Endotoxin Concentrations Research Articles

Urinary oxidative stress biomarkers in nephrotoxicity induced by PM2.5 in a rat model

Objective The present study evaluated urinary oxidative stress (OxS) biomarkers to explain the extrapulmonary effect of renal function decline due to subchronic inhalation exposure to particles smaller than 2.5 μm, as well as the correlation of the biomarkers with the particles’ endotoxin content. Materials and methods Adult male Sprague-Dawley rats were exposed to subchronic inhalation of particles smaller than 2.5 μm (8 weeks, 4 days/week, 5 h/day). The control group was exposed to filtered air. MiniVol and HiVol samplers were used to estimate the concentration and collected particles, respectively. Biomarkers were assessed in weekly urine samples harvested by the metabolic cage. The OxS biomarkers assessed were methylglyoxal, non-esterified fatty acids, malondialdehyde, advanced oxidative protein products, arginase, myeloperoxidase, glutathione S-transferase, and gamma-glutamyl transferase, all of which were evaluated by colorimetric assays. Creatinine was evaluated by the Jaffe reaction, and cystatin-C (Cys-C) and neutrophil gelatinase-associated lipocalin-2 were quantified using Luminex technology. Endotoxin content was analyzed with the Limulus Amebocyte Lysate Pyrochrome Chromogenic Test Kit. Results and discussion Subchronic exposure to PM2.5 increased OxS biomarkers in urine. Endotoxin content showed a positive correlation with the urinary OxS biomarkers evaluated. Additionally, urinary OxS biomarkers correlated with creatinine and the early kidney damage biomarkers Cys-C and neutrophil gelatinase-associated lipocalin-2, where the strongest and positive correlations were observed with the latter two biomarkers. Conclusions Inhalation of environmental airborne particles smaller than 2.5 μm increased urinary OxS biomarkers, correlated with endotoxin content and early kidney damage biomarkers. This finding corroborates the extrapulmonary nephrotoxic effect of inhaled particles.

Microplastic Materials for Inhalation Studies: Preparation by Solvent Precipitation and Comprehensive Characterization.

Assessing the inhalation hazard of microplastics is important but necessitates sufficient quantity of microplastics that are representative and respirable (<4µm). Common plastics are not typically manufactured in such small sizes. Here, solvent precipitation is used to produce respirable test materials from thermoplastics polyurethane (TPU), polyamide (PA-6), polyethylene terephthalate (PET), and low-density polyethylene (LDPE). Complementary methods verified that the desired size range is achieved both in number metrics and in mass metrics. To assess if the test materials are representative of their original plastic, a range of molecular properties, particle properties, and impurities are characterized: chemical composition, molecular weight, crystallinity, molecular mobility, density, surface charge, surface reactivity, particle size in mass and number metrics, particle shape, endotoxin content, and solvent content. The test materials obtained by precipitation are compared to commercial granules as references, and to alternative test materials obtained by other synthesis routes from LDPE, TPU, PET, PA-6, polystyrene (PS), and polyvinylchloride (PVC). Charge and surface reactivity of the precipitated test materials are low. Due to storage in water, microbial contamination needed to be monitored. For PET, PA-6, and TPU, the test materials are considered as representative and fit for purpose, whereas the inherent hydrophobicity of LDPE imposed strong aggregation.

Endotoxin-Free Outer Membrane Vesicles for Safe and Modular Anticancer Immunotherapy.

