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Inflammatory Factors (inflammatory + factor)
Selected AbstractsPolymorphism in the promoter region of the gene encoding human allograft inflammatory factor-1INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4 2001D. M. Turner Summary We have identified a new single nucleotide polymorphism within the promoter region of the human allograft inflammatory factor (AIF-1) gene. The polymorphism, defined by Genbank accession number AF097515, was characterized as a C/T single base pair substitution at position ,932. The T allele is associated with both HLA-DR2 and HLA-B7. Also, this allele creates the consensus binding site for the E-box that has high affinity for the basic helix-loop-helix (bHLH) family of transcription factors. [source] Thiazolidinediones as anti-inflammatory and anti-atherogenic agentsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2008Antonio Ceriello Abstract In the last few years, there has been increasing focus on the impact of interventions on cardiovascular outcomes in patients with type 2 diabetes. Insulin resistance and hyperglycaemia often co-exist with a cluster of risk factors for coronary artery disease, but the underlying mechanisms leading to the development of such vascular complications are complex. The over-production of free radicals in patients suffering from diabetes results in a state of oxidative stress, which leads to endothelial dysfunction and a greater risk of atherosclerosis. Moreover, inflammatory factors which play a critical role in atherothrombosis and plaque rupture are often found to be at elevated levels in this patient population. Thiazolidinediones (TZDs) are now routinely used to manage glucose levels, and have been suggested to influence other cardiovascular risk factors and therefore the pathways leading to macrovascular events. Consequently, recent studies have investigated the anti-inflammatory and anti-atherogenic properties of TZDs. The data available up to the present time, in the context of the emerging cardiovascular outcome profiles of rosiglitazone and pioglitazone, will be discussed here. Copyright © 2007 John Wiley & Sons, Ltd. [source] Lack of association between the G-2548A polymorphism of the leptin gene and psoriasis in a Turkish populationINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2007Nurten Kara PhD Background,, Psoriasis is a multifactorial disease in which genetic and inflammatory factors play important roles. Leptin is classified as a cytokine and plays an important role in the regulation of the T-helper response. A common polymorphism in the promoter of the human leptin gene (G-2548A) may have a role in the pathogenesis of psoriasis. Aim, To investigate the association between psoriasis and leptin gene polymorphism (G-2548A). Methods, The study involved 109 patients with psoriasis and 125 healthy controls. Analyses of G-2548A polymorphism of the leptin gene were made by the polymerase chain reaction-restriction fragment length polymorphism technique. The genotypes (GG, GA, and AA of leptin gene G-2548A) and alleles (G and A) were scored and the frequencies were estimated. The frequencies of alleles and genotypes in patients and controls were compared. The relationship between leptin gene polymorphism and the clinical features of the patients was analyzed. Results, Both genotype [odds ratio (OR), 0.921; 95% confidence interval (CI), 0.501,1.694; P = 0.792] and allele (OR, 0.864; 95% CI, 0.600,1.242; P = 0.429) frequencies were not significantly different between patient and control groups. In addition, there was no significant association between genotype and allele frequencies and the clinical characteristics of psoriasis. Conclusion, In this case,control study, no evidence of association between the G-2548A variant of the leptin gene and psoriasis was found. [source] Kidney Function as a Predictor of Loss of Lean Mass in Older Adults: Health, Aging and Body Composition StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2007Linda F. Fried MD OBJECTIVES: To assess the association between kidney function and change in body composition in older individuals. DESIGN: Prospective cohort study. SETTING: Two sites, Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Three thousand twenty-six well-functioning, participants aged 70 to 79 in the Health, Aging and Body Composition Study. MEASUREMENTS: Body composition (bone-free lean mass and fat mass) was measured using dual x-ray absorptiometry annually for 4 years. Kidney function was measured at baseline according to serum creatinine (SCr). Comorbidity and inflammatory markers were evaluated as covariates in mixed-model, repeated-measures analysis. RESULTS: High SCr was associated with loss of lean mass in men but not women, with a stronger relationship in black men (P=.02 for difference between slopes for white and black men). In white men, after adjustment for age and comorbidity, higher SCr remained associated with loss of lean mass (,0.07±0.03 kg/y greater loss per 0.4 mg/dL (1 standard deviation (SD)), P=.009) but was attenuated after adjustment for inflammatory factors (,0.05±0.03 kg/y greater loss per SD, P=.10). In black men, the relationship between SCr and loss of lean mass (,0.19±0.04 kg/y per SD, P<.001) persisted after adjustment for inflammation and overall weight change. CONCLUSION: Impaired kidney function may contribute to loss of lean mass in older men. Inflammation appeared to mediate the relationship in white but not black men. Future studies should strive to elucidate mechanisms linking kidney disease and muscle loss and identify treatments to minimize loss of lean mass and its functional consequences. [source] Downregulation of a rheumatoid arthritis-related antigen (RA-A47) by ra-a47 antisense oligonucleotides induces inflammatory factors in chondrocytesJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2003Takako Hattori Previously we have shown that the expression of RA-A47 (rheumatoid arthritis-related antigen) which is identical to HSP47, a collagen-binding chaperon, is downregulated in chondrocytes by tumor necrosis factor , (TNF,). RA-A47 was also found on the surface of chondrocytes where it is recognized as an antigen in the serum of rheumatoid arthritis (RA) patients. Its translocation to the cell surface from endoplasmic reticulum membrane where it is normally located was also enhanced by TNF,. To understand the significance of RA-A47 downregulation in chondrocytes independent from other effects of TNF,, we used an antisense oligonucleotide approach and investigated the effect of this treatment on the expression of molecules related to matrix degradation and production of growth factors for chondrocytic, endothelial, and synovial cells. Here we show that treatment of rabbit chondrocyes and human chondrosarcoma cells HCS-2/8 by ra-a47 antisense S -oligonucleotides significantly reduced the expression of ra-a47 both at mRNA and protein level. Interestingly, this TNF,-independent RA-A47 downregulation was associated with a strong induction of matrix metalloproteinase (MMP)-9 mRNA and inducible NO synthase (iNOS) mRNA. The induction of active-type MMP-9 was further detected by gelatin zymography. Under the same conditions, the release of basic fibroblast growth factor (bFGF) and connective tissue growth factor (CTGF) from HCS-2/8 cells into the conditioned medium (CM) was strongly enhanced. These effects were not a result of TNF, upregulation, since the ra-a47 antisense oligonucleotide treatment did not enhance TNF, synthesis. These observations indicate that downregulation of RA-A47 induces TNF,-independent cartilage-degrading pathways involving iNOS and MMP-9. Furthermore, the stimulation of bFGF and CTGF release from chondrocytes may stimulate the proliferation of adjacent endothelial and/or synovial cells. J. Cell. Physiol. 197: 94,102, 2003© 2003 Wiley-Liss, Inc. [source] Effects of statins on microgliaJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005Catharina Lindberg Abstract High serum cholesterol level has been shown as one of the risk factors for Alzheimer's disease (AD), and epidemiological studies indicate that treatment with cholesterol-lowering substances, statins, may provide protection against AD. An acute-phase reaction and inflammation, with increased levels of proinflammatory cytokines, are well known in the AD brain. Notably, there is evidence for antiinflammatory activities of statins, such as reduction in proinflammatory cytokines. Consequently, it is of interest to analyze the effects of statins on microglia, the main source of inflammatory factors in the brain, such as in AD. The aims of this study were to determine the effects of statins (atorvastatin and simvastatin) on microglial cells with regard to the secretion of the inflammatory cytokine interleukin-6 (IL-6) and cell viability after activation of the cells with bacterial lipopolysaccharides (LPS) or ,-amyloid1,40 (A,1,40) and in unstimulated cells. Cells of the human microglial cell line CHME-3 and primary cultures of rat neonatal cortical microglia were used. Incubation with LPS or A,1,40 induced secretion of IL-6, and