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Beneficial Role (beneficial + role)
Selected AbstractsMetabolic memory in diabetes,focus on insulinDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2005Derek LeRoith Abstract Large-scale clinical trials have demonstrated that metabolic control achieved early in the course of diabetes substantially reduces development and progression of diabetes and the associated microvascular complications. Additionally, prospective observational studies have demonstrated that atherogenic and inflammatory mediators are elevated even prior to the onset of diabetes and significantly contribute to subsequent development of macrovascular complications. Collectively, these data suggest that metabolic memories are stored early in the course of diabetes. We believe that insulin suppresses inflammation and also suppresses glucotoxicity and lipotoxicity (and the consequences thereof, such as the formation of advanced glycation end products and epigenetic phenomena), and thus has a pivotal and beneficial role. Comprehensive metabolic control, especially when instituted early, may alter the natural history of diabetic complications by affecting this metabolic memory. Thus, our overall goal is to understand in more detail the molecular mechanisms involved in these changes, thereby affording us opportunities to reduce the long-term effects of diabetes. Copyright © 2005 John Wiley & Sons, Ltd. [source] Role of Parasternal Data Acquisition During Contrast Enhanced Real-Time Three-Dimensional EchocardiographyECHOCARDIOGRAPHY, Issue 10 2007Attila Nemes M.D., Ph.D. Background: Recent technical developments have resulted in high-resolution real time three-dimensional echocardiography (RT3DE). The purpose of this study was to investigate the beneficial role of parasternal-acquired images in addition to apical-acquired images during contrast stress RT3DE. Methods: The study comprised 30 consecutive patients (52 ± 11 years, 18 males) with chest pain referred for routine stress testing. The contrast RT3DE images were acquired from the apical and parasternal window with a Sonos 7500 echo system attached to a X4 matrix array transducer. Results: From the apical and parasternal acquisition, 464 segments (91%) and 267 segments (52%) could be analyzed, respectively (P < 0.001). From the apical window, more basal segments were not analyzable (22 of 180, 12% vs. 24 of 330, 7%; P = 0.06). From the parasternal window, more apical segments were not analyzable (117 of 150, 78% vs. 126 of 360, 35%; P < 0.01). The mean image quality index of the 464 analyzable segments from the apical-acquired images was 2.43. Fourteen of 180 basal segments (8%), 12 of 180 midventricular segments (7%) and 2 of 150 apical segment (1%) were only available with parasternal data acquisition. In addition to these 28 segments, 79 segments (15%) already visualized from the apical window improved in quality. The overall mean image quality index, now assessed from 492 (96%) of all segments, using both the apical and parasternal acquired data, improved to 2.74 (P < 0.05). Conclusions: Addition of parasternal to apical acquisition of contrast RT3DE data can decrease the number of nonvisualized segments and improve mean image quality. [source] MR1-restricted V,19i T cells , a second population recognizing lipid antigens?EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007Jens Schümann Abstract There is increasing evidence that T cells recognizing lipid antigens contribute to the immunological regulation of different disease conditions including autoimmunity. The best-known subset is CD1d-restricted lipid-reactive T cells characterized by the expression of an invariant TCR, chain. Much less is known about the biology of another invariant T cell subset, which is restricted to the MHC class I-like molecule MR1. A beneficial role of MR1-restricted T cells has been suggested in a mouse EAE model. However, the nature of antigens that can be presented by MR1 to this invariant T cell subset remained largely unclear. An article in this issue of the European Journal of Immunology presents strong indications that derivatives of ,-mannosyl ceramide (,-ManCer), i.e. glycolipids, can serve as ligands for MR1-restricted invariant T cells. In addition to that, the structure of the ,-ManCer sphingosine chain influences the Th1-Th2 polarization of the cytokine response. These important new findings will foster further research on the identity of physiological ligands for MR1-restricted T cells and on their relation with immunoregulation. See accompanying article: http://dx.doi.org/10.1002/eji.200636689 [source] Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system,HEPATOLOGY, Issue 6 2006Muriel Lavie Serum amyloid A (SAA) is an acute phase protein produced by the liver. SAA concentration increases markedly in the serum following inflammation and infection. Large increases in SAA concentration during the acute phase response suggest that SAA has a beneficial role in host defense. This study sought to determine the effect of SAA on hepatitis C virus (HCV) infectivity using retroviral particles pseudotyped with HCV envelope glycoproteins (HCVpp) and the recently developed cell culture system for HCV (HCVcc). SAA inhibited HCVpp and HCVcc infection in a dose-dependent