Search

This article explores the impact of medical comorbidities, smoking, and alcohol on the progression and mortality of mycosis fungoides (MF), a common form of cutaneous T‐cell lymphoma. The study reveals that certain factors, such as heart disease, large cell transformation, MF treatment escalation, Medicaid insurance, and not consuming alcohol, are associated with shorter progression-free survival (PFS). However, factors like hypertension, hyperlipidemia, diabetes, obesity, smoking, and autoimmune diseases do not significantly affect PFS. The study also highlights that the stage of MF at diagnosis is the only significant predictor of MF-specific death. Overall, the findings emphasize the importance of monitoring comorbidities in MF patients, while reassuring them that these conditions do not impact the progression of MF. [Extracted from the article]

A single‐stage clarification was developed using a single‐use chromatographic clarification device (CCD) to recover a recombinant protein from Chinese Hamster Ovary (CHO) harvest cell culture fluid (HCCF). Clarification of a CHO HCCF is a complex and costly process, involving multiple stages of centrifugation and/or depth filtration to remove cells and debris and to reduce process‐related impurities such as host cell protein (HCP), nucleic acids, and lipids. When using depth filtration, the filter train consists of multiple filters of varying ratios, layers, pore sizes, and adsorptive properties. The depth filters, in combination with a 0.2‐micron membrane filter, clarify the HCCF based on size‐exclusion, adsorptive, and charge‐based mechanisms, and provide robust bioburden control. Each stage of the clarification process requires time, labor, and utilities, with product loss at each step. Here, use of the 3M™ Harvest RC Chromatographic Clarifier, a single‐stage CCD, is identified as an alternative strategy to a three‐stage filtration train. The CCD results in less overall filter area, less volume for flushing, and higher yield. Using bioprocess cost modeling, the single‐stage clarification process was compared to a three‐stage filtration process. By compressing the CHO HCCF clarification to a single chromatographic stage, the overall cost of the clarification process was reduced by 17%–30%, depending on bioreactor scale. The main drivers for the cost reduction were reduced total filtration area, labor, time, and utilities. The benefits of the single‐stage harvest process extended throughout the downstream process, resulting in a 25% relative increase in cumulative yield with comparable impurity clearance. [ABSTRACT FROM AUTHOR]

Defective T‐cell functions play a role in the persistence of HCV infection. Activated T cells express CD137, which costimulates antivirus T‐cell responses, and this activity is antagonized by soluble CD137 (sCD137). Here, we show that in sera of 81 patients with chronic HCV, sCD137 levels did not correlate with measures of viral infection, and did not decline after virus eradication using direct‐acting antivirals. Thus, serum sCD137 was similar in patients infected with HCV and in uninfected controls. Of note, in HCV patients with liver cirrhosis and patients with mostly alcohol‐associated liver cirrhosis, sCD137 was increased. A negative association of sCD137 and albumin existed in both cohorts. sCD137 concentrations were similar in hepatic and portal vein blood excluding the liver as the origin of higher levels. Recombinant sCD137 reduced Th1 and Th2 but not Th17 cell polarization in vitro, and accordingly lowered IFN‐γ, TNF, and IL‐13 in cell media. Serum sCD137 is associated with inflammatory states, and positively correlated with serum TNF in cirrhotic HCV patients following virus eradication. Our study argues against a role of sCD137 in HCV infection and suggests a function of sCD137 in liver cirrhosis, which yet has to be defined. [ABSTRACT FROM AUTHOR]

Previous lightning climatologies derived from Lightning Imaging Sensor (LIS) and Optical Transient Detector (OTD) total lightning measurements have quantified lightning frequency as a Flash Rate Density (FRD). This approach assumes that lightning flashes can be represented as points and quantifies the frequency of lightning centered in each grid cell. However, lightning has a finite extent that can reach hundreds of kilometers. A new climatology based on Flash Extent Density (FED) is constructed for LIS (including ISS‐LIS) and OTD that accounts for the horizontal dimension of lightning. The FED climatology documents the frequency that an observer can expect lightning to be visible overhead—regardless of where the flash began or ended. This new FED climatology confirms and elaborates on the previous global LIS/OTD FRD and Americas‐only Geostationary Lightning Mapper (GLM) findings. The FED climatology maintains Lake Maracaibo as the global lightning hotspot with an average of 389 flashes/day but designates Karabre in the Democratic Republic of the Congo as the global thunderstorm duty (percent of the total viewtime where lightning is observed) hotspot at 7.29%. Meanwhile, Kuala Lumpur is the national capital city with the most lightning, and its airport (KUL) is the top major airport affected by lightning (in terms of duty). The FED seasonal cycle and month‐to‐month changes in the "center of lightning" for the three continental chimney regions are also discussed. Plain Language Summary: How often does lightning occur around the world? This seemingly simple question is difficult to answer due to nuances in measuring lightning and calculating flash rates. A common methodology for answering this question is to use the concept of Flash Rate Density (FRD). This approach quantifies lightning rates by approximating lightning as points. Lightning flashes often have appreciable horizontal extents, however, that can even reach extreme sizes. In this study, we use the concept of Flash Extent Density (FED) to produce a climatology of lightning frequency that takes the horizonal scale of lightning into account. Instead of just incrementing a single grid point once for each flash, FED increments all grid point pixels that each flash touches by one. FED addresses the question of how many flashes per year an observer at a specific location can expect to see overhead. We find that despite these methodological differences from previous FRD studies, the same global hotspots are identified—with Lake Maracaibo chief among them. However, this new approach provides new insights on the previously noted lightning trends and elaborates on how frequent lightning impacts life on Earth. Key Points: LIS and OTD data are reprocessed to correct split lightning flashes and generate gridded products including Flash Extent Density (FED)A global lightning climatology is generated from FED data that take horizontal flash extent into accountThe new FED climatologies provide new perspectives on lightning frequency and human impact while confirming previous FRD findings [ABSTRACT FROM AUTHOR]