Bacterial outer membrane vesicles (OMVs) have emerged as promising vehicles for anticancer drug delivery due to their inherent tumor tropism, immune-stimulatory properties, and potential for functionalization with therapeutic proteins. Despite their advantages, the high lipopolysaccharide (LPS) endotoxin content in the OMVs raises significant safety and regulatory challenges. In this work, we produce LPS-attenuated and LPS-free OMVs and systematically assess the effects of LPS modification on OMVs' physicochemical characteristics, membrane protein content, immune-stimulatory capacity, tolerability, and anticancer efficacy. Our findings reveal that LPS removal increased the maximal tolerated dose of the OMVs by over 25-fold. When adjusted for comparable safety profiles, LPS-free OMVs exhibit superior anticancer effects compared with wild-type OMVs. Mechanistic investigations indicate that the LPS removal obviates immune cell death caused by LPS and reduces the negatory effects of wild type of OMVs on tumor immune cell infiltrates. We further show the functionality of the LPS-free OMV through the incorporation of an IL-2 variant protein (Neo-2/15). This functionalization augments OMV's ability of the OMV to inhibit tumor growth and promote lymphocyte infiltration into the tumor microenvironment. This study presents a safe and functionalizable OMV with improved translational prospect.

Recombinant Factor C as an In Vitro Assay for the Residual Pathogenicity Evaluation of Veterinary Autogenous Vaccines.

Veterinary autogenous vaccines, similar to all injectable pharmaceutical products, must be tested to assess endotoxin concentrations. The Limulus Amebocyte Lysate Test (LAL test) is widely used in in vitro quality control assays for endotoxin detection, although it presents some ethical issues related to the production of reagents and is also characterized by a low specificity due to other contaminants that can activate the reaction. For all these reasons, a new recombinant factor C LAL test was developed. In this study, we described the comparison between two LAL test methods for in vitro quality control of veterinary autogenous vaccines, with the aim of evaluating the most suitable method and establishing an endotoxin concentration range for two different matrices. Two hundred batches of two different vaccine matrices were tested using the kinetic chromogenic LAL test and recombinant factor C endotoxin detection assay commercial kits. Statistical analysis conducted after the validation of the recombinant factor C test exhibited a statistically significant correlation between the two methods and for both vaccine matrices, suggesting that the animal-free assay can be used as a routine quality control test for veterinary autogenous vaccines.

Highly sensitive and rapid optical fiber bio-sensor for endotoxin detection using anti-resonance effect

Endotoxin detection is critical to human health. Reported endotoxin assays usually rely on multistep enrichment or specific modification techniques to improve sensitivity, resulting in long response times (∼1 h) and greater sample consumption (>1 mL). By now, it is still challenging to implement a highly sensitive and ultra-fast response (∼seconds) biosensor for optical endotoxin assays with only micro/nanoliter volume. Here, a new approach is proposed to break the challenges by using an anti-resonance (AR) fiber-optic biosensors with the length-independent and volume-independent sensitivity. The AR fiber-optic biosensor is composed of a side-polished single-mode/hollow-core/single-mode fiber (SP-SHSF) structure, capable of achieving high sensitivity (∼7394 nm/RIU@RI=1.33–1.385 and 33,657.14 nm/RIU@RI=1.436–1.446) with a lowest sample volume limit of down to sub-nanoliter (∼600 pL). A standard Limulus Amebocyte Lysate (LAL) assay was combined to achieve refractive index (RI) increases during LAL gel formation, and endotoxin concentrations were quantified by fixing the response time required for a 5 nm resonance dip drift. The limit of detection (LOD) of endotoxin for the biosensor was measured to be 10−4 EU/mL with a fast response time of 344 s and only 5 μL consumption of LAL reagent per test. Compared with the traditional LAL test, the fiber-optic biosensor has more than two orders of magnitude lower LOD, about 9 times faster respond and 20 times less sample consumption. The proposed fiber-optic biosensor has the advantages of small size, high sensitivity, reusability, and online detection, which is of great significance for detecting endotoxin contamination in products for biopharmaceuticals and medical devices.

Residential fungal β-(1,3)-D-glucan exposure is associated with decreased pulmonary function in fibrotic pulmonary sarcoidosis.