manner by affecting an early step of the virus life cycle. Further characterization with HCVpp indicated that SAA blocks virus entry by interacting with the viral particle. In addition, the antiviral activity of SAA was strongly reduced when high-density lipoproteins (HDL) were coincubated with SAA. However, HDL had only a slight effect on the antiviral activity of SAA when HCVpp was first preincubated with SAA. Furthermore, analyses of SAA in sera of chronic HCV patients revealed the presence of variable levels of SAA with abnormally elevated concentrations in some cases. However, no obvious clinical correlation was found between SAA levels and HCV viral loads. In conclusion, our data demonstrate an antiviral activity for SAA and suggest a tight relationship between SAA and HDL in modulating HCV infectivity. (HEPATOLOGY 2006;44:1626,1634.) [source] Bezafibrate induces multidrug-resistance P-Glycoprotein 3 expression in cultured human hepatocytes and humanized livers of chimeric miceHEPATOLOGY RESEARCH, Issue 7 2007Junichi Shoda Aim and Methods: , A decreased function of multidrug-resistance 3 P-glycoprotein (MDR3), limiting the rate of biliary phospholipid secretion, predisposes individuals to cholestasis and/or cholangitis. Fibrates induce the expression of mdr2 (homolog of human MDR3) in rodents. To investigate the effects of bezafibrate (BF) on the expression levels of MDR3 in cultured human hepatocytes and human livers, the amount of protein and subcellular localization of MDR3 was assessed in HepG2 cells treated with BF and humanized livers of BF-treated chimeric mice. Results:, In HepG2 cells, while treatment with BF did not increase the protein levels of MDR3, the treatment caused a redistribution of MDR3 in the bile canaliculi. In humanized livers of chimeric mice, oral administration of BF induced a large increase in the protein amount of MDR3 and its redistribution in the bile canaliculi. Moreover, the modulatory effects of BF on key factors involved in hepatic cholesterol and bile acid metabolism in human subjects were traced in the humanized livers of BF-treated chimeric mice. Conclusion:, BF causes an induction of MDR3 expression in human livers. This provides a rationale for the beneficial role of BF in improving cholestasis and/or cholangitis associated with defective MDR3 expression and function in various types of cholestatic hepatobiliary diseases. [source] Fibre intake and renal cell carcinoma: A case-control study from ItalyINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Carlotta Galeone Abstract Only 2 previous studies, conducted in Australia, United States and northern Europe, considered the role of dietary fibre intake on renal cell carcinoma (RCC) risk, and both showed a modest, inverse association. Therefore, we investigated in depth the topic of fibres and RCC, using data from a multicenter case-control study conducted in Italy from 1992 to 2004, including 767 cases with incident, histologically confirmed RCC and 1,534 controls admitted to the same network of hospitals as cases with acute nonmalignant conditions. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained after allowance for major identified confounding factors, including total energy intake. The continuous OR for an increase in intake equal to the difference between the 80th and the 20th percentile were 0.94 (95% CI: 0.82,1.08) for total dietary fibre, 0.98 (95% CI: 0.85,1.13) for soluble noncellulose polysaccharides, 0.92 (95% CI: 0.80,1.05) for total insoluble fibre, 0.90 (95% CI: 0.78,1.04) for cellulose, 0.95 (95% CI: 0.84,1.06) for insoluble noncellulose polysaccharides and 1.06 (95% CI: 0.93,1.21) for lignin. With reference to the sources of fibre, we found an inverse association with vegetable fibre (OR = 0.84, 95% CI: 0.73,0.97), but no association with fruit (OR = 0.98, 95% CI: 0.86,1.12) and grain fibre (OR = 1.05, 95% CI: 0.95,1.15). The inverse association with vegetable fibre may reflect a real favorable effect, or be an indicator of a beneficial role of a diet rich in vegetable on RCC risk. © 2007 Wiley-Liss, Inc. [source] Antilisterial activity of lactic acid bacteria isolated from rigouta, a traditional Tunisian cheeseJOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2004T. Ghrairi Abstract Aims:, Screening for lactic acid bacteria (LAB) producing bacteriocins and other antimicrobial compounds is of a great significance for the dairy industry to improve food safety. Methods and Results:, Six-hundred strains of LAB isolated from ,rigouta', a Tunisian fermented cheese, were tested for antilisterial activity. Eight bacteriocinogenic strains were selected and analysed. Seven of these strains were identified as Lactococcus lactis and produced nisin Z as demonstrated by mass spectrometry analysis of the purified antibacterial compound. Polymerase chain reaction experiments using nisin gene-specific primers confirmed the presence of nisin operon. Plasmid profiles analysis suggests the presence of, at least, three different strains in this group. MMT05, the eighth strain of this antilisterial collection was identified, at molecular level, as Enterococcus faecalis. The purified bacteriocin produced by this strain showed a molecular mass of 10 201·33 ± 0·85 Da. This new member of class III bacteriocins was termed enterocin