Stage of colorectal cancer diagnosis for immigrants: a population-based retrospective cohort study in Ontario, Canada.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer death in Canada. Immigrants in Ontario, Canada's most populous province, are known to have lower rates of CRC screening, but differences in stage of CRC diagnosis are not known. METHODS: We utilized linked administrative databases to compare early (stage I-II) versus late (stage III-IV) stage of CRC diagnosis for immigrants versus long-term residents among patients diagnosed in Ontario between 2012 and 2017 (n = 37,717) and examined the association of immigration-related, sociodemographic, and healthcare-related factors with stage. RESULTS: Almost 45% of those with CRC were diagnosed at a late stage. Immigrants were slightly more likely to be diagnosed at a late stage than their long-term resident counterparts [Adjusted relative risks (ARRs) 1.06 (95% CI 1.02-1.10)], but after adjusting for age and sex, this difference was no longer significant. In fully adjusted models, we observed a higher likelihood of late-stage diagnosis for people with the fewest co-morbidities (ARR 0.86 [95% CI 0.83-0.89]) and those with no visits to primary care (versus a high level of continuity of care) [ARR 1.07 (95% CI 1.03-1.12)]. CONCLUSION: Immigrants were not more likely to have a late-stage CRC diagnosis after adjusting for relevant factors, but access to primary care and healthcare contact was significantly associated with diagnostic stage. IMPACT: Attachment to a primary care provider who provides regular preventive care may play a role in more favorable stage at diagnosis for CRC and thus should be a healthcare system priority.

Serious infections in patients with myasthenia gravis: population-based cohort study.

BACKGROUND AND PURPOSE: To characterize the frequency and risk of serious infections in patients with myasthenia gravis (MG) relative to age/sex/area-matched comparators. METHODS: This was a population-based cohort study in Ontario, Canada of patients with newly-diagnosed MG and 1:4 age/sex/area-matched general population comparators accrued from 1 April 2002 to 31 December 2015. The main outcome was a serious infection, defined by a primary diagnosis code on a hospitalization or emergency department record. We computed crude overall and sex-specific rates of infection among patients with MG and comparators, and the frequency of specific types of infection. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox regression. RESULTS: Among 3823 patients with MG, 1275 (33.4%) experienced a serious infection compared with 2973/15 292 (19.4%) of comparators over a mean follow-up of over 5 years. Crude infection rates among patients with MG were twice those in comparators (72.5 vs. 35.0 per 1000 person-years, respectively). The most common infection types were respiratory infections, particularly bacterial pneumonia. After adjustment for potential confounders, MG was associated with a 39% increased infection risk (adjusted hazard ratio, 1.39; 95% confidence intervals, 1.28-1.51). CONCLUSIONS: Patients with MG are at a significantly higher absolute and relative risk of serious infections compared with age/sex/area-matched comparators. This needs to be considered when selecting MG treatments and when planning vaccination/prophylaxis. Determining whether this risk is due to the use of immunosuppressive medications (vs. MG itself) is an important area for future research.

Phylogenetic position of the Drosophila fima and dentissima lineages, and the status of the D. melanogaster species group.

The subgenus Sophophora of Drosophila, which includes D. melanogaster, is an important model for the study of molecular evolution, comparative genomics, and evolutionary developmental biology. Numerous phylogenetic studies have examined species relationships in the well-known melanogaster, obscura, willistoni, and saltans species groups, as well as the relationships among these clades. In contrast, other species groups of Sophophora have been relatively neglected and have not been subjected to molecular phylogenetic analysis. Here, we focus on the endemic African Drosophila fima and dentissima lineages. We find that both these clades fall within the broadly defined melanogaster species group, but are otherwise distantly related to each other. The new phylogeny supports pervasive divergent and convergent evolution of male-specific grasping structures (sex combs). We discuss the implications of these results for defining the boundaries of the melanogaster species group, and weigh the relative merits of "splitting" and "lumping" approaches to the taxonomy of this key model system.

[Update on endocrine hypertension]. / Update endokrine Hypertonie.