Sarcoidosis is a multi-system disease frequently affecting the lungs. It is thought to be mediated by gene-environment interaction; for example, epidemiological data show organic aerosol exposure increases risk of pulmonary sarcoidosis. Does exposure to bioaerosol associate with worse lung disease in patients with pulmonary sarcoidosis? Using an observational, cohort study design, we measured residential exposure to fungal and bacterial cell wall material, β-(1,3)-D-glucan (BDG) and endotoxin, respectively, in healthy control subjects and those with pulmonary sarcoidosis. In the case cohort, we compared bioaerosol concentrations to pulmonary disease severity, assessed by pulmonary function testing, qualitative chest computed tomography (CT), and serum biomarkers. Log-transformed bioaerosol concentrations were compared to lung function and significance and correlation determined by Pearson correlation. Homes of subjects with sarcoidosis had higher BDG and endotoxin concentrations than control subjects. Patients with significant pulmonary fibrosis had greater disease severity (Wasfi severity score, visual analogue scale) and reduced pulmonary function compared to those without fibrosis (all P<0.01). Residential fungal BDG correlated with declining FVC, only in patients with fibrosis on CT imaging (P=0.02). Survey data revealed higher BDG concentrations were found in homes of cat-owners, and the number of houseplants owned correlated with declines in FVC and FEV1 (P=0.05 and 0.02, respectively). In patients without fibrosis, eight inflammatory markers correlated with BDG (6CKine/CCL21, IL-9, IL-17F, IL-21, IL-28A, I-309, MIP-1β, TARC), while in those with pulmonary fibrosis, BDG correlated with two inflammatory markers (Eotaxin-3, M-CSF), suggesting immune anergy to inhaled antigens in patients with fibrosis. In patients with pulmonary fibrosis, disease severity was correlated with residential exposure to fungal cell wall material, but not gram-negative bacterial cell wall material. These patients may experience immune anergy to inhaled antigens.

Hypertonic Saline Nasal Rinse Intervention: Immunomodulatory Effects in Dairy Workers

ABSTRACT Objective Increased risk of occupational exposure to bioaerosols has long been recognized in livestock operations including dairy facilities. Spanning the inhalable fraction (0–100 μm), dairy bioaerosols comprise a wide variety of inflammatory components that deposit in the nasopharyngeal region. The resultant inflammatory response from bioaerosol exposure is likely driving the increased prevalence of respiratory disease observed in dairy workers. It is also thought the microbiome of the upper respiratory system may help mediate this inflammation. We investigated the viability of a low-cost hypertonic saline nasal rinse intervention in modulating inflammatory responses in bioaerosol exposed dairy workers and its impact on microbial diversity. Methods Pre- and post-shift nasal rinses were administered and collected alongside full shift inhalable personal breathing zone (PBZ) samples for each participant for up to 5 consecutive days. Treatment group participants (n = 23) received hypertonic saline rinses while control group participants (n = 22) received normotonic saline rinses. Particulate matter (PM) and endotoxin concentrations were quantified from PBZ samples using gravimetric and enzymatic analytical methods, respectively. Pre- and post-shift rinses were analyzed for pro- and anti-inflammatory markers and microbial diversity using a multiplex assay and 16S rRNA sequencing, respectively. Results PM and endotoxin concentrations were comparable between groups indicating similar exposures. Post-shift pro-inflammatory markers were significantly higher than pre-shift for IL-13 (p = .047), IL-1β (p < .001), IL-6 (p < .001), IL-8 (p < .001), and TNF-α (p = .024). There was no evidence of a difference in log concentrations between intervention group or day among any of the measured inflammatory markers. Anti-inflammatory IL-10 concentrations increased across the 5 sample days, independent of treatment group suggesting tonicity may not be driving the change. However, this result was not significant (p = .217). Nasal microbiome alpha (within sample) and beta (between sample) diversity metrics did not differ significantly between group or day demonstrating no adverse washout intervention effects. Conclusion This study provided encouraging results that warrant future research to further evaluate saline nasal rinses as a workplace intervention.

