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Kinds of Circulating Terms modified by Circulating Selected AbstractsCirculating and synovial levels of IGF-I, cytokines, physical function and anthropometry differ in women awaiting total knee arthroplasty when compared to menJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2005Sonia M. C. Pagura Abstract Purpose: Determine if gender differences in osteoarthritis relate to cytokine and growth factor levels. Methods: Cross-sectional comparison of serum and synovial concentrations of cytokines (IL-1,,, TNF-,, IL-6), growth factors (IGF-I, TGF-,, IRAP), physical performance and perceived function in total knee arthroplasty candidates (TKAC) (n = 17) and healthy controls (n = 21) was done. Results: Serum IGF-I values were reduced in female (TKAC 137.6 ± 7.2; Controls 160.2 ± 26.2) but not male TKAC (TKAC 182.6 ± 18.4; Controls 184.0 ± 18.4) (p < 0.05). Serum and synovial levels of cytokines and growth factors did not differ significantly by group or gender. Physical performance testing (SPW, TUG) revealed significant group and gender differences (p = 0.001) with women demonstrating greater functional impairment. Discussion: A systemic, not local component to OA pathophysiology may exist for female TKAC. Male TKAC were less impaired, and their IGF-I levels differ little from Control values. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Increased circulating and intrahepatic T-cell-specific chemokines in chronic hepatitis C: relationship with the type of virological response to peginterferon plus ribavirin combination therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2004A. Apolinario Summary Aims :,To determine the serum and intrahepatic levels of T-helper-1-associated chemokines in patients with chronic hepatitis C before, during and after peginterferon plus ribavirin combination therapy and to search for correlations with baseline characteristics of hepatitis C virus-related chronic liver disease and type of therapeutic response. Methods :,Serum chemokine levels were determined by enzyme-linked immunosorbent assays and intrahepatic chemokine messenger RNA and protein levels were tested by ribonuclease protection assay and immunohistochemistry. Results :,Serum and intrahepatic chemokine levels were elevated in all patients with chronic hepatitis C and showed a marked decrease in patients who obtained a virological response vs. non-responders. Increased serum interferon-,-inducible protein-10 levels at baseline in genotype 1-infected patients were significantly associated with greater degrees of intrahepatic inflammation and fibrosis (P = 0.0046 and P = 0.02, respectively) and with virological non-response (P = 0.01). In patients with genotype 1, basal serum interferon-,-inducible protein-10 levels greater than 299 pg/mL identified 80% of non-responders and lower than 299 pg/mL identified 63% of responders. Conclusions :,Circulating and intrahepatic T-helper-1-associated chemokines are abnormally elevated in patients with chronic hepatitis C. Increased baseline serum interferon-,-inducible protein-10 levels in genotype 1-infected patients are associated with virological non-response to peginterferon plus ribavirin combination therapy. [source] Primate models in women's health: inflammation and atherogenesis in female cynomolgus macaques (Macaca fascicularis)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009Thomas C. Register Abstract Female cynomolgus monkeys are excellent models for understanding cardiovascular disease and the relationships between inflammatory processes and conditions such as atherogenesis. This review summarizes published research findings obtained through comprehensive, multidisciplinary, multi-investigator studies in nonhuman primates over the past two decades. These studies examined the effects of exogenous estrogens and dietary soy protein/isoflavones (IFs) on atherosclerosis, circulating biomarkers, and tissue inflammation in pre- and postmenopausal female cynomolgus monkeys. Inflammation may play a role in the initiation and progression of disease, be a consequence of the disease, or both. Circulating and tissue biomarkers with inflammatory and anti-inflammatory characteristics (including adhesion molecules such as e-selectin, VCAM-1, and ICAM-1, chemokines such as MCP-1, cytokines such as interleukins, and acute phase reactants such as CRP, and others) may be useful indicators of disease status. Treatment of postmenopausal subjects with estrogen resulted in significant reductions in several key inflammatory mediators as well as atherosclerosis, while dietary IF had a more limited effect on inflammation and atherogenesis. Circulating concentrations of key inflammatory proteins, including monocyte-chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), were associated with atherosclerosis and lesion characteristics in these animals. In premenopausal female monkeys, a diet enriched in soy protein reduced arterial inflammation as well as atherogenesis in comparison to a diet enriched in casein-lactalbumin. Expression levels of arterial inflammation associated genes (MCP-1, ICAM-1) and markers for inflammatory cell types (macrophages and T cells) correlated with plaque size, were differentially influenced by treatments, and represent potential targets for interventions. Arterial expression of estrogen receptor ,, the key mediator of estrogenic effects, was inversely correlated with plaque size and indices of inflammation, suggestive of an atheroprotective role. The findings provide additional evidence that circulating inflammatory markers (particularly MCP-1) may be useful indicators of atherosclerotic disease progression and responses to treatment in female primates, and that estrogens and dietary soy may inhibit atherogenesis in part through anti-inflammatory mechanisms. Am. J. Primatol. 71:766,775, 2009. © 2009 Wiley-Liss, Inc. [source] SHORT COMMUNICATION: Circulating and Decidual Th17 Cell Levels in Healthy PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010Akitoshi Nakashima Citation Nakashima A, Ito M, Yoneda S, Shiozaki A, Hidaka T, Saito S. Circulating and decidual Th17 cell levels in healthy pregnancy. Am J Reprod Immunol 2010; 63: 104,109 Problem, The Th1/Th2 paradigm has recently been reconstituted to include a third population, Th17 cells. It has been reported that Th2 type immunity is predominantly present in normal pregnancy. However, the level of Th17 cells during pregnancy is still unclear. We investigated the level of peripheral Th17 cells in healthy pregnancy subjects. Method of study, To evaluate the levels of Th17 cells, we investigated the proportion of peripheral blood mononuclear cells that produced IL-17 in the first, second, and third trimester pregnancy subjects using flow cytometry. We further studied the proportion of decidual lymphocytes that produced IL-17 in early pregnant subjects. Results, Most of the IL-17-producing cells were CD4+ T cells. The number of circulating Th17 cells did not change during pregnancy. In a paired t -test of early normal pregnant subjects, the proportion of IL-17+ decidual lymphocytes was significantly higher than that of peripheral blood lymphocytes. Conclusion, Th17 levels in peripheral blood lymphocytes do not change during normal pregnancy. [source] Circulating tumour-associated plasma DNA represents an independent and informative predictor of prostate cancerBJU INTERNATIONAL, Issue 3 2006FELIX K.