Upon viral infection, stressed or damaged cells can release alarmins like IL‐33 that act as endogenous danger signals alerting innate and adaptive immune cells. IL‐33 coming from nonhematopoietic cells has been identified as important factor triggering the expansion of antiviral CD8+ T cells. In LN the critical cellular source of IL‐33 is unknown, as is its potential cell‐intrinsic function as a chromatin‐associated factor. Using IL‐33‐GFP reporter mice, we identify fibroblastic reticular cells (FRC) and lymphatic endothelial cells (LEC) as the main IL‐33 source. In homeostasis, IL‐33 is dispensable as a transcriptional regulator in FRC, indicating it functions mainly as released cytokine. Early during infection with lymphocytic choriomeningitis virus (LCMV) clone 13, both FRC and LEC lose IL‐33 protein expression suggesting cytokine release, correlating timewise with IL‐33 receptor expression by reactive CD8+ T cells and their greatly augmented expansion in WT versus ll33−/− mice. Using mice lacking IL‐33 selectively in FRC versus LEC, we identify FRC as key IL‐33 source driving acute and chronic antiviral T‐cell responses. Collectively, these findings show that LN T‐zone FRC not only regulate the homeostasis of naïve T cells but also their expansion and differentiation several days into an antiviral response. [ABSTRACT FROM AUTHOR]

The Lightning Imaging Sensor (LIS) was launched to the International Space Station (ISS) in February 2017, detecting optical signatures of lightning with storm‐scale horizontal resolution during both day and night. ISS LIS data are available beginning 1 March 2017. Millisecond timing allows detailed intercalibration and validation with other spaceborne and ground‐based lightning sensors. Initial comparisons with those other sensors suggest flash detection efficiency around 60% (diurnal variability of 51–75%), false alarm rate under 5%, timing accuracy better than 2 ms, and horizontal location accuracy around 3 km. The spatially uniform flash detection capability of ISS LIS from low‐Earth orbit allows assessment of spatially varying flash detection efficiency for other sensors and networks, particularly the Geostationary Lightning Mappers. ISS LIS provides research data suitable for investigations of lightning physics, climatology, thunderstorm processes, and atmospheric composition, as well as real‐time lightning data for operational forecasting and aviation weather interests. ISS LIS enables enrichment and extension of the long‐term global climatology of lightning from space and is the only recent platform that extends the global record to higher latitudes (±55°). The global spatial distribution of lightning from ISS LIS is broadly similar to previous data sets, with globally averaged seasonal/annual flash rates about 5–10% lower. This difference is likely due to reduced flash detection efficiency that will be mitigated in future ISS LIS data processing, as well as the shorter ISS LIS period of record. The expected land/ocean contrast in the diurnal variability of global lightning is also observed. Plain Language Summary: The Lightning Imaging Sensor on the International Space Station (ISS LIS) has been operating on‐orbit since February 2017. The instrument has met all of its major science objectives, including detecting lightning day and night, identifying the specific locations within storms that are producing lightning, millisecond timing accuracy, and high probability of detecting lightning. The instrument also measures energy emitted by lightning, provides background images of storms and their surroundings, and delivers real‐time lightning data. This has enabled enrichment and extension of the long‐term global climatology of lightning from space and provides more recent extension of the global record to higher latitudes (±55°). In addition, the instrument is serving as a standard for comparison to other spaceborne lightning sensors, such as the Geostationary Lightning Mapper (GLM). The real‐time data from ISS LIS have enabled new applications for the benefit of the public, including weather forecasting and public safety. Finally, ISS LIS—in conjunction with other satellite instruments—is providing opportunities for new scientific study in areas such as lightning physics, thunderstorm processes, and atmospheric composition. Key Points: The Lightning Imaging Sensor (LIS) has been providing data from the International Space Station (ISS) since March 2017ISS LIS provides storm‐scale resolution (4 km) and millisecond timing of global lightning with spatially uniform detection efficiency (~60%)The 3‐year global lightning climatology is consistent with previous studies (within 5–10%), while extending results to higher latitudes [ABSTRACT FROM AUTHOR]

