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Nitrite/Nitrate responses to endotoxin in calves.

Plasma concentrations and urinary excretions of nitrite plus nitrate (NOx) increase in heifers after endotoxin-induced nitric oxide synthase activation. The rise can be enhanced by administration of arginine, the substrate for the production of nitric oxide, whose effects may be modified by the iron status. In 10-week-old veal calves (six Simmental x Red Holstein) arginine (0.5 g/kg body weight for 6 h) was intravenously infused. At 2 h after the start of the infusions Escherichia coli endotoxin O26:B6 (2 microg/kg body weight) was intravenously injected. This caused a rise of rectal temperature, heart rate, respiration rate, and of urinary NOx excretion, but not of plasma NOx concentrations, in contrast to the experience with older cattle to which the same amounts of arginine were infused before and during endotoxin administration. In 8-week-old veal calves (18 Simmental x Red Holstein) the question of whether oral supplementation with arginine and iron modifies NOx responses to endotoxin (2 microg/kg) was also investigated. The calves were divided between three groups (GrA-, GirA+, GrC) and before endotoxin injections GrA- was fed 0.5 g arginine/kg for 4 days, GrA+ was fed 0.5 g arginine/kg for 4 days plus 80 mg iron/kg milk for 2 weeks, whereas GrC was not supplemented with arginine or iron. Iron supplementation increased plasma iron concentrations and arginine supplementation increased plasma arginine and urea concentrations and urinary urea excretion. Ensuing administration of endotoxin enhanced plasma tumour necrosis factor-alpha concentrations, rectal temperature, heart rate, and respiration rate, but not plasma NOx concentrations in GrC and GrA- and only transiently and slightly increased plasma NOx concentrations in GrA+ but did not affect urinary NOx excretions. In conclusion, the expected stimulation of NOx responses to endotoxin by intravenous arginine infusion appears to be much weaker in young veal calves than in older cattle. The NOx responses in young veal calves were not modified if arginine was orally administered and plasma NOx were barely enhanced by combined oral supplementation of arginine and iron.

Age Factors↗

The value of endotoxin concentrations in expressed prostatic secretions for the diagnosis and classification of chronic prostatitis.

OBJECTIVE: To clarify the value of endotoxin concentrations in expressed prostatic secretions (EPS) in the diagnosis and classification of chronic prostatitis. PATIENTS, SUBJECTS AND METHODS: The study included 88 consecutive patients with chronic prostatitis and 15 controls with no urological disease. The diagnosis and classification were based on a history, symptoms, a digital rectal examination of the prostate, and a white blood cell count in the EPS. Endotoxin concentrations in the EPS or urine were measured using a colorimetric assay and standard microbiological methods used to identify bacterial growth. RESULTS: In men with chronic prostatitis caused by Gram-negative or combined Gram-negative and -positive bacteria, the endotoxin levels in urine collected immediately after prostatic massage were significantly greater (P < 0.01) than in a midstream urine sample, and the concentration in the EPS was significantly higher (P < 0.05) than that in the control group. The same was true of patients with chronic prostatitis and Gram-positive bacteria isolated from the EPS or urine after massage. In patients with chronic pelvic pain syndrome (grade IIIA) the endotoxin level in the urine after massage was also significantly higher (P < 0.05) than that of the midstream sample, but there was no significant difference between the concentration in these samples in patients with grade IIIB, and no significant difference between the endotoxin concentration of the EPS in patients with grade IIIB and that in controls. CONCLUSION: Endotoxin concentrations are increased in the EPS or urine (after prostatic massage) of men with bacterial chronic prostatitis or chronic pelvic pain syndrome grade IIIA. The current routine examinations (including bacterial culture and routine examination of EPS or urine) before diagnosis and classification of chronic prostatitis are insufficient to describe the cause and pathogenesis of this condition. The endotoxin concentration of the EPS or urine after massage may provide a supplementary tool to identify the cause of chronic prostatitis.

Adult↗

Portal hypertension enhances endotoxin-induced intercellular adhesion molecule 1 up-regulation in the rat.