Endocrine disorders are the most common causes of secondary hypertension. Early diagnosis and specific treatment are crucial for improvement of the prognosis. This article provides an overview on which clinical constellations point to an increased risk of secondary causes of hypertension. These include spontaneous hypokalemia, young age at onset of hypertension, adrenal incidentaloma and therapy refractive arterial hypertension. The basic diagnostics include determination of the aldosterone to renin ratio, measurement of free plasma metanephrines and a 1 mg dexamethasone suppression test. Borderline results require repeated control testing and/or confirmatory testing under standardized test conditions. In cases of repeatedly conspicuous results referral to a specialized clinic should be considered for further clarification and confirmation of the diagnosis. Imaging diagnostics may constitute an adjunct to laboratory testing after the diagnosis has been confirmed. Therapeutic algorithms vary depending on the underlying endocrine disease.

Impact of toll-like-receptor-9 (TLR9) deficiency on visceral adipose tissue adipokine expression during chronic DSS-induced colitis in mice.

BACKGROUND: Studies postulate an involvement of adipokines in inflammatory gastrointestinal diseases. Leptin-deficient ob/ob mice as well as TLR9-deficient mice have a more moderate course of chronic DSS-induced colitis (DSS-CC) and adipocytes do express functional TLR9 molecules. MATERIAL AND METHODS: Adipokine mRNA expression in visceral adipose tissue of mice before and after the induction of DSS-CC was investigated. Experiments were performed in both TLR9(wt/wt) and TLR9(-/-) mice. In vitro, the effect of TLR9 blocking peptide on leptin and visfatin protein secretion was studied in 3T3-L1 adipocytes. RESULTS: Induction of DSS-CC led to an upregulation of leptin mRNA expression in TLR9(wt/wt) mice, while TLR9(-/-) animals showed a significant reduction of leptin expression even below baseline. While visfatin expression remained unchanged in TLR9(wt/wt) animals, TLR9(-/-) mice exhibited a significant induction during DSS-CC. CTRP-3 expression was reduced after colitis induction only in TLR9(-/-) animals. Of note, IL-6 expression levels remained unchanged, while CXCL1/KC and cyclophilin A expression was reduced in DSS-CC. Inhibition of TLR9 signaling by using TLR9 blocking peptide led to reduced leptin protein secretion into cell culture supernatants in 3T3-L1 adipocytes, while visfatin protein secretion was enhanced. CONCLUSIONS: DSS-CC leads to differential adipokine expression profiles in the visceral fat pad in TLR9(wt/wt) vs. TLR9(-/-) mice. In vitro, inhibition of TLR9 signaling induces visfatin secretion while inhibiting leptin secretion in adipocytes. Thus, visceral adipokines are regulated by intact TLR9 signaling pathway and a specific interplay between the leptin- and the TLR9-pathways might be of pathophysiological importance in chronic intestinal inflammation.

Short-term regulation of Visfatin release in vivo by oral lipid ingestion and in vitro by fatty acid stimulation.

Visfatin represents a new adipokine secreted by visceral adipose tissue and possibly regulating insulin sensitivity. Data on the regulation of visfatin are sparse and contradictory. Our study investigates the regulation of serum visfatin concentrations in healthy and non-diabetic subjects in response to the ingestion of a newly developed oral lipid solution (OLI) in vivo. Furthermore, the effects of a broad spectrum of fatty acids on adipocytic visfatin release were investigated in vitro.100 (42 male and 58 female) healthy volunteers were included in the study. Anthropometric and laboratory parameters (lipoproteins, glucose, insulin, C-peptide) were measured after an overnight fast at 0 h and 2 h, 4 h, and 6 h after OLI. 3T3-L1 preadipocytes were differentiated into mature adipocytes and stimulated with increasing doses of 10 different fatty acids, and the release of visfatin into the supernatants was measured by ELISA.Serum triglycerides significantly rose after OLI. This was accompanied by a significant decrease of glucose, insulin and C-peptide. Serum visfatin levels significantly decreased after OLI. Fasting visfatin levels were negatively correlated with fasting glucose levels. Of the 5 saturated fatty acids tested, only palmitic acid exerted significant effects by strongly downregulating visfatin release by about 66%. The mono-unsaturated fatty acids palmitoleic acid and oleic acid exerted opposite effects decreasing/increasing visfatin release, respectively. Both of the poly-unsaturated fatty acids linoleic acid and arachidonic acid decreased visfatin release.Oral lipid ingestion is a physiological regulator of systemic visfatin release. Fatty acids differentially regulate visfatin release in vitro.

