Seven cases of probable endotoxin poisoning related to contaminated glutathione infusions.

We report seven cases of probable endotoxin poisoning linked to contaminated compounded glutathione. Five of the cases were using the infusions for treatment of Lyme disease highlighting the risks of using compounded sterile preparations for unapproved indications, especially if the quality of source products cannot be assured.

Risks associated with endotoxins in feed additives produced by fermentation.

Increasingly, feed additives for livestock, such as amino acids and vitamins, are being produced by Gram-negative bacteria, particularly Escherichia coli. The potential therefore exists for animals, consumers and workers to be exposed to possibly harmful amounts of endotoxin from these products. The aim of this review was to assess the extent of the risk from endotoxins in feed additives and to calculate how such risk can be assessed from the properties of the additive. Livestock are frequently exposed to a relatively high content of endotoxin in the diet: no additional hazard to livestock would be anticipated if the endotoxin concentration of the feed additive falls in the same range as feedstuffs. Consumer exposure will be unaffected by the consumption of food derived from animals receiving endotoxin-containing feed, because the small concentrations of endotoxin absorbed do not accumulate in edible tissues. In contrast, workers processing a dusty additive may be exposed to hazardous amounts of endotoxin even if the endotoxin concentration of the product is low. A calculation method is proposed to compare the potential risk to the worker, based on the dusting potential, the endotoxin concentration and technical guidance of the European Food Safety Authority, with national exposure limits.

Occupational exposure to pesticides and endotoxin and Parkinson disease in the Netherlands.

OBJECTIVES: Previous research has indicated that occupational exposure to pesticides and possibly airborne endotoxin may increase the risk of developing Parkinson disease (PD). We studied the associations of PD with occupational exposure to pesticides, specifically to the functional subclasses insecticides, herbicides and fungicides, and to airborne endotoxin. In addition we evaluated specific pesticides (active ingredients) previously associated with PD. METHODS: We used data from a hospital-based case-control study, including 444 patients with PD and 876 age and sex matched controls. Exposures to pesticides from application and re-entry work were estimated with the ALOHA+job-exposure matrix and with an exposure algorithm based on self-reported information on pesticide use. To assess exposure to specific active ingredients a crop-exposure matrix was developed. Endotoxin exposure was estimated with the DOM job-exposure matrix. RESULTS: The results showed almost no significant associations. However, ORs were elevated in the higher exposure categories for pesticides in general, insecticides, herbicides and fungicides, and below unity for endotoxin exposure. The analyses on specific active ingredients showed a significant association of PD risk with the fungicide benomyl. CONCLUSIONS: This study did not provide evidence for a relation between pesticide exposure and PD. However, the consistently elevated ORs in the higher exposure categories suggest that a positive association may exist. The possible association with the active ingredient benomyl requires follow-up in other studies. This study did not provide support for a possible association between endotoxin exposure and PD.

Household endotoxin levels and the risk of non-Hodgkin lymphoma.

OBJECTIVE: Endotoxin, a component of the outer membrane of gram-negative bacteria, elicits a strong innate and inflammatory immune response associated with the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α). Because TNF-α polymorphisms that increase TNF-α production are associated with an increased risk of non-Hodgkin lymphoma (NHL), we hypothesized that increased levels of household endotoxin would be associated with an increased NHL risk. METHODS: We evaluated this association in the National Cancer Institute/Surveillance, Epidemiology and End Results (NCI/SEER) NHL multicenter population-based case-control study. Used vacuum cleaner bags were collected from participants during a home interview. Dust samples from the bags of 594 cases and 442 controls were analyzed for endotoxin [endotoxin unit (EU)/mg of dust] using the kinetic chromogenic Limulus amebocyte lysate assay. Multivariable logistic regression was used to estimate the effect of endotoxin on NHL risk adjusted for age, sex, race, education, study center, and farm exposure. RESULTS: Endotoxin was not associated with NHL overall [odds ratio (OR) for highest quartile of endotoxin levels = 0.81, 95 % confidence interval (CI) = 0.55, 1.20; p for trend = 0.35] or with diffuse large B-cell lymphoma (OR = 0.63, 95 % CI = 0.34, 1.16; p = 0.31) or follicular lymphoma (OR = 1.07, 95 % CI = 0.61, 1.89; p = 0.73) subtypes. Both working and living on a farm were associated with higher household endotoxin levels compared to never working (p = 0.009) or living (p = 0.01) on a farm. Excluding farmers from the analysis did not change the results. CONCLUSIONS: We found no evidence of a role for household endotoxin in NHL etiology.