Influence of different cleaning methods on the concentration of airborne endotoxins and microbial aerosols in the oral clinical environment

AimThis study aims to evaluate the effectiveness of various cleaning methods in reducing airborne endotoxin and microbial aerosols during oral cleaning procedures.MethodForty patients undergoing oral cleaning procedures were randomly assigned to one of four groups (n = 10 per group). Group A received strong suction alone; Group B received strong suction combined with an air disinfection machine; Group C received strong suction combined with a dental electric suction machine; Group D received strong suction in conjunction with both an air disinfection machine and a dental electric suction machine. Airborne aerosol concentrations were assessed at four-time points: before treatment, 30 min into treatment, immediately after treatment, and 60 min after treatment ended. Samples were collected at distances of 20 cm, 60 cm, and 1 m from the patient’s oral cavity using the natural sedimentation method. T-test was used to evaluate the difference among tested groups.ResultsAirborne endotoxins and microbial aerosols levels increased significantly during treatment, with the highest levels observed at 20 cm from the patient’s mouth. During treatment, groups with additional cleaning methods (Groups B, C, and D) exhibited higher levels of airborne endotoxins and microbial aerosols compared to Group A (strong suction alone). However, post-treatment analysis revealed that Group D demonstrated the lowest level of airborne endotoxins and microbial aerosols, while Group A exhibited the highest.ConclusionsImplementing effective aerosol management strategies can significantly reduce aerosol dispersion in the oral clinical environment. Continuous monitoring aerosol concentrations and the application of appropriate control measures are essential for minimizing infection risks for both patients and healthcare providers during oral cleaning procedures.

Efficacy of prophylactic antibiotics in the adjuvant treatment of alcohol-related liver disease (ALD): A systematic review and meta-analysisProphylactic antibiotics in ALD

Introduction and ObjectivesThis research aims to evaluate the efficacy and safety of prophylactic antibiotics in patients with alcohol-related liver disease (ALD). Materials and MethodsWe systematically searched databases including PubMed, Embase, Cochrane, and Web of Science up to October 2023. Our scope encompassed the influence of prophylactic antibiotics on all-cause mortality, infection, variceal bleeding, hepatic encephalopathy (HE), hepatorenal syndrome (HRS), adverse events (AE), fungal infection, clostridioides difficile infection (CDI), and multidrug-resistant (MDR) bacterial infection. Additionally, total bilirubin, creatinine, platelet counts, and plasma endotoxin levels were also analyzed. ResultsAfter comprehensive selection, 10 studies with 974 participants were included for further analysis. The study demonstrated that prophylactic antibiotic therapy was associated with reductions in infection rates, HE incidence, variceal bleeding, and all-cause mortality. The treatment did not increase the incidence of AE, fungal infection, and CDI, but it did raise the MDR bacteria infection rate. The analysis revealed no significant protective effect of antibiotic prophylaxis on total bilirubin and creatinine levels. Furthermore, the administration of antibiotics led to marginal increases in platelet counts, a minor reduction in endotoxin concentrations, and a subtle enhancement in HRS; however, these changes did not reach statistical significance. ConclusionsProphylactic antibiotic therapy was an effective and safe treatment for advanced ALD. To mitigate the risk of MDR bacterial infections, a strategy of selective intestinal decontamination could be advisable. Future investigations should prioritize varied ALD patient populations with extended follow-up periods and assorted antibiotic regimens to solidify the efficacy and safety of ALD treatments.

Dietary Zn proteinate with moderate chelation strength alleviates heat stress-induced intestinal barrier function damage by promoting expression of tight junction proteins via the A20/NF-κB p65/MMP-2 pathway in the jejunum of broilers