A,1,40, but not LPS, reduced cell viability. Both atorvastatin and simvastatin reduced the basal secretion of IL-6 and the cell viability of the microglia, but only atorvastatin reduced LPS- and A,1,40 -induced IL-6 secretion. Both statins potentiated the A,1,40 -induced reduction in cell viability. The data indicate the importance of also considering the microglial responses to statins in evaluation of their effects in AD and other neurodegenerative disorders with an inflammatory component. © 2005 Wiley-Liss, Inc. [source] Neonatal C-reactive protein value in prediction of Outcome of Preterm Premature Rupture of Membranes: Comparison of Singleton and Twin PregnanciesJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4 2009Simin Taghavi Abstract Aim:, The clinical importance of preterm premature rupture of the membranes (PPROM) is its relationship to maternal and neonatal mortality and morbidity, especially in twin pregnancies. The aim of this study was to determine and compare the role of inflammatory factors as predictors of the PPROM outcome between singleton and twin pregnancies. Methods:, The medical records of 22 twins delivered between 28 and 34 weeks and complicated by PPROM were reviewed at the Al-Zahra Hospital in Tabriz, Iran. Also among singletons, 55 cases of matched gestational age were randomly selected as a control group. Three laboratory indices of neonatal white blood cell (WBC) count and C-reactive protein (CRP) in the two groups were measured immediately after delivery and the effects of two factors on neonatal outcome were assessed. Results:, In singletons, there was adverse relationship between the mean of WBC count and duration of latency (P = 0.007). Also, a positive relationship between the means of ventilation time and WBC count in second twins was found (P = 0.034). Positive CRP was the main predictor of neonatal intensive care unit admission in both singletons (odds ratio: 4.929, P = 0.042) and first twins (odds ratio: 9.000, P = 0.005). However, positive CRP did not influence the existence of metabolic acidosis or duration of latency in either of the two groups. Conclusion:, Neonatal WBC count was a predictor for the duration of latency in singletons and for ventilation time in twins. Positive neonatal CRP was an important factor for the prediction of neonatal intensive care unit admission in both types of pregnancy; its role in twins is clearer than in singletons. [source] Melatonin decreases TLR3-mediated inflammatory factor expression via inhibition of NF-,B activation in respiratory syncytial virus-infected RAW264.7 macrophagesJOURNAL OF PINEAL RESEARCH, Issue 1 2008Sheng-Hai Huang Abstract:, Double-stranded (ds) RNA has been identified as a ligand for Toll-like receptor 3 (TLR3). Respiratory syncytial virus (RSV), a single-stranded RNA virus and a major respiratory pathogen and pneumovirus in human infants pathogenesis of which relies on early inflammatory and immune events of the host in response to RSV, could be recognized by TLR3 sensing viral dsRNA produced during replication. The downstream signaling pathway from TLR3 leads to activation of IFN regulatory factor (IRF)-3 and/or NF-,B and subsequent expression of numerous proinflammatory factors. Melatonin (MT) is an effective regulator of the immune system. To determine the molecular mechanisms responsible for the suppressive effect of MT on RSV infection, we analyzed signaling molecules involved in the TLR3-mediated activation of inflammatory factors in macrophages infected with RSV and the modulatory role of MT on these mediators. We report that RSV infection of RAW264.7 macrophages time-dependently stimulate the rapid activation of TLR3 and NF-,B, as well as subsequent NF-,B-dependent gene expression such as those encoding TNF-, and inducible nitric oxide synthase. Moreover, we demonstrate that MT decreased TLR3-mediated downstream gene expression in RSV-infected macrophages in a dose- and time-dependent manner, and that MT inhibition of NF-,B activity seemed to be the key event required to explain the reduction in inflammatory gene expression caused by MT. But MT did not influence TLR3 at either the protein or mRNA level or MyD88 transcription. These results could be related to the beneficial immunoregulatory role of MT in RSV-infected macrophages and address the possible therapeutic potential of this indoleamine in human RSV diseases. [source] Frequency of Fish Consumption, Retinal Microvascular Signs and Vascular MortalityMICROCIRCULATION, Issue 1 2008Shweta Kaushik BMed (Hons) ABSTRACT Objective: Fish consumption has established