An evolutionary shift in the regulation of the Hippo pathway between mice and flies.

The Hippo pathway plays a key role in controlling organ growth in many animal species and its deregulation is associated with different types of cancer. Understanding the regulation of the Hippo pathway and discovering upstream regulators is thus a major quest. Interestingly, while the core of the Hippo pathway contains a highly conserved kinase cascade, different components have been identified as upstream regulators in Drosophila and vertebrates. However, whether the regulation of the Hippo pathway is indeed different between Drosophila and vertebrates or whether these differences are due to our limited analysis of these components in different organisms is not known. Here we show that the mouse Fat4 cadherin, the ortholog of the Hippo pathway regulator Fat in Drosophila, does not apparently regulate the Hippo pathway in the murine liver. In fact, we uncovered an evolutionary shift in many of the known upstream regulators at the base of the arthropod lineage. In this evolutionary transition, Fat and the adaptor protein Expanded gained novel domains that connected them to the Hippo pathway, whereas the cell-adhesion receptor Echinoid evolved as a new protein. Subsequently, the junctional adaptor protein Angiomotin (Amot) was lost and the downstream effector Yap lost its PDZ-binding motif that interacts with cell junction proteins. We conclude that fundamental differences exist in the upstream regulatory mechanisms of Hippo signaling between Drosophila and vertebrates.

How perfect are you with defective probes? Information on the results of the mini-trial on technical quality assurance during the "Ultraschall 2012" conference in Davos.

This article deals with the technical quality assurance of ultrasound B-systems. As part of a mini-trial during the Dreiländertreffen in Davos "Ultrasound 2012", we addressed the question as to whether physicians can detect faulty probes spontaneously during live scanning B-mode. For this purpose a special diagnostic device had been prepared so that groups of piezoelectric elements in the array were without function. Then the images had to be characterized by test persons without knowledge of the faulty elements. The results show that a deterioration of the image could be detected starting at five disabled elements. Due to the small number of test persons, our statements are only preliminary.

Regulation and function of C1Q/TNF-related protein-5 (CTRP-5) in the context of adipocyte biology.

BACKGROUND AND AIM: The C1q/TNF-related protein (CTRP) family represents a growing family of adiponectin paralogous proteins. CTRP-5 was detected in adipose tissue of mice and plays a role in the context of the metabolic syndrome. It was the aim to investigate the detailed expression profile of CTRP-5 in a variety of adipocytic cells and to determine whether CTRP-5 circulates in human serum. Moreover, regulation and function of CTRP-5 was studied in the context of adipocyte biology. MATERIAL AND METHODS: CTRP-5 serum levels were measured in 50 healthy subjects by ELISA. Genotype analysis was performed by direct sequencing in 200 probands. CTRP-5 mRNA and protein expression was analyzed by RT-PCR, real-time RT-PCR and Western blot. Recombinant CTRP-5 and fatty acids were used for stimulation experiments in 3T3-L1 adipocytes. siRNA-mediated knockdown of CTRP-3 was performed during adipocyte differentiation. RESULTS: CTRP-5 mRNA and protein was strongly expressed in a wide variety of human and murine adipocytic cells and was induced during adipocyte differentiation. Saturated fatty acids increased CTRP-5 expression in adipocytes. siRNA-mediated cellular knockdown of CTRP-3 in adipocytes resulted in an upregulation of CTRP-5 expression. CTRP-5 inhibited the release of resistin and adiponectin dose-dependently. CTRP-5 circulates abundantly in human sera with a broad interindividual variation. The SNP 1014 T/A was not associated with type 2 diabetes mellitus in 200 Caucasian probands. CONCLUSIONS: CTRP-5 might be a novel adipokine that circulates abundantly in human sera. CTRP-5 is functionally involved in adipocyte biology and there might exist a counter-regulatory connection with its family member, CTRP-3.

The novel adipokine C1q/TNF-related protein-3 is expressed in human adipocytes and regulated by metabolic and infection-related parameters.