BackgroundThe aim of this study was to determine whether and how Zn proteinate with moderate chelation strength (Zn-Prot M) can alleviate heat stress (HS)-induced intestinal barrier function damage of broilers. A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers. Under high temperature (HT), a 1 (Control, HT-CON) + 2 (Zn source) × 2 (added Zn level) factorial arrangement of treatments was used. The 2 added Zn sources were Zn-Prot M and Zn sulfate (ZnS), and the 2 added Zn levels were 30 and 60 mg/kg. Under normal temperature (NT), a CON group (NT-CON) and pair-fed group (NT-PF) were included.ResultsThe results showed that HS significantly reduced mRNA and protein expression levels of claudin-1, occludin, junctional adhesion molecule-A (JAMA), zonula occludens-1 (ZO-1) and zinc finger protein A20 (A20) in the jejunum, and HS also remarkably increased serum fluorescein isothiocyanate dextran (FITC-D), endotoxin and interleukin (IL)-1β contents, serum diamine oxidase (DAO) and matrix metalloproteinase (MMP)-2 activities, nuclear factor kappa-B (NF-κB) p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum. However, dietary supplementation with Zn, especially organic Zn as Zn-Prot M at 60 mg/kg, significantly decreased serum FITC-D, endotoxin and IL-1β contents, serum DAO and MMP-2 activities, NF-κB p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers, and notably promoted mRNA and protein expression levels of claudin-1, ZO-1 and A20.ConclusionsOur results suggest that dietary Zn, especially 60 mg Zn/kg as Zn-Prot M, can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.

The effect of dietary full-fat Hermetia illucens larvae meal on growth performance and intestine physiology in largemouth bass (Micropterus salmoides)

The present study aimed to investigate the effects of different inclusion levels of full-fat Hermetia illucens larvae (HI) meal as a protein source on the growth performance, intestinal morphology, health, and microbiota of largemouth bass. Five isonitrogenous and isolipidic diets were formulated by adding HI to replace 0 % (HI0, control), 10 % (HI10), 20 % (HI20), 30 % (HI30) and 40 % (HI40) of fish meal (FM) in diets. Each diet was randomly assigned to triplicate groups of 30 fish per aquarium. Fish were fed two times daily to apparent satiation for 80 days. The results indicated that weight gain rate, specific growth rate and protein efficiency ratio were not appreciably reduced until more than 30 % of the FM protein was replaced with HI. Fish fed HI40 diet had the lowest fatty acid (C18:3, C20:5, C22:6) contents (P < 0.05). Moreover, the villi height was decreased, villi width and goblet cell number in hindgut was increased in the HI40 group compared with the other groups, respectively. Meanwhile, serum diamine oxidase activity, D-lactate and endotoxin contents increased markedly as the proportion of HI increased (P < 0.05). Notably, the increased dietary HI levels down-regulated the mRNA expression levels of cldnd1b and ocel1 in intestine. Higher malondialdehyde content and down-regulated expression of sod and gpx1a in the intestine were also observed in the HI40 group. Accordingly, the increased dietary HI levels upregulated the expression of intestinal pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and down-regulated anti-inflammatory cytokines (transcriptional growth factor-β1 and interleukin-10) (P < 0.05). In addition, the abundance of both intestinal Lactobacillus and Streptococcus increased significantly, while the abundance of Cetobacterium decreased in the HI20 group (P < 0.05). Broken-line model analysis based on weight gain rate against dietary HI replacement level indicated that the optimum replacement level was 26.79 %. However, including too high proportion of HI could induce intestinal dysbiosis, impair the intestine physical barrier, and finally reduced growth of Micropterus salmoides.

Protective Effect of Coated Benzoic Acid on Intestinal Epithelium in Weaned Pigs upon Enterotoxigenic Escherichia coli Challenge.

The study was designed to investigate the protective effect of dietary supplementation with coated benzoic acid (CBA) on intestinal barrier function in weaned pigs challenged with enterotoxigenic Escherichia coli (ETEC). Thirty-two pigs were randomized to four treatments and given either a basal diet or a basal diet supplemented with 3.0 g/kg CBA, followed by oral administration of ETEC or culture medium. The results showed that CBA supplementation increased the average daily weight gain (ADWG) in the ETEC-challenged pigs (p < 0.05). CBA also increased the serum activity of total superoxide dismutase (T-SOD) and the total antioxidant capacity (T-AOC), as it decreased the serum concentrations of endotoxin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the ETEC-challenged pigs (p < 0.05). Interestingly, the CBA alleviated the ETEC-induced intestinal epithelial injury, as indicated by a reversal of the decrease in D-xylose absorption and a decrease in the serum levels of D-lactate and diamine oxidase (DAO) activity, as well as a decrease in the quantity of apoptotic cells in the jejunal epithelium following ETEC challenge (p < 0.05). Moreover, CBA supplementation significantly elevated the mucosal antioxidant capacity and increased the abundance of tight junction protein ZO-1 and the quantity of sIgA-positive cells in the jejunal epithelium (p < 0.05). Notably, CBA increased the expression levels of porcine beta defensin 2 (PBD2), PBD3, and nuclear factor erythroid-2 related factor 2 (Nrf-2), while downregulating the expression of toll-like receptor 4 (TLR4) in the jejunal mucosa (p < 0.05). Moreover, CBA decreased the expression levels of interleukin-1β (IL-1β), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB) in the ileal mucosa upon ETEC challenge (p < 0.05). These results suggest that CBA may attenuate ETEC-induced damage to the intestinal epithelium, resulting in reduced inflammation, enhanced intestinal immunity and antioxidant capacity, and improved intestinal epithelial function.