[Study on the anti-endotoxin effect of saponin from Tupistra chinensis].

OBJECTIVE: To investigate the effect of saponin from Tupistra chinensis Baker (STCB) on lethal toxicity of endotoxin in mice and explore the underlying mechanism. METHODS: Mouse models of endotoxin-induced death and endotoximia were established by intraperitoneal administration of KM mice with lipopolysaccharides (LPS) from Pseudomonas aeruginosa in doses of 60 mg/kg and 10 mg/kg respectively. Mouse survival rate and survival time were recorded and the serum levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in endotoximia mice were measured by enzyme-linked immunosorbent assay (ELISA). Mouse peritoneal exudate cells induced by LPS were used as an in vitro inflammatory model,which was then intervened with STCB and the levels of IL-1beta and TNF-alpha in the culture supernatants were measured by ELISA. RESULTS: The survival rates of mice prophylactically treated with STCB (200 and 400 mg/kg, in 5 consecutive days) were slightly higher compared with that in model group,but no statistical difference was observed (P>0.05). The survival time was much longer in the treated group (P<0.05). The serum levels of IL-1beta and TNF-alpha in STCB-treated mice (200 and 400 mg/kg, in 5 consecutive days) were significantly lower compared with those in model group (P<0.05). STCB (20 and 40 microg/mL) remarkably inhibited LPS-induced IL-1beta and TNF-alpha production by peritoneal exudate cells in vitro (P<0.05). CONCLUSION: Saponin from Tupistra chinensis showed beneficial effect on the prevention of mice from lipopolysaccharides-induced death, in which down regulation of IL-1beta and TNF-alpha expression might be involved.

Risk of lung cancer in relation to contiguous windows of endotoxin exposure among female textile workers in Shanghai.

OBJECTIVE: Exposure to endotoxin has been consistently associated with a reduced risk of lung cancer. However, there is a paucity of information regarding temporal aspects of this relationship. The objective of this study was to investigate the associations between contiguous windows of endotoxin exposure and risk of lung cancer. METHODS: Data were reanalyzed from a case-cohort study (602 cases, 3,038 subcohort) of female textile workers in Shanghai, China. Cumulative endotoxin exposure was partitioned into two windows: ≥20 and <20 years before risk. Exposure-response relations were examined using categorical and non-linear (semi-parametric) models, accounting for confounding by previous exposure windows. RESULTS: There was an inverse trend of decreasing risk of lung cancer associated with increasing levels of endotoxin exposure ≥20 years before risk (p trend = 0.02). Women in the highest two categories of cumulative exposures had hazard ratios of 0.78 (95% CI 0.60-1.03) and 0.77 (95% CI 0.58-1.02) for lung cancer, respectively, in comparison with unexposed textile workers. There was, however, a weaker association and not statistically significant between lung cancer and endotoxin exposure accumulated in the more recent window (<20 years before risk). CONCLUSION: Results provide further evidence that endotoxin exposure that occurred 20 years or more before risk confers the strongest protection against lung cancer, indicating a possible early anti-carcinogenic effect. Further studies are needed to better understand the underlying biological mechanisms for this effect.

Endotoxin exposure and lung cancer risk: a systematic review and meta-analysis of the published literature on agriculture and cotton textile workers.