BACKGROUND & AIMS: Liver disease or portosystemic shunting enhances th e sensitivity to endotoxin. The aim of this study was to investigate whether intercellular adhesion molecule 1 (ICAM-1) expression in response to endotoxin may be dysregulated in an animal model of portal hypertension. METHODS: Portal hypertension was induced by partial portal vein ligation. Sham-operated animals served as controls. ICAM-1 expression was measured using radiolabeled antibodies under baseline conditions or 5 hours after treatment with either endotoxin or recombinant tumor necrosis factor (TNF). Immunoreactive plasma TNF was also measured. RESULTS: Under baseline conditions, ICAM-1 expression in all organs studied was similar in portal-hypertensive and sham-operated rats. ICAM-1 up-regulation after a high dose of endotoxin (5 mg/kg) was similar in both groups of animals. However, portal-hypertensive animals showed a significantly higher ICAM-1 expression in response to low doses of endotoxin (0.1-10 microgram/kg). The response to a low (but not a high) dose of recombinant TNF was also significantly enhanced in portal-hypertensive animals. In addition, portal-hypertensive rats had higher plasma TNF levels after treatment with endotoxin or recombinant TNF. CONCLUSIONS: Portal hypertension induces an exaggerated ICAM-1 up-regulation in response to endotoxin, which is related to an increased production and decreased clearance of the cytokine.

Analysis of Variance↗

The effect of modified ultrafiltration on the amount of circulating endotoxins in children undergoing cardiopulmonary bypass.

OBJECTIVE: To determine whether the use of modified ultrafiltration during pediatric cardiopulmonary bypass (CPB) diminishes the load of circulating endotoxins. DESIGN: Single-arm prospective observational study. SETTING: A university hospital operating room and intensive care unit. PARTICIPANTS: Twenty children undergoing CPB for correction of various congenital heart diseases. INTERVENTIONS: The amount of endotoxins in plasma was measured during CPB and before and after modified ultrafiltration. The ultrafiltrate was assayed for the presence of endotoxins. Postoperatively, the children were followed with relevant infectious parameters and cultures. MEASUREMENTS AND MAIN RESULTS: The amount of endotoxins increased significantly during the CPB procedure (from a median of 1.3 ng [range, 0 to 13.7 ng] to 24.2 ng [range, 2.1 to 75.9 ng]). After termination of CPB, modified ultrafiltration was shown to lower the amount of circulating endotoxins in blood (from a median of 24.2 ng [range, 2.1 to 75.4 ng] to 9.0 [range, 0.1 to 40.6 ng]). The major bulk of this reduction in endotoxin load was retrieved in the ultrafiltrate (median of 11.9 ng [range, 0 to 12.1 ng]). CONCLUSION: This study strongly suggests that modified ultrafiltration decreases the amount of circulating endotoxins in children undergoing cardiac surgery.

Cardiopulmonary Bypass↗

Endotoxin-neutralizing capacity of serum from cardiac surgical patients.

OBJECTIVE: To determine if endotoxin core antibody (EndoCAb) from the serum of cardiac surgical patients neutralizes endotoxin in an ex vivo biologic assay. DESIGN: Prospective blinded cohort study. SETTING: Academic medical center. PARTICIPANTS: Patients (n = 203) undergoing cardiac surgery. INTERVENTIONS: Sera were obtained from patients preoperatively. MEASUREMENTS AND MAIN RESULTS: EndoCAb levels were determined by enzyme-linked immunosorbent assay. Sera were incubated for 15 minutes at 37 degrees C with varying concentrations of endotoxin from a clinically relevant bacterium (Escherichia coli serotype O18), then tested for the presence of endotoxin activity using the validated Limulus amebocyte lysate assay. Median (interquartile range) IgM and IgG EndoCAb levels were 118 median units (range, 31 to 259 median units) and 208 median units (range, 108 to 401 medium units). Increasing levels of IgM EndoCAb were associated with increased neutralization of endotoxin (p < 0.0001). Increasing levels of IgG EndoCAb were associated with increased neutralization of endotoxin (p < 0.0001). An additive effect of IgM and IgG EndoCAb levels on endotoxin neutralization was observed without evidence of synergistic or plateau effects. EndoCAb levels did not completely predict serum neutralization capacity. CONCLUSION: Anti-EndoCAbs of both classes (IgM and IgG) were able to neutralize lipopolysaccharide from a clinically relevant bacterium in an ex vivo model. Neither Igm nor IgG appeared to be more capable of neutralization in this model. These antibodies did not completely predict neutralization capacity; other endogenous factors in human serum must be capable of lipopolysaccharide neutralization.