-H. OBJECTIVE To investigate whether preoperative plasma levels of free DNA can discriminate between men with localized prostate cancer and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS In all, 161 referred patients suspicious for prostate cancer either by an elevated prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE) were included in this prospective study. Peripheral plasma was taken before prostate biopsy and genomic DNA was extracted from the plasma using the a commercial kit and a vacuum chamber. After controlling for age, PSA level, the percentage free/total (f/t) PSA and prostate volume, the median prostate cancer plasma DNA concentration served as diagnostic threshold in uni- and multivariate logistic regression models. Multivariate models were subjected to 200 bootstraps for internal validation and to reduce over-fit bias. RESULTS Subgroups consisted of 142 men with clinically localized prostate cancer and 19 with BPH. The median plasma concentration of cell-free DNA was 267 ng/mL in men with BPH vs 709 ng/mL in men with prostate cancer. In univariate analyses, plasma DNA concentration was a statistically significant and informative predictor (P = 0.032 and predictive accuracy 0.643). In multivariate analyses, it remained statistically significant after controlling for age, tPSA, f/tPSA and prostate volume, increasing the predictive accuracy by 5.6%. CONCLUSIONS Our data suggest that plasma DNA level is a highly accurate and informative predictor in uni- and multivariate models for the presence of prostate cancer on needle biopsy. The predictive accuracy was substantially increased by adding plasma DNA level. However, larger-scale studies are needed to further confirm its clinical impact on prostate cancer detection. [source] Circulating interleukin-10 and interleukin-12 in Parkinson's diseaseACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009M. Rentzos Background,,, Interleukin (IL)-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines. IL-10 is a pleiotropic cytokine produced by both lymphocytes and mononuclear phagocytes including microglia. Recent studies demonstrated the neuroprotective effect of IL-10. There is little information about the involvement of IL-12 or IL-10 in the pathophysiology of Parkinson's disease (PD). Objectives,,, The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with PD and to investigate whether IL-10, an immunosuppressive cytokine, may have a neuroprotective effect in the pathogenesis of PD. Patients and methods,,, We measured using immunoassay serum IL-12 and IL-10 levels in 41 patients with PD in comparison with serum levels in 19 healthy subjects (controls) age and sex matched. IL-12 and IL-10 levels were tested for correlation with sex, age, disease duration, Hoehn and Yahr stage and the UPDRS III score. Results,,, The PD group presented with significantly increased IL-10 levels when compared with the control group (P = 0.02). The increase observed was not affected by the treatment status. A strong and significant correlation between IL-10 and IL-12 levels was observed in patients with PD (RS = 0.7, P < 0.000001). Conclusions,,, Our findings suggest that IL-10 may be involved in the pathogenetic mechanisms of PD. The elevation of IL-10 and the significant correlation between IL-10 and IL-12, a proinflammatory cytokine, may suggest that immunological disturbances and neuroprotective mechanisms are involved in patients with PD. [source] Circulating ,/, T lymphocytes from systemic sclerosis (SSc) patients display a T helper (Th) 1 polarizationCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2001R. Giacomelli Systemic sclerosis (SSc) is a connective tissue disease in which immune system activation is evidenced by high levels of different cytokines in the sera and/or in the supernatants of cultured peripheral blood mononuclear cells (PBMC) and by the presence of specific autoantibodies. ,/, T cells accumulate in the lung and the skin of SSc patients suggesting their potential role in the development and maintenance of the disease. The aim of this study was to assess cytokine production and cytotoxic activity of circulating ,/, T lymphocytes obtained from SSc patients and to evaluate their potential role during this disorder. Our results showed that both the proportion and the absolute number of IFN- ,,/, -producing cells (i.e. displaying a Th1 polarization) in SSc was significantly higher than either the proportion and the absolute number of IL-4 ,/, -producing cells in SSc or the proportion and the absolute number of IFN- ,,/, -producing cells in healthy controls (P < 0·05 for both groups). Furthermore, the cytotoxic activity of enriched ,/, T cells was significantly increased in SSc patients compared with controls. The results concerning the V,1+ T cell subset paralleled those of total ,/, T lymphocytes. In contrast, ,/, T cells from SSc and control subjects displayed Th2 cytokine production. All these findings were independent of both disease subset and clinical status. Our data demonstrate that, although SSc is generally considered a Th2 autoimmune disease, Th1 polarization of ,/, T cells and an increase in their cytotoxic activity is observed in SSc, suggesting that ,/, T cells could have a relatively autonomous role in the pathogenesis in this disease. [source] Uridine adenosine tetraphosphate affects contractility of mouse aorta and decreases blood pressure in conscious rats and miceACTA PHYSIOLOGICA, Issue 2 2010P. B. Hansen Abstract Aim:, In the anaesthetized rat, uridine adenosine tetraphosphate (Up4A) is a circulating, endothelium-derived vasoconstrictor presumably operating as such in un-anaesthetized animals. The present study investigated the in vivo effects of Up4A in conscious mice and rats, and its direct vascular effects in the mouse aorta in vitro. Methods:,In vivo, Up4A was given as step-up infusion at rates of 8,512 nmol min,1 kg,1 for 30 min periods in chronically catheterized rodents. In vitro, the effect of Up4A on rings of mouse aortae mounted in a myograph was tested. Results:, High doses of Up4A (mice: 512 nmol min,1 kg,1; rats: 128 nmol min,1 kg,1) caused hypotension (99 ± 4 to 64 ± 7 mmHg and 114 ± 3 to 108 ± 3 mmHg, respectively, both P < 0.01). In rats, Up4A significantly decreased sodium excretion by >75% and potassium excretion by ,60% without significant changes in urine flow. Exposure of phenylephrine-contracted rings to increasing concentrations of Up4A elicited contraction at 10,7 and 10,6 mol L,1 (18 ± 2% and 76 ± 16% respectively); unexpectedly, 10,5 mol L,1 caused a biphasic response with a contraction (19 ± 6%) followed by a relaxation (,46 ± 6%). No relaxation was observed