MMT05. Conclusions:, Seven lactococcal strains producing nisin Z were selected and could be useful as bio-preservative starter cultures. Additional experiments are needed to evaluate the promising strain MMT05 as bio-preservative as Enterococci could exert detrimental or beneficial role in foods. Significance and Impact of the Study:, Only a few antibacterial strains isolated from traditional African dairy products were described. The new eight strains described herein contribute to the knowledge of this poorly studied environment and constitute promising strains for fermented food safety. [source] Influence of cardiac-specific overexpression of insulin-like growth factor 1 on lifespan and aging-associated changes in cardiac intracellular Ca2+ homeostasis, protein damage and apoptotic protein expressionAGING CELL, Issue 6 2007Qun Li Summary A fall in circulating levels of cardiac survival factor insulin-like growth factor 1 (IGF-1) contributes to cardiac aging. To better understand the role of IGF-1 in cardiac aging, we examined the influence of cardiac IGF-1 overexpression on lifespan, cardiomyocyte intracellular Ca2+ homeostasis, protein damage, apoptosis and expression of pro- and anti-apoptotic proteins in young and old mice. Mouse survival rate was constructed by the Kaplan,Meier curve. Intracellular Ca2+ was evaluated by fura-2 fluorescence. Protein damage was determined by protein carbonyl formation. Apoptosis was assessed by caspase-8 expression, caspase-3 and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assay. Pro- and anti-apoptotic proteins including Bax, p53, pp53, Bcl2, Omi/HtrA2, apoptosis repressor with caspase recruitment domain (ARC) and X-linked inhibitor of apoptosis protein (XIAP) were assessed by Western blot. Aging decreased plasma in IGF-1 levels, elevated myocyte resting intracellular Ca2+ levels, reduced electrically stimulated rise in intracellular Ca2+ and delayed intracellular Ca2+ decay associated with enhanced protein carbonyl formation, caspase-8 expression and caspase-3 activity in FVB mice, all of which with the exception of elevated resting intracellular Ca2+ were attenuated by IGF-1. Aging up-regulated expression of Bax, Bcl2 and ARC, down-regulated XIAP expression and did not affect p53, pp53 and Omi/HtrA2. The IGF-1 transgene attenuated or nullified aging-induced changes in Bax, Bcl2 and XIAP. Our data suggest a beneficial role for IGF-1 in aging-induced survival, cardiac intracellular Ca2+ homeostasis, protein damage and apoptosis possibly related to pro- and anti-apoptotic proteins. [source] OPTIMIZATION OF ENZYMATIC SYNTHESIS OF ISOMALTO-OLIGOSACCHARIDES PRODUCTIONJOURNAL OF FOOD BIOCHEMISTRY, Issue 3 2009M.C. RABELO ABSTRACT Glucosyltransferases can be applied in the synthesis of prebiotic oligosaccharides. Enzymatic synthesis using acceptors can be used to obtain these carbohydrates. When maltose is the acceptor, oligosaccharides containing one maltose moiety and up to eight glucose units linked by ,-1,6-glycosidic bonds are obtained as the product of dextransucrase acceptor reaction. In this work, the enzymatic synthesis of isomalto-oligosaccharides using dextransucrase from Leuconostoc mesenteroides NRRL B-512F was optimized by response surface methodology. The effect of maltose and sucrose concentrations on the acceptor reaction was evaluated in a batch reactor system. Partially purified enzyme was used to reduce the enzyme purification cost. The results showed that high sucrose concentrations in conjunction with high maltose levels enhanced the isomalto-oligosaccharide synthesis. A productivity of 42.95 mmol/L.h of isomalto-oligosaccharides was obtained at the optimal operating condition (100 mmol/L of sucrose and 200 mmol/L of maltose). PRATICAL APPLICATIONS Oligosaccharides as prebiotic have a large application in food formulations, and their beneficial role in human health have been extensively studied. Although the acceptor mechanism of dextransucrase has already been extensively studied, an industrial process has not been developed yet for enzyme synthesis of isomalto-oligosaccharide. The process studied in this work allows the large-scale preparation of isomalto-oligosaccharide using partially purified enzyme. [source] Grape Polyphenols Inhibit Chronic Ethanol-Induced COX-2 mRNA Expression in Rat BrainALCOHOLISM, Issue 3 2002Agnes Simonyi Background: Chronic ethanol has been shown to increase oxidative stress leading to neurodegenerative changes in the brain. Oxidative stress may up-regulate extracellular signal regulated kinases (ERK1/2) and, subsequently, the arachidonic acid cascade mediated by phospholipase A2 (PLA2) and cyclooxygenase (COX-2). Our earlier study showed that grape polyphenols (GP) could ameliorate oxidative damage to synaptic membrane proteins due to chronic ethanol treatment. This study was aimed at examining the effects of GP on mRNA expression of ERK1/2, cytosolic PLA2 (cPLA2), and COX-2 in different brain regions after chronic ethanol treatment. Methods: Male Sprague-Dawley rats were fed a Lieber-DeCarli liquid diet with ethanol or isocaloric amount of maltose, with or without GP for 2 months. In situ hybridization was carried out using coronal brain sections through the hippocampus. Results: Quantitative in situ hybridization showed no changes in ERK1 