OBJECTIVE: To examine the association between exposure to endotoxins and lung cancer risk by conducting a systematic review and meta-analysis of epidemiologic studies of workers in the cotton textile and agricultural industries; industries known for high exposure levels of endotoxins. METHODS: Risk estimates were extracted from studies published before 2009 that met predefined quality criteria, including 8 cohort, 1 case-cohort, and 2 case-control studies of cotton textile industry workers, and 15 cohort and 2 case-control studies of agricultural workers. Summary risk estimates were calculated using random effects meta-analyses. Potential sources of heterogeneity were explored through subgroup analyses. RESULTS: The summary risk of lung cancer was 0.72 (95% CI, 0.57-0.90) for textile workers and 0.62 (0.52-0.75) for agricultural workers. The relative risk of lung cancer was below 1.0 for most subgroups defined according to sex, study design, outcome, smoking adjustment, and geographic area. Two studies provided quantitative estimates of endotoxin exposure and both studies tended to support a dose-dependent protective effect of endotoxins on lung cancer risk. CONCLUSION: Despite several limitations, this meta-analysis based on high-quality studies adds weight to the hypothesis that occupational exposure to endotoxin in cotton textile production and agriculture is protective against lung cancer.

Endotoxin enhances microvascular thrombosis in mouse cremaster venules via a TLR4-dependent, neutrophil-independent mechanism.

Endotoxemia promotes adhesive interactions between platelets and microvascular endothelium in vivo. We sought to determine whether endotoxin (lipopolysaccharide, LPS) modified platelet thrombus formation in mouse cremaster venules and whether Toll-like receptor 4 (TLR4) and neutrophils were involved in the response. Intravital videomicroscopy was performed in the cremaster microcirculation of pentobarbital-anesthetized mice; venular platelet thrombi were induced with a light/dye endothelial injury model. C57BL/6 mice treated with Escherichia coli endotoxin had enhanced rates of venular platelet thrombus formation: the time to microvessel occlusion was reduced by approximately 50% (P < 0.005) compared with saline-treated animals. Enhanced microvascular thrombosis was evident as early as 2 h after LPS administration. LPS had no effect on thrombosis in either of two mouse strains with altered TLR4 signaling (C57BL/10ScNJ or C3H/HeJ), whereas it enhanced thrombosis in the control strains (C57BL/10J and C3H/HeN). LPS also enhanced platelet adhesion to endothelium in the absence of light/dye injury. Platelet adhesion, but not enhanced thrombosis, was inhibited by depletion of circulating neutrophils. LPS failed to enhance platelet aggregation ex vivo and did not influence platelet P-selectin expression, a marker of platelet activation. These findings support the notion that endotoxemia promotes platelet thrombus formation independent of neutrophils and without enhancement of platelet aggregation, via a TLR4-dependent mechanism.

Toxicity of several delta-endotoxins of Bacillus thuringiensis against Helicoverpa armigera (Lepidoptera: Noctuidae) from Spain.

Toxicity and larval growth inhibition of 11 insecticidal proteins of Bacillus thuringiensis were evaluated against neonate larvae of Helicoverpa armigera, a major pest of important crops in Spain and other countries, by a whole-diet contamination method. The most active toxins were Cry1Ac4 and Cry2Aa1, with LC50 values of 3.5 and 6.3 microg/ml, respectively. At the concentrations tested, Cry1Ac4, Cry2Aa1, Cry9Ca, Cry1Fa1, Cry1Ab3, Cry2Ab2, Cry1Da, and Cry1Ja1, produced a significant growth inhibition, whereas Cry1Aa3, Cry1Ca2, and Cry1Ea had no effect.

Metalworking fluid--the toxicity of a complex mixture.