Antibodies, Bacterial↗

Quantitative determination of endotoxins released by bacterial biofilms.

Residual endotoxins, commonly associated with bacterial biofilms colonizing reusable medical devices have been associated with pyrogenic reactions in patients. We have used a quantitative, sensitive and reproducible kinetic chromogenic adaptation of the Limulus Amebocyte Lysate assay to assess endotoxin recovery from an in-vitro bacterial biofilm. The 'recovery method' was based on a combination of physical treatment (vortexing and sonication) and chemical treatment (immersion in recovery solution). Five recovery solutions were investigated. The recovered endotoxin was greater when the biofilm was treated with a 1% SDS solution. The sensitive and reproducible method we have developed should allow the recovery and measurement of biofilm bacterial endotoxins on implanted and colonized medical devices. Moreover, the amount of endotoxin was sufficient (> 1000 endotoxin units/cm2 of substrate) to enable a substantial reduction by sterilization processes, the efficiency of which on biofilm endotoxins has yet to be proven.

Biofilms↗

Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects.

To evaluate the effect of endotoxin on the fibrinolytic response, we administered Escherichia coli endotoxin (4 ng per kilogram of body weight) intravenously to 19 healthy volunteers and measured fibrinolytic proteins, protease inhibitors, neutrophil elastase, and von Willebrand factor in serial blood samples obtained over 24 hours. One hour after endotoxin administration, the level of tissue plasminogen activator (t-PA) antigen rose from 10 to 23 ng per milliliter, peaking at 52 ng per milliliter at three hours. The level of alpha 2-plasmin inhibitor-plasmin complexes increased sevenfold, peaking at three hours. Plasminogen-activator inhibitor-1 activity rose more slowly, from 7 U per milliliter to a maximum of 49 U per milliliter at five hours. The concentrations of neutrophil elastase and von Willebrand antigen were unchanged at one hour, increased approximately threefold by 3 hours, and remained elevated at 24 hours. None of these measures changed in a control group (n = 5) given intravenous saline instead of endotoxin. We studied t-PA functional activity in four subjects. The level of activity rose rapidly, from 1.2 ng per milliliter at base line to 8.3 ng per milliliter at one hour and 13.9 ng per milliliter at two hours; it was undetectable at three hours. This increase in plasminogen activator activity was abolished in vitro by incubation of t-PA with an antiserum specific for human t-PA, suggesting that t-PA may be directly responsible for plasmin generation in the response to endotoxin. We conclude from this study of healthy subjects that endotoxin activates the fibrinolytic system, beginning with release of t-PA in the blood within one hour. The early activation of plasmin by endotoxin may prevent thrombosis, and the increase in fibrinolysis is then offset by the release of plasminogen activator inhibitor.

Adult↗

Allergen provocation augments endotoxin-induced nasal inflammation in subjects with atopic asthma.

BACKGROUND: Recent epidemiologic and in vivo studies have suggested that inhaled endotoxin plays an important role in asthma pathogenesis. OBJECTIVE: The present study examines the effect of nasal allergen provocation on subsequent endotoxin challenge in subjects with atopic asthma. METHODS: By using a split-nose randomized crossover design, individual nares of 12 asthmatic subjects underwent challenge and lavage as follows. Immediately after a baseline nasal lavage, one nares received normal saline, and the other received dust mite antigen. Four hours later, both nares were exposed to either saline or endotoxin. Dust mite antigen (Dermatophagoides farinae) and endotoxin (Escherichia coli 026:B6) doses were 100 AU and 1000 ng, respectively. Postchallenge lavages were done at 8 and 24 hours after the initial challenge. The subjects then returned a minimum of 3 weeks later for crossover to the study arm. Nasal lavage fluid was analyzed for total and differential cell counts, IL-8, IL-6, intercellular adhesion molecule 1, GM-CSF, eosinophil cationic protein, myeloperoxidase, and soluble CD14. RESULTS: A significant increase in the total inflammatory cell count was seen at 8 hours for the dust mite/endotoxin exposure compared with the saline/saline and saline/endotoxin exposures. Differential cell counts revealed a similar neutrophilic and eosinophilic inflammation for the dust mite/endotoxin exposure at 8 hours. CONCLUSIONS: These data demonstrate an interaction between allergen and endotoxin exposure in asthmatic subjects, suggesting that a prior allergen challenge significantly augments the endotoxin-induced inflammation. Moreover, these data provide further evidence that concomitant exposure to allergen and endotoxin may be an important factor in asthma pathogenesis.

