Escherichia coli or endotoxin.

OBJECTIVE: To determine whether apoptosis of neutrophils was accelerated during mastits experimentally induced by use of Escherichia coli or E coli endotoxin and whether differences were apparent in the response to E coli or endotoxin. ANIMALS: 11 healthy lactating Holstein cows. PROCEDURE: Blood samples were collected from cows at various intervals after intramammary inoculation with E coli or endotoxin. Percentage of apoptotic neutrophils detected after in vitro incubation for 3 hours was determined. Fluorescein isothiocyanate-labeled annexin-V in combination with propidium iodide was used to distinguish apoptosis and necrosis of neutrophils. Total and differential circulating leukocyte counts and rectal temperature were determined at the time of collection of blood samples. Milk yield and milk somatic cell counts were determined at the time of milking. RESULTS: Inoculation of endotoxin did not accelerate in vitro induction of neutrophil apoptosis. However, inoculation of E coli increased the percentage of apoptotic neutrophils. At 18 hours after inoculation, 20% of the neutrophils were apoptotic, compared with 5% before inoculation. Milk somatic cell count and rectal temperature increased, milk production and total leukocyte count decreased, and percentage of immature neutrophils increased after inoculation with E coli or endotoxin. However, kinetics of the responses were more rapid, more severe, and of shorter duration during endotoxin-induced mastitis. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro induction of apoptosis of neutrophils was accelerated only during E coli-induced mastitis and not during endotoxin-induced mastitis. Endotoxin inoculation as a model for studying coliform mastitis in dairy cows should be viewed with caution.

Animals↗
PubMed1994

Effect of feeding regimen on concentration of free endotoxin in ruminal fluid of cattle.

The influence of concentrate diets on endotoxin concentration in sterile filtrate of ruminal fluid was assessed in ruminally fistulated Jersey cows. Three cows underwent a change in diet from hay to a diet containing 3.0 kg and 14 d later 6.0 kg of a 12% CP concentrate. The cows had free access to water and a mineral-stone. A modified Limulus Amoebocyte Lysate technique was used for the endotoxin analyses. The endotoxin concentration in the ruminal fluid of cows fed on hay were 148 +/- 84 and 118 +/- 50 endotoxin units (EU)/mL (mean +/- SD) on two separate days and increased from the 2nd d of supplementation with 3.0 kg of concentrate to 408 +/- 198 EU/mL on d 5. When the cows were fed 6.0 kg of concentrate, the endotoxin concentrations increased to 1,599 +/- 944 EU/mL. To assess the influence on the ruminal endotoxin concentration of an adaptation of the ruminal environment to concentrate before hyperalimentation, four ruminally fistulated Jersey cows previously fed either hay or a high-concentrate diet for 1 mo were hyperalimented with 60 to 70 g of barley per kilogram BW. A relative increase in ruminal endotoxin concentration was determined only in the two cows previously fed concentrates. The results show that high-concentrate diets do not consistently relate to increases of ruminal endotoxin concentrations.

Adaptation, Physiological↗
PubMed1989

Endotoxin permeability through the round window.

The permeability of the round window membrane to Salmonella typhimurium derived endotoxin was examined using a total of 17 chinchillas. One mg of endotoxin was instilled into the tympanic cavity via the superior bulla. Endotoxin activity in middle ear effusions (MEEs), perilymph (both inoculated and non-inoculated side), and sera was determined by Limulus lysate assay after 12, 24, 48, 72, and 120 h following endotoxin instillation. Endotoxin was detected in perilymph on the inoculated side by 12 h after endotoxin instillation and persisted for 5 days during the present measurement period. Endotoxin level peaked at 24-48 h post-instillation, and steadily declined afterwards. This result suggests that the maximum penetration occurred during the active inflammatory stage. Histologic investigation revealed marked pathological changes in the inner ear, including bleeding and inflammatory cell recruitment, mostly in the perilymphatic spaces (e.g. scalae tympani and vestibuli, spiral ligament), strial swelling, and sensory cell degeneration. These results suggest that endotoxin, when introduced into the middle ear, can permeate through the round window membrane and can cause inner ear tissue damage in this animal model.

