The glycoprotein Ib-IX-V complex contributes to tissue factor-independent thrombin generation by recombinant factor VIIa on the activated platelet surface

NARCIS (Netherlands)

Weeterings, Cees; de Groot, Philip G.; Adelmeijer, Jelle; Lisman, Ton

2008-01-01

Several lines of evidence suggest that recombinant factor VIIa (rFVIIa) is able to activate factor X on an activated platelet, in a tissue factor-independent manner. We hypothesized that, besides the anionic surface, a receptor on the activated platelet surface is involved in this process. Here, we

Model of a ternary complex between activated factor VII, tissue factor and factor IX.

Science.gov (United States)

Chen, Shu-wen W; Pellequer, Jean-Luc; Schved, Jean-François; Giansily-Blaizot, Muriel

2002-07-01

Upon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.

Gout: a review of non-modifiable and modifiable risk factors

Science.gov (United States)

MacFarlane, Lindsey A.; Kim, Seoyoung C.

2014-01-01

Gout is a common inflammatory arthritis triggered by the crystallization of uric acid within the joints. Gout affects millions worldwide and has an increasing prevalence. Recent research has been carried out to better qualify and quantify the risk factors predisposing individuals to gout. These can largely be broken into non-modifiable risk factors such as sex, age, race, and genetics, and modifiable risk factors such as diet and lifestyle. Increasing knowledge of factors predisposing certain individuals to gout could potentially lead to improved preventive practices. This review summarizes the non-modifiable and modifiable risk factors associated with development of gout. PMID:25437279

THE EFFECTS OF GENETICALLY MODIFIED MAIZE SILAGE ON THE CONTENTS OF FATTY ACIDS IN BODY TISSUES OF LAMBS

Directory of Open Access Journals (Sweden)

Ewa SIMINSKA

2013-03-01

Full Text Available The aim of this work was the evaluation of fatty acids contents in meat and selected offal in lambs fed a diet containing silage of whole plants of genetically modified maize (Bt MON 810 line. The material consisted of 14 Polish Merino lambs of mean start body weight 24 kg. There were two feeding groups selected of 7 lambs each. In the control group (K the lambs were fed isogenic maize silage, which in the second group (GMO was substituted with the modified maize silage (Bt MON 810 line. After 70 days of feeding (feed portions were standardised according to the DLG system the lambs were slaughtered and dissected. The results were evaluated statistically and the significance of differences was calculated with the two factor variation analysis (nutrition, tissue. Feeding genetically modified maize silage did not change, in a statistically significant way, the contents of any main fatty acids in the pool of all acids nor the contents of the totals and their proportions, while the factor causing clear differences was the tissue. Differences for the majority of the results were statistically significant. Statistically significant interactions noted (nutrition x tissue are probably due to different values of these traits in the analysed tissues.

Chronic intermittent hypoxia activates nuclear factor-κB in cardiovascular tissues in vivo

International Nuclear Information System (INIS)

Greenberg, Harly; Ye Xiaobing; Wilson, David; Htoo, Aung K.; Hendersen, Todd; Liu Shufang

2006-01-01

Obstructive sleep apnea (OSA) is an important risk factor for cardiovascular morbidity and mortality. The mechanisms through which OSA promotes the development of cardiovascular disease are poorly understood. In this study, we tested the hypotheses that chronic exposure to intermittent hypoxia and reoxygenation (CIH) is a major pathologic factor causing cardiovascular inflammation, and that CIH-induces cardiovascular inflammation and pathology by activating the NF-κB pathway. We demonstrated that exposure of mice to CIH activated NF-κB in cardiovascular tissues, and that OSA patients had markedly elevated monocyte NF-κB activity, which was significantly decreased when obstructive apneas and their resultant CIH were eliminated by nocturnal CPAP therapy. The elevated NF-κB activity induced by CIH is accompanied by and temporally correlated to the increased expression of iNOS protein, a putative and important NF-κB-dependent gene product. Thus, CIH-mediated NF-κB activation may be a molecular mechanism linking OSA and cardiovascular pathologies seen in OSA patients

A hypothesis: factor VII governs clot formation, tissue repair and apoptosis.

Science.gov (United States)

Coleman, Lewis S

2007-01-01

A hypothesis: thrombin is a "Universal Enzyme of Energy Transduction" that employs ATP energy in flowing blood to activate biochemical reactions and cell effects in both hemostasis and tissue repair. All cells possess PAR-1 (thrombin) receptors and are affected by thrombin elevations, and thrombin effects on individual cell types are determined by their unique complement of PAR-1 receptors. Disruption of the vascular endothelium (VE) activates a tissue repair mechanism (TRM) consisting of the VE, tissue factor (TF), and circulating Factors VII, IX and X that governs localized thrombin elevations to activate clot formation and cellular effects that repair tissue damage. The culmination of the repair process occurs with the restoration of the VE followed by declines in thrombin production that causes Apoptosis ("programmed cell death") in wound-healing fibroblasts, which functions as a mechanism to draw wound edges together. The location and magnitude of TRM activity governs the location and magnitude of Factor VIII activity and clot formation, but the large size of Factor VIII prevents it from penetrating the clot formed by its activity, so that its effects are self-limiting. Factors VII, IX and X function primarily as tissue repair enzymes, while Factor VIII and Factor XIII are the only serine protease enzymes in the "Coagulation Cascade" that are exclusively associated with hemostasis.

Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells

OpenAIRE

Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

2009-01-01

Background: Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian ca...

Influence factors of photocatalytic activity of the filter media modified by TiO2

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Shen Rongyan

2014-01-01

Full Text Available The gangue filter media was modified by the titanium dioxide (TiO2 through the liquid phase deposition method. Some influence factors of photocatalytic activity were investigated, including the mole ratio of initial solution, the water bath temperature, the deposition time, the calcination temperature, and the heat preservation time of calcination. The morphology of the film was examined by SEM, EDS, and crystallite structure by X-Ray Diffraction (XRD. The SEM, EDS, and XRD data showed that new TiO2 crystal was found in the modified filter media. And the specific surface area of the modified filter media greatly increased. By the orthogonal experiment, the optimum parameters of modification were (NH42TiF6:H3BO3=1:2, water bath temperature of 80ºC, deposition time of 5h, calcination temperature of 500ºC, and 1h heat preservation time of calcination. Under above conditions, the heavy nitrogen wastewater of 1589.94 mg/L COD and 18750 times chroma was treated by the modified filter media. After 1h catalytic reaction, the decolorization rate and COD removal rate reached 65.89% and 47.87%, respectively.

Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

Directory of Open Access Journals (Sweden)

Xiaolin He

Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

Management of excessive movable tissue: a modified impression technique.

Science.gov (United States)

Shum, Michael H C; Pow, Edmond H N

2014-08-01

Excessive movable tissue is a challenge in complete denture prosthetics. A modified impression technique is presented with polyvinyl siloxane impression material and a custom tray with relief areas and perforations in the area of the excessive movable tissue. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.

Science.gov (United States)

Mast, Alan E

2016-01-01

Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients. © 2015 American Heart Association, Inc.

Quantitative PET Imaging of Tissue Factor Expression Using 18F-labled Active Site Inhibited Factor VII

DEFF Research Database (Denmark)

Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E

2016-01-01

Tissue factor (TF) is up regulated in many solid tumors and its expression is linked to tumor angiogenesis, invasion, metastasis and prognosis. A non-invasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII (FVII) is the natural ligand to TF. Here we...... report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of FVII. METHODS: Active site inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4......-[(18)F]-fluorobenzoate ([(18)F]SFB) and purified. The corresponding product, [(18)F]FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small animal PET/CT imaging 1, 2 and 4 hours after injection. Ex vivo biodistribution was performed...

Connective tissue activation. XVII

International Nuclear Information System (INIS)

Weiss, J.J.; Donakowski, C.; Anderson, B.; Meyers, S.; Castor, C.W.

1980-01-01

The platelet-derived connective tissue activating peptide (CTAP-III) has been shown to be an important factor stimulating the metabolism and proliferation of human connective tissue cell strains, including synovial tissue cells. The quantities of CTAP-III affecting the cellular changes and the amounts in various biologic fluids and tissues are small. The objectives of this study were to develop a radioimmunoassay (RIA) for CTAP-III and to ascertain the specificities of the anti-CTAP-III sera reagents. The antisera were shown not to cross-react with a number of polypeptide hormones. However, two other platelet proteins β-thromboglobulin and low affinity platelet factor-4, competed equally as well as CTAP-III for anti-CTAP-III antibodies in the RIA system. Thus, the three platelet proteins are similar or identical with respect to those portions of the molecules constituting the reactive antigenic determinants. The levels of material in normal human platelet-free plasma that inhibited anti-CTAP-III- 125 I-CTAP-III complex formation were determined to be 34+-13 (S.D.) ng/ml. (Auth.)

Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1 in Human Macrophages

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G. Chinetti-Gbaguidi

2016-01-01

Full Text Available Tissue factor (TF is the initiator of the blood coagulation cascade after interaction with the activated factor VII (FVIIa. Moreover, the TF/FVIIa complex also activates intracellular signalling pathways leading to the production of inflammatory cytokines. The TF/FVIIa complex is inhibited by the tissue factor pathway inhibitor-1 (TFPI-1. Peroxisome proliferator-activated receptor gamma (PPARγ is a transcription factor that, together with PPARα and PPARβ/δ, controls macrophage functions. However, whether PPARγ activation modulates the expression of TFP1-1 in human macrophages is not known. Here we report that PPARγ activation increases the expression of TFPI-1 in human macrophages in vitro as well as in vivo in circulating peripheral blood mononuclear cells. The induction of TFPI-1 expression by PPARγ ligands, an effect shared by the activation of PPARα and PPARβ/δ, occurs also in proinflammatory M1 and in anti-inflammatory M2 polarized macrophages. As a functional consequence, treatment with PPARγ ligands significantly reduces the inflammatory response induced by FVIIa, as measured by variations in the IL-8, MMP-2, and MCP-1 expression. These data identify a novel role for PPARγ in the control of TF the pathway.

The importance of residues 195-206 of human blood clotting factor VII in the interaction of factor VII with tissue factor

International Nuclear Information System (INIS)

Wildgoose, P.; Kisiel, W.; Kazim, A.L.

1990-01-01

Previous studies indicated that human and bovine factor VII exhibit 71% amino acid sequence identity. In the present study, competition binding experiments revealed that the interaction of human factor VII with cell-surface human tissue factor was not inhibited by 100-fold molar excess of bovine factor VII. This finding indicated that bovine and human factor VII are not structurally homologous in the region(s) where human factor VII interacts with human tissue factor. On this premise, the authors synthesized three peptides corresponding to regions of human factor VII that exhibited marked structural dissimilarity to bovine factor VII; these regions of dissimilarity included residues 195-206, 263-274, and 314-326. Peptide 195-206 inhibited the interaction of factor VII with cell-surface tissue factor and the activation of factor X by a complex of factor VIIa and tissue factor half-maximally at concentrations of 1-2 mM. A structurally rearranged form of peptide 195-206 containing an aspartimide residue inhibited these reactions half-maximally at concentrations of 250-300 μM. In contrast, neither peptide 263-274 nor peptide 314-326, at 2 mM concentration, significantly affected either factor VIIa interaction with tissue factor or factor VIIa-mediated activation of factor X. The data provide presumptive evidence that residues 195-206 of human factor VII are involved in the interaction of human factor VII with the extracellular domain of human tissue factor apoprotein

Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

Science.gov (United States)

Ollivier, V; Bentolila, S; Chabbat, J; Hakim, J; de Prost, D

1998-04-15

The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

Modifiable Risk Factors for Lymphedema in Breast Cancer Survivors

National Research Council Canada - National Science Library

Rossing, Mary A; Malone, Kathleen E

2004-01-01

.... In this study, we will assess whether modifiable factors, including body weight, physical activity, smoking and breast reconstruction, influence risk of arm lymphedema among women treated for breast cancer...

Modifiable Risk Factors for Lymphedema in Breast Cancer Survivors

National Research Council Canada - National Science Library

Rossing, Mary

2003-01-01

.... In this study, we will assess whether modifiable factors, including body weight, physical activity, smoking and breast reconstruction, influence risk of arm Lymphedema among women treated for breast cancer...

Expression and localization of tissue factor pathway inhibitor-2 in normal and atherosclerotic human vessels

NARCIS (Netherlands)

Crawley, James T. B.; Goulding, David A.; Ferreira, Valérie; Severs, Nicholas J.; Lupu, Florea

2002-01-01

Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type, serine protease inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein, plasmin, certain matrix metalloproteinases, and the tissue factor:activated factor VII complex. In this study, we investigated TFPI-2

Tissue Factor-Expressing Tumor-Derived Extracellular Vesicles Activate Quiescent Endothelial Cells via Protease-Activated Receptor-1

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Sara P. Y. Che

2017-11-01

Full Text Available Tissue factor (TF-expressing tumor-derived extracellular vesicles (EVs can promote metastasis and pre-metastatic niche formation, but the mechanisms by which this occurs remain largely unknown. We hypothesized that generation of activated factor X (FXa by TF expressed on tumor-derived EV could activate protease-activated receptors (PARs on non-activated endothelial cells to induce a pro-adhesive and pro-inflammatory phenotype. We obtained EV from TF-expressing breast (MDA-MB-231 and pancreatic (BxPC3 and Capan-1 tumor cell lines. We measured expression of E-selectin and secretion of interleukin-8 (IL-8 in human umbilical vein endothelial cells after exposure to EV and various immunologic and chemical inhibitors of TF, FXa, PAR-1, and PAR-2. After 6 h of exposure to tumor-derived EV (pretreated with factor VIIa and FX in vitro, endothelial cells upregulated E-selectin expression and secreted IL-8. These changes were decreased with an anti-TF antibody, FXa inhibitors (FPRCK and EGRCK, and PAR-1 antagonist (E5555, demonstrating that FXa generated by TF-expressing tumor-derived EV was signaling through endothelial PAR-1. Due to weak constitutive PAR-2 expression, these endothelial responses were not induced by a PAR-2 agonist peptide (SLIGKV and were not inhibited by a PAR-2 antagonist (FSLLRY after exposure to tumor-derived EV. In conclusion, we found that TF-expressing cancer-derived EVs activate quiescent endothelial cells, upregulating E-selectin and inducing IL-8 secretion through generation of FXa and cleavage of PAR-1. Conversion of resting endothelial cells to an activated phenotype by TF-expressing cancer-derived EV could promote cancer metastases.