and cPLA2 mRNA levels in cortical areas and hippocampus after ethanol and/or GP administration. However, a decrease in ERK2 and an increase in COX-2 mRNA level was found in the hippocampus of ethanol-treated animals. GP completely inhibited the increase in COX-2 due to ethanol treatment. Conclusion: Increase in COX-2 expression may be an underlying mechanism for the increase in oxidative stress induced by chronic ethanol administration. Dietary supplementation of GP may have a beneficial role in inhibiting certain alcohol effects. [source] Endocannabinoids and liver disease , reviewLIVER INTERNATIONAL, Issue 5 2005Ezra Gabbay Abstract: Aims: Endocannabinoids are endogenous compounds that bind to the same receptors as tetrahydrocannabinol, the active component in marijuana and hashish. They have been found to have many physiological and patho-physiological functions, including mood alteration, control of feeding and appetite, motor and co-ordination activities, analgesia, immune modulation and gut motility. In this review we aim to elucidate current knowledge as to their role in liver physiology and disease. Methods: The major findings published to date concerning endocannabinoids and liver disease are described, and their implications with regard to understanding disease mechanisms, and the development of new treatments is considered. Results: Recently, endocannabinoids have been implicated in the hemodynamic alterations occurring in cirrhosis. These changes appear to be mediated via specific cannabinoid receptors (CB1) on splanchnic and hepatic vascular endothelium. Plasma levels of endocannabinoids also seem to be elevated in hepatitis, and are involved in apoptosis of hepatocytes by a membrane mechanism not related to a specific receptor. Other studies suggest a beneficial role for cannabinoids in reducing the inflammation of experimental hepatitis. In an animal model of acute hepatic failure, both endocannabinoids and the antagonist to the CB1 receptor have been found to have a beneficial effect on neurological and cognitive function. Conclusions: Endocannabinoids appear to be involved in several aspects of acute and chronic liver disease, including vascular changes, modulation of inflammatory process and neurological function, Further research may provide new insights into the pathophysiology of liver disease, as well as a basis for novel treatment modalities. [source] Mediators of rat ischemic hepatic preconditioning after cold preservation identified by microarray analysisLIVER TRANSPLANTATION, Issue 11 2006Àurea Navarro-Sabaté Hepatic ischemia-reperfusion injury associated with liver transplantation is an as yet unresolved problem in clinical practice. Preconditioning protects the liver against the deleterious effects of ischemia, although the mechanism underlying this preconditioning is still unclear. To profile gene expression patterns involved in hepatic ischemic preconditioning, we analyzed the changes in gene expression in rat livers by DNA microarray analysis. Approximately 116 genes were found to have altered gene expression after 8 hours of cold ischemia. Moreover, the expression of 218 genes was modified by classic preconditioning followed by the same ischemia process. Given the importance of the effects of ischemic preconditioning (IP) in minimizing the liver damage induced by sustained ischemia before reperfusion, this study analyzed the putative genes involved in the beneficial role of IP in liver grafts undergoing cold ischemia before its implantation in the recipient (IP+I). Great differences were found in the gene expression pattern of ischemic preconditioning + long cold ischemia (IP+I) group when compared with the long cold ischemia alone condition (I), which could explain the protective regulatory mechanisms that take place after preconditioning. Twenty-six genes that were downregulated in cold ischemia were found upregulated after preconditioning preceding a long cold ischemia period. These would be genes activated or maintained by preconditioning. Heat shock protein genes and 3-hydroxy-3-methylglutaryl-coenzyme A reductase are among the most markedly induced transcripts. Liver Transpl. 12:1615,1625, 2006. © 2006 AASLD. [source] Latex-induced occupational asthma: time trend in incidence and relationship with hospital glove policiesALLERGY, Issue 3 2009O. Vandenplas Background:, Natural rubber latex (NRL) has become as a major cause of occupational asthma (OA) in workers using NRL gloves. Few population-based studies have assessed the impact of changes in the patterns of glove usage on the incidence of NRL-induced OA. Objective:, To characterize the time trends in incident cases of NRL-induced OA in Belgium and examine whether incidence rates were related to the types of gloves used in hospitals. Methods:, Incident cases of NRL-induced OA were identified through a retrospective review of all claims submitted to the Workers' Compensation Board up to December 2004. Based on the results of diagnostic procedures, the diagnosis of NRL-induced OA was categorized as definite, probable, unlikely, or indeterminate. The patterns of glove usage were characterized through a questionnaire survey of Belgian hospitals. Results:, A total of 298 claims for NRL-induced OA were identified, including 127 subjects with definite