Background Chemerin is associated with insulin resistance and is expressed in the liver. Nonalcoholic fatty liver disease ( NAFLD) is related to impaired insulin sensitivity, but studies evaluating hepatic and serum chemerin in NAFLD resulted in discordant data. Materials and methods Chemerin mRNA was determined in the liver tissue obtained from 33 controls and 76 NAFLD patients. Chemerin serum levels were measured in a different cohort of patients with ultrasound-diagnosed NAFLD and the respective controls. Hepatic stellate cells and hepatocytes were exposed to selected metabolites and nuclear receptor agonists to study the regulation of chemerin. Effect of recombinant chemerin on hepatocyte released proteins was analysed. Results Hepatic chemerin expression was not related to BMI, gender, type 2 diabetes and hypertension. Chemerin mRNA did not correlate with steatosis and was negatively associated with inflammation, fibrosis and nonalcoholic steatohepatitis ( NASH) score. Patients with NASH had lower chemerin mRNA compared to those with borderline NASH and controls. Factors with a role in NASH mostly did not regulate chemerin in the liver cells. Of note, liver X receptor agonist reduced chemerin protein. Serum chemerin was not changed in NAFLD. Levels positively correlated with age, waist-to-hip ratio, systolic blood pressure, serum FGF21 and lipocalin 2, and negatively with transferrin saturation. Chemerin induced FGF21 in supernatants of primary human hepatocytes. Hepcidin, a major regulator of iron homoeostasis and lipocalin 2, were not regulated by chemerin. Conclusion Chemerin mRNA is reduced in the liver of NASH patients, and liver X receptor seems to have a role herein. [ABSTRACT FROM AUTHOR]

Release of inflammatory monocytes from the bone marrow (BM) into the blood is an important physiological response to infection, but the mechanisms regulating this phenomenon during viral infection are not completely defined. Here, we show that low-dose infection with lymphocytic choriomeningitis virus (LCMV) caused rapid, transient inflammatory monocytosis that required type I interferon (IFN) and Toll-like receptor (TLR) 7 signaling. Type I IFN and TLR7 signals were critical for induction of IFN-stimulated gene expression and CCR2 ligand upregulation in the BM microenvironment in response to LCMV infection. Experiments utilizing BM chimeric mice demonstrated that type I IFN and TLR7 signaling on either hematopoietic or nonhematopoietic cells was sufficient to initiate monocytosis in response to LCMV infection. BM plasmacytoid dendritic cells (pDCs) generated type I IFN directly ex vivo, suggesting that pDCs are a hematopoietic contributor of type I IFN in the BM early during LCMV infection. Overall, we describe novel roles for type I IFN and TLR7 signaling in nonhematopoietic cells and BM pDCs in directing IFN-stimulated gene and CCR2 ligand expression in the BM to initiate an increase in blood inflammatory monocytes during viral infection. [ABSTRACT FROM AUTHOR]

Objective Obesity, a sirtuin-1 (SIRT-1) -deficient state, increases morbidity and resource utilization in critically ill patients. SIRT-1 deficiency increases microvascular inflammation and mortality in early sepsis. The objective of the study was to study the effect of resveratrol (RSV), a SIRT-1 activator, on microvascular inflammation in obese septic mice. Methods ob/ob and C57Bl/6 (WT) mice were pretreated with RSV versus dimethyl sulfoxide (DMSO) (vehicle) prior to cecal ligation and puncture (sepsis). We studied (1) leukocyte/platelet adhesion, (2) E-selectin, ICAM-1, and SIRT-1 expression in small intestine, and (3) 7-day survival. A group of RSV-treated mice received SIRT-1 inhibitor (EX-527) with sepsis induction, and leukocyte/platelet adhesion and E-selectin/ICAM-1 expression were studied. We treated endothelial (HUVEC) cells with RSV to study E-selectin/ICAM-1 and p65-acetylation (AC-p65) in response to lipopolysaccharide (LPS). Results RSV treatment decreased leukocyte/platelet adhesion and E-selectin/ICAM-1 expression with increased SIRT-1 expression in septic ob/ob and WT mice, decreased E-selectin/ICAM-1 expression via increased SIRT-1 expression, and decreased AC-p65 expression in HUVEC. EX-527 abolished RSV-induced attenuation of microvascular inflammation in ob/ob septic mice. Finally, ob/ob mice in the sepsis+RSV group had significantly increased 7-day survival versus the sepsis+vehicle group. Conclusions RSV increases SIRT-1 expression in ob/ob septic mice to reduce microvascular inflammation and improves survival. [ABSTRACT FROM AUTHOR]

Examines the position of artisanal bakers within various hegemonic social formations during different historical periods in East Germany, beginning with early and advanced capitalism, followed by communism and ending with its demise in 1989-90. Working conditions and coping mechanisms; Familial nature of private artisanry; Nature of the new eastern German capitalism.

The article presents updates on the articles published in the "European Journal of Clinical Investigation" (EJCI) in the year 2012. It notes that obesity and insulin resistance affect oxidative stress development. Data that suggests that weight loss after bariatric surgery is connected with complement C3 and risks of metabolic and atherosclerotic processes is presented. It highlights relationship between cardiovascular diseases in peripheral arterial disease and myeloperoxidase levels.