when the concentration was increased further. Bolus exposure to 10,5 mol L,1 of Up4A caused contraction (+80 ± 2%). Added successively to untreated vessels, increasing concentrations of Up4A (10,7,10,5 mol L,1) induced a biphasic response of contraction followed by relaxation. Conclusion:, Up4A has direct biphasic effects on vascular smooth muscle of the mouse aorta but vasoconstriction dominates at low concentrations. In conscious rodents, step-up infusions of Up4A elicit hypotension and electrolyte retention. [source] In humans the adiponectin receptor R2 is expressed predominantly in adipose tissue and linked to the adipose tissue expression of MMIF-1DIABETES OBESITY & METABOLISM, Issue 4 2010K. Kos In this study, the regional adipose tissue-adiponectin (AT-ADN) and adiponectin receptor (R1 and R2) expression and their relation with metabolic parameters, circulating and AT-derived cytokine expressions were compared. Paired subcutaneous adipose tissue (SCAT) and visceral adipose tissue (VAT) were taken from 18 lean and 39 obese humans, AT-mRNA expression of adipokines analysed by RT-PCR and corresponding serum levels by enzyme-linked immunosorbent assay (ELISA). R1 and R2 adipocyte expression was compared with 17 other human tissues. ADN-gene expression was lower in VAT than SCAT [mean (SD) 1.54 (1.1) vs. 2.84 (0.87); p < 0.001], and lower in obese subjects (VAT : p = 0.01;SCAT : p < 0.001). SCAT-ADN correlated positively with serum ADN (r = 0.33;p = 0.036) but not VAT-ADN. AT expressions of ADN and macrophage migration inhibiting factor (MMIF), IL18 and cluster of differentiation factor 14 (CD14) in both depots showed inverse correlations. R1 and R2 were expressed ubiquitously and R2 highest in SCAT, and this is much higher (×100) than R1 (×100). R expression was similar in lean and obese subjects and unrelated to the metabolic syndrome, however, receptors correlated with VAT-MMIF (R 1: r = 0.4;p = 0.008;R 2: r = 0.35,p = 0.02) and SCAT-MMIF expression (R 2: r = 0.43;p = 0.004). Unlike ADN, its receptors are expressed in many human tissues. Human R2 expression is not highest in the liver but in AT where it is associated with MMIF expression. The adiponectin-dependent insulin-sensitizing action of thiazolidinediones is thus probably to differ amongst species with weaker effects on the human liver. [source] Altered reproduction in fish exposed to pulp and paper mill effluents: Roles of individual compounds and mill operating conditionsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2008L. Mark Hewitt Abstract For the last 20 years, studies conducted in North America, Scandinavia, and New Zealand have shown that pulp and paper mill effluents affect fish reproduction. Despite the level of effort applied, few leads are available regarding the factors responsible. Effluents affect reproduction in multiple fish species, as evidenced by decreased gonad size, decreased circulating and gonadal production of reproductive steroids, altered expression of secondary sex characteristics, and decreased egg production. Several studies also have shown that effluent constituents are capable of accumulating in fish and binding to sex steroid receptors/binding proteins. Studies aimed at isolating biologically active substances within the pulping and papermaking process have provided clues about their source, and work has progressed in identifying opportunities for in-mill treatment technologies. Following comparisons of manufacturing processes and fish responses before and after process changes, it can be concluded that effluent from all types of mill processes are capable of affecting fish reproduction and that any improvements could not be attributed to a specific process modification (because mills normally performed multiple modifications simultaneously). Improved reproductive performance in fish generally was associated with reduced use of molecular chlorine, improved condensate handling, and liquor spill control. Effluent biotreatment has been effective in reducing some effects, but biotreated effluents also have shown no difference or an exacerbation of effects. The role of biotreatment in relation to effects on fish reproduction remains unclear and needs to be resolved. [source] Severe vitamin B12 deficiency resulting in pancytopenia, splenomegaly and leukoerythroblastosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2008Thorvardur R. Halfdanarson Abstract Deficiency of vitamin B12 is a well known cause of megaloblastic anemia and pancytopenia. Splenomegaly and leukoerythroblastosis are much less well known manifestations of B12 deficiency. We report a B12 deficient female with severe pancytopenia including normocytic anemia who also had enlarged spleen and circulating nucleated red blood cells as well as circulating immature myeloid cells. Although these findings are reported in the earlier literature, more modern reviews of the subject often fail to mention this association. We review the literature on these unusual manifestations of B12 deficiency and remind clinicians that splenomegaly and erythroblastosis can serve as diagnostic clues in cases of severe megaloblastic anemia secondary to B12 deficiency. [source] Structural and compositional changes in very low density lipoprotein triacylglycerols during basal lipolysisFEBS JOURNAL, Issue 24 2002Jyrki J. Ågren Triacylglycerols secreted by liver and carried by very low density lipoprotein (VLDL) are hydrolysed in circulation by lipoprotein and hepatic lipases. These enzymes have been shown to have positional and fatty acid specificity in vitro. If there were specificity in basal lipolysis in vivo, triacylglycerol compositions of circulating and newly secreted VLDL would be different. To study this we compared the composition of normal fasting VLDL triacylglycerol of Wistar rats to that obtained after blocking lipolysis by Triton WR1339, which increased plasma VLDL triacylglycerol concentration about 4.7-fold in 2 h. Analyses of molecular species of sn -1,2- and sn -2,3-diacylglycerol moieties and stereospecific triacylglycerol analysis revealed major differences between the groups in the VLDL triacylglycerol composition. In nontreated rats, the proportion of 16:0 was higher and that of 18:2n-6 lower in the sn -1 position. The proportion of 14:0 was lower in all positions and that of 18:0 was lower in the sn -1 and sn -3 positions in nontreated rats whereas the proportions of 20:4n-6, 20:5n-3, 22:5n-3 and 22:6n-3 were higher in the sn -1 and lower in the sn -2 position. These results suggest that the fatty acid of the sn -1 position is the most decisive factor in determining the sensitivity for hydrolysis of the triacylglycerol. In addition, triacylglycerol species with highly unsaturated fatty acids in the sn -2 position also favoured hydrolysis. The in vivo substrate specificity followed only partly that obtained in in vitro studies indicating that the nature of molecular association of fatty acids in natural triacylglycerol affects its susceptibility to lipolysis. To conclude, our results indicate that preferential