OA and 68 with probable OA. Categorized by the year of asthma onset, the incident cases of definite and probable NRL-induced OA markedly decreased from 1999 onwards. The use of powdered NRL gloves fell from 80.9% in 1989 to 17.9% in 2004. Powdered NRL gloves were predominantly substituted with NRL-free gloves, especially in the case of non-sterile procedures. Conclusion:, These national compensation-based data confirm that a persistent decline in the incidence of NRL-induced OA has occurred since late 1990s. This downward trend has temporally been associated with a decreasing usage of powdered NRL, further supporting a beneficial role of changes in glove policies. [source] Micronutrients and the Risk of Type 1 Diabetes: Vitamin D, Vitamin E, and NicotinamideNUTRITION REVIEWS, Issue 9 2004Elina Hypponen Ph.D., M.P.H., M.Sc. Evidence from animal experiments and human observational studies suggests that some dietary micronutrients may protect against the development of type 1 diabetes. The most promising data so far have been obtained for a beneficial role of vitamin D. Beneficial effects of vitamin E (or other antioxidants) in diabetes development remain hypothetical. Despite plausible theoretical background evidence from animal experiments and supportive data from pilot studies, randomized, controlled trials using nicotinamide have not provided any evidence for a beneficial effect. [source] Proanthocyanidin protects against cisplatin-induced nephrotoxicityPHYTOTHERAPY RESEARCH, Issue 12 2009Ahmed Amir Radwan Sayed Abstract Cisplatin (CP) [cis -diamminedichloroplatinum (II)] is one of the most widely therapeutic agents used for treating many types of cancer. At effective doses, CP causes nephrotoxicity which has been attributed to the induction of reactive oxygen species (ROS). In the present investigation proanthocyanidin (PA) was studied to demonstrate its therapeutic efficacy against CP-induced nephrotoxicity in mice. Cp treatment caused significant elevation of urea, creatinine and IL-6. In addition, CP enhanced malondialdehyde (MDA) levels and lowered the glutathione (GSH) content in kidney. On the other hand, superoxide dismutase (SOD) activity was decreased. These alterations were reversed by PA in a dose-dependent manner. These findings suggested a beneficial role of PA in attenuating CP-induced oxidative renal toxicity. Copyright © 2009 John Wiley & Sons, Ltd. [source] Systemic steroid reduces long-term hearing loss in experimental pneumococcal meningitis,THE LARYNGOSCOPE, Issue 9 2010Lise Worsøe MD Abstract Objectives/Hypothesis: Sensorineural hearing loss is a common complication of pneumococcal meningitis. Treatment with corticosteroids reduces inflammatory response and may thereby reduce hearing loss. However, both experimental studies and clinical trials investigating the effect of corticosteroids on hearing loss have generated conflicting results. The objective of the present study was to determine whether systemic steroid treatment had an effect on hearing loss and cochlear damage in a rat model of pneumococcal meningitis. Study Design: Controlled animal study of acute bacterial meningitis. Methods: Adult rats were randomly assigned to two experimental treatment groups: a group treated with systemic steroid (n = 13) and a control group treated with saline (n = 13). Treatment was initiated 21 hours after infection and repeated once a day for three days. Hearing loss and cochlear damage were assessed by distortion product otoacoustic emissions (DPOAE), auditory brainstem response (ABR) at 16 kHz, and spiral ganglion neuron density. Results: Fifty-six days after infection, steroid treatment significantly reduced hearing loss assessed by DPOAE (P < .05; Mann-Whitney) and showed a trend toward reducing loss of viable neurons in the spiral ganglion (P = .0513; Mann-Whitney). After pooling data from day 22 with data from day 56, we found that systemic steroid treatment significantly reduced loss of spiral ganglion neurons (P = .0098; Mann-Whitney test). Conclusions: Systemic steroid treatment reduces long-term hearing loss and loss of spiral ganglion neurons in experimental pneumococcal meningitis in adult rats. The findings support a beneficial role of anti-inflammatory agents in reducing hearing loss and cochlear damage in meningitis. Laryngoscope, 2010 [source] Effect of diets containing different levels of highly unsaturated fatty acids on physiological and immune responses in Pacific whiteleg shrimp Litopenaeus vannamei (Boone) exposed to handling stressAQUACULTURE RESEARCH, Issue 16 2009Laurence Mercier Abstract Juveniles fed a diet containing a low or a high level of highly unsaturated fatty acids (HUFA) for 38 days were exposed to handling stress. In a first experiment, stress was applied daily for 30 days, after which the physiological and immunological variables were measured, whereas in a second experiment, stress was applied once and samples were obtained 1 and 24 h after the stressor event. Shrimp that were stressed for 30 days showed significantly lower survival, final weight and feed consumption compared with unstressed shrimp. The concentration of the high-density lipoprotein ,-glucan-binding protein was significantly higher in shrimp fed the high-HUFA diet. The glucose concentration in the haemolymph was