SUMMARY This paper presents a new implementation of a constitutive model commonly used to represent plastic bonded explosives in finite element simulations of thermomechanical response. The constitutive model, viscoSCRAM, combines linear viscoelasticity with isotropic damage evolution. The original implementation was focused on short duration transient events; thus, an explicit update scheme was used. For longer duration simulations that employ significantly larger time step sizes, the explicit update scheme is inadequate. This work presents a new semi-implicit update scheme suitable for simulations using relatively large time steps. The algorithm solves a nonlinear system of equations to ensure that the stress, damaged state, and internal stresses are in agreement with implicit update equations at the end of each increment. The crack growth is advanced in time using a sub-incremental explicit scheme; thus, the entire implementation is semi-implicit. The theory is briefly discussed along with previous explicit integration schemes. The new integration algorithm and its implementation into the finite element code, Abaqus, are detailed. Finally, the new and old algorithms are compared via simulations of uniaxial compression and beam bending. The semi-implicit scheme has been demonstrated to provide higher accuracy for a given allocated computational time for the quasistatic cases considered here. Published 2014. This article is a US Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Background Omentin is a visceral fat-derived adipokine associated with endothelium-dependent vasodilation. Impaired endothelial function is a major cause of portal hypertension in liver cirrhosis. The aim was to assess associations of omentin with systemic markers of endothelial function, namely arginine and asymmetric dimethylarginine ( ADMA) and complications of portal hypertension in liver cirrhosis. Materials and methods Systemic omentin was measured by ELISA in portal venous serum ( PVS), systemic venous serum ( SVS) and hepatic venous serum ( HVS) of 40 patients with liver cirrhosis and 10 liver-healthy controls. ADMA and arginine were determined in SVS of the patients by ELISA. Results Omentin is elevated in PVS and tends to be increased in SVS and HVS of patients with liver cirrhosis compared with controls. Omentin is principally expressed in visceral fat, and PVS omentin tends to be higher than SVS levels. Lower HVS than PVS omentin suggests that omentin may be partly removed from the circulation by the liver. Omentin in serum is not associated with stages of liver cirrhosis defined by CHILD- POUGH or MELD score and is not affected in patients with ascites. HVS omentin tends to be reduced in patients with large varices compared with patients without/with small varices. Arginine/ ADMA ratio is reduced in patients with massive ascites but is not associated with variceal size. Further, Arginine/ ADMA ratio does not correlate with omentin. Conclusion Current data show that PVS omentin is increased in liver cirrhosis but is not associated with complications of portal hypertension. [ABSTRACT FROM AUTHOR]

SUMMARY Discrete element methods (DEMs) are used for layered geomaterials to investigate the dependency of traditional engineering constants on material properties and loading conditions. Shear deformations and compression tests parallel and perpendicular to layering are conducted on samples of varying kerogen volume fractions, confining pressures, porosities, and layer geometries. The goal of this article is to develop a method to better characterize oil shale (a transversely isotropic layered geomaterial) while eliminating high experimental costs. The DEM simulations conducted in this study demonstrate strong dependencies of Young's modulus, Poisson's ratio, and shear modulus on kerogen volume fraction and porosity. Furthermore, a rule of thumb for layer thickness and particle resolution is proposed for simulation design. Results agree well with robust effective medium theories, solidify the ability of DEM to model the mechanical properties of layered heterogenous materials, and encourage the use of DEM to study more complicated layered media and material failure. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