Association of Geographical Factors With Administration of Tissue Plasminogen Activator for Acute Ischemic Stroke

OpenAIRE

Kunisawa, Susumu; Morishima, Toshitaka; Ukawa, Naoto; Ikai, Hiroshi; Otsubo, Tetsuya; Ishikawa, Koichi B.; Yokota, Chiaki; Minematsu, Kazuo; Fushimi, Kiyohide; Imanaka, Yuichi

2013-01-01

Background Intravenous tissue plasminogen activator (tPA) is an effective treatment for acute ischemic stroke if administered within a few hours of stroke onset. Because of this time restriction, tPA administration remains infrequent. Ambulance use is an effective strategy for increasing tPA administration but may be influenced by geographical factors. The objectives of this study are to investigate the relationship between tPA administration and ambulance use and to examine how patient trave...

Measurement of microparticle tissue factor activity in clinical samples: A summary of two tissue factor-dependent FXa generation assays.

Science.gov (United States)

Hisada, Yohei; Alexander, Wyeth; Kasthuri, Raj; Voorhees, Peter; Mobarrez, Fariborz; Taylor, Angela; McNamara, Coleen; Wallen, Hakan; Witkowski, Marco; Key, Nigel S; Rauch, Ursula; Mackman, Nigel

2016-03-01

Thrombosis is a leading cause of morbidity and mortality. Detection of a prothrombotic state using biomarkers would be of great benefit to identify patients at risk of thrombosis that would benefit from thromboprophylaxis. Tissue factor (TF) is a highly procoagulant protein that under normal conditions is not present in the blood. However, increased levels of TF in the blood in the form of microparticles (MPs) (also called extracellular vesicles) are observed under various pathological conditions. In this review, we will discuss studies that have measured MP-TF activity in a variety of diseases using two similar FXa generation assay. One of the most robust signals for MP-TF activity (16-26 fold higher than healthy controls) is observed in pancreatic cancer patients with venous thromboembolism. In this case, the TF+ MPs appear to be derived from the cancer cells. Surprisingly, cirrhosis and acute liver injury are associated with 17-fold and 38-fold increases in MP-TF activity, respectively. Based on mouse models, we speculate that the TF+ MPs are derived from hepatocytes. More modest increases are observed in patients with urinary tract infections (6-fold) and in a human endotoxemia model (9-fold) where monocytes are the likely source of the TF+ MPs. Finally, there is no increase in MP-TF activity in the majority of cardiovascular disease patients. These studies indicate that MP-TF activity may be a useful biomarker to identify patients with particular diseases that have an increased risk of thrombosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tissue factor activated thromboelastography correlates to clinical signs of bleeding in dogs

DEFF Research Database (Denmark)

Wiinberg, Bo; Jensen, Asger Lundorff; Rozanski, Elizabeth

2009-01-01

The ability of a laboratory assay to correlate to clinical phenotype is crucial for the accurate diagnosis and monitoring of haemostasis and is therefore challenging with currently used routine haemostasis assays. Thromboelastography (TEG) is increasingly used to evaluate haemostasis in humans...... and may well be of value in the workup of dogs suspected of having a haemostatic disorder. This study was undertaken to evaluate prospectively how tissue factor (TF) activated TEG correlated to clinical signs of bleeding in dogs, compared to a routine coagulation profile. A prospective case-control study...... was performed over a 2 year period from 2004-2006. Eligible dogs were those where the primary clinician requested a coagulation profile to evaluate haemostasis. The dogs were simultaneously evaluated with a TF-activated TEG assay. Twenty-seven dogs, characterised as hypo-coagulable based on the TEG parameter G...

The influence of thiazolidinediones on adipogenesis in vitro and in vivo: potential modifiers of intramuscular adipose tissue deposition in meat animals.

Science.gov (United States)

Hausman, G J; Poulos, S P; Pringle, T D; Azain, M J

2008-04-01

Thiazolidinediones (TZD) are insulin sensitizing agents currently used for the treatment of type 2 diabetes and are widely used as adipogenic agents because they are ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), a key adipogenic transcription factor. In vivo and in vitro studies of TZD as potential modifiers of intramuscular or marbling adipogenesis are reviewed. Thiazolidinedione-induced adipogenesis has been reported in numerous cell culture systems, including rodent, human, bovine, and porcine adipose tissue stromal-vascular (S-V) cell cultures. Studies of porcine S-V cell cultures derived from semitendinosus muscle show that TZD can potentially modify intramuscular or marbling adipogenesis. Preadipocyte recruitment was TZD-dependent in muscle S-V cultures but TZD-independent in adipose S-V cultures. There appear to be differences between adipocytes in muscle and subcutaneous adipose tissue, reminiscent of differences observed in adipocytes from different adipose tissue depots. Troglitazone, a TZD, induces marbling adipogenesis without inhibiting myogenesis when cells are grown on laminin precoated culture dishes. Additionally, troglitazone treatment does not increase lipid content in porcine adipose tissue or muscle S-V cell cultures. Thiazolidinedione treatment increases lipid content of muscle in rodents and humans; however, rosiglitazone treatment for 49 d in pigs did not influence muscle lipid content and meat quality, but several significant changes in muscle fatty acid composition were observed. Although timing of treatment with TZD needs to be optimized, evidence suggests these compounds may enhance marbling deposition in swine.

Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

Directory of Open Access Journals (Sweden)

Federica Novelli

Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

Alveolar ridge augmentation by connective tissue grafting using a pouch method and modified connective tissue technique: A prospective study.

Science.gov (United States)

Agarwal, Ashish; Gupta, Narinder Dev

2015-01-01

Localized alveolar ridge defect may create physiological and pathological problems. Developments in surgical techniques have made it simpler to change the configuration of a ridge to create a more aesthetic and more easily cleansable shape. The purpose of this study was to compare the efficacy of alveolar ridge augmentation using a subepithelial connective tissue graft in pouch and modified connective tissue graft technique. In this randomized, double blind, parallel and prospective study, 40 non-smoker individuals with 40 class III alveolar ridge defects in maxillary anterior were randomly divided in two groups. Group I received modified connective tissue graft, while group II were treated with subepithelial connective tissue graft in pouch technique. The defect size was measured in its horizontal and vertical dimension by utilizing a periodontal probe in a stone cast at base line, after 3 months, and 6 months post surgically. Analysis of variance and Bonferroni post-hoc test were used for statistical analysis. A two-tailed P connective tissue graft proposed significantly more improvement as compare to connective tissue graft in pouch.

Modifiable risk factors of hypertension and socio demographic ...

African Journals Online (AJOL)

Background: Factors associated with the development of hypertension can be categorized into modifiable and non‑modifiable risk factors. The modifiable risk factors include obesity, physical inactivity, high salt diet, smoking alcohol consumption and others. Aim: This study was aimed to determine the prevalence of ...

Surface modified electrospun nanofibrous scaffolds for nerve tissue engineering

International Nuclear Information System (INIS)

Prabhakaran, Molamma P; Venugopal, J; Chan, Casey K; Ramakrishna, S

2008-01-01

The development of biodegradable polymeric scaffolds with surface properties that dominate interactions between the material and biological environment is of great interest in biomedical applications. In this regard, poly-ε-caprolactone (PCL) nanofibrous scaffolds were fabricated by an electrospinning process and surface modified by a simple plasma treatment process for enhancing the Schwann cell adhesion, proliferation and interactions with nanofibers necessary for nerve tissue formation. The hydrophilicity of surface modified PCL nanofibrous scaffolds (p-PCL) was evaluated by contact angle and x-ray photoelectron spectroscopy studies. Naturally derived polymers such as collagen are frequently used for the fabrication of biocomposite PCL/collagen scaffolds, though the feasibility of procuring large amounts of natural materials for clinical applications remains a concern, along with their cost and mechanical stability. The proliferation of Schwann cells on p-PCL nanofibrous scaffolds showed a 17% increase in cell proliferation compared to those on PCL/collagen nanofibrous scaffolds after 8 days of cell culture. Schwann cells were found to attach and proliferate on surface modified PCL nanofibrous scaffolds expressing bipolar elongations, retaining their normal morphology. The results of our study showed that plasma treated PCL nanofibrous scaffolds are a cost-effective material compared to PCL/collagen scaffolds, and can potentially serve as an ideal tissue engineered scaffold, especially for peripheral nerve regeneration.

Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI.

Directory of Open Access Journals (Sweden)

Cristina Puy

Full Text Available Factor (F XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα, in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin.Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma.Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP.

Tissue regenerating functions of coagulation factor XIII

DEFF Research Database (Denmark)

Soendergaard, C; Kvist, P H; Seidelin, J B

2013-01-01

The protransglutaminase factor XIII (FXIII) has recently gained interest within the field of tissue regeneration, as it has been found that FXIII significantly influences wound healing by exerting a multitude of functions. It supports haemostasis by enhancing platelet adhesion to damaged......-receptor 2 and the αVβ3 integrin is important for angiogenesis supporting formation of granulation tissue. Chronic inflammatory conditions involving bleeding and activation of the coagulation cascade have been shown to lead to reduced FXIII levels in plasma. Of particular importance for this review...

Factors affecting release of ethanol vapour in active modified atmosphere packaging systems for horticultural products

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Weerawate Utto

2014-04-01

Full Text Available The active modified atmosphere packaging (active MAP system , which provides interactive postharvest control , using ethanol vapour controlled release, is one of the current interests in the development of active packaging for horticultural products. A number of published research work have discussed the relationship between the effectiveness of ethanol vapour and its concentration in the package headspace, including its effect on postharvest decay and physiological controls. This is of importance because a controlled release system should release and maintain ethanol vapour at effective concentrations during the desired storage period. A balance among the mass transfer processes of ethanol vapour in the package results in ethanol vapour accumulation in the package headspace. Key factors affecting these processes include ethanol loading, packaging material, packaged product and storage environment (temperature and relative h umidity. This article reviews their influences and discusses future work required to better understand their influences on ethanol vapour release and accumulations in active MAP.

Monitoring modifiable risk factors for breast cancer: an obligation for health professionals

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Verónica Guerra Guerrero

2017-06-01

Full Text Available SYNOPSIS Worldwide, breast cancer is the most common disease in women and constitutes the second leading cause of cancer death in this population. The factors that contribute to the risk of occurrence are divided into nonmodifiable and modifiable factors. Although there are interventions in primary care to prevent the disease, these measures have not produced the desired changes in women’s health. This article reviews the major modifiable risk factors for breast cancer and describes how these factors can affect the incidence of cancer in women. This information shows that modifiable risk factors (such as physical activity, diet, obesity, and use of alcohol and tobacco can influence the occurrence of breast cancer, in part depending on the life stage of a woman, including menopausal status. Timely prevention at the primary care level is one of the most important areas on which health professionals need to focus in order to help reduce the incidence of breast cancer.

Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment.

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Yu, Yuanjie; Böing, Anita N; Hau, Chi M; Hajji, Najat; Ruf, Wolfram; Sturk, Auguste; Nieuwland, Rienk

2018-06-01

 Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored.  This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains.  Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption. Plasma membranes were fractionated by OptiPrep gradient ultracentrifugation, and the presence of TF, flotillin, caveolin, clathrin, protein disulphide isomerase (PDI), TF pathway inhibitor (TFPI) and phosphatidylserine (PS) were determined.  Plasma membranes contain two detergent-resistant membrane (DRM) compartments differing in density and biochemical composition. High-density DRMs (DRM-H) have a density ( ρ ) of 1.15 to 1.20 g/mL and contain clathrin, whereas low-density DRMs (DRM-L) have a density between 1.09 and 1.13 g/mL and do not contain clathrin. Both DRMs contain TF, flotillin and caveolin. PDI is detectable in DRM-H, TFPI is not detectable in either DMR-H or DRM-L and PS is detectable in DRM-L. The DRM-H-associated TF (> 95% of the TF antigen) lacks detectable coagulant activity, whereas the DRM-L-associated TF triggers coagulation. This coagulant activity is inhibited by lactadherin and thus PS-dependent, but seemed insensitive to 16F16, an inhibitor of PDI.  Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity. Schattauer GmbH Stuttgart.

Tissue Factor and Thrombin in Sickle Cell Anemia

OpenAIRE

Chantrathammachart, Pichika; Pawlinski, Rafal

2012-01-01

Sickle cell anemia is an inherited hematologic disorder associated with hemolytic and vaso-occlusive complications. An activation of coagulation is also a prominent feature of sickle cell anemia. Growing evidence indicates that coagulation may contribute to the inflammation and vascular injury in sickle cell anemia. This review focuses on tissue factor expression and its contribution to the activation of coagulation, thrombosis and vascular inflammation in sickle cell anemia.

Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

DEFF Research Database (Denmark)

Bladbjerg, E-M; Skouby, S O.; Andersen, L F

2002-01-01

BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor...... pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i). cyclic oral estrogen/progestin (n = 25); (ii). long-cycle oral estrogen......: No variations were observed in the reference group. There was a substantial decrease in TFPI concentrations in the HRT groups irrespective of the type of progestin. In women receiving long-cycle treatment, all factor VII measures increased during the unopposed estrogen periods, and the increase was reversed...

Stem cell signaling. An integral program for tissue renewal and regeneration : Wnt signaling and stem cell control

NARCIS (Netherlands)

Clevers, Hans; Loh, Kyle M; Nusse, Roel

2014-01-01

Stem cells fuel tissue development, renewal, and regeneration, and these activities are controlled by the local stem cell microenvironment, the "niche." Wnt signals emanating from the niche can act as self-renewal factors for stem cells in multiple mammalian tissues. Wnt proteins are lipid-modified,

Modifiable risk factors for increased arterial stiffness in outpatient nephrology.

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Usama Elewa

Full Text Available Arterial stiffness, as measured by pulse wave velocity (PWV, is an independent predictor of cardiovascular events and mortality. Arterial stiffness increases with age. However, modifiable risk factors such as smoking, BP and salt intake also impact on PWV. The finding of modifiable risk factors may lead to the identification of treatable factors, and, thus, is of interest to practicing nephrologist. We have now studied the prevalence and correlates of arterial stiffness, assessed by PWV, in 191 patients from nephrology outpatient clinics in order to identify modifiable risk factors for arterial stiffness that may in the future guide therapeutic decision-making. PWV was above normal levels for age in 85/191 (44.5% patients. Multivariate analysis showed that advanced age, systolic BP, diabetes mellitus, serum uric acid and calcium polystyrene sulfonate therapy or calcium-containing medication were independent predictors of PWV. A new parameter, Delta above upper limit of normal PWV (Delta PWV was defined to decrease the weight of age on PWV values. Delta PWV was calculated as (measured PWV - (upper limit of the age-adjusted PWV values for the general population. Mean±SD Delta PWV was 0.76±1.60 m/sec. In multivariate analysis, systolic blood pressure, active smoking and calcium polystyrene sulfonate therapy remained independent predictors of higher delta PWV, while age, urinary potassium and beta blocker therapy were independent predictors of lower delta PWV. In conclusion, arterial stiffness was frequent in nephrology outpatients. Systolic blood pressure, smoking, serum uric acid, calcium-containing medications, potassium metabolism and non-use of beta blockers are modifiable factors associated with increased arterial stiffness in Nephrology outpatients.

Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration

DEFF Research Database (Denmark)

Ohki, Makiko; Ohki, Yuichi; Ishihara, Makoto

2010-01-01

tissue regeneration is not well understood. Bone marrow (BM)-derived myeloid cells facilitate angiogenesis during tissue regeneration. Here, we report that a serpin-resistant form of tPA by activating the extracellular proteases matrix metalloproteinase-9 and plasmin expands the myeloid cell pool......-A. Remarkably, transplantation of BM-derived tPA-mobilized CD11b(+) cells and VEGFR-1(+) cells, but not carrier-mobilized cells or CD11b(-) cells, accelerates neovascularization and ischemic tissue regeneration. Inhibition of VEGF signaling suppresses tPA-induced neovascularization in a model of hind limb...... and mobilizes CD45(+)CD11b(+) proangiogenic, myeloid cells, a process dependent on vascular endothelial growth factor-A (VEGF-A) and Kit ligand signaling. tPA improves the incorporation of CD11b(+) cells into ischemic tissues and increases expression of neoangiogenesis-related genes, including VEGF...

Soft Tissue Closure of Grafted Extraction Sockets in the Anterior Maxilla: A Modified Palatal Pedicle Connective Tissue Flap Technique.

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El Chaar, Edgard; Oshman, Sarah; Cicero, Giuseppe; Castano, Alejandro; Dinoi, Cinzia; Soltani, Leila; Lee, Yoonjung Nicole

Localized ridge resorption, the consequence of socket collapse, following tooth extraction in the anterior maxilla can adversely affect esthetics, function, and future implant placement. Immediate grafting of extraction sockets may help preserve natural ridge contours, but a lack of available soft tissue can compromise the final esthetic outcome. The presented modified rotated palatal pedicle connective tissue flap is a useful technique for simultaneous soft tissue coverage and augmentation of grafted sockets to improve esthetic outcome. This article delineates its advantages through the presentation of a four-case series using this new technique.

Quantitative and qualitative analysis of telomerase activity in benign and malignant thyroid tissues

International Nuclear Information System (INIS)

Zheng Rongxiu; Fang Peihua; Tan Jian; Lu Mei; Li Yigong

2002-01-01

Objective: To study the status of telomerase activity during the development of thyroid tumors, and to determine whether telomerase activity can be used clinically as a molecular marker in the differential diagnosis of thyroid cancer. Methods: Telomerase activity was measured in 37 thyroid carcinomas, 33 benign thyroid lesions and 30 normal thyroid tissue samples by means of a modified TRAP-PCR. The assay was also applied to 15 fine needle aspirates (FNAs) of thyroid carcinomas to test its sensitivity. Results: Thirty-one of 37 thyroid carcinomas (83.8%), 7 of 33 benign thyroid lesions (21.2%), and 4 of 30 adjacent normal thyroid tissue samples expressed telomerase activity, 15 FNAs also had positive telomerase activity, just as their corresponding tissue specimens. The quantitative analysis showed that the telomerase activity was significantly higher in thyroid carcinomas than that in benign thyroid tissue samples. And medullary carcinomas and anaplastic carcinomas had higher levels of telomerase activity than papillary carcinomas. Conclusions: Telomerase activity is a good marker for thyroid carcinomas. The quantitative TRAP-PCR might have more potential application in the differential diagnosis of tumors and the estimation of tumor progression and prognosis. And this sensitive assay could become a useful new modality for supplementing microscopic cytopathology in the detection of cancer cells in small tissue samples and FNAs

Regulating expressin of cell and tissue-specific genes by modifying transcription

Energy Technology Data Exchange (ETDEWEB)

Beachy, Roger N. [Donald Danforth Plant Science Center, St. Louis, MO (United States); Dai, Shunhong [Donald Danforth Plant Science Center, St. Louis, MO (United States)

2009-12-15

Transcriptional regulation is the primary step to control gene expression, therefore function. Such regulation is achieved primarily via a combination of the activities of the promoter cis regulatory DNA elements and trans regulatory proteins that function through binding to these DNA elements. Our research supported by this program has led to the identification of rice bZIP transcription factors RF2a, RF2b and RLP1 that play key roles in regulating the activity of a vascular tissue specific promoter isolated from Rice Tungro Bacilliform Virus (RTBV) through their interactions with the Box II essential cis element located in the promoter. RF2a, RF2b and RLP1 possess multiple regulatory domains. Functional characterization reveals that those domains can activate or repress the activity of the RTBV promoter. Studies of transcriptional regulation of the RTBV promoter by this group of bZIP proteins not only provide insights about gene expression in the vascular tissue, but also insights about general mechanisms of transcription activation and repression. The knowledge gained from this research will also enable us to develop a well-described set of tools that can be used to control expression of multiple genes in transgenic plants and to improve biofuel feedstock.

Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site-Inhibited Factor VII.

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Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E; Jensen, Mette M; Kristensen, Lotte K; Madsen, Jacob; Petersen, Lars C; Kjaer, Andreas

2016-01-01

Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of factor VII. Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-(18)F-fluorobenzoate and purified. The corresponding product, (18)F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of (18)F-FVIIai in the tumors measured in vivo by PET imaging. The PET images showed high uptake of (18)F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of (18)F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of (18)F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of (18)F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. (18)F-FVIIai is a promising PET tracer for

Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

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Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

2009-12-15

Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

Tissue response to intraperitoneal implants of polyethylene oxide-modified polyethylene terephthalate.

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Desai, N P; Hubbell, J A

1992-01-01

Polyethylene terephthalate films surface modified with polyethylene oxide of mol wt 18,500 g/mol (18.5 k) by a previously described technique, were implanted in the peritoneal cavity of mice, along with their respective untreated controls, for periods of 1-28 d. The implants were retrieved and examined for tissue reactivity and cellular adherence. The control polyethylene terephthalate surfaces showed an initial inflammatory reaction followed by an extensive fibrotic response with a mean thickness of 60 microns at 28 d. By contrast, polyethylene oxide-modified polyethylene terephthalate showed only a mild inflammatory response and no fibrotic encapsulation throughout the implantation period: at 28 d a cellular monolayer was observed. Apparently either the polyethylene oxide-modified surface was stimulating less inflammation, which was in turn stimulating less fibroblastic overgrowth, or the cellular adhesion to the polyethylene oxide-modified surface was too weak to support cellular multilayers.

Alveolar ridge augmentation by connective tissue grafting using a pouch method and modified connective tissue technique: A prospective study

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Ashish Agarwal

2015-01-01

Full Text Available Background: Localized alveolar ridge defect may create physiological and pathological problems. Developments in surgical techniques have made it simpler to change the configuration of a ridge to create a more aesthetic and more easily cleansable shape. The purpose of this study was to compare the efficacy of alveolar ridge augmentation using a subepithelial connective tissue graft in pouch and modified connective tissue graft technique. Materials and Methods: In this randomized, double blind, parallel and prospective study, 40 non-smoker individuals with 40 class III alveolar ridge defects in maxillary anterior were randomly divided in two groups. Group I received modified connective tissue graft, while group II were treated with subepithelial connective tissue graft in pouch technique. The defect size was measured in its horizontal and vertical dimension by utilizing a periodontal probe in a stone cast at base line, after 3 months, and 6 months post surgically. Analysis of variance and Bonferroni post-hoc test were used for statistical analysis. A two-tailed P < 0.05 was considered to be statistically significant. Results: Mean values in horizontal width after 6 months were 4.70 ± 0.87 mm, and 4.05 ± 0.89 mm for group I and II, respectively. Regarding vertical heights, obtained mean values were 4.75 ± 0.97 mm and 3.70 ± 0.92 mm for group I and group II, respectively. Conclusion: Within the limitations of this study, connective tissue graft proposed significantly more improvement as compare to connective tissue graft in pouch.

Factors Modifying Burnout in Osteopathic Medical Students.

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Lapinski, Jessica; Yost, Morgan; Sexton, Patricia; LaBaere, Richard J

2016-02-01

The purposes of the current study are to examine factors modifying burnout and identify which of these factors place osteopathic medical students at risk for developing burnout. The current study used a cross-sectional study design and an anonymous, web-based survey to assess burnout and depression in osteopathic medical students. The survey included Maslach Burnout Inventory, the Patient Health Questionnaire, the Stressors and their impact scale, students' sleeping and studying habits, and students' extracurricular involvement. In total, 1294 osteopathic medical students completed the survey. Burnout was present in 516 (39.9%) osteopathic medical students, and 1006 (77.0%) met criteria for depression. Females were 1.5 times more likely to be burned out in comparison to males. For the burnout subscales, males had lower emotional exhaustion, slightly higher depersonalization, and lower personal accomplishment. Lesbian/gay/bisexual/asexual students were 2.62 times more likely to be burned out compared with heterosexual students. Depression and academic, personal, and family stressors were all strongly linked to overall burnout. Finally, for modifiable factors, average hours of sleep, average hours spent studying, and club involvement appeared to be linked to burnout. The current study suggested that a variety of factors, including non-modifiable, situational, and modifiable, impact burnout in osteopathic medical students. Future research is necessary since burnout in physicians affects the quality of care provided to patients.

New trends in the use of biological response modifiers for treatment of malignant neoplasm

International Nuclear Information System (INIS)

Saad, Sherif Y.

2002-01-01

Biological response modifiers are critical controllers of cell division and hence tissue, growth, migration development and differentiation. The family of biological response modifiers includes interferons, tumor necrosis factor, interleukins, colony stimulating factors and hematopoietic growth factors as well as tumor vaccines and monoclonal antibodies. Biological response modifiers have important roles in cancer development and progression, control of cell replication and apoptosis and modulation of immune reactions such as sensitization. This article reviews the biology, pharmacology and clinical application of biological response modifiers in oncology. The antitumor activity of biological response modifiers may be augmented immune response including activation of natural killer lymphocytes and enhanced expression of cell surface antigens (MHC I and II). Combination of biological therapy with chemotherapy improves the response of those tumors refractory to conventional therapies. Colony stimulating factors are used for manipulating immune system to fight against cancer and to prevent chemotherapy-induced neutropenia. Recent advances in tumor immunology, most notably the identification of genes encoding for cancer regression antigens, have paved the way for the development of a variety of novel and specific vaccines and monoclonal antibody approaches. These approaches are discussed from a therapeutic perspective. (author)

Pivotal role of tissue plasminogen activator in the mechanism of action of electroconvulsive therapy.

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Hoirisch-Clapauch, Silvia; Mezzasalma, Marco A U; Nardi, Antonio E

2014-02-01

Electroconvulsive therapy is an important treatment option for major depressive disorders, acute mania, mood disorders with psychotic features, and catatonia. Several hypotheses have been proposed as electroconvulsive therapy's mechanism of action. Our hypothesis involves many converging pathways facilitated by increased synthesis and release of tissue-plasminogen activator. Human and animal experiments have shown that tissue-plasminogen activator participates in many mechanisms of action of electroconvulsive therapy or its animal variant, electroconvulsive stimulus, including improved N-methyl-D-aspartate receptor-mediated signaling, activation of both brain-derived neurotrophic factor and vascular endothelial growth factor, increased bioavailability of zinc, purinergic release, and increased mobility of dendritic spines. As a result, tissue-plasminogen activator helps promote neurogenesis in limbic structures, modulates synaptic transmission and plasticity, improves cognitive function, and mediates antidepressant effects. Notably, electroconvulsive therapy seems to influence tissue-plasminogen activator metabolism. For example, electroconvulsive stimulus increases the expression of glutamate decarboxylase 65 isoform in γ-aminobutyric acid-releasing neurons, which enhances the release of tissue-plasminogen activator, and the expression of p11, a protein involved in plasminogen and tissue-plasminogen activator assembling. This paper reviews how electroconvulsive therapy correlates with tissue-plasminogen activator. We suggest that interventions aiming at increasing tissue-plasminogen activator levels or its bioavailability - such as daily aerobic exercises together with a carbohydrate-restricted diet, or normalization of homocysteine levels - be evaluated in controlled studies assessing response and remission duration in patients who undergo electroconvulsive therapy.

Tissue-specifically regulated site-specific excision of selectable marker genes in bivalent insecticidal, genetically-modified rice.

Science.gov (United States)

Hu, Zhan; Ding, Xuezhi; Hu, Shengbiao; Sun, Yunjun; Xia, Liqiu

2013-12-01

Marker-free, genetically-modified rice was created by the tissue-specifically regulated Cre/loxP system, in which the Cre recombinase gene and hygromycin phosphotransferase gene (hpt) were flanked by two directly oriented loxP sites. Cre expression was activated by the tissue-specific promoter OsMADS45 in flower or napin in seed, resulting in simultaneous excision of the recombinase and marker genes. Segregation of T1 progeny was performed to select recombined plants. The excision was confirmed by PCR, Southern blot and sequence analyses indicating that efficiency varied from 10 to 53 % for OsMADS45 and from 12 to 36 % for napin. The expression of cry1Ac and vip3A was detected by RT-PCR analysis in marker-free transgenic rice. These results suggested that our tissue-specifically regulated Cre/loxP system could auto-excise marker genes from transgenic rice and alleviate public concerns about the security of GM crops.

Connective tissue activation. XXXII. Structural and biologic characteristics of mesenchymal cell-derived connective tissue activating peptide-V.