basal lipolysis leads to major structural differences between circulating and newly secreted VLDL triacylglycerol. These differences extend beyond those anticipated from analysis of total fatty acids and constitute a previously unrecognized feature of VLDL triacylglycerol metabolism. [source] Method of calculation of heat transfer coefficient of the heater in a circulating fluidized bed furnaceHEAT TRANSFER - ASIAN RESEARCH (FORMERLY HEAT TRANSFER-JAPANESE RESEARCH), Issue 7 2002J.F. Lu Abstract Knowledge of heat transfer coefficients is important in the design and operation of CFB boilers. It is the key to determining the area and the layout of the heat transfer surfaces in a CFB furnace. Local bulk density has a close relationship to the local heat transfer coefficient. Using a heat flux probe and bulk density sampling probe, the local bed to wall heat transfer coefficient in the furnace of a 75 t/h CFB boiler was measured. According to the experimental results and theoretical analysis of the facts that influence the heat transfer, the heat transfer coefficient calculation method for the CFB furnace was developed. The heat transfer surface configuration, heating condition, and the material density are considered in this method. The calculation method has been used in the design of CFB boilers with a capacity from 130 t/h to 420 t/h. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(7): 540,550, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10056 [source] Associations Between Helicobacter pylori Infection, Co-Morbid Infections, Gastrointestinal Symptoms, and Circulating Cytokines in African ChildrenHELICOBACTER, Issue 2 2010Sarah Cherian Abstract Background:, Refugee children have complex medical needs and often have multiple infections. The relationship between infection, gastrointestinal symptoms, and systemic inflammation is poorly understood. We investigated these parameters in refugee children with a high prevalence of Helicobacter pylori, helminth, and malaria infection. Materials and Methods:, African refugee children were recruited at resettlement health screening. Data were collected on demography, gastrointestinal symptoms, co-morbid infection, and serum for peripheral cytokine levels. Helicobacter pylori infection was diagnosed by a fecal-based immunoassay. Results:, Data from 163 children were analyzed, of which 84.0% were positive for H. pylori. Infected children were significantly older (9.2 years ± 3.7 vs 7.1 years ± 3.9, p = .01). Half the cohort (84/163, 51.5%) described gastrointestinal symptoms but these were not strongly associated with co-morbid infections. Helicobacter pylori -infected children had significantly lower circulating log-interleukin-8 (IL-8) (odds ratio 0.61, 95% confidence interval (CI) 0.40, 0.94, p = .025). Helminth infections were common (75/163, 46%) and associated with elevated log-IL-5 (,: 0.42, 95% CI 0.077, 0.76). Children with malaria (15/163, 9.2%) had elevated log-tumor necrosis factor-, (TNF,) and log-IL-10 (,: 0.67, 95% CI 0.34, 1.0 and ,: 1.3, 95% CI 0.67, 1.9, respectively). IL-10 : IL-12 ratios were increased in H. pylori- infected children with malaria or helminth infections. Symptoms were generally not associated with levels of circulating peripheral cytokines irrespective of co-morbid infection diagnosis. Conclusions:, There is a high prevalence of asymptomatic H. pylori infection in recently resettled African refugee children. Gastrointestinal symptoms were not predictive of H. pylori nor of helminth infections. Serum cytokines, particularly IL-5, IL-10, and TNF,, were significantly elevated in children with malaria and helminth infections but not in those with H. pylori infection. [source] Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic ParkinsonismHELICOBACTER, Issue 4 2005Part 1: Eradication of Helicobacter in the Cachexia of Idiopathic Parkinsonism ABSTRACT Background., Neuronal damage in idiopathic parkinsonism may be in response to ubiquitous occult infection. Since peptic ulceration is prodromal, Helicobacter is a prime candidate. Aim., To consider the candidature of Helicobacter in parkinsonism with cachexia. Methods., We explore the relationship between being underweight and inflammatory products in 124 subjects with idiopathic parkinsonism and 195 controls, and present the first case-series evidence of efficacy of Helicobacter eradication, in parkinsonism advanced to the stage of cachexia. Results., Association of a low body mass index with circulating interleukin-6 was specific to parkinsonism (p = .002), unlike that with antibodies against Helicobacter vacuolating-toxin and cytotoxicity-associated gene product (p < .04). Marked reversibility in both cachexia and disability of idiopathic parkinsonism followed Helicobacter heilmannii eradication in one case, Helicobacter pylori eradication in another, follow-up being , 3.5 years. The latter presented with postprandial bloating, and persistent nausea: following eradication, radioisotope gastric-emptying returned towards normal, and upper abdominal symptoms regressed. Reversibility of their cachexia/disability contrasts with the outcome of anti- Helicobacter therapy where eradication repeatedly failed (one case), and in non- Helicobacter gastritis (three cases). Anti-parkinsonian medication remained constant. Intestinal absorption and barrier function were normal in all. Conclusion., Categorization, according to presence or absence of Helicobacter infection, was a useful therapeutic tool in late idiopathic parkinsonism. [source] Identification of plasma membrane autoantigens in autoimmune hepatitis type 1 using a proteomics tool,,HEPATOLOGY, Issue 3 2008Fatima Tahiri Autoimmune hepatitis (AIH) is a liver disease with circulating autoantibodies predominantly directed against widely held cellular components. Because AIH is a liver-specific disease, autoantibodies against plasma membrane antigens may be involved in its pathogenesis and have been reported; however, no definite identification has been described. We thus investigated the fine specificity of anti-hepatocyte plasma membrane autoantibodies in type 1 AIH (AIH-1) using a proteomic tool. A plasma membrane,enriched fraction was validated using enzymatic activity and western blot analysis experiments. Sera from AIH-1 patients (n = 65) and from 90 controls, that is, healthy blood donors (n = 40) and patients with systemic diseases (n = 20) or other liver diseases (n = 30), were studied by immunoblot performed with plasma membrane proteins resolved by either sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) or 2-dimensional (2D) electrophoresis. Proteins contained in the immunoreactive spots were identified by sequences provided by ion-trap mass spectrometry. Hepatocytes probed with sera were also studied using confocal immunofluorescence and immunoelectron microscopy. The more prominent bands stained by patient sera were located at 38 kDa, 48, 50, 52 kDa, 62 kDa, 70 kDa, and a 95-kDa double band. Six proteins with known potential plasma membrane expression were identified: liver arginase (38 kDa), cytokeratins (CK) 8 and 18 (48-52 kDa), heat shock proteins (HSP) of 60, 70, 90 kDa, and valosin-containing protein (VCP) of 92 kDa. The presence of anti-membrane antibodies was confirmed by immunofluorescence and immunoelectron microscopy. Conclusion: Overall, our data demonstrate that liver arginase, CK 8/18, HSP 60, HSP 70, HSP 90, and VCP represent potential candidate targets on liver membrane for autoantibodies in AIH-1. (HEPATOLOGY 2008;47:937,948.) [source] Mutual changes of thioredoxin and nitrosothiols during biliary cirrhosis: Results from humans and cholestatic rats,HEPATOLOGY, Issue 2 2007Ignazio Grattagliano Cholestasis is associated with changes in NO metabolism and thiol oxidation. Thioredoxin contributes to regulate vascular tone and intracellular redox status by cleaving nitrosothiols and maintaining ,SH groups. This study investigated the changes in circulating thioredoxin and nitrosothiols and the relationship with protein sulfhydryls (PSH), hepatic concentrations, hyaluronate, and histology in patients with primary biliary cirrhosis (PBC) and in rats with bile duct ligation (BDL). PSH in erythrocytes were significantly decreased in stage III and IV PBC and at day 10 after BDL. Compared with controls, erythrocyte thioredoxin levels were higher in stage I through III PBC and lower in stage IV patients. Serum thioredoxin levels were significantly higher in PBC stages I and II and lower in stages III and IV. Serum nitrosothiols were higher in all PBC patients and inversely related to thioredoxin and hyaluronate. In rats, serum, hepatic, and mitochondrial thioredoxin had initially increased after BDL (day 1-3) and then decreased. After day 7 BDL, nitrosothiols were 10-fold increased in serum and liver, and even higher in mitochondria. In the liver, thioredoxin was inversely related to both nitrosothiols and PSH. In rats, the difference in time average changes from baseline among serum, hepatic, and erythrocyte thioredoxin suggests that most of circulating thioredoxin originates from the liver. Conclusion: Our findings indicate that cholestasis is associated with significant mutual and interrelated changes between circulating and hepatic thioredoxin and nitrosothiols. The increase of hepatic, mitochondrial, and circulating nitrosothiols with ongoing cholestasis suggests an active participation of NO in both liver injury and extrahepatic changes. (HEPATOLOGY 2007;45:331,339.) [source] Long time investigation of the effect of fouling on the super-heaters in a circulating fluidized biomass boilerINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 13 2006Jan Sandberg Abstract The present investigation involves measurements and theories on the mechanisms of the forming of deposit layers on super-heater tubes in a biomass-fired CFD boiler. The deposit layer thickness and the soot-blowing frequency effect on the super-heaters heat transfer are the main subject of the study that has been conducted over a 3-year period. The measurements show a deposit growth rate on the super-heaters of approximately 4 g m,2 h,1. The distribution of the deposit material varies significantly between the windward and the leeward side of the tubes, with the thickest layers on the windward side. Further down stream of the first super-heater, the fouling problem on the super-heater and re-heater tubes are not so severe. A theoretical model shows that a deposit layer of 20 mm will decrease the heat transfer rate of the first super-heater by nearly 40%. The soot-blowing system shows a strong positive effect on the heat transfer rate of the super-heater a few hours after a soot-blowing sequence has been completed. However in the long run, the varied soot-blowing frequency does not have a significant influence on the deposit layer growth rate. Copyright © 2006 John Wiley & Sons, Ltd. [source] Effect of pressure on thermal aspects in the riser column of a pressurized circulating fluidized bedINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 3 2006A. V. S. S. K. S. Gupta Abstract In the present paper the effect of pressure on bed-to-wall heat transfer in the riser column of a pressurized circulating fluidized bed (PCFB) unit is estimated through a modified mechanistic model. Gas,solid flow structure and average cross-sectional solids concentration play a dominant role in better understanding of bed-to-wall heat transfer mechanism in the riser column of a PCFB. The effect of pressure on average solids concentration fraction ,c' in the riser column is analysed from the experimental investigations. The basic cluster renewal model of an atmospheric circulating fluidized bed has been modified to consider the effect of pressure on different model parameters such as cluster properties, gas layer thickness, cluster, particle, gas phase, radiation and bed-to-wall heat transfer coefficients, respectively. The cluster thermal conductivity increases with system pressure as well as with bed temperature due to higher cluster thermal properties. The increased operating pressure enhances the particle and dispersed phase heat transfer components. The bed-to-wall heat transfer coefficient increases with operating pressure, because of increased particle concentration. The predicted results from the model are compared with the experimentally measured values as well as with the published literature, and a good agreement has been observed. The bed-to-wall heat transfer coefficient variation along the riser height is also reported for different operating pressures. Copyright © 2005 John Wiley & Sons, Ltd. [source] Parametric analysis of a coal based combined cycle power plantINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 1 2006T. Srinivas Abstract In the present paper thermodynamic analyses, i.e. both energy and exergy analyses have been conducted for a coal based combined cycle power plant, which consists of pressurized circulating fluidized bed (PCFB) partial gasification unit and an atmospheric circulating fluidized bed (ACFB) char combustion unit. Dual pressure steam cycle is considered for the bottoming cycle to reduce irreversibilities during heat transfer from gas to water/steam. The effect of operating variables such as pressure ratio, gas turbine inlet temperature on the performance of combined cycle power plant has been investigated. The pressure ratio and maximum temperature (gas turbine inlet temperature) are identified as the dominant parameters having impact on the combined cycle plant performance. The work output of the topping cycle is found to increase with pressure ratio, while for the bottoming cycle it decreases. However, for the same gas turbine inlet temperature the overall work output of the combined cycle plant increases up to a certain pressure ratio, and thereafter not much increase is observed. The entropy generation, the irreversibilities in each component of the combined cycle and the exergy destruction/losses are also estimated. Copyright © 2005 John Wiley & Sons, Ltd. [source] Experimental investigation into cavity-type inertial separators,a novel technique