Low temperature exposure influences nitrogen metabolism resulting in decreased Cry1Ac insecticidal endotoxin content in cotton seeds

BackgroundSudden temperature drops, resulting from extreme weather events, often occur during the boll-setting period of cotton in Xinjiang, China, causing decreased expression of Bacillus thuringiensis (Bt) insecticidal proteins in cotton bolls. The precise threshold temperatures and durations that lead to significant changes in Cry1Ac endotoxin levels under low temperatures remain unclear. To address this, we investigated the effects of different temperatures and stress durations on Cry1Ac endotoxin levels in cotton bolls. In 2020–2021, two Bt transgenic cotton varieties, conventional Sikang1 and hybrid Sikang3, were selected as experimental materials. Various low temperatures (ranging from 16 to 20 °C) with different durations (12 h, 24 h and 48 h) were applied during the peak boll-setting period.ResultsAs the temperature decreased, the Cry1Ac endotoxin content in the boll shell, fiber, and seed exhibited a declining trend. Moreover, the threshold temperature which caused a significant reduction in Cry1Ac endotoxin content increased with the prolonged duration of low-temperature stress. Among the components of cotton bolls, seeds were most affected by low-temperature stress, with the threshold temperature for a significant reduction in Cry1Ac endotoxin content ranging from 17 °C to 19 °C. Correlation analysis indicated that low temperatures led to a decrease in protein synthesis capacity and an increase in degradation ability, resulting in reduced Cry1Ac endotoxin content. Pathway analysis revealed that both free amino acid and peptidase had significant negative effects on Cry1Ac endotoxin content.ConclusionIn summary, when the daily average temperature was ≤ 19 °C, implementing cultural practices to reduce free amino acid content and peptidase activity could serve as effective cold defense strategies for Bt cotton production.

Recombinant fibrous protein biomaterials meet skin tissue engineering.

Natural biomaterials, particularly fibrous proteins, are extensively utilized in skin tissue engineering. However, their application is impeded by batch-to-batch variance, limited chemical or physical versatility, and environmental concerns. Recent advancements in gene editing and fermentation technology have catalyzed the emergence of recombinant fibrous protein biomaterials, which are gaining traction in skin tissue engineering. The modular and highly customizable nature of recombinant synthesis enables precise control over biomaterial design, facilitating the incorporation of multiple functional motifs. Additionally, recombinant synthesis allows for a transition from animal-derived sources to microbial sources, thereby reducing endotoxin content and rendering recombinant fibrous protein biomaterials more amenable to scalable production and clinical use. In this review, we provide an overview of prevalent recombinant fibrous protein biomaterials (collagens, elastin, silk proteins and their chimeric derivatives) used in skin tissue engineering (STE) and compare them with their animal-derived counterparts. Furthermore, we discuss their applications in STE, along with the associated challenges and future prospects.