significantly higher in long-term stressed shrimp compared to controls. The lactate level in the haemolymph was significantly lower in shrimp fed the high-HUFA diet. Lactate and glucose in the haemolymph increased in the 1-h stressed shrimp, but returned to normal levels in 24-h stressed shrimp. A negative effect of repeated-handling stress applied for 30 days was mainly observed on biological performance, whereas the single-stressor event had a more pronounced effect on shrimp physiological and immune responses measured 1 and 24 h after the stressor. A beneficial role of enrichment with HUFA on tolerance to handling stress was observed on immune response capacity. [source] Inhibition of lymphangiogenesis and lymphatic drainage via vascular endothelial growth factor receptor 3 blockade increases the severity of inflammation in a mouse model of chronic inflammatory arthritisARTHRITIS & RHEUMATISM, Issue 9 2009Ruolin Guo Objective This study was undertaken to investigate the effect of lymphatic inhibition on joint and draining lymph node (LN) pathology during the course of arthritis progression in mice. Methods Tumor necrosis factor (TNF),transgenic mice were used as a model of chronic inflammatory arthritis. Mice were subjected to contrast-enhanced magnetic resonance imaging to obtain ankle and knee joint synovial volumes and draining popliteal LN volumes before and after 8 weeks of treatment with vascular endothelial growth factor receptor 3 (VEGFR-3) neutralizing antibody, VEGFR-2 neutralizing antibody, or isotype IgG. Animals were subjected to near-infrared lymphatic imaging to determine the effect of VEGFR-3 neutralization on lymph transport from paws to draining popliteal LNs. Histologic, immunohistochemical, and reverse transcriptase,polymerase chain reaction analyses were used to examine lymphatic vessel formation and the morphology of joints and popliteal LNs. Results Compared with IgG treatment, VEGFR-3 neutralizing antibody treatment significantly decreased the size of popliteal LNs, the number of lymphatic vessels in joints and popliteal LNs, lymphatic drainage from paws to popliteal LNs, and the number of VEGF-C,expressing CD11b+ myeloid cells in popliteal LNs. However, it increased the synovial volume and area of inflammation in ankle and knee joints. VEGFR-2 neutralizing antibody, in contrast, inhibited both lymphangiogenesis and joint inflammation. Conclusion These findings indicate that lymphangiogenesis and lymphatic drainage are reciprocally related to the severity of joint lesions during the development of chronic arthritis. Lymphatic drainage plays a beneficial role in controlling the progression of chronic inflammation. [source] Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the futureCANCER SCIENCE, Issue 2 2009Yoshinao Oda In the present paper, recent advances in the molecular pathology of soft tissue sarcomas (STS) and the implications for their prognostic value are reviewed, and the potential targets of molecular therapy are discussed. According to the molecular genetic aspect, STS are divided into two groups: chromosome translocation-associated sarcomas and sarcomas without specific translocation. In the former group, specific fusion transcripts, such as SS18,SSX, EWS,FLI1, and PAX3,FKHR, could be detected in synovial sarcoma, Ewing's sarcoma and primitive neuroectodermal tumor, and alveolar rhabdomyosarcoma, respectively. The direct or indirect interactions between these fusion transcripts and cell cycle regulators have been elucidated by several investigators. Therefore, these fusion transcripts are promising candidates as molecular targets. As evaluated in carcinomas, alterations of several tumor-suppressor genes and adhesion molecules and overexpression of growth factors and their receptors have been extensively assessed in STS. In mixed-type STS, epidermal growth factor receptor overexpression was associated with decreased overall survival, suggesting the beneficial role of epidermal growth factor receptor inhibitors in STS. In malignant rhabdoid tumor and epithelioid sarcoma, frequent alteration of the SMARCB1/INI1tumor-suppressor gene and the loss of its protein have been demonstrated, indicating that this molecule could be an effective target of these sarcomas. In sarcomas with epithelioid differentiation, such as synovial sarcoma and epithelioid sarcoma, overexpression of dysadherin, which downregulates E-cadherin expression, was a poor prognostic factor. In conclusion, further studies are necessary to search for effective and specific molecules for the inhibition of tumor growth in each type of STS, especially in sarcomas without specific translocation. (Cancer Sci 2009; 100: 200,208) [source] Antioxidants modulate the IL-6 induced inhibition of negative acute-phase protein secretion in HepG2 cellsCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2008Mohamed A. El-Saadany Abstract Despite increasing evidence on the potential of dietary antioxidants in modulating the etiology of certain chronic diseases such as cancer and cardiovascular diseases, little is known about their beneficial role in acute-phase responses and inflammatory diseases. From this viewpoint the aim of this study was to investigate the effect of selected dietary antioxidants in modulating the secretion of negative acute-phase