for development of subcompact circulating fluidized bed boilersINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 14 2005Animesh Dutta Abstract Cavity-type inertial separators developed by GRI (Patent no. 2, 159, 949, Canada, 2002) were tested in a semi-industrial size circulating fluidized bed pilot plant operated at room temperature. Three rows of separators were hung from the roof of the pilot plant where one row was kept inside the riser and the others were kept in the primary separation chamber, located between the back-pass and the riser. Parameters measured were axial pressure drops along the height of the riser, vertical solids flux on the separator walls, lateral outwards solids flux in the riser with and without separator and local temperatures on the separator walls. A net downwards solids flux is on the inner wall of the separators; however, no downwards solids flux is on the outer walls of the separators. Heat transfer coefficients on the outer wall are found higher than those on the inner walls of the separator. It is also found that the presence of inertial separators not only provides additional heat transfer surfaces but also indirectly increases the heat transfer coefficients on the riser wall. Copyright © 2005 John Wiley & Sons, Ltd. [source] Fundamental heat transfer mechanism between bed-to-membrane water-walls in circulating fluidized bed combustorsINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 9 2003B.V. Reddy Abstract In the present work, the fundamental mechanism between bed-to-membrane water-walls in the riser column of a circulating fluidized bed (CFB) combustor is presented. The bed-to-membrane water-wall heat transfer depends on the contributions of particle heat transfer, dispersed phase heat transfer and radiation heat transfer. The fundamental mechanism of particle heat transfer and the effect of fraction of wall exposed to clusters and gas gap thickness between cluster and wall on particle heat transfer coefficient and bed-to-wall heat transfer coefficient are investigated. The influence of operating parameters like cross-sectional average volumetric solids concentration and bed temperature on particle and bed-to-wall heat transfer are also reported. The present work contributes some fundamental information on particle heat transfer mechanism, which is responsible for increasing the bed-to-wall heat transfer coefficient (apart from dispersed phase convection and radiation heat transfer). The details on particle heat transfer mechanism will enable to understand the basic heat transfer phenomena between bed-to-membrane water-walls in circulating fluidized bed combustors in a detailed way, which in turn will aid for better design of CFB combustor units. The particle heat transfer mechanism is significantly influenced by the fraction of wall exposed to clusters and gas gap thickness between clusters and wall. Copyright © 2003 John Wiley & Sons, Ltd. [source] Effect of pressure and temperature on cluster and particle heat transfer in a pressurized circulating fluidized bedINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 14 2001B. V. Reddy Abstract The present work reports the influence of pressure and bed temperature on particle-to-wall heat transfer in a pressurized circulating fluidized bed (PCFB). The particle convection heat transfer plays a dominant role in determining the bed-to-wall heat transfer coefficient. So far, no information is reported on the effect of pressure and bed temperature on particle-to-wall heat transfer in a PCFB in the published literature. The present investigation reports some information in this direction. The effect of system pressure and bed temperature are investigated to study their influence on cluster and particle heat transfer. The particle convection heat transfer coefficient increases with system pressure and bed temperature due to higher cluster thermal conductivity. The increase in particle concentration (suspension density) results in greater cluster solid fraction and also the particle concentration near the wall is enhanced. This results in higher cluster and particle convection heat transfer between the bed and the wall. Higher particle convection heat transfer coefficient results in enhanced heat transfer between the bed and the wall. The results will also help to understand the bed-to-wall heat transfer mechanism in a better way in a PCFB. Copyright © 2001 John Wiley & Sons, Ltd. [source] Bone mineralization defects and vitamin D deficiency: Histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675,patientsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2010Matthias Priemel Abstract Parathyroid hormone (PTH) is only one measurable index of skeletal health, and we reasoned that a histomorphometric analysis of iliac crest biopsies would be another and even more direct approach to assess bone health and address the required minimum 25-Hydroxyvitamin D [25(OH)D] level. A cohort from the northern European population with its known high prevalence of vitamin D deficiency therefore would be ideal to answer the latter question. We examined 675 iliac crest biopsies from male and female individuals, excluding all patients who showed any signs of secondary bone diseases at autopsy. Structural histomorphometric parameters, including osteoid indices, were quantified using the Osteomeasure System according to ASBMR standards, and serum 25(OH)D levels were measured for all patients. Statistical analysis was performed by Student's t test. The histologic results demonstrate an unexpected high prevalence of mineralization defects, that is, a pathologic increase in osteoid. Indeed, 36.15% of the analyzed patients presented with an osteoid surface per bone surface (OS/BS) of more than 20%. Based on the most conservative threshold that defines osteomalacia at the histomorphometric level with a pathologic increase in osteoid volume per bone volume (OV/BV) greater than 2% manifest mineralization defects were present in 25.63% of the patients. The latter were found independent of bone volume per trabecular volume (BV/TV) throughout all ages and affected both sexes equally. While we could not establish a minimum 25(OH)D level that was inevitably associated with mineralization defects, we did not find pathologic accumulation of osteoid in any patient with circulating 25(OH)D above 75,nmol/L. Our data demonstrate that pathologic mineralization defects of bone occur in patients with a serum 25(OH)D below 75,nmol/L and strongly argue that in conjunction with a sufficient calcium intake, the dose of vitamin D supplementation should ensure that circulating levels of 25(OH)D reach this minimum threshold (75,nmol/L or 30,ng/mL) to maintain skeletal health. © 2010 American Society for Bone and Mineral Research [source] Hypothalamic sensing of circulating lactate regulates glucose productionJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 11-12 2009Andrea Kokorovic Abstract Emerging studies indicate that hypothalamic hormonal signalling pathways and nutrient metabolism regulate glucose homeostasis