BACKGROUND: The growing family of C1Q/TNF-related proteins is characterized by structural homologies to the anti-inflammatory adipokine adiponectin. CTRP-3 was recently reported to function as an anti-inflammatory LPS-antagonist in vitro. MATERIAL AND METHODS: Human subcutaneous and visceral adipocytes and murine 3T3-L1 adipocytes were used for analysis of CTRP-3 expression and function. Western blot analysis of CTRP-3, siRNA mediated knockdown of CTRP-3, Oil red O staining, assessment of basal and epinephrine-induced lipolysis, ELISA-based measurements of supernatant chemokines, recombinant CTRP-3 protein expression, and Staphylococcus aureus (S. aureus) infection assays were used. RESULTS: CTRP-3 is expressed in subcutaneous and visceral adipocytes. CTRP-3 is positively regulated by insulin, whereas chronic LPS-exposure inhibits terminal adipocyte differentiation and CTRP-3 expression. Intracellular infection of adipocytes by S. aureus also decreases CTRP-3 expression. As demonstrated by siRNA-mediated cellular knockdown of CTRP-3 in adipocytes, CTRP-3 regulates resistin secretion and lipolysis. CONCLUSION: CTRP-3 is expressed in human adipocytes and plays an important role in adipocyte physiology such as lipolysis and adipokine secretion. Both, metabolic factors and infection/inflammation-related factors regulate CTRP-3 expression.

Investigation of the suitability of tissue phantoms for testing the constancy of ultrasonic transducer arrays in quality assurance.

PURPOSE: To ensure high quality ultrasound diagnostics, proper functioning of the devices used is a necessary prerequisite. Ultrasound transducers have proven to be the most failure-prone part of the signal chain. Their technical monitoring is possible in principle with the help of tissue phantoms. The background of the present study is to determine which type of phantoms and which measurement parameters are best suited to a consistency test as part of routine quality assurance of ultrasound imaging systems. MATERIALS AND METHODS: A classic wire-type phantom (ATS Mod. 539, ATS Labs Bridgeport, USA) and a 3 D cyst phantom (TCC, Timelkam, Austria) were used for the studies and comparative tests were conducted between intact transducers and those in which faults had been simulated. The collected measurement data show a relatively large scatter. Therefore, statistical analysis methods were used, and the discrimination analysis proved to be a useful tool. RESULTS: Local failures which arise, e. g. due to the breakdown of individual piezoelectric elements or element groups in the transducer array, can be detected with the help of the gray value targets of the ATS phantom, but only in those cases in which the error-affected sound field part actually overlaps with the target under consideration. The TCC phantom is not suitable for the detection of such errors. Global transducer failures, i. e. those that affect the entire array, can even be detected with both types of phantoms. CONCLUSION: When the emphasis of quality assessment is on the detection of local defects in the array that make up the largest part of the transducer faults, studies with conventional phantoms are only of limited value.

Effects of antimicrobial peptides on methanogenic archaea.

As members of the indigenous human microbiota found on several mucosal tissues, Methanobrevibacter smithii and Methanosphaera stadtmanae are exposed to the effects of antimicrobial peptides (AMPs) secreted by these epithelia. Although antimicrobial and molecular effects of AMPs on bacteria are well described, data for archaea are not available yet. Besides, it is not clear whether AMPs affect them as the archaeal cell envelope differs profoundly in terms of chemical composition and structure from that of bacteria. The effects of different synthetic AMPs on growth of M. smithii, M. stadtmanae, and Methanosarcina mazei were tested using a microtiter plate assay adapted to their anaerobic growth requirements. All three tested methanoarchaea were highly sensitive against derivatives of human cathelicidin, of porcine lysin, and a synthetic antilipopolysaccharide peptide (Lpep); however, sensitivities differed markedly among the methanoarchaeal strains. The potent AMP concentrations affecting growth were below 10 µM, whereas growth of Escherichia coli WBB01 was not affected at peptide concentrations up to 10 µM under the same anaerobic growth conditions. Atomic force microscopy and transmission electron microscopy revealed that the structural integrity of the methanoarchaeal cells is destroyed within 4 h after incubation with AMPs. The disruption of the cell envelope of M. smithii, M. stadtmanae, and M. mazei within a few minutes of exposure was verified by using LIVE/DEAD staining. Our results strongly suggest that the release of AMPs by eukaryotic epithelial cells is a potent defense mechanism targeting not only bacteria, but also methanoarchaea.

Hypothalamic vasopressin system regulation by maternal separation: its impact on anxiety in rats.