Adult↗

Different effects of endotoxin versus mite and cat allergen exposure on T-cell differentiation in infants.

BACKGROUND: Early exposure to bacterial endotoxin has been proposed to protect against allergy development in children. Whether endotoxin is able to direct T-cell differentiation into a predominance of type 1 immunity is still unresolved. OBJECTIVE: We sought to compare the effects of endotoxin and mite and cat allergens on T-cell differentiation in infants. METHODS: In a random population sample of 135 2-year-old children of an ongoing birth-cohort study, peripheral blood CD4+ and CD8+ T-cell subsets were defined by the expression of the chemokine receptors CCR5 and CCR3 as surrogate markers for type 1 and type 2 T cells, respectively. Endotoxin and mite and cat allergens were measured in house dust collected from the mother's mattress at the child's age of 3 months to assess early exposure. RESULTS: In the CD4+ T-cell subset, endotoxin levels were positively associated with high proportions of type 1 CCR5+ cells (odds ratio for fourth exposure quartile [OR(Q4)], 7.68; 95% CI, 1.35-43.75), whereas cat allergen levels were associated with increased proportions of type 2 CCR3+ cells (OR(Q4), 4.07; 95% CI, 1.05-15.85). In contrast to endotoxin, allergen levels were associated with CD8+ T cells, showing an inverse relationship between mite allergen concentrations and high proportions of CCR5+ or CCR3+ cells (CCR5+ cells: OR(Q4), 0.14; 95% CI, 0.03-0.74; CCR3+ cells: OR(Q4), 0.16; 95% CI, 0.03-0.89) and a positive association of cat allergen levels with increased proportions of CCR5+ cells (OR(Q4), 9.24, 95% CI, 1.61-53.10), as well as CCR3+ cells (OR(Q3), 6.64; 95% CI, 1.21-36.51). CONCLUSION: Our results indicate that endotoxin has the potential to promote the development of type 1 CD4+ T cells, whereas mite and cat allergens primarily modify the proportion of CD8+ cells of both types.

Allergens↗

TLR4 gene variants modify endotoxin effects on asthma.

BACKGROUND: Environmental exposure to endotoxin might have a crucial role in immune maturation and development of asthma. OBJECTIVE: The aim of this study was to investigate whether the effect of endotoxin concentration in settled house dust on asthma is modified by the presence of variation in the TLR4 gene. METHODS: We performed a cross-sectional study within the German follow-up of the European Community Respiratory Health Survey. Multivariate logistic regression analysis and nonparametric effect estimates (S-Plus) were applied to examine the association between endotoxin exposure and diagnosed asthma, related clinical symptoms, and bronchial hyperreactivity (BHR) stratified for noncarriers and carriers of G299/I399 polymorphism in the TLR4 gene. RESULTS: In the noncarrier group (n = 279), the prevalence of asthma was significantly increased with elevated endotoxin levels in house dust with adjusted odds ratio 6.24 (95% CI, 1.33-29.17) in the second tertile, and 4.54 (95% CI, 0.94-21.96) in the third tertile compared with the lowest endotoxin tertile. The carriers of the polymorphisms (n = 55) showed a nonsignificant trend to have a lower risk of asthma (crude odds ratio, 0.67; 95% CI, 0.06-8.06 for the second tertile and 1.33; 95% CI, 0.17-10.58 for the third tertile). We found a similar association for wheeze and endotoxin exposure that was also attenuated in subjects with G299/I399 polymorphisms. CONCLUSIONS: The G299/I399 polymorphisms were associated with a modified response to endotoxin, but the functional relationship still needs clarification.