SUMMARY For granular mechanics studies, efficiently creating a realistic consolidated pack is a challenging task. To achieve this, particle shapes are traditionally restricted to simple shapes (disks, ellipses, spheres, ellipsoids) or constructed from a library, loosely populated, and subsequently settled under gravity. These methods suffer from both a lack of physicality in terms of the particle shapes and impractically long sample preparation times. To address these shortcomings, we introduce a method to generate and pack polyhedra within arbitrary boundaries through a tetrahedral element erosion process. This approach yields tightly packed systems of convex hulls for traditional discrete element calculations and internal tetrahedral meshing of the individual bodies for use in finite-discrete element or finite element calculations. To demonstrate the method, we present its application to packing sphere-like and ellipsoid-like particles for simple and complex bounding volumes. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2012; 42 (11): 1213-1220 Abstract Background Chemerin is an adipokine that regulates insulin sensitivity and insulin secretion. Prolonged hyperinsulinaemia is associated with higher systemic chemerin, and insulin induces adipose tissue chemerin release. These findings led us to hypothesize that systemic chemerin may be associated with post-prandial glucose metabolism and/or may even be induced after oral glucose load. Therefore, the effect of insulin on adipocyte chemerin levels and systemic chemerin in mice was analysed. Further, systemic levels of chemerin after oral glucose load in nondiabetic individuals were studied. Design and methods Chemerin levels were determined in adipocytes after short-term and long-term treatment with insulin. Effects of acute hyperinsulinaemia were studied in mice. Chemerin was measured during oral glucose tolerance test in 66 healthy, nondiabetic individuals stratified for established body mass index categories. Results Insulin induces chemerin release from adipocytes within 24 h, while cellular levels are not affected. Short-term hyperinsulinaemia also upregulates adipocyte chemerin in vitro but has no effect on adipose tissue and chemerin serum levels of mice. Systemic chemerin is higher in overweight/obese than normal-weight controls and positively correlates with total cholesterol. Chemerin is not associated with markers of insulin sensitivity like fasting glucose or insulin. Fasting chemerin levels are similar to concentrations measured 1 and 2 h after oral glucose uptake in overweight and obese donors. Conclusions Post-prandial hyperinsulinaemia does not contribute to higher chemerin levels in nondiabetic individuals. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (outcomes) Level of Evidence 2c What's known on the subject? and What does the study add? Although renal transplantation represents a well established surgical procedure, the learning curve for this procedure has not been studied so far. The published data on surgical complications do not discriminate between surgeons and their stage of expertise. The present study highlights the importance of a structurized programme in urological sub-speciality training. Renal transplanation represents a standardized procedure with a low learning-curve for uncompliciated cases. When comparing experienced urological transplant surgeons with inexperienced surgeons, the postoperative complications and functional outcome were similar. One exception is seen in ureteroneocystostomy, which should be considered in clinical practice. OBJECTIVE To determine how postoperative and functional outcomes after deceased donor renal transplantation (DDRT) are related to surgeon experience., PATIENTS AND METHODS The outcomes of 484 adult DDRT performed by 13 urological surgeons were retrospectively reviewed., After completion of a staged renal transplant training programme under supervision of an attending urological transplant surgeon, the 13 surgeons were either assigned to the inexperienced group ( n= 8) or the experienced group ( n= 5)., Surgeons in the experienced group had performed more than 30 unsupervised DDRT in a standard fashion with routine ureteric stenting., Between 1988 and 2005, inexperienced surgeons performed 152 DDRT, whereas experienced surgeons performed 332 DDRT., RESULTS Patient and graft survival at 2 hyears were 98% and 94.7%, respectively., Early graft loss in five recipients was unrelated to surgeon experience., Delayed graft function occurred in 29% of cases and median 1-year serum-creatinine was 1.48 mg/dL, with no difference between surgeon groups., Postoperative bleeding and lymphocele formation were the most frequent surgical complications, with an equal distribution between groups., Ureteric complications had a significantly higher incidence among inexperienced surgeons (6.6% versus 2.7%; P= 0.04)., CONCLUSION We conclude that DDRT as performed by inexperienced urological renal transplant surgeons has both acceptable short- and long-term outcomes. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2011; 41 (11): 1149-1163 [ABSTRACT FROM AUTHOR]

Abstract: Transforming growth factor (TGF) β is the central cytokine in fibrotic liver diseases. We analyzed whether hepatoprotective adiponectin directly interferes with TGFβ1 signaling in primary human hepatocytes (PHH). Adiponectin induces the TGFβ decoy receptor BMP-and activin-membrane-bound inhibitor (BAMBI) in PHH. Overexpression of BAMBI in hepatoma cells impairs TGFβ-mediated phosphorylation of SMAD2 and induction of connective tissue growth factor. BAMBI is lower in human fatty liver with a higher susceptibility to liver fibrosis and negatively correlates with BMI of the donors. Hepatic BAMBI is reduced in rodent models of liver inflammation and fibrosis. In summary, the current data show that hepatoprotective effects of adiponectin include induction of BAMBI which is reduced in human fatty liver and rodent models of metabolic liver injury. [Copyright &y& Elsevier]

Abstract: Adiponectin whose systemic levels are reduced in obesity-related diseases ameliorates insulin sensitivity and regulates biological processes like apoptosis, proliferation, migration and inflammation. Adiponectin binds to adiponectin receptors, AdipoR1 and AdipoR2, which are ubiquitously expressed. Clathrin-dependent endocytosis of AdipoR1 and adiponectin has been demonstrated to modulate adiponectin bioactivity. Recently, APPL1 has been identified as an AdipoR1 and AdipoR2 binding protein. Furthermore, activated protein kinase C1, endoplasmic reticulum protein 46 and protein kinase CK2β subunit form a complex with AdipoR1. This review summarizes recent studies exploiting heterologous expression of adiponectin receptors in yeast, and the type and function of the recently described adiponectin receptor associated proteins. [ABSTRACT FROM AUTHOR]

Background The adipokine chemerin modulates the function of innate immune cells and may link obesity and inflammation, and therefore, a possible relation of chemerin to inflammatory proteins in obesity and type 2 diabetes (T2D) was analysed. As visceral fat contributes to systemic inflammation, chemerin was measured in portal venous (PVS), hepatic venous (HVS) and systemic venous (SVS) blood of patients with liver cirrhosis. Patients and methods Systemic chemerin was determined by ELISA in the serum of normal-weight, overweight and T2D males, in the serum of T2D patients of both sexes, and in PVS, HVS and SVS of patients with liver cirrhosis. Results Circulating chemerin was similar in T2D and obese individuals but was significantly elevated in both cohorts compared to normal-weight individuals. Chemerin positively correlated with leptin, resistin and C-reactive protein (CRP). In T2D, chemerin was similar in male and female patients and increased in patients with elevated CRP. Chemerin was similar in PVS and SVS, indicating that visceral fat is not a major site of chemerin synthesis. Higher levels of chemerin in HVS demonstrate that chemerin is also released by the liver. Conclusions Visceral fat is not a major site of chemerin release, and elevated systemic levels of chemerin in obesity and T2D seem to be associated with inflammation rather than body mass index. [ABSTRACT FROM AUTHOR]