Potentially pathogenic culturable bacteria in hemodialysis waters

BackgroundHemodialysis patients are at risk of acquiring healthcare-related infections due to using non-sterile water to prepare hemodialysis fluid. Therefore, microbiological control and monitoring of used water are of crucial importance.Materials and methodsIn this work, we identified bacterial populations occupying a hemodialysis water distribution system for almost a 6-month period in Ahvaz city, southwest of Iran. A total of 18 samples from three points were collected. We found high colony counts of bacteria on R2A agar. 31 bacteria with different morphological and biochemical characteristics were identified by molecular-genetic methods based on 16 S rRNA gene sequencing. Endotoxin concentrations were measured, using Endosafe® Rapid LAL Single-Test Vials.ResultsA diverse bacterial community was identified, containing predominantly Gram-negative bacilli. The most frequently isolated genus was Sphingomonas. Five species including M. fortuitum, M. lentiflavum, M.szulgai, M. barrassiae, and M. gordonae was identified .Despite the presence of Gram-negative bacteria the endotoxin analysis of all samples revealed that their endotoxin values were below the detection limit.ConclusionThe members of Sphingomonas genus along with Bosea and mycobacteria could be regarded as pioneers in surface colonization and biofilm creation. These bacteria with others like Pelomonas, Bradyrhizobium, staphylococcus, and Microbacterium may represent a potential health risk to patients under hemodialysis treatment.

The Effect of Systemic Endotoxinemia on the Structure of the Brachiocephal Arteries Wall or a Potential Clinical Model for Assessing the Efficacy of Anti-Aging Measures

Integrated indicators of systemic endotoxemia (SEE): the level of endotoxin (ET) and the concentration of antibodies to the hydrophobic (AT-LPS-FOB) and hydrophilic (AT-LPS-PIL) forms of the lipopolysaccharide (LPS) molecule in the general circulation can be used to determine the risk category of atherosclerosis development and progression, which dynamics is an objective marker of aging rate. The comparison of images the structure of brachycephalic arteries wall in dynamics with changes in blood parameters is one of the most successful models for monitoring the atherosclerotic process in a clinical setting. 42 people were examined without the presence of recognized risk factors for the progression of atherosclerosis at baseline and after 1.5-2 years. It was found that lipid profile indicators, such as the concentration of total cholesterol, low and high density lipoproteins, triglycerides, atherogenic index had no prognostic value. Whereas in the group with the progression of damage to the arterial wall, an increase in the concentration of ET was noted with a decrease in the concentration of AT-LPS-FOB and AT-LPS-PIL. In the group with regression of atherosclerotic changes, on the contrary, against the background of a decrease in the concentration of ET, an increase in AT was noted. A prospective study revealed an extremely important fact of a decrease in the concentration of LPS in the blood of patients with positive dynamics of morphological manifestations of atherosclerosis, indicating both the reversibility of the atherosclerotic process and the participation of ET in atherogenesis, which is a real way for extending the life of an individual and indicates the direction to achieve this goal – “antiendotoxin therapy”.

Relationship between Endotoxin Content in Vaccine Preclinical Formulations and Animal Welfare: An Extensive Study on Historical Data to Set an Informed Threshold.

The most widely known pyrogen impurity in vaccines is the Gram-negative bacterial endotoxin lipopolysaccharide (LPS). When administered at toxic doses, endotoxin triggers inflammatory responses, which lead to endotoxic shock. The literature on endotoxic content (EC) for preclinical vaccines' formulations used in animal studies is very poor, and the recommended thresholds are solely based on commercial vaccine limits set for humans and are, therefore, not connected to the actual impact of EC on animal welfare for species used in preclinical research studies. An extensive study to evaluate the presence of a potential relationship between endotoxin content in formulations administered to mice (the most common species used in preclinical research studies) and their welfare was conducted to calculate an EC threshold for formulations of candidate vaccines. Three years of historical data, from more than 500 formulations of different antigen types (i.e., proteins, glycoconjugates, OMV/GMMA) injected into more than 5000 mice, was evaluated with two alternative statistical methodologies, both demonstrating that there is no significant relationship between actual endotoxin levels and mouse welfare. The calculation of thresholds was, therefore, performed by consistency versus formulations that demonstrated no impact on animal welfare.