Adult↗

Suppression by developing ovarian follicles of the low-dose endotoxin-induced glomerular inflammatory reaction in the pregnant rat.

OBJECTIVE: In the current study the role of developing ovarian follicles in the control of the endotoxin-induced pregnancy-specific inflammatory reaction was evaluated. STUDY DESIGN: Follicular development was induced in pregnant rats (n = 20) by means of daily intraperitoneal injections of follicle-stimulating hormone from day 11 of pregnancy until the end of the experiment. Control pregnant rats (n = 20) received daily sodium chloride injections. All pregnant rats were infused for 1 hour with either 2 mL endotoxin solution (1.0 microg/kg body weight) or 2 mL sodium chloride solution on day 14 and killed 4 hours or 3 days later. At death, the left kidneys were snap-frozen and immunohistologically stained for the presence of polymorphonuclear leukocytes and monocytes. RESULTS: The results show that in control pregnant rats endotoxin significantly increased glomerular polymorphonuclear leukocyte and monocyte numbers at both 4 hours and 3 days after endotoxin infusion. Induction of follicular development did not affect glomerular polymorphonuclear leukocyte number after endotoxin infusion but significantly decreased the number of monocytes in the glomeruli at both 4 hours and 3 days after endotoxin infusion. CONCLUSION: We conclude that follicles stimulated with follicle-stimulating hormone produce a follicular factor or factors that are able to prevent the endotoxin-induced influx of monocytes into the glomeruli of pregnant rats. It is suggested that these factors play a role in the control of inflammatory processes associated with reproduction, including the disease of pregnancy, preeclampsia.

Animals↗

The fetal maturational and inflammatory responses to different routes of endotoxin infusion in sheep.

OBJECTIVES: In clinical practice, chorioamnionitis has been observed to enhance fetal lung maturation in the short term but may predispose to chronic lung disease thereafter. Using the sheep model, we have previously shown that injection of endotoxin into the amniotic cavity results in inflammatory responses and profoundly enhances newborn lung function after preterm birth. The fetus tolerates intra-amniotic doses of endotoxin considerably greater than those that are lethal if given intramuscularly. This study aimed to explore the mechanisms by which endotoxin matures the lungs by determining whether the route of administration influenced the maturational responses of the fetus. STUDY DESIGN: Date-mated ewes at 118 days of pregnancy were allocated at random to receive endotoxin (Escherichia coli lipopolysaccharide 055;B5) directly into the trachea (n = 7), stomach (n = 6), amniotic cavity (n = 7), or peritoneal cavity (n = 4) of the fetal lamb by surgical implantation of an osmotic pump delivering 1 mg of endotoxin over a 24-hour period. Results were compared with those obtained in saline solution-infused controls (n = 9). The lambs were delivered by cesarean section at 125 days' gestation (term is 150 days). RESULTS: Endotoxin infusion into the trachea, stomach, and amniotic cavity each resulted in inflammatory responses in lung fluid and improved postnatal lung function, and effects were similar for each route of administration. These effects occurred with minimal features of systemic inflammation. Intraperitoneal infusion resulted in severe fetal acidosis or death. CONCLUSION: These findings provide further evidence that the lung-maturing effects of intra-amniotic endotoxin are mediated by local factors in the respiratory system rather than by systemic inflammatory responses. Chorioamnionitis may alter lung function and possibly lead to chronic injury without clinical features of systemic inflammation or compromise.

Acidosis↗

Intra-amniotic endotoxin induces lung maturation by direct effects on the developing respiratory tract in preterm sheep.