Maternal separation (MS) has been used to model the causal relationship between early life stress and the later stress-over-reactivity and affective disorders. Arginine vasopressin (AVP) is among several factors reported to be abnormal. The role of AVP on anxiety is still unclear. In order to further investigate this causal relationship and its possible role in anxiogenesis, male rat pups were separated from their dams for 3h daily (3 hMS) from post-natal day (PND) 2 to PND15. Fos expression in AVP+ neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) triggered by 3 hMS, and AVP-mRNA expression, were examined at PND10 and PND21 respectively, whereas AVP-mRNA expression, PVN and SON volumes and plasma AVP concentration were assessed in adulthood. Elevated plus maze test (EPM) and Vogel conflict test (VCT) were also performed to evaluate unconditioned and conditioned anxious states at PND70-75. At PND10, a single 3hMS event increased Fos expression in AVP+ neurons fourfold in PVN and six to twelvefold in SON. AVP-mRNA was over-expressed in whole hypothalamus, PVN and SON between 122% and 147% at PND21 and PND63. Volumes of AVP-PVN and AVP-SON measured at PND75 had marked increases as well as AVP plasma concentration at 12h of water deprivation (WD). MS rats demonstrated a high conditioned anxious state under VCT paradigm whereas no difference was found under EPM. These data demonstrate direct relationships between enhanced AVP neuronal activation and a potentiated vasopressin system, and this latter one with high conditioned anxiety in MS male rats.

In vitro production of GHB in blood and serum samples under various storage conditions.

UNLABELLED: The in vitro production of GHB was observed in freshly collected, untreated whole blood samples using glass BD-Vacutainers and polypropylene S-monovettes. GHB concentrations were determined daily over a period of one week and after 3, 6 and 9 weeks again. Furthermore, the GHB concentration in 40 untreated random whole blood samples stored at 4°C for a longer period of time (10 samples 12 month, 10 samples 24 month and 20 samples 36 month) was also determined. For comparison, the in vitro production of GHB in freshly collected and prepared serum samples was observed. GHB serum concentrations were determined three times over a period of one week and once again after six weeks. Sample preparation was performed by means of methanolic extraction following the precipitation of whole blood and serum samples. A methanolic standard calibration was done in a low range of 0.005-0.1 µg/mL (LOD: 0.004, LLOQ: 0.013). For quantification a spiked blood bank serum with a determined GHB concentration of 0.09 µg/mL was used. Corrected calibrations in the range of 0.09-5.09 µg/mL were used (LOD: 0.08 µg/mL, LLOQ: 0.30 µg/mL), recovery: 91.3% (high level: 4.09 µg/mL) 50.5% (low level: 0.19 µg/mL). RESULTS: Relevant elevation of GHB was observed in all whole blood samples stored in liquid form (4°C or room temperature). In two of the 40 whole blood samples stored over a longer period of time at 4°C, GHB concentrations in the range of 13 µg/mL were even determined. These findings constitute grounds for caution. Even a GHB cut-off level of 5 µg/mL cannot be considered as "absolutely positive" proof of a case of exogenous administration, at least in untreated liquid blood samples in long time storage. However, no significant elevations of GHB were otherwise observed in any of the serum samples independently of storage temperature nor in the whole blood samples that were frozen for storage. CONCLUSIONS: The results suggest that the cut-off for exogenous GHB of 5 µg/mL could be lowered significantly, with the consequence of winning valuable time for the potential victim, but only if serum is collected for GHB determination or if the whole blood sample is frozen immediately after collection and the procedure well documented.

Type 2 diabetes and lipoprotein metabolism affect LPS-induced cytokine and chemokine release in primary human monocytes.