Various chemicals are used in the manufacture of cooling and lubricating fluids and fall into the classes of straight, soluble, semisynthetic, and synthetic metalworking fluids. The diversity of chemicals and in-use contaminants makes the risk assessment of metalworking fluids quite difficult. Toxicologists have used a number of methods to evaluate the component(s) responsible for the adverse pulmonary effects of metal working fluid aerosols encountered in the workplace. Although investigators have studied the adverse effects of metalworking fluid chemicals alone and in combination, the majority of evidence strongly suggests that the microbial changes that occur in fluid composition, during use and storage in the workplace, are responsible for the pulmonary effects reported for workers exposed to metalworking fluid aerosols. This review discusses the methodologies used to examine the toxicity of the complex nature of modern metalworking fluids and the findings that point toward bacterial endotoxin as a major contributor to their adverse effects.

Organic dust exposure and work-related effects among recycling workers.

OBJECTIVE: Organic dust exposure and work-related symptoms and effects among household waste recycling workers in Materials Recovery Facilities (MRFs) are a concern. MRFs are a central operation where source-segregated, dry, recyclable materials (paper, plastics, cans, etc.) are sorted, mechanically or manually, to market specifications for processing into secondary materials. METHODS: One hundred and fifty-nine MRF workers (91%) from nine MRFs participated. Measurements of airborne total dust, endotoxin, (1-->3)-beta-D-glucan, and a questionnaire survey were carried out. Blood data was restricted to MRFs 3, 6, and 9 (45 workers). Blood sampling investigated differential cell counts, erythrocyte sedimentation rate (ESR), and immunoglobulin (Ig)E. RESULTS: Workers exposed to higher amounts of endotoxin and (1-->3)-beta-D-glucan had an increased risk for respiratory symptoms as compared to those with lower exposure. Stomach problems was associated to higher (1-->3)-beta-D-glucan exposure. MRF 3 had a higher (1-->3)-beta-d-glucan exposure compared to 6 and 9, and respiratory symptoms, unusual tiredness, and vomiting were reported more often in MRF 3. Monocyte numbers and ESR were significantly decreased in MRF 3 compared to MRF 6 and 9, but all measured values were within normal ranges. CONCLUSIONS: The results suggest that MRF workers exposed to higher levels of endotoxin and (1-->3)-beta-D-glucan at their work sites exhibit various work-related symptoms, and that the longer a worker is in the MRF environment, the more likely he is to become affected by various respiratory and gastrointestinal symptoms.

Staghorn calculus endotoxin expression in sepsis.

Staghorn calculi are infrequent and generally are infected stones. Struvite or apatite calculi are embedded with gram-negative bacteria, which can produce endotoxin. Sepsis syndrome may occur after surgical therapy or endoscopic manipulation of infected or staghorn calculi. Sepsis, which can occur despite perioperative antibiotic use, may be due to bacteremia or endotoxemia. We present a child with an infected staghorn calculus who developed overwhelming sepsis and died after percutaneous stone manipulation. Endotoxin assay of stone fragments demonstrated an extremely high level of endotoxin despite low colony bacterial culture growth. This is the first reported case in which endotoxin was demonstrated in stone fragments from a child who died of severe sepsis syndrome after percutaneous staghorn stone manipulation.

Leptin deficiency enhances sensitivity to endotoxin-induced lethality.

Leptin is induced by lipopolysaccharide (LPS) and cytokines. We investigated the role of leptin in LPS-induced toxicity using leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice. Sensitivity to LPS-induced mortality is significantly greater in ob/ob mice compared with their own lean littermates but not in db/db mice. LPS reduced serum glucose in both ob/ob and db/db mice but induced corticosterone only in db/db mice. Despite the very high basal levels of serum leptin in db/db mice, a twofold increase in serum leptin levels was observed after LPS in both db/db mice and their lean littermates. No differences were detected in LPS-induced serum levels of interleukin (IL)-1beta, tumor necrosis factor, macrophage inflammatory protein-1alpha, and interferon-gamma in ob/ob mice compared with their own littermates. In contrast, a blunted induction of IL-10 and IL-1 receptor antagonist (IL-1Ra) was observed in ob/ob mice compared with their littermates. In vitro, leptin induced IL-1Ra production and upregulated the IL-1Ra induction by LPS in macrophages. Moreover, treatment with leptin reversed the increased sensitivity to LPS-induced lethality found in ob/ob mice. These results suggest that leptin participates in the host response to inflammation by modulating the host immune and cytokine responses after LPS.