OBJECTIVE: Our purpose was to determine whether improved preterm lung function caused by intraamniotic endotoxin treatment requires endotoxin entry into the respiratory tract. STUDY DESIGN: We assessed lung inflammation 2 days after intra-amniotic endotoxin (10 mg, Escherichia coli 055:B5) or saline solution in preterm lambs (123 days' gestation) that had undergone surgery to isolate the gastrointestinal or respiratory systems from the amniotic sac. In other sheep longer-term effects were assessed 7 days after we isolated the fetal respiratory tract and gave endotoxin or saline solution directly to the lungs or into the amniotic sac. We measured pulmonary inflammation, lung function, and surfactant 1 week after treatment (approximately 125 days). RESULTS: Pulmonary inflammation was present after intra-amniotic endotoxin only if there was communication between the respiratory tract and the amniotic sac. Lung function was improved and surfactant was increased only in preterm lambs that received direct pulmonary endotoxin. CONCLUSION: Endotoxin causes functional improvement of the preterm lung by direct effects on the developing respiratory system.

Amnion↗

Measurement of zinc flux through plasma in normal and endotoxin-stressed pigs and the effects of Zn supplementation during stress.

1. The rates of transport of zinc through plasma have been investigated in normal and endotoxin-stressed pigs. 2.65Zn added to porcine plasma in vitro rapidly equilibrated with the Zn originally present. 3. 65 Zn bound to albumin and injected intravascularly into pigs rapidly equilibrated with two kinetically distinguishable pools. The first of these pools was mainly associated with the plasma but was significantly larger than the plasma volume and substantially so in Zn-deficient pigs. The second pool appeared to represent a summation of the rapidly-exchangeable Zn within the extravascular tissues. 4. In non-stressed animals, the flux of Zn from the plasma of Zn-deficient pigs was only half that in Zn-supplemented animals. 5. Administration of endotoxin reduced the plasma Zn concentration of Zn-supplemented pigs but not of Zn-deficient animals. The fractional turnover rates of Zn were not altered in eight of the two pools following endotoxin. 6. At 10 h after giving endotoxin neither the Zn content of the two pools nor the flux of Zn through them differed significantly between Zn-deficient and control pigs. 7. Intravascular infusion of Zn at the rate which essentially prevented the usual depression in plasma Zn concentration following endotoxin failed to alleviate the effects of endotoxin on Zn-supplemented pits. 8. The reduction in plasma Zn concentration following endotoxin stress appears to be a normal physiological response which is not indicative of an increased metabolic requirement for Zn.

Animals↗

Pathophysiological effects of endotoxins in ruminants. 2. Metabolic aspects.

Metabolic disturbances following intravenous and intramammary administration of endotoxins in ruminants are described. In contrast to the similarity in response of blood biochemical parameters after intravenous and intramammary administrations of endotoxins, responses in plasma concentrations of enzyme activities, the thyroid hormones, cortisol, and somatotropin differ markedly. Biochemical changes in blood after endotoxin administration are predominantly dose-dependent; thus some of the biochemical parameters - especially plasma concentrations of Fe and Zn - serve also to evaluate the effects of certain drugs in endotoxin models. Changes in milk composition have been documented only after intramammary infusion of endotoxins and can partly be explained by the increased permeability of the blood/milk barrier. Appearance and production of milk returns to normal within a week after intramammary endotoxin treatment, indicating that the mammary gland is only temporarily damaged by endotoxin-induced mastitis.

Animals↗

Endotoxin potentiates ozone-induced pulmonary chemokine and inflammatory responses.

Urban air consists of a combination of environmental pollutants. Recent studies have suggested that normally innocuous doses of a particular pollutant may be rendered more toxic to the lung if primed by earlier events. Pulmonary inflammation has been observed in humans and in many animal species after endotoxin and ozone exposures. The present study was designed to test the hypothesis that inhalation of low levels of endotoxin following ozone exposure will potentiate ozone-induced lung injury. We exposed 8-week-old C57BL/6J mice to 1 ppm ozone for 24 hours; inhalation of low-dose endotoxin (37.5 EU) for 10 minutes; or 1 ppm ozone immediately followed by endotoxin inhalation (37.5 EU). The mice were examined 4 or 24 hours post exposure. After 24 hours of recovery, significant increases were measured in bronchoalveolar lavage (BAL) fluid levels of protein and lavageable polymorphonuclear neutrophils (PMNs) after coexposure to ozone followed immediately by endotoxin inhalation as compared to exposures individually. Messages encoding macrophage inflammatory protein (MIP)-1beta, MIP-1alpha, MIP-2, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-1alpha, IL-1beta, IL-1Ra, IL-6, and Macrophage Migration Inhibitory Factor (MIF) were significantly elevated 24 hours post ozone followed by endotoxin as compared to exposure to ozone or endotoxin individually. These results demonstrate that preexposure to ozone, which primarily attacks the epithelium, can cause sensitization to a secondary stimulus through a mechanism that culminates in a greater and prolonged onset of inflammatory cell recruitment, pulmonary edema, and increased expression of chemokine and cytokine messages.