in rodents. Although hypothalamic lactate-sensing mechanisms have been described to lower glucose production (GP), it is currently unknown whether the hypothalamus senses lactate in the blood circulation to regulate GP and maintain glucose homeostasis in vivo. To examine whether hypothalamic sensing of circulating lactate is required to regulate GP, we infused intravenous (i.v.) lactate in the absence or presence of inhibition of central/hypothalamic lactate-sensing mechanisms in normal rodents. Inhibition of central/hypothalamic lactate-sensing mechanisms was achieved by three independent approaches. Tracer-dilution methodology in combination with the pancreatic clamp technique was used to assess the effect of i.v. and central/hypothalamic administrations on glucose metabolism in vivo. In the presence of physiologically relevant increases in the levels of plasma lactate, inhibition of central lactate-sensing mechanisms by lactate dehydrogenase inhibitor oxamate (OXA) or ATP-sensitive potassium channels blocker glibenclamide increased GP. Furthermore, direct administration of OXA into the mediobasal hypothalamus increased GP in the presence of similar elevation of circulating lactate. Together, these data indicate that hypothalamic sensing of circulating lactate regulates GP and is required to maintain glucose homeostasis. [source] Development of a membrane-assisted hybrid bioreactor for ammonia and COD removal in wastewatersJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 2 2005Vinka Oyanedel Abstract A new membrane-assisted hybrid bioreactor was developed to remove ammonia and organic matter. This system was composed of a hybrid circulating bed reactor (CBR) coupled in series to an ultrafiltration membrane module for biomass separation. The growth of biomass both in suspension and biofilms was promoted in the hybrid reactor. The system was operated for 103 days, during which a constant ammonia loading rate (ALR) was fed to the system. The COD/N-NH4+ ratio was manipulated between 0 and 4, in order to study the effects of different organic matter concentrations on the nitrification capacity of the system. Experimental results have shown that it was feasible to operate with a membrane hybrid system attaining 99% chemical oxygen demand (COD) removal and ammonia conversion. The ALR was 0.92 kg N-NH4+ m,3 d,1 and the organic loading rate (OLR) achieved up to 3.6 kg COD m,3 d,1. Also, the concentration of ammonia in the effluent was low, 1 mg N-NH4+ dm,3. Specific activity determinations have shown that there was a certain degree of segregation of nitrifiers and heterotrophs between the two biomass phases in the system. Growth of the slow-growing nitrifiers took place preferentially in the biofilm and the fast-growing heterotrophs grew in suspension. This fact allowed the nitrifying activity in the biofilm be maintained around 0.8 g N g,1 protein d,1, regardless of the addition of organic matter in the influent. The specific nitrifying activity of suspended biomass varied between 0.3 and 0.4 g N g,1 VSS d,1. Copyright © 2004 Society of Chemical Industry [source] The presence of local and circulating autoreactive B cells in patients with advanced periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2002Tord Berglundh Abstract Aim: The aim of the present investigation was to study the local (gingival) and systemic occurrence of autoreactive B cells (CD5+CD19 positive) in subjects with a high or low susceptibility to periodontitis. Material and Methods: 2 groups of subjects (Group A and B) susceptible to periodontitis were included. Group A consisted of 22 adult patients (7 females and 15 males, aged 24,66 years) with advanced and generalized chronic periodontitis and group B comprised 7 children (4 girls and 3 boys aged 9,13 years) with localized aggressive periodontitis. 26 periodontally healthy subjects, Group C (aged 23,80 years, mean 49.6±16.3), were also recruited. Assessment of clinical and radiographical characteristics of periodontal disease was performed. Gingival biopsies and peripheral blood samples were obtained and prepared for immunohistochemical analysis. Blood samples only were obtained from the periodontally healthy subjects (group C). Results: The proportion of autoreactive B cells (CD5+CD19 positive) of peripheral blood lymphocytes was about 6 times higher in group A and 4 times higher in group B than in the samples from the control subjects (group C). About 40,50% of the B cells in the peripheral blood of the periodontitis susceptible individuals expressed markers for autoreactive features while less than 15% of the circulating B cells in the subjects of group C exhibited such markers. The periodontitis lesion in the adult periodontitis patients contained a substantial number of B cells out of which about 30% demonstrated autoreactive features. Conclusion: It is suggested that both circulating and local B cells in periodontitis susceptible individuals have a higher propensity to autoreactive properties than B cells of patients with a low susceptibility to periodontitis. Zusammenfassung Zielsetzungen: Untersuchung des lokalen (in der Gingiva) und systemischen Vorkommens autoreaktiver B-Zellen (CD5 und CD19 positiv) bei Individuen mit hoher und niedriger Anfälligkeit für Parodontitis. Material und Methoden: 2 Gruppen von Personen, die anfällig für Parodontitis waren, nahmen an der Studie teil: Gruppe A: 22 erwachsenen Patienten (im Alter von 24,66 Jahren; 7 weiblich) mit fortgeschrittener generalisierter chronischer Parodontitis; Gruppe B: 7 Kinder (9,13 Jahre; 4 Mädchen) mit lokalisierter aggressiver Parodontitis. Zusätzlich wurden 26 parodontal gesunde Personen (23,80 Jahre) untersucht. Klinische und röntgenologische parodontale Parameter wurden erhoben. In den Gruppen A und B, wurden Gingivabiopsien und periphere Blutproben, in Gruppe C nur Blutproben entnommen. Ergebnisse: Der Anteil autoreaktiver B-Zellen an den Lymphozyten im peripheren Blut war etwa 6 mal höher in gruppe A und 4 mal höher in Gruppe B als in Proben der Kontrollgruppe (Gruppe C). Etwa 40,50% der B-Zellen im peripheren Blut der für Parodontitis anfälligen Patienten exprimierten Marker für autoreaktive Eigenschaften während weniger als 15% der zirkulierenden B-Zellen der Individuen aus Gruppe C solche Marker aufwiesen. Die parodontalen Läsionen der erwachsenen Parodontitispatienten enthielten eine hohe Zahl von B-Zellen, von denen etwa 30% autoreaktive Eigenschaften aufwiesen. Schlussfolgerungen: Sowhol lokale als auch zirkulierende B-Zellen von für Parodontitis anfälligen Patienten zeigen mit größerer Häufigkeit autoreaktive Eigenschaften als die B-Zellen von Patienten mit geringer Parodontitisanfälligkeit. Résumé But: Le but de cette recherche était d'étudier la présence locale (gingivale) et systémique de cellules B auto réactives (CD5+CD19 positives) chez des sujets présentant une forte ou une faible susceptibilitéà la parodontite. Matériaux et méthodes: 2 groupes de sujet (A et B) susceptible à la parodontite furent inclus. Le groupe A était constitué de 22 patients adultes (7 femmes et 15 hommes âgés de 24 a 66 ans) présentant une parodontite chronique avancée et généralisée et le groupe B était constitué de 7 enfants (4 filles et 3 garçons ages de 9 à 13 ans) présentant une pardontite agressive localisée. 