cardiovascular and cerebrovascular benefits, but its effects on microvascular structure have not been examined in population-based studies. We investigated this association, in relation to vascular mortality in an Australian cohort (1992,2004). Methods: Of 3654 participants aged 49+ years, 2683 (73%) with available data were included. Retinal arteriolar and venular diameters were measured, and signs of arterio-venous nicking and retinopathy were assessed from digital retinal images. Fish consumption was evaluated using a food frequency questionnaire. Results: Both wider mean arteriolar diameter (p = 0.002) and narrower venular diameter (p = 0.02) were associated with increasing frequency of consuming any or oily fish, after adjusting for cardiovascular risk factors, diet, inflammatory factors and socioeconomic status. This association was mainly present in persons with hypertension. Greater frequency of fish consumption was associated with a reduced prevalence of arterio-venous nicking and a borderline significant trend for reduced retinopathy prevalence. Ten year stroke-related mortality was significantly lower in persons consuming fish at least once per week compared to less frequent consumption (hazard ratio 0.57, 95% CI: 0.35 to 0.93). Conclusions: Recent evidence shows that narrower arterioles and wider venules may predict vascular events. Our new findings suggest that the vascular protective effects of consuming fish could act, in part, by preventing pathological microvasculature change. [source] A histopathological and lectin-histochemical study of the lining epithelium in postoperative maxillary cystsORAL DISEASES, Issue 5 2002M Maruyama OBJECTIVE:,Histopathological and lectin-histochemical characteristics were studied in the lining epithelium of postoperative maxillary cysts (POMC). MATERIALS AND METHODS:,Histological (HE, PAS, AB), immunohistochemical (CD3 and L26) and lectin (wheat germ agglutinin, WGA; Ulex europaeus agglutinin I, UEA-I; concanavalin A, ConA) stainings were performed in the 360 POMC specimens. The number of goblet cells and inflammatory cells was counted and statistically analyzed. RESULTS:,The lining epithelium was classified into three types based on histopathological characteristics; pseudostratified ciliated epithelium (pSCE), transitional epithelium (TE) and stratified squamous epithelium (SSE). Local infiltration of inflammatory cells into the cyst wall was associated with an increased number of goblet cells in the lining epithelium. The observed association between the infiltration of inflammatory cells and an increase in the number of goblet cells was statistically significant in groups with lining pSCE and TE. Glycoconjugate histochemical analysis revealed that the surfaces of the lining epithelium with squamous metaplasia showed an increased degree of staining reactivity with UEA-I, whereas the staining reactivity with ConA was reduced. Goblet cells were able to be stained with WGA and UEA-I, but showed extremely low reactivity with ConA. CONCLUSION:,Changes in the glycoconjugate expression of the metaplastic lining epithelium and goblet cell development play an important role in the local defense mechanisms against inflammatory factors in POMC. [source] Ghrelin and leptin modulate immunity and liver function in overweight childrenPEDIATRICS INTERNATIONAL, Issue 1 2009Yuki Okamatsu Abstract Background:, The rising prevalence of obesity represents a growing worldwide public health problem. Interactions of adipocytokines and low-grade systemic inflammation presently are considered important in the development of obesity, as well as associated chronic disease including bronchial asthma, obesity-related liver disease and type 2 diabetes mellitus. The purpose of the present study was to investigate metabolic, hormonal, immunologic and inflammatory factors in overweight children and to further clarify possible immunomodulatory effects of obesity-related hormones and cytokines. Methods:, Forty-nine prepubertal overweight children and 49 age-matched controls of normal weight without underlying disease were enrolled. Levels of plasma ghrelin and serum leptin, cytokines (interleukin [IL]-4, IL-10, IL-12, 1L-13), C-reactive protein, immunoglobulin, and insulin were measured, and liver function tests were done to better understand their status in the setting of obesity. Results:, Overweight subjects had significantly higher measures of adiposity (body mass indexI, % body fat) and had significantly higher serum levels of IgG, IgA and IgE than non-obese children (P = 0.038, 0.0043, 