Science.gov (United States)

Cabral, A R; Cole, L A; Walz, D A; Castor, C W

1987-12-01

Connective tissue activating peptide-V (CTAP-V) is a single-chain, mesenchymal cell-derived anionic protein with large and small molecular forms (Mr of 28,000 and 16,000, respectively), as defined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The proteins have similar specific activities with respect to stimulation of hyaluronic acid and DNA formation in human synovial fibroblast cultures. S-carboxymethylation or removal of sialic acid residues did not modify CTAP-V biologic activity. Rabbit antibodies raised separately against each of the purified CTAP-V proteins reacted, on immunodiffusion and on Western blot, with each antigen and neutralized mitogenic activity. The amino-terminal amino acid sequence of the CTAP-V proteins, determined by 2 laboratories, confirmed their structural similarities. The amino-terminal sequence through 37 residues was demonstrated for the smaller protein. The first 10 residues of CTAP-V (28 kd) were identical to the N-terminal decapeptide of CTAP-V (16 kd). The C-terminal sequence, determined by carboxypeptidase Y digestion, was the same for both CTAP-V molecular species. The 2 CTAP-V peptides had similar amino acid compositions, whether residues were expressed as a percent of the total or were normalized to mannose. Reduction of native CTAP-V protein released sulfhydryl groups in a protein:disulfide ratio of 1:2; this suggests that CTAP-V contains 2 intramolecular disulfide bonds. Clearly, CTAP-V is a glycoprotein. The carbohydrate content of CTAP-V (16 kd) and CTAP-V (28 kd) is 27% and 25%, respectively. CTAP-V may have significance in relation to autocrine mechanisms for growth regulation of connective tissue cells and other cell types.

Chemical stability and osteogenic activity of plasma-sprayed boron-modified calcium silicate-based coatings.

Science.gov (United States)

Lu, Xiang; Li, Kai; Xie, Youtao; Huang, Liping; Zheng, Xuebin

2016-11-01

In recent years, CaSiO 3 bio-ceramic coatings have attracted great attention because of their good bioactivity. However, their high degradation rates in physiological environment restrict their practical applications. In this work, boron-modified CaSiO 3 ceramic (Ca 11 Si 4 B 2 O 22 , B-CS) coating was developed on Ti substrates by plasma-spraying technique attempting to obtain enhanced chemical stability and osteogenic activity. The B-CS coating possessed significantly increased chemical stability due to the introduction of boron and consequently the modified crystal structure, while maintaining good bioactivity. Scanning electron microscope and immunofluorescence studies showed that better cellular adhesion and extinctive filopodia-like processes were observed on the B-CS coating. Compared with the pure CaSiO 3 (CS) coating, the B-CS coating promoted MC3T3-E1 cells attachment and proliferation. In addition, enhanced collagen I (COL-I) secretion, alkaline phosphatase activity, and extracellular matrix mineralization levels were detected from the B-CS coating. According to RT-PCR results, notable up-regulation expressions of mineralized tissue-related genes, such as runt-related transcription factor 2 (Runx2), bone sialoprotein and osteocalcin, and bone morphogenetic protein 7 (BMP-7) were observed on the B-CS coating compared with the CS coating. The above results suggested that Ca 11 Si 4 B 2 O 22 coatings possess excellent osteogenic activity and might be a promising candidate for orthopedic applications.

HTCC-Modified Nanoclay for Tissue Engineering Applications: A Synergistic Cell Growth and Antibacterial Efficiency

Directory of Open Access Journals (Sweden)

Majid Aliabadi

2013-01-01

Full Text Available This paper deals with the synthesis of a biocompatible chitosan ammonium salt N-(2-hydroxy propyl-3-trimethylammonium chitosan chloride (HTCC and using it in montmorillonite ion-exchange process. HTCC-modified montmorillonite (Mt with different chemical ratios was successfully synthesized, and their characteristics have been verified by XRD and FTIR analyses. Produced samples have been evaluated in terms of antibacterial efficiency and biocompatibility (cell culture test. Antibacterial efficiency of synthesized HTCC/Mt samples has been confirmed against both gram negative bacteria (Escherichia coli and gram positive bacteria (Staphylococcus aureus. The results disclosed that the antibacterial efficiency of HTCC-modified montmorillonite was unexpectedly even more than HTCC. This excellent synergistic effect has been referred to entrapping bacteria between the intercalated structures of HTCC-modified montmorillonite. Then HTCC on clay layers can seriously attack and damage the entrapped bacteria. An extraordinary biocompatibility, cell attachment, and cell growth even more than tissue culture polystyrene (TCPS have been recorded in the case of this novel kind of modified clay. Due to existing concerns about serious and chronic infections after implant placement, this natural-based bioactive and antibacterial modified clay can be used in electrospun nanofibers and other polymeric implants with promising mechanical properties for tissue engineering applications.

Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

Science.gov (United States)

Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

2016-03-01

Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

Extracellular Histones Increase Tissue Factor Activity and Enhance Thrombin Generation by Human Blood Monocytes.

Science.gov (United States)

Gould, Travis J; Lysov, Zakhar; Swystun, Laura L; Dwivedi, Dhruva J; Zarychanski, Ryan; Fox-Robichaud, Alison E; Liaw, Patricia C

2016-12-01

Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. Tissue factor (TF) activity assays were performed on histone-treated THP-1 cells and blood monocytes. Exposure of monocytic cells to histones resulted in increases in TF activity, TF antigen, and phosphatidylserine exposure. Histones modulate the procoagulant activity via engagement of Toll-like receptors 2 and 4, and this effect was abrogated with inhibitory antibodies. Increased TF activity of histone-treated cells corresponded to enhanced thrombin generation in plasma determined by calibrated automated thrombography. Finally, TF activity was increased on monocytes exposed to plasma from septic patients, an effect that was attenuated in plasma from patients receiving unfractionated heparin (UFH). Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment.

Decreased expression of connective tissue growth factor in non-small cell lung cancer is associated with clinicopathological variables and can be restored by epigenetic modifiers.

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Drzewiecka, Hanna; Gałęcki, Bartłomiej; Jarmołowska-Jurczyszyn, Donata; Kluk, Andrzej; Dyszkiewicz, Wojciech; Jagodziński, Paweł P

2016-09-01

Recent studies indicated undisputed contribution of connective tissue growth factor (CTGF) in the development of many cancers, including non-small cell lung cancer (NSCLC). However, the functional role and regulation of CTGF expression during tumorigenesis remain elusive. Our goal was to determine CTGF transcript and protein levels in tumoral and matched control tissues from 98 NSCLC patients, to correlate the results with clinicopathological features and to investigate whether the CTGF expression can be epigenetically regulated in NSCLC. We used quantitative PCR, Western blotting and immunohistochemistry to evaluate CTGF expression in lung cancerous and histopathologically unchanged tissues. We tested the impact of 5-Aza-2'-deoxycytidine (5-dAzaC) and trichostatin A (TSA) on CTGF transcript and protein levels in NSCLC cells (A549, Calu-1). DNA methylation status of the CTGF regulatory region was evaluated by bisulfite sequencing. The influence of 5-dAzaC and TSA on NSCLC cells viability and proliferation was monitored by the trypan blue assay. We found significantly decreased levels of CTGF mRNA and protein (both p cancerous tissues of NSCLC patients. Down-regulation of CTGF occurred regardless of gender in all histological subtypes of NSCLC. Moreover, we showed that 5-dAzaC and TSA were able to restore CTGF mRNA and protein contents in NSCLC cells. However, no methylation within CTGF regulatory region was detected. Both compounds significantly reduced NSCLC cells proliferation. Decreased expression of CTGF is a common feature in NSCLC; however, it can be restored by the chromatin-modifying agents such as 5-dAzaC or TSA and consequently restrain cancer development.

Modifiable risk factors for schizophrenia and autism--shared risk factors impacting on brain development.

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Hamlyn, Jess; Duhig, Michael; McGrath, John; Scott, James

2013-05-01

Schizophrenia and autism are two poorly understood clinical syndromes that differ in age of onset and clinical profile. However, recent genetic and epidemiological research suggests that these two neurodevelopmental disorders share certain risk factors. The aims of this review are to describe modifiable risk factors that have been identified in both disorders, and, where available, collate salient systematic reviews and meta-analyses that have examined shared risk factors. Based on searches of Medline, Embase and PsycINFO, inspection of review articles and expert opinion, we first compiled a set of candidate modifiable risk factors associated with autism. Where available, we next collated systematic-reviews (with or without meta-analyses) related to modifiable risk factors associated with both autism and schizophrenia. We identified three modifiable risk factors that have been examined in systematic reviews for both autism and schizophrenia. Advanced paternal age was reported as a risk factor for schizophrenia in a single meta-analysis and as a risk factor in two meta-analyses for autism. With respect to pregnancy and birth complications, for autism one meta-analysis identified maternal diabetes and bleeding during pregnancy as risks factors for autism whilst a meta-analysis of eight studies identified obstetric complications as a risk factor for schizophrenia. Migrant status was identified as a risk factor for both autism and schizophrenia. Two separate meta-analyses were identified for each disorder. Despite distinct clinical phenotypes, the evidence suggests that at least some non-genetic risk factors are shared between these two syndromes. In particular, exposure to drugs, nutritional excesses or deficiencies and infectious agents lend themselves to public health interventions. Studies are now needed to quantify any increase in risk of either autism or schizophrenia that is associated with these modifiable environmental factors. Copyright © 2012 Elsevier Inc

Role of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in psychological stress and depression.

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Tsai, Shih-Jen

2017-12-22

Major depressive disorder is a common illness worldwide, but the pathogenesis of the disorder remains incompletely understood. The tissue-type plasminogen activator-plasminogen proteolytic cascade is highly expressed in the brain regions involved in mood regulation and neuroplasticity. Accumulating evidence from animal and human studies suggests that tissue-type plasminogen activator and its chief inhibitor, plasminogen activator inhibitor-1, are related to stress reaction and depression. Furthermore, the neurotrophic hypothesis of depression postulates that compromised neurotrophin brain-derived neurotrophic factor (BDNF) function is directly involved in the pathophysiology of depression. In the brain, the proteolytic cleavage of proBDNF, a BDNF precursor, to mature BDNF through plasmin represents one mechanism that can change the direction of BDNF action. We also discuss the implications of tissue-type plasminogen activator and plasminogen activator inhibitor-1 alterations as biomarkers for major depressive disorder. Using drugs that increase tissue-type plasminogen activator or decrease plasminogen activator inhibitor-1 levels may open new avenues to develop conceptually novel therapeutic strategies for depression treatment.

Surface-modified polymers for cardiac tissue engineering.

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Moorthi, Ambigapathi; Tyan, Yu-Chang; Chung, Tze-Wen

2017-09-26

Cardiovascular disease (CVD), leading to myocardial infarction and heart failure, is one of the major causes of death worldwide. The physiological system cannot significantly regenerate the capabilities of a damaged heart. The current treatment involves pharmacological and surgical interventions; however, less invasive and more cost-effective approaches are sought. Such new approaches are developed to induce tissue regeneration following injury. Hence, regenerative medicine plays a key role in treating CVD. Recently, the extrinsic stimulation of cardiac regeneration has involved the use of potential polymers to stimulate stem cells toward the differentiation of cardiomyocytes as a new therapeutic intervention in cardiac tissue engineering (CTE). The therapeutic potentiality of natural or synthetic polymers and cell surface interactive factors/polymer surface modifications for cardiac repair has been demonstrated in vitro and in vivo. This review will discuss the recent advances in CTE using polymers and cell surface interactive factors that interact strongly with stem cells to trigger the molecular aspects of the differentiation or formulation of cardiomyocytes for the functional repair of heart injuries or cardiac defects.

Preoperative modifiable risk factors in colorectal surgery

DEFF Research Database (Denmark)

van Rooijen, Stefanus; Carli, Francesco; Dalton, Susanne O

2017-01-01

in higher mortality rates and greater hospital costs. The number and severity of complications is closely related to patients' preoperative performance status. The aim of this study was to identify the most important preoperative modifiable risk factors that could be part of a multimodal prehabilitation...... program. METHODS: Prospectively collected data of a consecutive series of Dutch CRC patients undergoing colorectal surgery were analyzed. Modifiable risk factors were correlated to the Comprehensive Complication Index (CCI) and compared within two groups: none or mild complications (CCI ... complications (CCI ≥20). Multivariate logistic regression analysis was done to explore the combined effect of individual risk factors. RESULTS: In this 139 patient cohort, smoking, malnutrition, alcohol consumption, neoadjuvant therapy, higher age, and male sex, were seen more frequently in the severe...

Variations on metabolic activities of legume tissues through radiation in tissue culture

International Nuclear Information System (INIS)

Batra, Amla

1977-01-01

Cell cultures from Arachis hypogaea L. cultivated in a modified medium developed by Murashige and Skoog (1962) showed vigorous qrowth after radiation treatment. Investigations on the effect of various sugars on the chlorophyll formation and growth of the irradiated tissues showed that sucrose was superior to maltose, glucose or fructose as a carbon source. Lactose and mannitol supported growth and development of chlorophyll to a less degree. On prolonging the cultures on a sugar free medium, the tissues failed to regain either growth or chlorophyll content. (author)

Variations on metabolic activities of legume tissues through radiation in tissue culture

Energy Technology Data Exchange (ETDEWEB)

Batra, A [Rajasthan Univ., Jaipur (India). Dept. of Botany

1977-12-01

Cell cultures from Arachis hypogaea L. cultivated in a modified medium developed by Murashige and Skoog (1962) showed vigorous qrowth after radiation treatment. Investigations on the effect of various sugars on the chlorophyll formation and growth of the irradiated tissues showed that sucrose was superior to maltose, glucose or fructose as a carbon source. Lactose and mannitol supported growth and development of chlorophyll to a less degree. On prolonging the cultures on a sugar free medium, the tissues failed to regain either growth or chlorophyll content.

Novel electrospun nanofibers of modified gelatin-tyrosine in cartilage tissue engineering

International Nuclear Information System (INIS)

Agheb, Maria; Dinari, Mohammad; Rafienia, Mohammad; Salehi, Hossein

2017-01-01

In natural cartilage tissues, chondrocytes are linked to extracellular matrix (ECM) through cell-surface binding proteins. Surface modification of gelatin can provide a new generation of biopolymers and fibrous scaffolds with chemical, mechanical, and biological properties. In this study tyrosine protein and 1,2,3-triazole ring were utilized to functionalize gelatin without Cu catalyst. Their molecular structure was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ( 1 HNMR). Chemical cross-linkers such as glutaraldehyde (GA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysulfosuccinimide (NHS) were used to electrospin the modified gelatin. The modification of gelatin and cross-linking effects were confirmed by scanning electron microscopy (SEM), contact angle measurement, and mechanical tests. MTT assay using chondrocyte cells showed cell viability of electrospun modified gelatin scaffolds. In vitro cell culture studies showed that electrospun engineered protein scaffolds would support the attachment and growth of cells. The results also showed that cross-linked nanofibers with EDC/NHS could be considered excellent matrices in cell adhesion and proliferation before electrospinning process and their potential substrate in tissue engineering applications, especially in the field of cartilage engineering.