proteins caused by interleukin-6 (IL-6) in HepG2 cells. Cells were first stimulated with a fixed dose of IL-6 for 24,h then incubated for a further 8,h with varying concentrations of eight antioxidants, ,-lipoic acid (LA), (,)-epicatechin (EC), (,)-epicatechin gallate (ECG), (,)-epigallocatechin (EGC), (,)-epigallocatechin gallate (EGCG), ,-tocopherol (TOC), ascorbic acid (AA) and N-acetylcysteine (NAC). The culture supernatants were assayed for transthyretin (TTR) and retinol binding protein (RBP) using ELISA. The data revealed that IL-6 significantly reduced TTR and RBP secretion compared with the basal production. All tested antioxidants attenuate the reduction in TTR and RPB levels. The strongest effects were achieved with the highest concentration of each antioxidant. The order of effect were LA,>,EGCG,>,ECG,>,TOC,>,EGC,>,EC,>,NAC,>,AA. In conclusion, these results provide evidence that the dietary antioxidants can play a fundamental role in inflammatory processes. Copyright © 2007 John Wiley & Sons, Ltd. [source] CD3 expression distinguishes two ,,T cell receptor subsets with different phenotype and effector function in tuberculous pleurisyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009N. Yokobori Summary Tuberculous pleurisy is a naturally occurring site of Mycobacterium tuberculosis (Mtb) infection. Herein, we describe the expression of activation, natural killer (NK) and cell migration markers, as well as effector functions from ,,T cells in peripheral blood (PB) and pleural effusion (PE) from tuberculosis patients (TB). We observed a decreased percentage of circulating ,,T from TB patients and differential expression of NK as well as of chemokine receptors on PB and PE. Two subsets of ,,T cells were differentiated by the CD3/,,T cell receptor (,,TCR) complex. The ,,TCRlow subset had a higher CD3 to TCR ratio and was enriched in V,2+ cells, whereas most V,1+ cells belonged to the ,,TCRhigh subset. In PB from TB, most ,,TCRhigh were CD45RA+CCR7 - and ,,TCRlow were CD45RA+/,CCR7+CXCR3+. In the pleural space the proportion of CD45RA - CCR7+CXCR3+ cells was higher. Neither spontaneous nor Mtb -induced interferon (IFN)-, production was observed in PB-,,T cells from TB; however, PE-,,T cells showed a strong response. Both PB- and PE-,, T cells expressed surface CD107a upon stimulation with Mtb. Notably, PE-,,TCRlow cells were the most potent effector cells. Thus, ,,T cells from PB would acquire a further activated phenotype within the site of Mtb infection and exert full effector functions. As ,,T cells produce IFN-, within the pleural space, they would be expected to play a beneficial role in tuberculous pleurisy by helping to maintain a T helper type 1 profile. [source] Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosisCLINICAL ENDOCRINOLOGY, Issue 1 2009Matthias J. Bahr Summary Objective, Patients with liver cirrhosis have a high incidence of insulin resistance and diabetes. This study was designed to determine circulating levels and hepatic production of retinol-binding protein 4 (RBP4) in relation to parameters of hepatic and systemic metabolism in patients with liver cirrhosis. Design and method, Circulating RBP4 levels were measured in 19 patients with liver cirrhosis at different clinical stages of the disease and in 20 age-, sex- and body mass index (BMI)-matched controls. Hepatic production rates of RBP4 and glucose were assessed by measuring the arterial hepatic venous concentration difference together with hepatic blood flow. Insulin resistance was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI) and the homeostasis model assessment of insulin resistance (HOMA-IR), energy expenditure by indirect calorimetry and body composition by bioelectrical impedance analysis (BIA). Results, Compared with controls, RBP4 levels in cirrhosis were decreased (8·1 ± 1·8 vs. 22·6 ± 2·4 mg/l, P < 0·001) due to decreased hepatic production (P < 0·05). RBP4 correlated with hepatic protein synthesis capacity (P < 0·01), but not with insulin resistance, energy expenditure, BMI or body fat mass. Plasma RBP4 correlated with hepatic glucose production (P < 0·05). Conclusions, These data demonstrate that RBP4 in cirrhosis (i) is decreased due to reduced hepatic production, (ii) is not associated with insulin resistance, and (iii) might have a beneficial role by decreasing hepatic glucose production and could thus also be regarded as a hepatokine. [source] Time- and dose-dependent mitogenic effect of basic fibroblast growth factor combined with different bone graft materials: an in vitro studyCLINICAL ORAL IMPLANTS RESEARCH, Issue 5 2006Xanthippi E. Dereka Abstract Objectives: In periodontal regeneration, the growth factor concentrations and the delivery system used are of great importance. In an attempt to assess the mitogenic effect of basic fibroblast growth factor (bFGF) on periodontal ligament (PDL) cells combined with different bone replacement materials, two allografts of cortical (DFDBA) and cancellous (DFBA) bone and an anorganic bovine material with a synthetic peptide (ABM P-15) were used. The purpose of this study was to evaluate the in vitro mitogenic effect of different doses of bFGF alone or in combination with DFDBA, DFBA and ABM P-15 on human PDL cells in a time-dependent mode. Material and methods: PDL cell cultures