0.0034, respectively); the opposite was true for IgM (P = 0.025). The incidence of presumed non-alcoholic fatty liver disease was 28.6% in overweight children. In overweight children, serum leptin levels were associated with liver function index (aspartate aminotransferase/alanine aminotransferase ratio) and serum insulin levels. Some elevated immunoglobulin levels significantly correlated with plasma ghrelin levels and liver function index. Conclusions:, It is possible that appetite-regulating hormones modulate both humoral immunity and liver function. Further studies with a larger number of subjects are needed to clarify the precise mechanisms of this association. [source] Control of Dkk-1 ameliorates chondrocyte apoptosis, cartilage destruction, and subchondral bone deterioration in osteoarthritic kneesARTHRITIS & RHEUMATISM, Issue 5 2010Lin-Hsiu Weng Objective Perturbation of Wnt signaling components reportedly regulates chondrocyte fate and joint disorders. The Wnt inhibitor Dkk-1 mediates remodeling of various tissue types. We undertook this study to examine whether control of Dkk-1 expression prevents joint deterioration in osteoarthritic (OA) knees. Methods Anterior cruciate ligament transection,and collagenase-induced OA in rat knees was treated with end-capped phosphorothioate Dkk-1 antisense oligonucleotide (Dkk-1,AS). Articular cartilage destruction, cartilage degradation markers, bone mineral density (BMD), and subchondral trabecular bone volume of injured knee joints were measured using Mankin scoring, enzyme-linked immunosorbent assay, dual x-ray absorptiometry, and histomorphometry. Dkk-1,responsive molecule expression and apoptotic cells in knee tissue were detected by quantitative reverse transcriptase,polymerase chain reaction, immunoblotting, and TUNEL staining. Results Up-regulated Dkk-1 expression was associated with increased Mankin score and with increased serum levels of cartilage oligomeric matrix protein and C-telopeptide of type II collagen (CTX-II) during OA development. Dkk-1,AS treatment alleviated OA-associated increases in Dkk-1 expression, Mankin score, cartilage fibrillation, and serum cartilage degradation markers. Dkk-1,AS also alleviated epiphyseal BMD loss and subchondral bone exposure associated with altered serum levels of osteocalcin and CTX-I. The treatment abrogated chondrocyte/osteoblast apoptosis and subchondral trabecular bone remodeling in OA. Dkk-1 knockdown increased levels of nuclear ,-catenin and phosphorylated Ser473 -Akt but attenuated expression of inflammatory factors (Toll-like receptor 4 [TLR-4], TLR-9, interleukin-1,, and tumor necrosis factor ,), the apoptosis regulator Bax, matrix metalloproteinase 3, and RANKL in OA knee joints. Conclusion Interference with the cartilage- and bone-deleterious actions of Dkk-1 provides therapeutic potential for alleviating cartilage destruction and subchondral bone damage in OA knee joints. [source] Review article: Is obesity an inflammatory illness?BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2006Role of low-grade inflammation, macrophage infiltration in human white adipose tissue There are at least two scientific evidences of human obesity as a chronic inflammatory illness: first, the well-described moderate increase of inflammatory factors in the circulation in obese subjects, and second, the recent identification of macrophage cells infiltrating the white adipose tissue (WAT). These observations led to a revision of the physiopathology of obesity and its co-morbidities. It has been suggested that the ,low-grade' inflammatory state associates with metabolic and cardiovascular complications of obesity. Weight loss is able to improve this inflammatory state by both significantly decreasing circulating inflammatory molecules and macrophage cell infiltration in WAT depots. However, the mechanisms of WAT macrophage recruitment into the adipose tissue and their role in obesity complications have not been defined. This review aims to point out the knowledge on inflammatory cytokines associated with obesity and focuses on macrophage infiltration in human WAT, discussing their recruitment and role. The interactions of macrophages with adipocytes will certainly be the subject of intense investigations in the future. [source] Daintain/AIF-1 promotes breast cancer proliferation via activation of the NF-,B/cyclin D1 pathway and facilitates tumor growthCANCER SCIENCE, Issue 5 2008Shou Liu Recent research indicates that inflammatory factors play important roles in the initiation and progression of cancers, including breast