26 sujets sains d'un point de vue parodontal (groupe C, âgés de 23 à 80 ans, age moyen 49.6±16.3) furent également recrutés. L'observation des caractéristiques cliniques et radiographiques de la maladie parodontale fut réalisée. Des biopsies gingivales et des échantillons sanguins furent prélevées et préparées pour des analyses immunohistochemiques. Seuls des prélèvements sanguins furent pris sur le groupe des patients sains. Résultats: La proportion de cellules B auto réactives (CD5+CD19 positives) des lymphocytes du sang périphérique était 6× plus élevée dans le groupe A et 4× plus élevée dans le groupe B que chez les sujets contrôles du groupe C. Environ 40 a 50% des cellules B du sang périphérique des individus susceptibles à la parodontite exprimaient des marqueurs pour des caractéristiques auto réactives alors que moins de 15% des cellules B circulantes des sujets du groupe C présentaient de tels marqueurs. La lésion parodontale de patients atteints de parodontite de l'adulte contenait un nombre substantiel de cellule B parmi lesquels environ 30% présentaient des caractéristiques auto réactives. Conclusions: Cela suggère que les cellules B locales et circulantes des individus susceptibles à la maladie parodontale aient une puls grande propension aux propriétés auto réactives que les cellules B des patients ayant une susceptibilité faible à la parodontite. [source] Low expression of XIAP-associated factor 1 in human colorectal cancersJOURNAL OF DIGESTIVE DISEASES, Issue 1 2005Tian Le MA OBJECTIVE: Eight cellular homologs of the inhibitors-of-apoptosis proteins (IAP) have been identified in humans and of them, the X-linked IAP (XIAP) is the most potent. XIAP-associated factor 1 (XAF1) is a newly discovered XIAP-binding protein that negatively regulates the caspase-inhibiting activity of XIAP. It is either not expressed or present at extremely low levels in many cancer cell lines. The aims of the present study were: (i) to investigate the expression of XAF1 in human colorectal cancers (CRC) both in vitro and in vivo, and (ii) to evaluate the possibility of XAF1 as a new tumor marker. METHODS: The expression of XAF1 in four human colon cancer cell lines (Colo205, Colo320, SW1116, LoVo) and in samples from 70 patients with CRC was analyzed by reverse transcriptase-polymerase chain reaction. XAF1 concentrations were also detected in the peripheral circulation of the 70 patients, as well as three traditional circulating cancer-associated antigens. RESULTS: A low concentration of XAF1 mRNA was detectable in the three colon cancer cell lines other than Colo205, which showed the strongest expression of XAF1. The expression of XAF1 in tissue was relatively lower in primary CRC compared with a relatively higher level in benign colorectal tumors (P < 0.01). Although the XAF1 expression in circulation of those with CRC was also lower than in those with benign tumors, there was no statistical significance (P > 0.05). CONCLUSIONS: The present results suggest that the low expression of XAF1 in tumor tissue coincides with a similar level in the peripheral circulation, which contributes at least part to the malignant behavior of CRC. Integrating the XAF1 relative expression value with the other three traditional tumor biomarkers created a four-parameter assay that significantly improved the rate of diagnosis of CRC. [source] Muscle precursor cells isolated from aged rats exhibit an increased tumor necrosis factor-, responseAGING CELL, Issue 1 2009Simon J. Lees Summary Improving muscle precursor cell (MPC, muscle-specific stem cells) function during aging has been implicated as a key therapeutic target for improving age-related skeletal muscle loss. MPC dysfunction during aging can be attributed to both the aging MPC population and the changing environment in skeletal muscle. Previous reports have identified elevated levels of tumor necrosis factor-, (TNF-,) in aging, both circulating and locally in skeletal muscle. The purpose of the present study was to determine if age-related differences exist between TNF-,-induced nuclear factor-kappa B (NF-,B) activation and expression of apoptotic gene targets. MPCs isolated from 32-month-old animals exhibited an increased NF-,B activation in response to 1, 5, and 20 ng mL,1 TNF-,, compared to MPCs isolated from 3-month-old animals. No age differences were observed in the rapid canonical signaling events leading to NF-,B activation or in the increase in mRNA levels for TNF receptor 1, TNF receptor 2, TNF receptor-associated factor 2 (TRAF2), or Fas (CD95) observed after 2 h of TNF-, stimulation. Interestingly, mRNA levels for TRAF2 and the cell death-inducing receptor, Fas (CD95), were persistently upregulated in response to 24 h TNF-, treatment in MPCs isolated from 32-month-old animals, compared to 3-month-old animals. Our data indicate that age-related differences may exist in the regulatory mechanisms responsible for NF-,B inactivation, which may have an effect on TNF-,-induced apoptotic signaling. These findings improve our understanding of the interaction between aged MPCs and the changing environment associated with age, which is critical for the development of potential clinical interventions aimed at improving MPC function with age. [source] Hypocholesterolemic and Anti-Obesity Effects of Saponins from Platycodon grandiflorum in Hamsters Fed Atherogenic DietsJOURNAL OF FOOD SCIENCE, Issue 8 2008H.L. Zhao ABSTRACT:, Platycodins, a group of saponin glycosides from Platycodon grandiflorum, are believed to possess anti-obesity and cholesterol-lowering properties. The aim of the present study was to investigate whether dietary platycodins affect plasma, hepatic, or fecal cholesterol concentrations, as well as cholesterol absorption and fractional synthesis rates in a dose-dependent manner. Golden Syrian hamsters (n= 45) were fed atherogenic (0.25% cholesterol) diets enriched with platycodins in the forms of either aqueous extracts (containing 0.3% to 0.5% of platycodins of diet mass) or crude saponins fractions (containing 0.9% to 1.0% of platycodins of diet mass) for 28 d. {3, 4},13C-cholesterol and 2H2O tracers were administered on days 26 and 28 to assess cholesterol absorption and biosynthesis, respectively. After platycodin intervention, total cholesterol concentrations in plasma and liver were reduced (P < 0.05) by 13% to 28% and 41% to 79%, respectively, whereas cholesterol concentrations in feces were increased (P < 0.05) up to 2.5-fold compared to controls. Platycodin feeding increased (P < 0.001) cholesterol absorption up to 60%, but not cholesterol synthesis. These results suggest that platycodin-enriched diets can lower circulating and whole body cholesterol contents, and thus reduce the risk of cardiovascular diseases through mechanisms independent from cholesterol absorption or synthesis. [source] |