Animals↗

Endotoxin and antiendotoxin antibodies in patients with acute pancreatitis.

OBJECTIVE: To elucidate the time course of endotoxaemia and antiendotoxin antibodies in patients with acute pancreatitis. DESIGN: Prospective clinical study. SETTING: University hospital, Germany. SUBJECTS: 25 patients with oedematous (n = 9) or necrotising (n = 16) pancreatitis, and 20 healthy controls. MAIN OUTCOME MEASURES: Concentrations of endotoxin and immunoglobulins (classes G, M, and A) directed at two lipid A molecules, four lipopolysaccharides, and alpha-haemolysin of Staphylococcus aureus measurements in plasma during a 12 day period. RESULTS: There were no differences in the degree of endotoxaemia between patients with oedematous and necrotising pancreatitis on admission. However, from the day after admission and throughout the observation period patients with necrotising pancreatitis had significantly higher concentrations of endotoxin than those with oedematous pancreatitis. Concentrations of IgM specific for endotoxin peaked at day 4, and then decreased in patients with oedematous pancreatitis while remaining high for those with necrotising pancreatitis. There was only a slight increase in IgA specific for endotoxin, and IgG and immunoglobulins to gamma-haemolysin remained steady throughout the observation period. There was strong cross-reactivity (r > 0.7) between IgM specific for endotoxin (70%), but this was less with IgA (52%), and IgG (20%). CONCLUSIONS: Necrotising pancreatitis is accompanied by persistent endotoxaemia with an extended rise in antiendotoxin antibodies. Patients with oedematous pancreatitis have a transient endotoxaemia with a temporary increase of Ig specific for endotoxin. Endotoxin stimulates the synthesis of specific antibodies (IgM) despite general immunosuppression.

Acute Disease↗

Local treatment of generalised peritonitis in rats; effects on bacteria, endotoxin and mortality.

OBJECTIVE: To assess the effect of debridement, intraoperative lavage with saline, and additional instillation of taurolidine or imipenem/cilastatin in rats with faecal peritonitis. DESIGN: Laboratory study. SETTING: University hospital, The Netherlands. MATERIAL: 60 male Wistar rats. INTERVENTIONS: Rats were given an intraperitoneal injection of a faecal suspension containing Escherichia coli and Bacteroides fragilis. Six groups of 10: sham operation, debridement, debridement with saline lavage, debridement with saline lavage with intraperitoneal instillation of saline or taurolidine, or imipenem/cilastatin, were studied. MAIN OUTCOME MEASURES: Bacterial growth and endotoxin concentration in abdominal exudate and plasma, abscess formation, and mortality. RESULTS: Debridement temporarily reduced bacterial growth and the concentration of endotoxin in abdominal exudate, and delayed mortality. Lavage with saline further reduced bacterial growth and the endotoxin concentration. It also reduced the plasma endotoxin concentration, and mortality. Additional instillation of taurolidine did not reduce bacterial growth, but did initially reduce the endotoxin concentration in abdominal exudate and plasma. Instillation of imipenem/cilastatin, after debridement and lavage, significantly reduced all variables measured. CONCLUSION: In rats with faecal peritonitis, debridement, lavage with saline, and additional instillation of imipenem/cilastatin, all have cumulatively reducing effect on bacterial growth, endotoxin concentrations, abscess formation, and mortality. Instillation of taurolidine reduces only the amount of endotoxin.

Abdominal Abscess↗