Novel electrospun nanofibers of modified gelatin-tyrosine in cartilage tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Agheb, Maria [Biosensor Research Center, Isfahan University of Medical Sciences, Isfahan 81744176 (Iran, Islamic Republic of); Dinari, Mohammad [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Rafienia, Mohammad, E-mail: m_rafienia@med.mui.ac.ir [Biosensor Research Center, Isfahan University of Medical Sciences, Isfahan 81744176 (Iran, Islamic Republic of); Salehi, Hossein [Biosensor Research Center, Isfahan University of Medical Sciences, Isfahan 81744176 (Iran, Islamic Republic of)

2017-02-01

In natural cartilage tissues, chondrocytes are linked to extracellular matrix (ECM) through cell-surface binding proteins. Surface modification of gelatin can provide a new generation of biopolymers and fibrous scaffolds with chemical, mechanical, and biological properties. In this study tyrosine protein and 1,2,3-triazole ring were utilized to functionalize gelatin without Cu catalyst. Their molecular structure was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ({sup 1}HNMR). Chemical cross-linkers such as glutaraldehyde (GA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysulfosuccinimide (NHS) were used to electrospin the modified gelatin. The modification of gelatin and cross-linking effects were confirmed by scanning electron microscopy (SEM), contact angle measurement, and mechanical tests. MTT assay using chondrocyte cells showed cell viability of electrospun modified gelatin scaffolds. In vitro cell culture studies showed that electrospun engineered protein scaffolds would support the attachment and growth of cells. The results also showed that cross-linked nanofibers with EDC/NHS could be considered excellent matrices in cell adhesion and proliferation before electrospinning process and their potential substrate in tissue engineering applications, especially in the field of cartilage engineering.

Potential Role of Activating Transcription Factor 5 during Osteogenesis

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Luisa Vicari

2016-01-01

Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

Potential Role of Activating Transcription Factor 5 during Osteogenesis.

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Vicari, Luisa; Calabrese, Giovanna; Forte, Stefano; Giuffrida, Raffaella; Colarossi, Cristina; Parrinello, Nunziatina Laura; Memeo, Lorenzo

2016-01-01

Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB) family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2), encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

How modifiable factors influence parental decision-making about organ donation.

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Luberda, Kamila; Cleaver, Karen

2017-11-07

A global shortage of organs from children and adults available for transplantation is compounded by the failure of next of kin to consent for organs to be donated after death. Non-modifiable and modifiable factors influence decision-making in this area. Modifiable factors are of interest when examining families' decision-making about the donation of organs from their deceased child. A scoping review was undertaken to determine how modifiable factors influence parental decision-making about organ donation. Thematic analysis identified two themes: interactions with healthcare professionals and pre-disposition to organ donation. Satisfaction with experiences of hospital care, the information provided and the way it was communicated, as well as interactions pertaining to emotional support were all found to be modifiable factors that influenced decision making. Likewise, a predisposition to organ donation and knowing the deceased's wishes were associated with the consent decision. Nurses working in critical care environments need to be able to support parents during this difficult time. This article aims to raise awareness of modifiable factors that influence parental decision-making, highlighting their relevance for children's nursing practice. ©2017 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer.

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Cui, X Y; Tinholt, M; Stavik, B; Dahm, A E A; Kanse, S; Jin, Y; Seidl, S; Sahlberg, K K; Iversen, N; Skretting, G; Sandset, P M

2016-02-01

ESSENTIALS: A hypoxic microenvironment is a common feature of tumors that may influence activation of coagulation. MCF-7 and SK-BR-3 breast cancer cells and breast cancer tissue samples were used. The results showed transcriptional repression of tissue factor pathway inhibitor expression in hypoxia. Hypoxia-inducible factor 1α may be a target for the therapy of cancer-related coagulation and thrombosis. Activation of coagulation is a common finding in patients with cancer, and is associated with an increased risk of venous thrombosis. As a hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia-inducible factor (HIF)-1α in breast cancer cells and their correlation in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. Time-dependent and dose-dependent downregulation of TFPI mRNA (quantitative RT-PCR) and of free TFPI protein (ELISA) were observed in hypoxia. Western blotting showed parallel increases in the levels of HIF-1α protein and TF. HIF-1α inhibitor abolished or attenuated the hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and HIF-1α overexpression caused strong repression of TFPI promoter activity. Subsequent chromatin immunoprecipitation and mutagenesis analysis demonstrated a functional hypoxia response element within the TFPI promoter, located at -1065 to -1060 relative to the transcriptional start point. In breast cancer tissue samples, gene expression analyses showed a positive correlation between the mRNA expression of TFPI and that of HIF-1α. This study demonstrates that HIF-1α is involved in the transcriptional regulation of the TFPI gene, and suggests that a hypoxic microenvironment inside a breast tumor may

PET Imaging of Tissue Factor in Pancreatic Cancer Using 64Cu-Labeled Active Site-Inhibited Factor VII

DEFF Research Database (Denmark)

Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Lotte K

2016-01-01

with advanced stage, increased microvessel density, metastasis, and poor overall survival. Imaging of TF expression is of clinical relevance as a prognostic biomarker and as a companion diagnostic for TF-directed therapies currently under clinical development. Factor VII (FVII) is the natural ligand to TF......UNLABELLED: Tissue factor (TF) is the main initiator of the extrinsic coagulation cascade. However, TF also plays an important role in cancer. TF expression has been reported in 53%-89% of all pancreatic adenocarcinomas, and the expression level of TF has in clinical studies correlated...

Tissue Engineering Using Transfected Growth-Factor Genes

Science.gov (United States)

Madry, Henning; Langer, Robert S.; Freed, Lisa E.; Trippel, Stephen; Vunjak-Novakovic, Gordana

2005-01-01

A method of growing bioengineered tissues includes, as a major component, the use of mammalian cells that have been transfected with genes for secretion of regulator and growth-factor substances. In a typical application, one either seeds the cells onto an artificial matrix made of a synthetic or natural biocompatible material, or else one cultures the cells until they secrete a desired amount of an extracellular matrix. If such a bioengineered tissue construct is to be used for surgical replacement of injured tissue, then the cells should preferably be the patient s own cells or, if not, at least cells matched to the patient s cells according to a human-leucocyteantigen (HLA) test. The bioengineered tissue construct is typically implanted in the patient's injured natural tissue, wherein the growth-factor genes enhance metabolic functions that promote the in vitro development of functional tissue constructs and their integration with native tissues. If the matrix is biodegradable, then one of the results of metabolism could be absorption of the matrix and replacement of the matrix with tissue formed at least partly by the transfected cells. The method was developed for articular chondrocytes but can (at least in principle) be extended to a variety of cell types and biocompatible matrix materials, including ones that have been exploited in prior tissue-engineering methods. Examples of cell types include chondrocytes, hepatocytes, islet cells, nerve cells, muscle cells, other organ cells, bone- and cartilage-forming cells, epithelial and endothelial cells, connective- tissue stem cells, mesodermal stem cells, and cells of the liver and the pancreas. Cells can be obtained from cell-line cultures, biopsies, and tissue banks. Genes, molecules, or nucleic acids that secrete factors that influence the growth of cells, the production of extracellular matrix material, and other cell functions can be inserted in cells by any of a variety of standard transfection techniques.

Hemophilia B with mutations at glycine-48 of factor IX exhibited delayed activation by the factor VIIa-tissue factor complex.

Science.gov (United States)

Wu, P C; Hamaguchi, N; Yu, Y S; Shen, M C; Lin, S W

2000-10-01

Gly-48 is in the conserved DGDQC sequence (residues 47-51 of human factor IX) of the first EGF (EGF-1)-like domain of factor IX. The importance of the Gly-48 is manifested by two hemophilia B patients; factor IXTainan and factor IXMalmo27, with Gly-48 replaced by arginine (designated IXG48R) and valine (IXG48V), respectively. Both patients were CRM+ exhibiting mild hemophilic episodes with 25% (former) and 19% (latter) normal clotting activities. We characterize both factor IX variants to show the roles of Gly-48 and the conservation of the DGDQC sequence in factor IX. Purified plasma and recombinant factor IX variants exhibited approximately 26%-27% normal factor IX's clotting activities with G48R or G48V mutation. Both variants depicted normal quenching of the intrinsic fluorescence by increasing concentrations of calcium ions and Tb3+, indicating that arginine and valine substitution for Gly-48 did not perturb the calcium site in the EGF-1 domain. Activation of both mutants by factor XIa appeared normal. The reduced clotting activity of factors IXG48R and IXG48V was attributed to the failure of both mutants to cleavage factor X: in the presence of only phospholipids and calcium ions, both mutants showed a 4 to approximately 7-fold elevation in Km, and by adding factor VIIIa to the system, although factor VIIIa potentiated the activation of factor X by the mutants factor IXaG48R and factor IXaG48V, a 2 to approximately 3-fold decrease in the catalytic function was observed with the mutant factor IXa's, despite that they bound factor VIIIa on the phospholipid vesicles with only slightly reduced affinity when compared to wild-type factor IXa. The apparent Kd for factor VIIIa binding was 0.83 nM for normal factor IXa, 1.74 nM for IXaG48R and 1.4 nM for IXaG48V. Strikingly, when interaction with the factor VIIa-TF complex was examined, both mutations were barely activated by the VIIa-TF complex and they also showed abnormal interaction with VIIa-TF in bovine

Pre-Diabetes Non-Modifiable Risk Factors

Science.gov (United States)

... Artery Disease Venous Thromboembolism Aortic Aneurysm More Pre-diabetes Non-modifiable Risk Factors Updated:Nov 9,2015 ... This content was last reviewed August 2015. Pre-diabetes • Introduction • About Pre-diabetes • What's the Problem? Intro ...

Aberrant innate immune activation following tissue injury impairs pancreatic regeneration.

Directory of Open Access Journals (Sweden)

Alexandra E Folias

Full Text Available Normal tissue architecture is disrupted following injury, as resident tissue cells become damaged and immune cells are recruited to the site of injury. While injury and inflammation are critical to tissue remodeling, the inability to resolve this response can lead to the destructive complications of chronic inflammation. In the pancreas, acinar cells of the exocrine compartment respond to injury by transiently adopting characteristics of progenitor cells present during embryonic development. This process of de-differentiation creates a window where a mature and stable cell gains flexibility and is potentially permissive to changes in cellular fate. How de-differentiation can turn an acinar cell into another cell type (such as a pancreatic β-cell, or a cell with cancerous potential (as in cases of deregulated Kras activity is of interest to both the regenerative medicine and cancer communities. While it is known that inflammation and acinar de-differentiation increase following pancreatic injury, it remains unclear which immune cells are involved in this process. We used a combination of genetically modified mice, immunological blockade and cellular characterization to identify the immune cells that impact pancreatic regeneration in an in vivo model of pancreatitis. We identified the innate inflammatory response of macrophages and neutrophils as regulators of pancreatic regeneration. Under normal conditions, mild innate inflammation prompts a transient de-differentiation of acinar cells that readily dissipates to allow normal regeneration. However, non-resolving inflammation developed when elevated pancreatic levels of neutrophils producing interferon-γ increased iNOS levels and the pro-inflammatory response of macrophages. Pancreatic injury improved following in vivo macrophage depletion, iNOS inhibition as well as suppression of iNOS levels in macrophages via interferon-γ blockade, supporting the impairment in regeneration and the

Sensitive detection of oversulfated chondroitin sulfate in heparin sodium or crude heparin with a colorimetric microplate based assay.

Science.gov (United States)

Sommers, Cynthia D; Mans, Daniel J; Mecker, Laura C; Keire, David A

2011-05-01

In this work we describe a 96-well microplate assay for oversulfated chondroitin sulfate A (OSCS) in heparin, based on a water-soluble cationic polythiophene polymer (3-(2-(N-(N'-methylimidazole))ethoxy)-4-methylthiophene (LPTP)) and heparinase digestion of heparin. The assay takes advantage of several unique properties of heparin, OSCS, and LPTP, including OSCS inhibition of heparinase I and II activity, the molecular weight dependence of heparin-LPTP spectral shifts, and the distinct association of heparin fragments and OSCS to LPTP. These factors combine to enable detection of the presence of 0.003% w/w spiked OSCS in 10 μg of heparin sodium active pharmaceutical ingredient (API) using a plate reader and with visual detection to 0.1% levels. The same detection limit for OSCS was observed in the presence of 10% levels of dermatan sulfate (DS) or chondroitin sulfate A (CSA) impurities. In addition, we surveyed a selection of crude heparin samples received by the agency in 2008 and 2009 to determine average and extreme DS, CSA, and galactosamine weight percent levels. In the presence of these impurities and the variable heparin content in the crude heparin samples, spiked OSCS was reliably detected to the 0.1% w/w level using a plate reader. Finally, authentically OSCS contaminated heparin sodium API and crude samples were distinguished visually by color from control samples using the LPTP/heparinase test.

In vitro evaluation of tissue adhesives composed of hydrophobically modified gelatins and disuccinimidyl tartrate

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Miyuki Matsuda

2012-01-01

Full Text Available The effect of the hydrophobic group content in gelatin on the bonding strength of novel tissue–penetrating tissue adhesives was evaluated. The hydrophobic groups introduced into gelatin were the saturated hexanoyl, palmitoyl, and stearoyl groups, and the unsaturated oleoyl group. A collagen casing was employed as an adherend to model soft tissue for the in vitro determination of bonding strength of tissue adhesives composed of various hydrophobically modified gelatins and disuccinimidyl tartrate. The adhesive composed of stearoyl-modified gelatin (7.4% stearoyl; 10Ste and disuccinimidyl tartrate showed the highest bonding strength. The bonding strength of the adhesives decreased as the degree of substitution of the hydrophobic groups increased. Cell culture experiments demonstrated that fluorescein isothiocyanate-labeled 10Ste was integrated onto the surface of smooth muscle cells and showed no cytotoxicity. These results suggest that 10Ste interacted with the hydrophobic domains of collagen casings, such as hydrophobic amino acid residues and cell membranes. Therefore, 10Ste–disuccinimidyl tartrate is a promising adhesive for use in aortic dissection.