AIMS/HYPOTHESIS: Obesity and insulin resistance are characterized by a chronic and low grade state of inflammation and the pro-inflammatory response of monocytes is affected in type 2 diabetes mellitus (T2D). We aimed to investigate whether LPS-induced monocytic cytokine and chemokine release depends on serum lipoprotein parameters in T2D patients. METHODS: Primary human monocytes were isolated from 29 patients with known T2D and from 20 healthy volunteers. Anthropometric and disease-related parameters such as age, gender, BMI, WHR, diabetes duration, diabetes complications, and diabetes control (HbA1c) were documented. Monocytes were stimulated for 18 h with LPS (1 µg/ml). Unstimulated monocytes served as control. The supernatant concentrations of CCL2, CCL3, CCL4, CCL5, MIF and resistin were measured by ELISA. RESULTS: LPS-stimulation significantly (p<0.001) increased CCL chemokine and resistin concentrations in healthy controls and in patients with T2D, whereas MIF release was not affected in both groups. LPS-induced CCL2 and resistin concentrations were significantly higher in T2D patients when compared to healthy controls. In T2D patients, LPS-induced CCL3 concentration was higher in males when compared to females (p=0.039) and supernatant resistin concentration upon stimulation with LPS showed a significant and positive correlation with age (r=0.6; p=0.001). LPS-induced CCL2 concentration was significantly and positively correlated with serum triglyceride concentration (r=0.4; p=0.009) in T2D patients. Furthermore, LPS-induced CCL4 concentration was significantly and positively correlated with total (r=0.4; p=0.035) and LDL cholesterol (r=0.4; p=0.033) concentration. CONCLUSIONS: LPS responsiveness of monocytes is altered in T2D and is affected by the respective serum lipoprotein metabolism.

Automatic bone and plaque removal using dual energy CT for head and neck angiography: feasibility and initial performance evaluation.

PURPOSE: We sought to evaluate the feasibility and efficiency of dual energy (DE) bone and plaque removal in head and neck CT angiography. MATERIALS AND METHODS: 20 patients with suspected carotid stenoses received head and neck DE-CTA as part of their pre-interventional workup. Visual grading using multiplanar reformations (MPR), thick slab maximum intensity projections (MIP) and quantitative vessel analysis (QVA) of stenoses was performed prior and after DE bone removal. Results were evaluated for the detection of relevant stenoses (vessel area reduction >70%). Vessel segmentation errors were analyzed. RESULTS: Segmentation errors occurred in 19% of all vessel segments. Nevertheless, most post-bone removal artifacts could be recognized using the MPR technique for reading. Compared to MPR reading prior to bone removal, sensitivity, specificity, positive and negative predictive values after bone removal were 100%, 98%, 88% and 100% for MPR reading and 100%, 91%, 63% and 100% for exclusive MIP reading, respectively. There was a good agreement between the QVA results prior and post-DE plaque removal (r(2)=0.8858). CONCLUSION: DE bone and plaque removal for head and neck angiography is feasible and offers a rapid and highly sensitive overview over vascular head and neck studies. Due to a slightly limited specificity of the MIP technique due to segmentation errors, possible stenoses should be verified and graded using MPR techniques.

Fatty acids as metabolic mediators in innate immunity.

BACKGROUND: Increasing data support the hypothesis of a local and systemic crosstalk between adipocytes and monocytes mediated by fatty acids. The aim of this study was to characterize the immunomodulatory effects of a large panel of fatty acids on cytokines and chemokines in monocytic THP-1 cells and primary human monocytes. We tested whether anti-inflammatory fatty acids are able to inhibit the binding of lipopolysaccharide (LPS) to its receptor, toll-like receptor/MD-2 (TLR4/MD-2). MATERIALS AND METHODS: Resistin, monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor (TNF) were measured by enzyme-linked immunosorbent assay. Proteins were analysed by Western blot. A designed Flag-tagged TLR4/MD-2 fusion protein (LPS trap) was used to investigate the effect of fatty acids on binding of LPS to its receptor. In 30 patients with type 2 diabetes mellitus (T2D), the correlation of serum triglyceride levels with LPS-induced monocyte activation was analysed. RESULTS: Eleven fatty acids investigated exerted differential effects on the monocytic release of cytokines and chemokines. Eicosapentaenoic acid had potent anti-inflammatory effects on human primary monocytes and THP-1 cells; 100 and 200 microM eicosapentaenoic acid dose-dependently inhibited LPS binding to the LPS trap. LPS-induced release of monocytic MCP-1 and TNF was significantly and positively correlated with serum triglyceride levels in 30 patients with T2D. CONCLUSIONS: Monocytic activation is differentially regulated by fatty acids and depends on triglyceride levels in T2D. The main finding of the present study shows that eicosapentaenoic acid inhibits the specific binding of LPS to TLR4/MD-2. Eicosapentaenoic acid represents a new anti-inflammatory LPS-antagonist.