Poisoning of cattle and sheep in Uruguay by sawfly (Perreyia flavipes) larvae.

From June to early October of 1993, 1994 and 1995 at least 40 outbreaks of a highly lethal disease occurred in cattle and sheep in the central region of Uruguay. During 1995 total cattle losses probably exceeded 1000 head. Mortalities were 1.6%, 7.0% and 1.3% for calves, yearlings and adults, respectively, but mortalities up to 28% occurred on some farms. Sheep were less frequently affected than cattle. Most animals were just found dead. Cattle had weakness, muscular tremors, depression, stupor and death. Others became highly excited and aggressive. Most affected cattle died within 2 d. Jaundice and mild photosensitization were observed in cattle that survived longer. Gross and microscopic lesions were severe periacinar or massive necrosis of hepatocytes with prominent edema of the gall bladder wall and its attachments. Edema, ecchymoses and petechiae on serous membranes, ascites and dry content of the omasum, colon and rectum were also observed. Invariably larval body fragments and heads of P flavipes were found in the rumen and omasum. The diagnosis of sawfly poisoning was confirmed by experimental feeding of 3 sheep and 2 calves with 9 to 40 g of P flavipes larvae/kg body weight.

The hepatic and duodenal activities of some drug metabolizing enzymes in chickens: influence of infection with Escherichia coli endotoxin and coccidiosis.

The activities of the drug metabolizing enzymes aminopyrine-N-demethylase, aniline hydroxylase and UDP-glucuronyl transferase, together with protein concentration, were measured in liver microsomes and duodenal mucosa from healthy chickens and chickens experimentally infected with Escherichia coli endotoxin, or naturally infected with Eimeria necatrix and Eimeria tenella (clinically classified as slight, moderate or severe infections). E. coli (2 mg/kg, 3 days) and severe coccidiosis significantly decreased the activities of the three enzymes in the liver and duodenum. However, infection by the E. coli endotoxin at lower doses (0.5 and 1 mg/kg, 3 days) and moderate or slight coccidial infections had no significant effect on the activities of these enzymes. Neither E. coli nor coccidial infections significantly affected the liver/body weight ratio. However, infection with the E. coli endotoxin (2 mg/kg, 3 days) and the moderate or severe coccidial infections significantly reduced microsomal protein concentration in the liver.

[The informational and morphometric characteristics of the liver acini in dogs with systemic endotoxinemia]. / Informatsionno-morfometricheskaia kharakteristika atsinusov pecheni sobak pri sistemnoi éndotoksinemii.

Dog liver was examined in systemic endotoxemia induced by i.v. injection of E. coli lipopolysaccharide in dose 2 mg/kg. Morphometric study helped obtain quantitative characteristics of changes in different acinus zones in the course of poisoning, and information analysis showed critical periods in the development of liver insufficiency.

The effects of immune globulin on endotoxemia.

Ten patients (mean age, 40 years; 2 women) with endotoxemia received 2.5 gm of immune globulin daily for 4 days or 5 gm daily for 2 days. In all patients, plasma endotoxin levels decreased to normal levels (< or = 9.8 pg/ml) within a mean of 3.2 days after starting immune globulin treatment, and body temperatures decreased to < 37 degrees C within 4.5 days. In 10 antibiotic-treated (control) patients with endotoxemia who did not receive immune globulin, plasma endotoxin levels declined to normal levels in 6 and their body temperatures dropped to normal levels within 5.0 days; no changes in body temperature were noted in the 4 patients whose plasma endotoxin levels did not decrease.