Hypoxia-Inducible Factor-1α: A Potential Factor for the Enhancement of Osseointegration between Dental Implants and Tissue-Engineered Bone

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Duohong Zou

2011-07-01

Full Text Available Introduction: Tissue-engineered bones are widely utilized to protect healthy tissue, reduce pain, and increase the success rate of dental implants. one of the most challenging obstacles lies in obtaining effective os-seointegration between dental implants and tissue-engineered structures. Deficiencies in vascularization, osteogenic factors, oxygen, and other nutrients inside the tissue-engineered bone during the early stages following implantation all inhibit effective osseointe-gration. Oxygen is required for aerobic metabolism in bone and blood vessel tissues, but oxygen levels inside tissue-engineered bone are not suf-ficient for cell proliferation. HIF-1α is a pivotal regulator of hypoxic and ischemic vascular responses, driving transcriptional activation of hundreds of genes involved in vascular reactivity, angiogenesis, arteriogenesis, and osteogenesis.The hypothesis: Hypoxia-Inducible Factor-1α seems a potential factor for the enhancement of osseointegration between dental implants and tissue-engineered bone.Evaluation of the hypothesis: Enhancement of HIF-1α protein expression is recognized as the most promising approach for angiogenesis, because it can induce multiple angiogenic targets in a coordinated manner. Therefore, it will be a novel potential therapeutic methods targeting HIF-1α expression to enhance osseointegration be-tween dental implants and tissue-engineered bone.

Tissue factor pathway inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study.

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Aurélie Di Bartolomeo

Full Text Available The study aimed to evaluate if the rate of tissue factor pathway inhibitor during pregnancy and following delivery could be a predictive factor for placenta-mediated adverse pregnancy outcomes in high-risk women.This was a prospective multicentre cohort study of 200 patients at a high risk of occurrence or recurrence of placenta-mediated adverse pregnancy outcomes conducted between June 2008 and October 2010. Measurements of tissue factor pathway inhibitor resistance (normalized ratio and tissue factor pathway inhibitor activity were performed for the last 72 patients at 20, 24, 28, 32, and 36 weeks of gestation and during the postpartum period.Overall, 15 patients presented a placenta-mediated adverse pregnancy outcome. There was no difference in normalized tissue factor pathway inhibitor ratios between patients with and without placenta-mediated adverse pregnancy outcomes during pregnancy and in the post-partum period. Patients with placenta-mediated adverse pregnancy outcomes had tissue factor pathway inhibitor activity rates that were significantly higher than those in patients without at as early as 24 weeks of gestation. The same results were observed following delivery.Among high-risk women, the tissue factor pathway inhibitor activity of patients with gestational vascular complications is higher than that in other patients. Hence, these markers could augment a screening strategy that includes an analysis of angiogenic factors as well as clinical and ultrasound imaging with Doppler measurement of the uterine arteries.

PET Imaging of Tissue Factor in Pancreatic Cancer Using 64Cu-Labeled Active Site-Inhibited Factor VII.

Science.gov (United States)

Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Lotte K; Jensen, Mette M; El Ali, Henrik H; Madsen, Jacob; Wiinberg, Bo; Petersen, Lars C; Kjaer, Andreas

2016-07-01

Tissue factor (TF) is the main initiator of the extrinsic coagulation cascade. However, TF also plays an important role in cancer. TF expression has been reported in 53%-89% of all pancreatic adenocarcinomas, and the expression level of TF has in clinical studies correlated with advanced stage, increased microvessel density, metastasis, and poor overall survival. Imaging of TF expression is of clinical relevance as a prognostic biomarker and as a companion diagnostic for TF-directed therapies currently under clinical development. Factor VII (FVII) is the natural ligand to TF. The purpose of this study was to investigate the possibility of using active site-inhibited FVII (FVIIai) labeled with (64)Cu for PET imaging of TF expression. FVIIai was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with (64)Cu ((64)Cu-NOTA-FVIIai). Longitudinal in vivo PET imaging was performed at 1, 4, 15, and 36 h after injection of (64)Cu-NOTA-FVIIai in mice with pancreatic adenocarcinomas (BxPC-3). The specificity of TF imaging with (64)Cu-NOTA-FVIIai was investigated in subcutaneous pancreatic tumor models with different levels of TF expression and in a competition experiment. In addition, imaging of orthotopic pancreatic tumors was performed using (64)Cu-NOTA-FVIIai and PET/MRI. In vivo imaging data were supported by ex vivo biodistribution, flow cytometry, and immunohistochemistry. Longitudinal PET imaging with (64)Cu-NOTA-FVIIai showed a tumor uptake of 2.3 ± 0.2, 3.7 ± 0.3, 3.4 ± 0.3, and 2.4 ± 0.3 percentage injected dose per gram at 1, 4, 15, and 36 h after injection, respectively. An increase in tumor-to-normal-tissue contrast was observed over the imaging time course. Competition with unlabeled FVIIai significantly (P < 0.001) reduced the tumor uptake. The tumor uptake observed in models with different TF expression levels was significantly different from each other (P < 0.001) and was in agreement with

Methamphetamine Administration Modifies Leukocyte Proliferation and Cytokine Production in Murine Tissues

Science.gov (United States)

Peerzada, Habibullah; Ghandi, Jay A.; Guimaraes, Allan J.; Nosanchuk, Joshua D.; Martinez, Luis R.

2013-01-01

Methamphetamine (METH) is a potent and highly addictive central nervous system (CNS) stimulant. Additionally, METH adversely impacts immunological responses, which might contribute to the higher rate and more rapid progression of certain infections in drug abusers. However no studies have shown the impact of METH on inflammation within specific organs, cellular participation and cytokine production. Using a murine model of METH administration, we demonstrated that METH modifies, with variable degrees, leukocyte recruitment and alters cellular mediators in the lungs, liver, spleen and kidneys of mice. Our findings demonstrate the pleotropic effects of METH on the immune response within diverse tissues. These alterations have profound implications on tissue homeostasis and the capacity of the host to respond to diverse insults, including invading pathogens. PMID:23518444

Pre-analytical and Analytical Variables Affecting the Measurement of Plasma-Derived Microparticle Tissue Factor Activity

Science.gov (United States)

Lee, RD; Barcel, DA; Williams, JC; Wang, JG; Boles, JC; Manly, DA; Key, NS; Mackman, N

2011-01-01

Introduction Elevated levels of tissue factor positive (TF+) microparticles (MPs) are observed in plasma from a variety of patients with an increased risk of thrombosis. We and others have described the measurement of TF activity in MPs isolated from plasma. The aim of this study was to investigate the effects of pre-analytical and analytical variables on TF activity of MPs isolated from blood of healthy volunteers treated ex vivo with or without bacterial lipopolysaccharide. Materials and Methods We evaluated the following parameters: use of different centrifugation speeds to isolate the MPs; comparison of TF activity of MPs isolated from platelet poor plasma versus platelet free plasma; effect of freeze/thaw on MP TF activity; and comparison of the MP TF activity assay with the measurement of TF protein by ELISA or flow cytometry. Results MPs prepared from platelet poor plasma by centrifugation at 20,000 × g or 100,000 × g for 15 minutes had similar levels of TF activity. However, significantly less TF activity was found in MPs isolated from platelet free plasma compared with platelet poor plasma. Interestingly, freeze/thawing of the plasma showed donor to donor variation in MP TF activity, with a moderate increase in some individuals. Conclusion TF+ MPs can be quantitatively isolated from platelet poor or platelet free plasma by centrifugation at 20,000 × g for 15 minutes. Measurement of MP TF activity in plasma can be used to detect a prothrombotic state in patients with various diseases. PMID:21737126

Effects of AVX-470, an Oral, Locally Acting Anti-Tumour Necrosis Factor Antibody, on Tissue Biomarkers in Patients with Active Ulcerative Colitis.

Science.gov (United States)

Hartman, Deborah S; Tracey, Daniel E; Lemos, Brenda R; Erlich, Emma C; Burton, Randall E; Keane, David M; Patel, Rutvij; Kim, Skaison; Bhol, Kailash C; Harris, M Scott; Fox, Barbara S

2016-06-01

AVX-470 is an orally administered, bovine-derived, anti-tumour necrosis factor (TNF) antibody with local activity in the gastrointestinal tract. In the first-in-human clinical trial of AVX-470 in active ulcerative colitis, we evaluated inflammatory biomarkers in colon tissue as measures of disease activity and early response to treatment. Thirty-six patients received active drug (AVX-470 at 0.2, 1.6 or 3.5g/day) or placebo over 4 weeks. Colon biopsy samples were collected from 5 regions of colon at baseline and week 4. Tissue inflammatory biomarkers were evaluated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), epithelial cell apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and bovine immunoglobulin by immunohistochemistry and mass spectrometry. Endoscopic activity (Ulcerative Colitis Endoscopic Index of Severity [UCEIS]) at colonoscopy was assessed in each colonic region by a central reader. Bovine immunoglobulin was observed in mucosal tissue before and after dosing in lamina propria and submucosal layers of biopsy tissue. Baseline levels of TNF, myeloperoxidase (MPO), CD68 and interleukin (IL)-1β and, to a lesser extent, IL-6 mRNA were 2- to 3-fold higher in distal vs proximal colon tissue, corresponding to the 2- to 3-fold differences in baseline severities of endoscopic scores. Reductions of >10-fold in TNF and, to lesser extents, in MPO and epithelial cell apoptosis were observed in proximal and distal colon biopsies after 4 weeks of AVX-470 3.5g/day treatment. Reductions in TNF scores were correlated with changes in MPO and CD3 immunohistochemistry scores. These results are consistent with anti-TNF activity of orally administered AVX-470 in colon mucosal tissue in ulcerative colitis patients and demonstrate the utility of tissue biomarkers in assessing disease and treatment response in early clinical studies. This trial was registered with Clinicaltrials.gov as study NCT

Physical activity as a health factor modifying heart rate variability (HRV

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Nowosielska-Swadzba Danuta

2015-03-01

Full Text Available Purpose: The aim of the research was the evaluation of the selected HRV factors of the training volleyball players in two training periods and non-training people. Materials and methods : The study involved 8 leading volleyball players aged 20-23 and 13 non-training persons aged 19-26. The study of the training players was conducted twice: in the pre-competition and in the competition period. The study for the non-training persons was conducted once. The selected factors of the spectral analysis have been evaluated: TP [ms 2], share of LF and HF power [n.u], LF/HF indicator and time analysis factors: RR [ms], HR [1/min], RMSSD [ms]. Results : Statistically significant differences appeared only in the selected time analysis factors (RR, HR, between the group of the training and non-training persons. Other differences in the evaluated parameters were not statistically significant. Conclusions : Physical activity influences on the HRV growth. HRV measurement may serve for the control of the changes taking place in the AUN under the influence of the physical activity.

Large enhancement of functional activity of active site-inhibited factor VIIa due to protein dimerization: insights into mechanism of assembly/disassembly from tissue factor.

Science.gov (United States)

Stone, Matthew D; Harvey, Stephen B; Martinez, Michael B; Bach, Ronald R; Nelsestuen, Gary L

2005-04-26

Active site-inhibited blood clotting factor VIIa (fVIIai) binds to tissue factor (TF), a cell surface receptor that is exposed upon injury and initiates the blood clotting cascade. FVIIai blocks binding of the corresponding enzyme (fVIIa) or zymogen (fVII) forms of factor VII and inhibits coagulation. Although several studies have suggested that fVIIai may have superior anticoagulation effects in vivo, a challenge for use of fVIIai is cost of production. This study reports the properties of dimeric forms of fVIIai that are cross-linked through their active sites. Dimeric wild-type fVIIai was at least 75-fold more effective than monomeric fVIIai in blocking fVIIa association with TF. The dimer of a mutant fVIIai with higher membrane affinity was 1600-fold more effective. Anticoagulation by any form of fVIIai differed substantially from agents such as heparin and showed a delayed mode of action. Coagulation proceeded normally for the first minutes, and inhibition increased as equilibrium binding was established. It is suggested that association of fVIIa(i) with TF in a collision-dependent reaction gives equal access of inhibitor and enzyme to TF. Assembly was not influenced by the higher affinity and slower dissociation of the dimer. As a result, anticoagulation was delayed until the reaction reached equilibrium. Properties of different dissociation experiments suggested that dissociation of fVIIai from TF occurred by a two-step mechanism. The first step was separation of TF-fVIIa(i) while both proteins remained bound to the membrane, and the second step was dissociation of the fVIIa(i) from the membrane. These results suggest novel actions of fVIIai that distinguish it from most of the anticoagulants that block later steps of the coagulation cascade.

Expression of modified tocopherol content and profile in sunflower tissues.

Science.gov (United States)

Del Moral, Lidia; Fernández-Martínez, José M; Pérez-Vich, Begoña; Velasco, Leonardo

2012-01-30

Alpha-tocopherol is the predominant tocopherol form in sunflower seeds. Sunflower lines that accumulate increased levels of beta-, gamma- and delta-tocopherol in seeds as well as lines with reduced and increased total seed tocopherol content have been developed. The objective of this research was to evaluate whether the modified tocopherol levels are expressed in plant tissues other than seeds. Lines with increased levels of beta-, gamma- and delta-tocopherol in seeds also possessed increased levels of these tocopherols in leaves, roots and pollen. Correlation coefficients for the proportion of individual tocopherols in different plant tissues were significantly positive in all cases, ranging from 0.68 to 0.97. A line with reduced tocopherol content in seeds also showed reduced content in roots and pollen. Genetic modifications producing altered seed tocopherol profiles in sunflower are also expressed in leaves, roots and pollen. Reduced total seed tocopherol content is mainly expressed at the root and pollen level. The expression of tocopherol mutations in other plant tissues will enable further studies on the physiological role of tocopherols and could be of interest for early selection for these traits in breeding programmes. Copyright © 2011 Society of Chemical Industry.

The tRNA synthetase paralog PoxA modifies elongation factor-P with (R)-ß-lysine

DEFF Research Database (Denmark)

Roy, Hervé; Zou, S Betty; Bullwinkle, Tammy J

2011-01-01

The lysyl-tRNA synthetase paralog PoxA modifies elongation factor P (EF-P) with a-lysine at low efficiency. Cell-free extracts containing non-a-lysine substrates of PoxA modified EF-P with a change in mass consistent with addition of ß-lysine, a substrate also predicted by genomic analyses. EF......-P was efficiently functionally modified with (R)-ß-lysine but not (S)-ß-lysine or genetically encoded a-amino acids, indicating that PoxA has evolved an activity orthogonal to that of the canonical aminoacyl-tRNA synthetases....