Abstract: Galectin-3 plays a role in atherosclerotic diseases, and the effect of adiponectin that protects from atherosclerotic diseases on monocytic galectin-3 was analysed. Adiponectin reduced galectin-3 mRNA, its cellular and soluble form, and this effect was impaired in T2D cells. Cellular galectin-3 was higher in monocytes of overweight than normal-weight donors and was highest in T2D cells. Cellular galectin-3 positively correlated with the BMI of the donors and negatively with soluble monocyte galectin-3. Circulating levels of total adiponectin did not correlate with cellular or soluble galectin-3 indicating that additional factors contribute to higher cellular monocytic galectin-3 in obesity and T2D. [Copyright &y& Elsevier]

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 μM 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. [ABSTRACT FROM AUTHOR]

Background CD163 is a monocyte/macrophage specific receptor whose soluble form (sCD163) is elevated in inflammatory diseases. Obesity is associated with chronic inflammation and low adiponectin, an anti-inflammatory adipokine. Adiponectin, 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR) and metformin activate the AMP-kinase that exerts anti-inflammatory effects, and the influence of adiponectin and these drugs on monocytic CD163 was analysed, and cellular and sCD163 were determined in obesity and type 2 diabetes. Materials and methods Monocytes were incubated with adiponectin, AICAR or metformin. Furthermore, monocytes and serum were obtained from type 2 diabetic patients (T2D), overweight (defined as a body mass index ≥ 25 kg m−2) and normal-weight (NW) controls. CD163 was analysed by immunoblot and sCD163 was measured by enzyme-linked immunosorbent assay in the supernatants of the monocytes and in serum. Results In monocytes, adiponectin reduced cellular and surface CD163, whereas sCD163 was not altered in the corresponding supernatants. Further, metformin and AICAR downregulated CD163. Monocytic CD163 was higher in T2D and obesity, whereas sCD163 in the supernatants was not elevated and neither correlated with serum sCD163 nor systemic adiponectin. There was a positive correlation of monocytic sCD163 with serum but not with monocytic IL-6. In the serum of obese controls and T2D patients, sCD163 was significantly higher compared to NW donors and was positively associated with systemic IL-6. Conclusions This study indicates that monocytic CD163 and systemic sCD163 are elevated in T2D and obesity. Adiponectin reduces CD163 in vitro, but additional factors related to obesity like IL-6 may be more relevant in vivo. [ABSTRACT FROM AUTHOR]

Background: Adiponectin is a circulating protein with hepatoprotective effects. Aims: To study the relationship of excessive alcohol consumption and serum adiponectin levels (SAL). Patients and Methods: The SAL were determined in (i) heavy drinkers without advanced liver damage during the course of alcohol withdrawal, (ii) patients with chronic hepatitis C virus (HCV) infection, (iii) patients with alcohol-associated cirrhosis, and (iv) healthy volunteers that consumed excessive amounts of alcohol for only a short period of time. Further, primary human hepatocytes (PHH) and adipocytes were incubated in vitro with alcohol or serum of patients. Results: Patients with chronic alcohol consumption had significantly higher SAL than HCV-patients with comparable degrees of liver damage. In alcoholics, but not in HCV patients, SAL positively correlated with serum levels of aminotransferases. Further, SAL correlated with the amount of alcohol consumption but declined during the course of alcohol abstinence. After short-term excessive alcohol consumption SAL were not elevated in healthy individuals. Adiponectin mRNA was detectable in adipocytes but not in hepatocytes, and alcohol failed to induce adiponectin in both cell types. In contrast, serum of active drinkers induced adiponectin expression in adipocytes while serum from the same individuals collected after alcohol withdrawal had no effect. Conclusions: Alcohol exhibits a specific effect on SAL that is dose and time dependent, and correlates with the degree of hepatic damage. Alcohol does not seem to affect adiponectin expression directly in adipocytes but potentially via mediators systemically released as a result of the chronic alcohol intake. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze Toll-like receptor (TLR) expression in preadipocytes and mature adipocytes and to investigate whether TLR ligands influence the release of cytokines, chemokines, and adipokines. Murine 3T3-L1 preadipocytes and mature adipocytes were used for stimulation experiments. The effects of lipopolysaccharide (LPS), flagellin, Poly (U), Poly (I:C), macrophage-activating lipopeptide-2 (MALP2), Pam3Cys, and CpG on the release of interleukin-6 (IL-6), resistin, and monocyte chemoattractant protein-1 (MCP-1) were determined by enzyme-linked immunosorbent assay (ELISA). Nuclear translocation and promoter binding of NFκB were analyzed by electrophoretic mobility shift assays. TLR expression was investigated by reverse-transcriptase (RT-PCR). All TLRs except TLR5 and TRL7 are expressed in the stromal vascular cell (SVC) fraction and in mature adipocytes of different fat stores. Whereas basal and LPS-induced IL-6 release is higher in preadipocytes, basal and LPS-induced MCP-1 release is higher in mature adipocytes. Mature adipocytes respond to corticosterone regarding MCP-1 and resistin release. The ligands for TLRs influence IL-6, MCP-1, and resistin release differentially. Some of these ligands induce nuclear translocation and promoter binding of NFκB. Besides TLR5, that is not expressed in mature adipocytes, all TLR family members are involved. There exists a functional TRL pathway in adipocytes that connects innate immunity with adipocyte function. As a consequence, the role of the adipose tissue in both immunity and metabolism has to be investigated in future studies. The results of this approach will help to explain the metabolic changes such as insulin resistance observed during infection and the immunological phenomena such as macrophage infiltration of adipose tissue seen in obesity.Obesity (2009) 17 4, 648–656. doi:10.1038/oby.2008.607 [ABSTRACT FROM AUTHOR]