cancer. Daintain/allograft inflammatory factor-1 (AIF-1) is a crucial mediator in the inflammatory response, but it has not yet been reported whether daintain/AIF-1 is involved in the development of breast cancers. In this study, immunohistochemical analysis found strong positive expression of daintain/AIF-1 in breast ductal tumor epithelia, but only weakly positive or negative expression in the adjacent histologically normal ductal epithelia. Then, the effect of daintian/AIF-1 on the proliferation of the breast cancer cell line MDA-MB-231 was explored via transduction of the daintian/AIF-1 gene into the cells, and via inhibition of the expression of daintain/AIF-1 through short interference RNA. The results demonstrated that up-regulation and down-regulation of daintain/AIF-1 expressions promoted and inhibited the proliferation of MDA-MB-231, respectively. More interestingly, daintain/AIF-1 overexpression facilitated tumor growth in female nude mice. Furthermore, we found that daintain/AIF-1 overexpression up-regulated the expression of cyclin D1 and enhanced the transcriptional activity of nuclear factor-kappa B (NF-,B), a regulator of cyclin D1 expression. In contrast, the down-regulation of daintain/AIF-1 expression decreased cyclin D1 expression and inhibited the transcriptional activity of NF-,B. These results strongly suggest that daintain/AIF-1 can promote the growth of breast tumors via activating NF-,B signaling, which consequently up-regulates the expression of cyclin D1, implying that daintain/AIF-1 may be a novel target molecule for the prognosis and therapy of breast cancer. (Cancer Sci 2008; 99: 952,957) [source] Protective effects of lithium treatment for spatial memory deficits induced by tau hyperphosphorylation in splenectomized ratsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2010Wen-Fei Tan Summary 1. Postoperative cognitive dysfunction has become more prevalent in recent years. We used a splenectomized rat model with postoperative spatial learning and memory deficits to investigate the role of tau hyperphosphorylation and glycogen synthase kinase-3, (GSK-3,) within the hippocampus. 2. Cognitive function was assessed in a Y-maze 1 day before and 1, 3 and 7 days after surgery. We measured site-specific phosphorylation of hippocampal tau (Thr-205 and Ser-396), GSK-3, activity and expression of interleukin-1, (IL-1,), tumour necrosis factor-, (TNF-,) mRNA and protein as markers of inflammation. We also tested the effects of treatment with lithium chloride (LiCl), a GSK-3, inhibitor. 3. Splenectomy was associated with learning and memory impairment 3 days later, as well as a rapid and massive hyperphosphorylation of hippocampal tau at Thr-205 and Ser-396, activated GSK-3,, and increased IL-1, and TNF-, expression. LiCl completely restored tau hyperphosphorylation to control levels. 4. These data from the splenectomized rat model suggest that inflammatory factors affect tau pathology through the GSK-3, signalling pathway and that LiCl is a promising treatment for postoperative cognitive deficits. [source] HIGH GLUCOSE-INDUCED HUMAN UMBILICAL VEIN ENDOTHELIAL CELL HYPERPERMEABILITY IS DEPENDENT ON PROTEIN KINASE C ACTIVATION AND INDEPENDENT OF THE Ca2+,NITRIC OXIDE SIGNALLING PATHWAYCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2005Lei Dang SUMMARY 1.,Endothelial barrier dysfunction plays a pivotal role in the pathogenesis of diabetic vascular complications. The precise molecular mechanisms by which hyperglycaemia causes the increased permeability in endothelial cells are not yet well understood. In the present study, we investigated whether high concentrations of glucose induce endothelial permeability through the activation of protein kinase C (PKC) and/or the calcium,nitric oxide (NO) signalling pathway in human umbilical vein endothelial cells (HUVEC). 2.,Endothelial permeability was measured by albumin diffusion across endothelial monolayers under the stimuli of high glucose (HG; 20 mmol/L), 100 nmol/L phorbol-myristate-acetate (PMA) or 100 nmol/L histamine. The intracellular calcium concentration ([Ca2+]i) was detected in HUVEC using the fluorescent probe fura-2 AM. The effects of PKC inhibitors (LY379196 and hypocrellin A) and the NO synthase (NOS) inhibitor NG -monomethyl- l -arginine (l -NMMA) on endothelial permeability and [Ca2+]i were determined. 