Gut barrier dysfunction, endotoxemia and inflammatory response in STEMI patients and effect of primary PCI

BackgroundGut-derived bacterial and endotoxin translocation induce systemic inflammation, which exerts a pivotal pathogenetic role in all phases of atherosclerosis. ObjectivesTo investigate prospectively the gut barrier function, endotoxin translocation and inflammatory response in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary artery intervention (PPCI). MethodsTwenty-seven patients with STEMI that underwent successful PPCI were subjected to peripheral blood sampling at 3-time points; before PPCI (day0), 24 h (day1) and 96 h (day4) after PPCI and were compared with 20 chronic coronary syndrome (CCS) patients and 11 healthy controls. Serum ZO-1, I-FABP and endotoxin concentrations were determined by ELISA. Concentrations of cytokines IL-1β, -6, -8, -10 and TNF-α were determined by flow cytometry. ResultsPatients with STEMI before PPCI (day0) had increased serum ZO-1 and endotoxin, both at significantly higher levels compared to CCS patients. STEMI induced also significant increases of the cytokines IL-6, -8 and -10. After PPCI, a significant improvement of gut barrier integrity (ZO-1) and endotoxemia was observed from the first day. At day4 post PPCI, systemic endotoxin and cytokines IL-6, -8 and -10 levels were reduced to control levels. Serum ZO-1 levels were positively correlated with systemic IL-10 concentrations (r = 0.471). ConclusionSTEMI is associated with gut barrier dysfunction, systemic endotoxemia and inflammatory response, which improve rapidly following successful PPCI.

Endotoxins in Household Dust in Northern China: Associations with Home Environment Factors and Childhood Asthma and Allergies

The available information on endotoxin in Chinese households is limited and there is inconsistency regarding its impact on asthma and allergies in children. A case-control study was performed in 324 homes in Tianjin, China. Linear regression analysis was performed to identify the determinants of endotoxin concentrations in household dust. Logistic regression models were employed to investigate the associations of endotoxin concentrations with asthma and allergies in children. Endotoxin concentrations were determined from 284 valid dust samples, ranging from 94 to 11,625 EU/g, with a mean concentration of 3638 EU/g. We found a significant positive association between endotoxin concentrations and children’s current asthma. Old houses, ventilation systems without exhaust fans and windows opened infrequently were related to higher concentrations of endotoxins. In conclusion, endotoxin exposure in the home might be a risk factor for current asthma in children. Strategies for controlling endotoxin concentrations such as building maintenance and ventilation improvements are recommended.

Household indoor air quality in northeast China: On-site inspection and measurement in 399 Tianjin area residences

There has been an increased concern on indoor air quality (IAQ) in residences since the majority of individuals’ time is mainly spent indoors. We inspected and measured indoor environmental parameters in 399 homes in northeast China in order to study IAQ. We systematically measured multilevel environmental parameters (physical, chemical, and biological) in children’s bedrooms during all seasons. The results indicated that the median values for indoor temperature, relative humidity, total volatile organic compounds (TVOC), and formaldehyde concentrations throughout the year were within the Chinese national standards. However, the median carbon dioxide concentrations exceeded 1000 ppm during spring, autumn, and winter. In the same seasons, the air change rate (ACR) was below the minimum required level of 0.5 h−1. Di-2-ethylhexyl phthalate (DEHP), di-n-butyl phthalate (DnBP), and di-isobutyl phthalate (DiBP) were predominantly detected in settled dust, displaying median concentrations of 126.9, 41.5, and 16.3 μg/g, respectively. Notably, phthalate concentrations were significantly higher in urban houses as compared to rural houses. Furthermore, median concentrations of Dermatophagoides farinae (Der f) and endotoxin were 689.4 ng/g and 3689.1 EU/g, respectively, trending higher in winter than summer. There was a negative correlation between ACR and chemical pollutants (TVOC, formaldehyde, and DiBP). In conclusion, northeast Chinese homes had poor indoor air quality with ubiquitous exposure to modern chemical compounds and insufficient ventilation.