Background Visceral adipose tissues secret a variety of adipokines; however, it is not known whether they are present in the peritoneal fluid. It was the aim of this study to investigate peritoneal fluid concentrations of novel (cartonectin, omentin) and classical adipokines (leptin, adiponectin, resistin, visfatin) in patients with ascites. Material and methods Ninety-six patients (71 men and 25 women) undergoing paracentesis were included. Of these, 76 suffered from liver cirrhosis. Adipokines were measured by enzyme-linked immunosorbent assay or Western blot. Results Each adipokine was detected in ascites with a broad range. Serum–ascites ratios (SAR) correlated with clinical and laboratory parameters. The main variables influencing peritoneal fluid adipokine concentrations were body mass index (BMI), local inflammation, systemic inflammation and serum adipokine concentrations. Resistin was significantly higher in patients with peritonitis and showed a positive correlation with peripheral leucocytes (white blood cell count). Leptin was correlated with the underlying disease. Visfatin correlated with peripheral white blood cell and C-reactive protein levels. Omentin expression was correlated with ascitic leucocyte count, ascitic albumin concentration and low albumin SAR. BMI was correlated positively with ascitic leptin levels and cartonectin protein levels. Conclusions Peritoneal fluid adipokine concentrations are characterized by individual SARs, depend on the presence of peritonitis, and correlate with underlying disease, BMI and systemic inflammation. The data open a new field of research on the role of the peritoneum and visceral adipokines in gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

To study the effects of fatty acids and the involvement of the Toll-like receptor-4/nuclear factor-κB (TLR-4/NF-κB) pathway with respect to the secretion of adipokines from adipocytes 3T3-L1 adipocytes were stimulated with increasing doses of fatty acids. The secretion of adiponectin, resistin and monocyte chemoattractant protein-1 (MCP-1) was measured by enzyme-linked immunosorbent assay. The NF-κB p65 nuclear translocation and TLR-4 expression were investigated by Western blot. The effects mediated by NF-κB were tested using a specific NF-κB-inhibitor and TLR-4-induced effects were analysed with a neutralizing TLR-4 antibody. Binding of 14C-labelled fatty acids to TLR-4/MD-2 was investigated using a FLAG-tagged extracellular part of TLR-4 fused to full-length MD-2 via a linker (lipopolysaccharide-Trap). The messenger RNA (mRNA) expression of adipokines in abdominal adipose tissue of rats fed a standard chow or a high-fat diet was investigated by reverse transcription–polymerase chain reaction. The TLR-4 is induced during adipocyte differentiation and its expression is enhanced following fatty acid stimulation. The stimulatory effects of stearic and palmitic acids on MCP-1 secretion and of palmitoleic acid on resistin secretion are mediated via NF-κB. The stimulatory effects of stearic, palmitic and palmitoleic acids on resistin secretion and the stimulatory effect of stearic acid on MCP-1 secretion are mediated via TLR-4. Fatty acid-mediated effects are caused by an endogenous ligand because fatty acids were shown not to bind directly to TLR-4/MD-2. Adipose tissue mRNA expression and serum levels of adipokines did not differ in rats fed a high-fat diet. These data provide a new molecular mechanism by which fatty acids can link nutrition with innate immunity. [ABSTRACT FROM AUTHOR]

Abstract: Aldehyde oxidase 1 (AOX1) is highly abundant in the liver and oxidizes aldehydes thereby generating reactive oxygen species. Enzymes involved in detoxification of aldehydes are expressed in adipocytes and alter adipogenesis, therefore the functional role of AOX1 in adipocytes was analyzed. AOX1 mRNA was higher in visceral compared to subcutaneous human adipose tissue but AOX1 protein was detected in both fat depots. AOX1 expression in adipocytes was confirmed by immunohistochemistry and immunoblot. AOX1 was induced during adipocytic differentiation and was downregulated by fenofibrate in differentiated cells. Knock-down of AOX1 in preadipocytes led to impaired lipid storage and adiponectin release in the differentiated cells. These data indicate that AOX1 is essential for adipogenesis and may link energy and drug metabolism. [Copyright &y& Elsevier]