Animals↗
PubMed1986

Oral administration of antibiotics and intestinal flora associated endotoxin in mice.

The contribution of aerobic and anaerobic gram-negative intestinal bacteria to the release of endotoxin in the intestinal tract was investigated during oral administration of various nonabsorbable antimicrobial drugs to C3H/Law mice. The intestinal endotoxin release was studied by determination of the endotoxin concentration in faecal supernatants with the Limulus amebocyte lysate assay. Selective elimination of aerobic gram-negative bacteria by oral treatment with polymyxin, aztreonam or temocillin resulted in a reduction of the endotoxin concentration of faecal supernatants to 10% of the untreated control. Further decrease of the endotoxin concentration to 1% was achieved by total decontamination of the intestinal tract by oral cephalothin/neomycin treatment. Endotoxin determination with the Limulus amebocyte lysate assay appeared to be unaffected by the antibiotics present in the faecal supernatants after oral treatment. On basis of these experiments, it is concluded that in mice 90% of the faeces derived endotoxin can be ascribed to release of endotoxin by intestinal aerobic gram-negative bacteria.

Administration, Oral↗
PubMed1988

Extension of oxygen tolerance by treatment with endotoxin: means to improve its potential therapeutic safety in man.

Treatment of adult rats with low doses of bacterial lipopolysaccharide (endotoxin) consistently results in a marked protective effect against O2-induced lung damage and lethality. We report here two means to improve the therapeutic ratio of endotoxin (ratio of dose producing desired beneficial effect/dose producing undesired toxic effects), which could make it a more acceptable pharmacologic agent for possible use in patients who require prolonged hyperoxic therapy. (a) Rats made "tolerant" to the lethal/toxic effects of high doses of endotoxin (25 mg/kg) by pretreatment with very low doses of endotoxin (10 ng----10 micrograms/kg) were found to still respond to a standard protective dose of endotoxin (500 micrograms/kg) with marked resistance to O2 toxicity. (Survival in greater than 95% O2 X 72 h = 19/20 (95%), vs. 4/17 (24%) for controls.) (b) Two chemically modified native endotoxin preparations ("endotoxoids"), with approximately 100 X decreased toxic potential, were found to have retained their ability to protect adult rats from prolonged hyperoxic exposure (90%-100% survival rates). These two experimental manipulations (use of the "endotoxin tolerance" phenomenon and treatment with partially detoxified "endotoxoids") were associated with increased lung antioxidant enzyme activities during O2 exposure in the treated animals. Continued research may eventuate in the possible clinical application of a safe form of endotoxin treatment for the prevention of O2 toxicity in humans.

Animals↗
PubMed1985

Factors influencing calcium influx in endotoxin-challenged fibroblasts.

The role of cell density and pH on calcium influx was studied in normal and endotoxin-challenged cultured 3T6 fibroblasts. In normal fibroblasts, at low cell densities, there was no marked difference in calcium influx at pH 6.6, 7.4, and 7.8, whereas at high cell densities, the calcium influx was markedly higher at pH 6.6 as compared to that at pH 7.8. Endotoxin treatment for 4 hr at low cell density and in alkaline pH (7.4-7.8) increased calcium influx in a dose-dependent manner. In contrast, at high cell density and low pH (6.6), endotoxin treatment markedly decreased calcium influx in a dose- and time-dependent manner. These endotoxin-induced changes in calcium influx were not fully compensated by altered calcium efflux because total calcium content of the cells was found to be altered. The efficacy of the endotoxin varied depending on the bacterial source of the endotoxin and the method of purification. There was a relationship between the effect of different endotoxins on the increase in calcium influx and the inhibition of cell proliferation. Endotoxin did not decrease, but slightly increased cell proliferation when added to high cell density cultures even at a concentration of 200 micrograms/ml.

Animals↗