Plasma Tissue Factor Pathway Inhibitor Levels in Angiographically Defined Coronary Artery Disease Among Saudis

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Syed Shahid Habib

2013-05-01

Full Text Available Objectives: This study was aimed to determine plasma levels of total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA in a cohort of Saudi patients with chronic stable angiographically defined coronary artery disease (CAD and to determine its correlation with its severity.Methods: This cross sectional study was conducted in the department of physiology and department of cardiology, College of Medicine, and King Khalid University Hospital and King Saud University, Riyadh. Sixty known cases of CAD who had undergone angiography (35 males and 25 females were selected. A control group included 39 (20 males and 19 females healthy subjects. Fasting venous blood samples were analyzed for total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA. Gensini scores and vessel scores were determined for assessing CAD severity.Results: There were non-significant differences between age, body mass index (BMI and Blood pressure between the controls and CAD subjects. A comparison of hemostatic markers between control and CAD patients showed significantly higher levels of Fibrinogen, PAI-1, TFPI-T and TFPI-F in CAD patients compared to control subjects. But there was no difference in plasma t-PA levels. TFPI-T had a significant positive correlation with severity of disease determined by Gensini Scores (r=0.344; p=0.006 and vessel scores (r=0.338; p=0.015.Conclusion: Plasma levels of total tissue factor pathway inhibitor are significantly related with the presence and severity of CAD. Elevated levels of TFPI-T may be considered as useful diagnostic and prognostic markers in patients with CAD.

A Modified Porous Titanium Sheet Prepared by Plasma-Activated Sintering for Biomedical Applications

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Yukimichi Tamaki

2010-01-01

Full Text Available This study aimed to develop a contamination-free porous titanium scaffold by a plasma-activated sintering within an originally developed TiN-coated graphite mold. The surface of porous titanium sheet with or without a coated graphite mold was characterized. The cell adhesion property of porous titanium sheet was also evaluated in this study. The peak of TiC was detected on the titanium sheet processed with the graphite mold without a TiN coating. Since the titanium fiber elements were directly in contact with the carbon graphite mold during processing, surface contamination was unavoidable event in this condition. The TiC peak was not detectable on the titanium sheet processed within the TiN-coated carbon graphite mold. This modified plasma-activated sintering with the TiN-coated graphite mold would be useful to fabricate a contamination-free titanium sheet. The number of adherent cells on the modified titanium sheet was greater than that of the bare titanium plate. Stress fiber formation and the extension of the cells were observed on the titanium sheets. This modified titanium sheet is expected to be a new tissue engineering material in orthopedic bone repair.

Vitamin D modulates tissue factor and protease-activated receptor 2 expression in vascular smooth muscle cells.

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Martinez-Moreno, Julio M; Herencia, Carmen; Montes de Oca, Addy; Muñoz-Castañeda, Juan R; Rodríguez-Ortiz, M Encarnación; Díaz-Tocados, Juan M; Peralbo-Santaella, Esther; Camargo, Antonio; Canalejo, Antonio; Rodriguez, Mariano; Velasco-Gimena, Francisco; Almaden, Yolanda

2016-03-01

Clinical and epidemiologic studies reveal an association between vitamin D deficiency and increased risk of cardiovascular disease. Because vascular smooth muscle cell (VSMC)-derived tissue factor (TF) is suggested to be critical for arterial thrombosis, we investigated whether the vitamin D molecules calcitriol and paricalcitol could reduce the expression of TF induced by the proinflammatory cytokine TNF-α in human aortic VSMCs. We found that, compared with controls, incubation with TNF-α increased TF expression and procoagulant activity in a NF-κB-dependent manner, as deduced from the increased nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells protein 65 (p65-NF-κB) and direct interaction of NF-κB to the TF promoter. This was accompanied by the up-regulation of TF signaling mediator protease-activated receptor 2 (PAR-2) expression and by the down-regulation of vitamin D receptor expression in a miR-346-dependent way. However, addition of calcitriol or paricalcitol blunted the TNF-α-induced TF expression and activity (2.01 ± 0.24 and 1.32 ± 0.14 vs. 3.02 ± 0.39 pmol/mg protein, P < 0.05), which was associated with down-regulation of NF-κB signaling and PAR-2 expression, as well as with restored levels of vitamin D receptor and enhanced expression of TF pathway inhibitor. Our data suggest that inflammation promotes a prothrombotic state through the up-regulation of TF function in VSMCs and that the beneficial cardiovascular effects of vitamin D may be partially due to decreases in TF expression and its activity in VSMCs. © FASEB.

Cartilaginous extracellular matrix-modified chitosan hydrogels for cartilage tissue engineering.

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Choi, Bogyu; Kim, Soyon; Lin, Brian; Wu, Benjamin M; Lee, Min

2014-11-26

Cartilaginous extracellular matrix (ECM) components such as type-II collagen (Col II) and chondroitin sulfate (CS) play a crucial role in chondrogenesis. However, direct clinical use of natural Col II or CS as scaffolds for cartilage tissue engineering is limited by their instability and rapid enzymatic degradation. Here, we investigate the incorporation of Col II and CS into injectable chitosan hydrogels designed to gel upon initiation by exposure to visible blue light (VBL) in the presence of riboflavin. Unmodified chitosan hydrogel supported proliferation and deposition of cartilaginous ECM by encapsulated chondrocytes and mesenchymal stem cells. The incorporation of native Col II or CS into chitosan hydrogels further increased chondrogenesis. The incorporation of Col II, in particular, was found to be responsible for the enhanced cellular condensation and chondrogenesis observed in modified hydrogels. This was mediated by integrin α10 binding to Col II, increasing cell-matrix adhesion. These findings demonstrate the potential of cartilage ECM-modified chitosan hydrogels as biomaterials to promote cartilage regeneration.

Breast Cancer Risk From Modifiable and Non-Modifiable Risk Factors among Women in Southeast Asia: A Meta-Analysis

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Nindrea, Ricvan Dana; Aryandono, Teguh; Lazuardi, Lutfan

2017-12-28

Objective: The aim of this study was to determine breast cancer risk from modifiable and non-modifiable factors among women in Southeast Asia. Methods: This meta-analysis was performed on research articles on breast cancer risk factors in PubMed, ProQuest and EBSCO databases published between 1997 and October 2017. Pooled odds ratios (OR) are calculated using fixed and random-effect models. Data were processed using Review Manager 5.3 (RevMan 5.3). Results: From a total of 1,211 articles, 15 studies (1 cohort and 14 case control studies) met the criteria for systematic review. Meta-analysis results showed that of the known modifiable risk factors for breast cancer, parity (nulipara) had the highest odd ratio (OR = 1.85 [95% CI 1.47-2.32]) followed by body mass index (overweight) (OR = 1.61 [95% CI 1.43-1.80]) and use of oral contraceptives (OR = 1.27 [95% CI 1.07-1.51]). Of non-modifiable risk factors, family history of breast cancer had the highest odd ratio (OR = 2.53 [95% CI 1.25-5.09]), followed by age (≥ 40 years) (OR = 1.53 [95% CI 1.34-1.76]) and menopausal status (OR = 1.44 [95% CI 1.26-1.65]). Conclusion: This analysis confirmed associations between both modifiable risk factors (parity, body mass index and use of oral contraceptives) and non-modifiable risk factors (family history of breast cancer, age and menopausal status) with breast cancer. Creative Commons Attribution License

[Significant decrease in factor VII activity by tissue thromboplastin derived from rabbit brain in a patient with congenital factor VII deficiency (FVII Padua)].

Science.gov (United States)

Sekiya, Akiko; Morishita, Eriko; Maruyama, Keiko; Asakura, Hidesaku; Nakao, Shinji; Ohtake, Shigeki

2012-03-01

Congenital factor VII (FVII) deficiency is a bleeding disorder that requires optimal hemostatic management for each case due to its wide variety of bleeding symptoms. We experienced a patient with inherited FVII deficiency who demonstrated different FVII activities depending on tissue thromboplastins used for assays. An 82-year-old woman without any episodes of abnormal bleeding was found to have different FVII activities of 1.4% and 32% when assayed using thromboplastins from rabbit brain and human placenta, respectively. DNA sequencing analysis revealed a homozygous missense mutation of G10828A (FVII Padua) that caused an amino acid substitution of Arg304 to Gln (R304Q). Carriers of 304Q alleles are usually clinically asymptomatic and do not require FVII replacement therapies even in cases of homozygotes. In case a prolonged prothrombin time or reduced FVII activity is detected, re-examination using thromboplastins of other sources can be helpful for preliminary diagnosis of R304Q, in order to prevent unnecessary FVII replacement therapies.

Exogenous Bradykinin Inhibits Tissue Factor Induction and Deep Vein Thrombosis via Activating the eNOS/Phosphoinositide 3-Kinase/Akt Signaling Pathway

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Ruolan Dong

2015-11-01

Full Text Available Background/Aims: Bradykinin has been shown to exert a variety of protective effects against vascular injury, and to reduce the levels of several factors involved in the coagulation cascade. A key determinant of thrombin generation is tissue factor (TF. However, whether bradykinin can regulate TF expression remains to be investigated. Methods: To study the effect of bradykinin on TF expression, we used Lipopolysaccharides (LPS to induce TF expression in human umbilical vein endothelial cells and monocytes. Transcript levels were determined by RT-PCR, protein abundance by Western blotting. In the in vivo study, bradykinin and equal saline were intraperitoneally injected into mice for three days ahead of inferior cava vein ligation that we took to induce thrombus formation, after which bradykinin and saline were injected for another two days. Eventually, the mice were sacrificed and tissues were harvested for tests. Results: Exogenous bradykinin markedly inhibited TF expression in mRNA and protein level induced by LPS in a dose-dependent manner. Moreover, the NO synthase antagonist L-NAME and PI3K inhibitor LY294002 dramatically abolished the inhibitory effects of bradykinin on tissue factor expression. PI3K/Akt signaling pathway activation induced by bradykinin administration reduced the activity of GSK-3ß and MAPK, and reduced NF-κB level in the nucleus, thereby inhibiting TF expression. Consistent with this, intraperitoneal injection of C57/BL6 mice with bradykinin also inhibited the thrombus formation induced by ligation of inferior vena cava. Conclusion: Bradykinin suppressed TF protein expression in human umbilical vein endothelial cells and monocytes in vitro; in line with this, it inhibits thrombus formation induced by ligation of inferior vena cava in vivo.

Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid

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Ryan C. Bates

2015-08-01

Full Text Available Neural tissue exposure to valproic acid (VPA increases several pro-survival phospho-proteins that can be used as biomarkers for indicating a beneficial drug response (pAktSer473, pGSK3βSer9, pErk1/2Thr202/Tyr204. Unfortunately, targeting VPA to neural tissue is a problem due to severe asymmetrical distribution, wherein the drug tends to remain in peripheral blood rather than localizing within the brain. Intracerebral delivery of an amide-linked VPA–PEG conjugate could address these issues by enhancing retention and promoting cerebro-global increases in pro-survival phospho-proteins. It is necessary to assay for the retained bioactivity of a PEGylated valproic acid molecule, along with locating an intracranial cannula placement that optimizes the increase of a known downstream biomarker for chronic VPA exposure. Here we show an acute injection of VPA–PEG conjugate within brain tissue increased virtually all of the assayed phospho-proteins, including well-known pro-survival factors. In contrast, an acute injection of VPA expectedly decreased signaling throughout the hour. Needle penetration into whole brain tissue is the intentional cause of trauma in this procedure. The trauma to brain tissue was observed to overcome known phospho-protein increases for unmodified VPA in the injected solution, while VPA–PEG conjugate appeared to induce significant increases in pro-survival phospho-proteins, despite the procedural trauma.

Active containment systems incorporating modified pillared clays

International Nuclear Information System (INIS)

Lundie, P.; McLeod, N.

1997-01-01

The application of treatment technologies in active containment systems provides a more advanced and effective method for the remediation of contaminated sites. These treatment technologies can be applied in permeable reactive walls and/or funnel and gate systems. The application of modified pillared clays in active containment systems provides a mechanism for producing permeable reactive walls with versatile properties. These pillared clays are suitably modified to incorporate reactive intercalatants capable of reacting with both a broad range of organic pollutants of varying molecular size, polarity and reactivity. Heavy metals can be removed from contaminated water by conventional ion-exchange and other reactive processes within the clay structure. Complex contamination problems can be addressed by the application of more than one modified clay on a site specific basis. This paper briefly describes the active containment system and the structure/chemistry of the modified pillared clay technology, illustrating potential applications of the in-situ treatment process for contaminated site remediation

Critical illness induces alternative activation of M2 macrophages in adipose tissue.

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Langouche, Lies; Marques, Mirna B; Ingels, Catherine; Gunst, Jan; Derde, Sarah; Vander Perre, Sarah; D'Hoore, André; Van den Berghe, Greet

2011-01-01

We recently reported macrophage accumulation in adipose tissue of critically ill patients. Classically activated macrophage accumulation in adipose tissue is a known feature of obesity, where it is linked with increasing insulin resistance. However, the characteristics of adipose tissue macrophage accumulation in critical illness remain unknown. We studied macrophage markers with immunostaining and gene expression in visceral and subcutaneous adipose tissue from healthy control subjects (n = 20) and non-surviving prolonged critically ill patients (n = 61). For comparison, also subcutaneous in vivo adipose tissue biopsies were studied from 15 prolonged critically ill patients. Subcutaneous and visceral adipose tissue biopsies from non-surviving prolonged critically ill patients displayed a large increase in macrophage staining. This staining corresponded with elevated gene expression of "alternatively activated" M2 macrophage markers arginase-1, IL-10 and CD163 and low levels of the "classically activated" M1 macrophage markers tumor necrosis factor (TNF)-α and inducible nitric-oxide synthase (iNOS). Immunostaining for CD163 confirmed positive M2 macrophage staining in both visceral and subcutaneous adipose tissue biopsies from critically ill patients. Surprisingly, circulating levels and tissue gene expression of the alternative M2 activators IL-4 and IL-13 were low and not different from controls. In contrast, adipose tissue protein levels of peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor required for M2 differentiation and acting downstream of IL-4, was markedly elevated in illness. In subcutaneous abdominal adipose tissue biopsies from surviving critically ill patients, we could confirm positive macrophage staining with CD68 and CD163. We also could confirm elevated arginase-1 gene expression and elevated PPARγ protein levels. Unlike obesity, critical illness evokes adipose tissue accumulation of alternatively activated M2

Tissue factor-expressing tumor cells can bind to immobilized recombinant tissue factor pathway inhibitor under static and shear conditions in vitro.