3.,High glucose and PMA increased endothelial permeability associated with decreased [Ca2+]i, whereas histamine triggered significant increases in endothelial permeability, accompanied by increases in [Ca2+]i in HUVEC. Hypocrellin A (HA) and LY379196 reversed both HG- and histamine-induced endothelial permeability. The NOS inhibitor l -NMMA only abolished histamine- and not HG-induced endothelial permeability. Neither LY379196, HA nor l -NMMA had any significant effects on alterations in [Ca2+]i caused by HG and histamine. 4.,These results indicate that increased endothelial permeability in HUVEC induced by HG is dependent on PKC activity and is independent of the [Ca2+]i,NO pathway. Increased endothelial permeability due to other inflammatory factors, such as histamine, may also be mediated by the PKC pathway. Thus, PKC inhibitors would be a potential therapeutic approach to endothelial dysfunction induced by hyperglycaemia, as well as other inflammatory factors, in diabetes. [source] Effects of TNF-alpha antagonism on E-selectin in obese subjects with metabolic dysregulationCLINICAL ENDOCRINOLOGY, Issue 1 2010Markella V. Zanni Summary Objective, Endothelial adhesion molecules like E-selectin play an important role in leukocyte recruitment and development of atherosclerotic plaque. E-selectin is increased in obesity, yet little is known regarding the specific factors contributing to elevated E-selectin in obesity and whether tumour necrosis factor alpha (TNF-alpha) increases E-selectin in vivo in this population. The objectives of this study were to: (1) determine the body composition, metabolic and inflammatory factors associated with increased E-selectin and (2) determine the role of TNF-alpha in the physiological regulation of E-selectin by antagonism of TNF-alpha with etanercept among obese subjects. Methods, E-selectin levels, body composition, metabolic parameters and inflammatory cytokines were assessed in 51 obese subjects and 37 non-obese healthy controls. Obese subjects were randomized to etanercept 50 mg weekly or placebo for 4 weeks. Changes in E-selectin were compared between treatment groups. Results, Obese subjects had higher E-selectin than non-obese controls (47·4 [32·7,58·8] vs. 27·2 [20·3,42·1] ng/ml, obese vs. non-obese, P < 0·0001). E-selectin was significantly associated with multiple body composition measures and metabolic parameters, along with specific measures of TNF-alpha activation, including soluble tumour necrosis factor receptors 1 (P = 0·03) and 2 (P = 0·02). In multivariate modelling, visceral adipose tissue, but not other measures of body composition, remained significantly associated with E-selectin. Among obese subjects, treatment with etanercept significantly decreased E-selectin (,5·7 ± 8·7 vs. 0·5 ± 6·0 ng/ml, etanercept vs. placebo, P = 0·005). Conclusions, E-selectin is increased in obesity, in relationship to increased visceral adiposity and markers of TNF-alpha activation. TNF-alpha antagonism with etanercept reduces E-selectin in obese subjects, providing evidence that the systemic circulatory release of E-selectin is regulated at least in part by TNF-alpha in obesity. [source] Inflammatory mediators in perinatal asphyxia and infectionACTA PAEDIATRICA, Issue 2002M Xanthou Aim: To determine serum levels of interleukin-6 (IL-6), IL-1,, tumor necrosis factor-, (TNF-,), soluble intercellular adhesion molecule-1 (sICAM-1) and C-reactive protein (CRP) in asphyxiated neonates and compare these inflammatory factors with those found in neonates with perinatal infection. Methods: 88 neonates were studied, of whom 36 were asphyxiated, 18 were infected and the remaining 34 were controls. Peripheral blood samples were obtained on the 1st, 3rd and 5th postnatal days. Results: Cytokines IL-6 and IL-1, as well as sICAM-1 serum levels did not differ between asphyxiated and infected neonates; however, at most time periods, their values were significantly higher than controls. TNF-, was similar in the three groups of neonates. CRP serum values were significantly higher in the infected neonates than in the asphyxiated or control subjects. Among the 54 asphyxiated and infected neonates, 15 were considered as severe cases and 39 as mild. The severe cases, at most time periods, had significantly higher IL-6, IL-1, and sICAM-1 levels compared with the mild ones. Through receiver operating characteristic curves the cut-off points, sensitivities, and specificities for distinguishing neonates at risk or at high risk for brain damage were established. Conclusion: Similar increases in serum levels of IL-6, IL-1, and sICAM-1 were found in perinatally asphyxiated and infected neonates. As these increases correlated with the severity of the perinatal insults, neonates at high risk for brain damage might be detected. [source] | ||||||||||||||||||||||