Abstract: The abundance of the adiponectin receptors, AdipoR1 and AdipoR2, and the effects of the antidiabetic adipokine adiponectin in monocytes of normal-weight and overweight controls and type 2 diabetic patients (T2D) were analyzed. AdipoR1 and AdipoR2 mRNAs were increased in monocytes of obese controls and T2D patients when compared to normal-weight controls, and AdipoR1 mRNA positively correlated to AdipoR2 mRNA, the waist to hip ratio and systemic adiponectin. However, AdipoR1 and AdipoR2 proteins were lower in monocytes of T2D compared to normal-weight donors. Induction of IL-6 and IL-8 by adiponectin, an effect involving p38 MAPK, was also reduced in T2D monocytes. [Copyright &y& Elsevier]

Alcohol exposure is known to sensitize acinar cells to various insults but the pathophysiological mechanisms of alcoholic pancreatitis remain unknown. Alcohol abuse has been shown to mediate an anti-inflammatory response and periods of immune suppression seem to be associated with organ injury and mortality. The purpose of this study was to determine the mechanisms by which alcohol exerts transcriptional activities in the rat pancreas and how alcohol alters the inflammatory response. Using the Lieber-DeCarli alcohol/control diet, rats that were fed with alcohol over 14 weeks demonstrated a decrease of inflammatory cells in pancreatic tissue compared to controls. The anti-inflammatory effects of alcohol were confirmed by decreased expression of pro-inflammatory cytokines including TNFα, IL-1β, IL-18, TGFβ, and MCP-1. In addition, alcohol significantly increased the activity of PPARγ, which is a known anti-inflammatory transcription factor, while pro-inflammatory factors including AP-2 and EGR-1 were significantly suppressed. NFκB binding showed a tendency towards a reduction. Electron microscopy studies revealed enlarged and injured mitochondria and lysosomes, accompanied by peri-cellular fibrosis. Furthermore, alcohol exposure increased the activities of trypsin and cathepsin B, both known to be critical in initiating acinar cell injury and pancreatitis. Despite the known alcohol-mediated acinar cell and mitochondrial injury, the mitochondrial-mediated apoptotic pathway was attenuated. These data demonstrate that the pancreas exposed to alcohol maintains an anti-inflammatory state by activating PPARγ. Intracellular mitochondrial and lysosomal damage after chronic alcohol exposure induces premature activation of digestive enzymes and establishment of peri-cellular fibrosis in the absence of inflammation. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents the research which assessed the regulation and function of collagenous repeat containing sequence of 26-kDa protein gene product cartonectin. Based on the outcome of the study, researchers suggest cartonectin, encoded by the CORS-26 gene, to represent a new adipokine belonging to the C1q-complement family of proteins with a N-terminal collagenous domain.

An innovative process to uniformly incorporate dispersed nanoscale ceramic inclusions within a polymer matrix was demonstrated. Micron-sized high density polyethylene particles were coated with ultrathin alumina films by atomic layer deposition in a fluidized bed reactor at 77°C. The deposition of alumina on the polymer particle surface was confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Conformal coatings of alumina were confirmed by transmission electron microscopy and focused ion beam cross-sectional scanning electron microscopy. The results of inductively coupled plasma atomic emission spectroscopy suggested that there was a nucleation period. The results of scanning electron microscopy, particle size distribution, and surface area of the uncoated and nanocoated particles showed that there was no aggregation of particles during the coating process. The coated polymer particles were extruded by a heated extruder at controlled temperatures. The successful dispersion of the crushed alumina shells in the polymer matrix following extrusion was confirmed using cross-sectional transmission electron microscopy. The dispersion of alumina flakes can be controlled by varying the polymer particle size. [ABSTRACT FROM AUTHOR]

Estimates of pelagic larval duration (PLD) for 10 species of Pomacentridae and two species of Gobiidae were made. In eight of the 12 species examined, within-population mean PLDs differed between sampling times, locations within regions and among regions. In contrast, the range of these same PLD estimates overlapped at all spatial and temporal scales examined in 11 of the 12 species, but not between regions in one species ( Amphiprion melanopus). Therefore, despite tight error estimates typically associated with estimates of PLD taken from a particular population at a particular time in some taxa, the overlapping ranges in PLD reported here indicate that the length of the pelagic larval phase is a much more plastic trait than previously appreciated. Within-species variation in PLD has considerable potential to provide further insights into the ecology and evolution of tropical reef fishes. [ABSTRACT FROM AUTHOR]

Abstract: The adiponectin paralog CORS-26 (collagenous repeat-containing sequence of 26kDa protein) is a member of the C1q/TNF-α molecular superfamily. CORS-26 is a secreted protein and baculovirus-produced CORS-26 released in the supernatant of insect cells forms stable trimers. Adiponectin exerts anti-inflammatory effects in LPS-treated monocytic cells and CORS-26 also reduces IL-6 and TNF-α secretion but does not increase IL-10. Suppression of NFκB signalling may explain the anti-inflammatory actions of CORS-26. Furthermore CORS-26 protein was detected in human monocytic and dendritic cells. The present data demonstrate for the first time that CORS-26 forms trimers, exerts anti-inflammatory properties and that it is expressed in monocytic cells. Therefore CORS-26 may provide a new target for pharmacological drugs in inflammatory diseases like the metabolic syndrome. [Copyright &y& Elsevier]