were derived from the mid-root of four maxillary premolars. Cells were grown and reached confluence. On day 2 of quiescence, new medium was added along with (1) 1, 5, 10 and 25 ng/ml of bFGF alone, (2) 10 mg of DFDBA, DFBA and ABM P-15 alone and (3) their combination. The mitogenic effect was determined at 24 and 48 h of culture by using a hemocytometer chamber. The cells were counted under a phase contrast microscope. Results: The results revealed that bFGF at the highest concentrations and after 48 h exerted a significant mitogenic effect on PDL cells, and also DFDBA and DFBA supported cell proliferation. Furthermore, DFDBA and DFBA enriched with bFGF had a significant mitogenic effect after 48 h of culture. ABM P-15 with 10 and 25 ng/ml of bFGF up-regulated PDL cell proliferation after 48 h of incubation. Conclusions: The findings of this study demonstrate the beneficial role of bFGF combined with DFDBA and DFBA as carriers in periodontal repair. [source] Sirt1's beneficial roles in neurodegenerative diseases , a chaperonin containing TCP-1 (CCT) connection?AGING CELL, Issue 5 2010Bin Qi Gan Summary Sir2/Sirt1 and its orthologues are known lifespan extension factors in several aging models from yeast to invertebrates. Sirt1 activation is also known to be beneficial and protective in both invertebrate and mammalian models of neurodegenerative disease. Sirt1's lifespan extension effect, as well as the beneficial outcome of its activation in models of aging-associated diseases, is often attributed to its ability to instill a gene expression profile that is pro-survival and anti-aging. A recent report from Nyström and colleagues showed that the yeast Sir2p affects the function of the polarisome in segregation and retrograde transport of damaged and aggregated proteins from the bud to the mother cell, thereby ensuring the generation of a ,rejuvenated' daughter cell. Interestingly, the role of Sir2p in this case involves deacetylation and activation of cytoplasmic chaperonin containing TCP-1 (CCT, or TriC), thereby enhancing actin folding and polymerization. In view of a previously documented role of CCT in modulating polyglutamine-containing protein aggregation and toxicity, we hypothesized that CCT deacetylation may also underlie Sirt1's beneficial effects in several neurodegenerative diseases precipitated by toxic aggregates. Other than alterations in gene expression profile, another major way whereby Sirt1 activation may counter neural aging could be to promote neuronal survival via prevention of toxic aggregate formation through CCT. [source] Potential roles of Alzheimer precursor protein A4 and ,-amyloid in survival and function of aged spinal motor neurons after axonal injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2003Yuanyun Xie Abstract To study the potential role of Alzheimer precursor protein A4 (APP) and ,-amyloid (A/,) on aging motor neuron survival, expression of APP, A/,, and choline acetyltransferase (ChaT) were investigated in aged rats after either distal axotomy or root avulsion injury. Approximately 45% in number of total aged spinal motor neuron were normally APP-positive. A/,-positive neurites were observed normally in the spinal ventral horn of aged rats. After distal axotomy, without apparent neurodegeneration such as cell loss and decreased ChaT-immunoreactivity, increased levels of APP expression were observed in the spinal cords of aged rats post-injury. In contrast, after avulsion, expression of APP and A/, were downregulated in the spinal ventral horn of aged rats, and marked loss of spinal motor neurons and downregulated ChaT expression were observed. Our data indicate that APP and A/, might play beneficial roles in neuronal survival of aged spinal motor neurons after axonal injury. © 2003 Wiley-Liss, Inc. [source] Effects of lutein and zeaxanthin on aspects of eye healthJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 1 2010Le Ma Abstract Lutein and zeaxanthin are members of the oxygenated carotenoids found particularly in egg yolks and dark-green leafy vegetables. A great deal of research has focused on their beneficial roles in eye health. The present article summarises the current literature related to the bioactivity of these carotenoids, emphasising their effects and possible mechanisms of action in relation to human eye health. Available evidence demonstrates that lutein and zeaxanthin are widely distributed in a number of body tissues and are uniquely concentrated in the retina and lens, indicating that each has a possible specific function in these two vital ocular tissues. Most of epidemiological studies and clinical trials support the notion that lutein and zeaxanthin have a potential role in the prevention and treatment of certain eye diseases such as age-related macular degeneration, cataract and retinitis pigmentosa. The biological mechanisms for the protective effects of these carotenoids may include powerful blue-light filtering activities and antioxidant properties. Although most studies point towards significant health benefits from lutein and zeaxanthin, further large-scale randomised supplementation trials are needed to define their effects on ocular function in health and disease. Copyright © 2009 Society of Chemical Industry [source] | |||||||||||||||||||||||||||||||