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Sara P Y Che

Full Text Available Mammary tumors and malignant breast cancer cell lines over-express the coagulation factor, tissue factor (TF. High expression of TF is associated with a poor prognosis in breast cancer. Tissue factor pathway inhibitor (TFPI, the endogenous inhibitor of TF, is constitutively expressed on the endothelium. We hypothesized that TF-expressing tumor cells can bind to immobilized recombinant TFPI, leading to arrest of the tumor cells under shear in vitro. We evaluated the adhesion of breast cancer cells to immobilized TFPI under static and shear conditions (0.35 - 1.3 dyn/cm2. We found that high-TF-expressing breast cancer cells, MDA-MB-231 (with a TF density of 460,000/cell, but not low TF-expressing MCF-7 (with a TF density of 1,400/cell, adhered to recombinant TFPI, under static and shear conditions. Adhesion of MDA-MB-231 cells to TFPI required activated factor VII (FVIIa, but not FX, and was inhibited by a factor VIIa-blocking anti-TF antibody. Under shear, adhesion to TFPI was dependent on the TFPI-coating concentration, FVIIa concentration and shear stress, with no observed adhesion at shear stresses greater than 1.0 dyn/cm2. This is the first study showing that TF-expressing tumor cells can be captured by immobilized TFPI, a ligand constitutively expressed on the endothelium, under low shear in vitro. Based on our results, we hypothesize that TFPI could be a novel ligand mediating the arrest of TF-expressing tumor cells in high TFPI-expressing vessels under conditions of low shear during metastasis.

Asthma Morbidity, Comorbidities, and Modifiable Factors Among Older Adults.

Science.gov (United States)

Hsu, Joy; Chen, Jessica; Mirabelli, Maria C

Asthma morbidity is increased among older adults, especially older adult women. Interventions to improve asthma control in this population are not well described. The objective of this study was to identify risk factors (including modifiable factors) associated with asthma-related hospitalizations and emergency department or urgent care center visits (ED/UCV) among older adults. A secondary objective was to investigate sex differences in variables relevant to asthma control. Data were obtained from 14,076 older adults ≥65 years with active asthma participating in the 2006-2010 Behavioral Risk Factor Surveillance System Asthma Call-back Survey (a random-digit dialed survey) in 40 US states, the District of Columbia, and Puerto Rico, representative of >2.6 million persons. Weighted, adjusted logistic regression was conducted. One or more asthma-related hospitalizations in the past year were reported by 5.7% (95% confidence interval [95% CI] = 5.0% to 6.4%) of participants; 10.6% (95% CI = 9.7% to 11.5%) reported ≥1 asthma-related ED/UCV. Compared with older adults without asthma-related hospitalizations, adjusted odds were higher among those with ≥1 asthma-related hospitalization for chronic obstructive pulmonary disease (COPD), coronary artery disease, depression, cockroaches or mold in the home, and cost barriers to asthma-related health care or medication. All these factors, except for cockroaches, were associated with asthma-related ED/UCV. Compared with males, adjusted odds were higher among females for COPD, depression, obesity, and cost barriers to asthma-related health care or medication. Among older adults, asthma-related hospitalizations and ED/UCV were associated with clinical comorbidities, mold in the home, and financial barriers to asthma-related health care. Interventions addressing modifiable factors could reduce asthma morbidity among older adults. Published by Elsevier Inc.

High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors.

Science.gov (United States)

Koizume, Shiro; Ito, Shin; Yoshioka, Yusuke; Kanayama, Tomohiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Yamada, Roppei; Ochiya, Takahiro; Ruf, Wolfram; Miyagi, Etsuko; Hirahara, Fumiki; Miyagi, Yohei

2016-01-01

Thromboembolic events occur frequently in ovarian cancer patients. Tissue factor (TF) is often overexpressed in tumours, including ovarian clear-cell carcinoma (CCC), a subtype with a generally poor prognosis. TF-coagulation factor VII (fVII) complexes on the cell surface activate downstream coagulation mechanisms. Moreover, cancer cells secrete extracellular vesicles (EVs), which act as vehicles for TF. We therefore examined the characteristics of EVs produced by ovarian cancer cells of various histological subtypes. CCC cells secreted high levels of TF within EVs, while the high-TF expressing breast cancer cell line MDA-MB-231 shed fewer TF-positive EVs. We also found that CCC tumours with hypoxic tissue areas synthesised TF and fVII in vivo, rendering the blood of xenograft mice bearing these tumours hypercoagulable compared with mice bearing MDA-MB-231 tumours. Incorporation of TF into EVs and secretion of EVs from CCC cells exposed to hypoxia were both dependent on the actin-binding protein, filamin-A (filA). Furthermore, production of these EVs was dependent on different protease-activated receptors (PARs) on the cell surface. These results show that CCC cells could produce large numbers of TF-positive EVs dependent upon filA and PARs. This phenomenon may be the mechanism underlying the increased incidence of venous thromboembolism in ovarian cancer patients.

Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

NARCIS (Netherlands)

Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

2017-01-01

Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor beta induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

NARCIS (Netherlands)

Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

2017-01-01

Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

Dietary leucine--an environmental modifier of insulin resistance acting on multiple levels of metabolism.

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Yazmin Macotela

Full Text Available Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor--leucine--can modify insulin resistance by acting on multiple tissues and at multiple levels of metabolism. Mice were placed on a normal or high fat diet (HFD. Dietary leucine was doubled by addition to the drinking water. mRNA, protein and complete metabolomic profiles were assessed in the major insulin sensitive tissues and serum, and correlated with changes in glucose homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum. Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling without altering food intake or weight gain. Increased dietary leucine was also associated with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest changes in a single environmental/nutrient factor can modify multiple metabolic and signaling pathways and modify HFD induced metabolic syndrome by acting at a systemic level on multiple tissues. These data also suggest that increasing dietary leucine may provide an adjunct in the management of obesity-related insulin resistance.

Characterizing Stressors and Modifiable Health Risk Factors among Homeless Smokers: An Exploratory Pilot Study

Science.gov (United States)

Kendzor, Darla E.; Reitzel, Lorraine R.; Businelle, Michael S.

2015-01-01

This pilot study was conducted to explore the associations between stressors related to homelessness and modifiable health risk factors (poor diet, insufficient physical activity, and overweight/obesity) and to provide direction for future research. Participants (N = 57) were homeless adults enrolled in a smoking cessation program. Analyses were…

Modifying Risk Factors in the Management of Erectile Dysfunction: A Review

Directory of Open Access Journals (Sweden)

Kenneth J DeLay

2016-08-01

Full Text Available Erectile dysfunction (ED is prevalent among men and its presence is often an indicator of systemic disease. Risk factors for ED include cardiovascular disease, hypertension, diabetes mellitus (DM, tobacco use, hyperlipidemia, hypogonadism, lower urinary tract symptoms, metabolic syndrome, and depression. Addressing the modifiable risk factors frequently improves a patient’s overall health and increases lifespan. The literature suggests that smoking cessation, treatment of hyperlipidemia, and increasing physical activity will improve erectile function in many patients. How the treatment of DM, depression, and hypogonadism impacts erectile function is less clear. Clinicians need to be aware that certain antihypertensive agents can adversely impact erectile function. The treatment of men with ED needs to address the underlying risk factors to ameliorate the disease process.

Connective Tissue Growth Factor Domain 4 Amplifies Fibrotic Kidney Disease through Activation of LDL Receptor-Related Protein 6.

Science.gov (United States)

Johnson, Bryce G; Ren, Shuyu; Karaca, Gamze; Gomez, Ivan G; Fligny, Cécile; Smith, Benjamin; Ergun, Ayla; Locke, George; Gao, Benbo; Hayes, Sebastian; MacDonnell, Scott; Duffield, Jeremy S

2017-06-01

Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction. These effects required the WNT receptor LDL receptor-related protein 6 (LRP6). Additionally, pericytes isolated from these mice became hypermigratory and hyperproliferative on overexpression of CTGF. CTGF is cleaved in vivo into distinct domains. Treatment with recombinant domain 1, 1+2 (N terminus), or 4 (C terminus) independently activated myofibroblast differentiation and wound healing responses in cultured pericytes, but domain 4 showed the broadest profibrotic activity. Domain 4 exhibited low-affinity binding to LRP6 in in vitro binding assays, and inhibition of LRP6 or critical signaling cascades downstream of LRP6, including JNK and WNT/ β -catenin, inhibited the biologic activity of domain 4. Administration of blocking antibodies specifically against CTGF domain 4 or recombinant Dickkopf-related protein-1, an endogenous inhibitor of LRP6, effectively inhibited inflammation and fibrosis associated with ureteral obstruction in vivo Therefore, domain 4 of CTGF and the WNT signaling pathway are important new targets in fibrosis. Copyright © 2017 by the American Society of Nephrology.

Modifiers of notch transcriptional activity identified by genome-wide RNAi

Directory of Open Access Journals (Sweden)

Firnhaber Christopher B

2010-10-01

Full Text Available Abstract Background The Notch signaling pathway regulates a diverse array of developmental processes, and aberrant Notch signaling can lead to diseases, including cancer. To obtain a more comprehensive understanding of the genetic network that integrates into Notch signaling, we performed a genome-wide RNAi screen in Drosophila cell culture to identify genes that modify Notch-dependent transcription. Results Employing complementary data analyses, we found 399 putative modifiers: 189 promoting and 210 antagonizing Notch activated transcription. These modifiers included several known Notch interactors, validating the robustness of the assay. Many novel modifiers were also identified, covering a range of cellular localizations from the extracellular matrix to the nucleus, as well as a large number of proteins with unknown function. Chromatin-modifying proteins represent a major class of genes identified, including histone deacetylase and demethylase complex components and other chromatin modifying, remodeling and replacement factors. A protein-protein interaction map of the Notch-dependent transcription modifiers revealed that a large number of the identified proteins interact physically with these core chromatin components. Conclusions The genome-wide RNAi screen identified many genes that can modulate Notch transcriptional output. A protein interaction map of the identified genes highlighted a network of chromatin-modifying enzymes and remodelers that regulate Notch transcription. Our results open new avenues to explore the mechanisms of Notch signal regulation and the integration of this pathway into diverse cellular processes.

Factors Influencing Urban Consumers' Acceptance of Genetically Modified Foods

OpenAIRE

Jae-Hwan Han; R. Wes Harrison

2007-01-01

Linkages between consumer beliefs and attitudes regarding the risks and benefits of genetically modified foods and consumer purchase intentions for these foods are examined. Factors that hinder consumer purchases of genetically modified foods are also tested. Results show that purchase intentions for consumers willing to buy genetically modified crops and meats are primarily affected by their belief that these foods are safe. On the other hand, intentions of consumers who decide not to buy ge...

Modifiable risk factors in periodontitis: at the intersection of aging and disease.

Science.gov (United States)

Reynolds, Mark A

2014-02-01

Chronic inflammation is a prominent feature of aging and of common age-related diseases, including atherosclerosis, cancer and periodontitis. This volume examines modifiable risk factors for periodontitis and other chronic inflammatory diseases. Oral bacterial communities and viral infections, particularly with cytomegalovirus and other herpesviruses, elicit distinct immune responses and are central in the initiation of periodontal diseases. Risk of disease is dynamic and changes in response to complex interactions of genetic, environmental and stochastic factors over the lifespan. Many modifiable risk factors, such as smoking and excess caloric intake, contribute to increases in systemic markers of inflammation and can modify gene regulation through a variety of biologic mechanisms (e.g. epigenetic modifications). Periodontitis and other common chronic inflammatory diseases share multiple modifiable risk factors, such as tobacco smoking, psychological stress and depression, alcohol consumption, obesity, diabetes, metabolic syndrome and osteoporosis. Interventions that target modifiable risk factors have the potential to improve risk profiles for periodontitis as well as for other common chronic diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A new automated method for continuous registration of factor VII activation in vitro. Activation is accelerated by the concentration of factor VII and the activity state of the protein

DEFF Research Database (Denmark)

Bladbjerg, Else-Marie; Jespersen, J; Gram, J

1994-01-01

When a plasma sample is exposed to tissue factor, single-chain factor VII (FVII) is gradually converted to the active two-chain form (FVIIa). In the present study, we have constructed a measurement system, which allows continuous registration of the activation of FVII to FVIIa in vitro....... In this system, FVII activation follows parabolic kinetic after an initial lag-phase. The slope of the linear phase is a measure of the protein concentration of factor VII (FVIItotal), while the length of the non-linear phase represents the velocity of FVII activation. The time required for complete activation...

Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

International Nuclear Information System (INIS)

Sawada, Keigo; Takedachi, Masahide; Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki; Lee, Chun Man; Okura, Hanayuki; Matsuyama, Akifumi; Kitamura, Masahiro; Murakami, Shinya

2015-01-01

Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation

Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

Energy Technology Data Exchange (ETDEWEB)

Sawada, Keigo [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Takedachi, Masahide, E-mail: takedati@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Lee, Chun Man [Medical Center for Translational Research, Osaka University Hospital, Osaka (Japan); Okura, Hanayuki; Matsuyama, Akifumi [Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka (Japan); Kitamura, Masahiro; Murakami, Shinya [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan)

2015-08-14

Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation.

Bio-active molecules modified surfaces enhanced mesenchymal stem cell adhesion and proliferation

International Nuclear Information System (INIS)

Mobasseri, Rezvan; Tian, Lingling; Soleimani, Masoud; Ramakrishna, Seeram; Naderi-Manesh, Hossein

2017-01-01

Surface modification of the substrate as a component of in vitro cell culture and tissue engineering, using bio-active molecules including extracellular matrix (ECM) proteins or peptides derived ECM proteins can modulate the surface properties and thereby induce the desired signaling pathways in cells. The aim of this study was to evaluate the behavior of human bone marrow mesenchymal stem cells (hBM-MSCs) on glass substrates modified with fibronectin (Fn), collagen (Coll), RGD peptides (RGD) and designed peptide (R-pept) as bio-active molecules. The glass coverslips were coated with fibronectin, collagen, RGD peptide and R-peptide. Bone marrow mesenchymal stem cells were cultured on different substrates and the adhesion behavior in early incubation times was investigated using scanning electron microscopy (SEM) and confocal microscopy. The MTT assay was performed to evaluate the effect of different bio-active molecules on MSCs proliferation rate during 24 and 72 h. Formation of filopodia and focal adhesion (FA) complexes, two steps of cell adhesion process, were observed in MSCs cultured on bio-active molecules modified coverslips, specifically in Fn coated and R-pept coated groups. SEM image showed well adhesion pattern for MSCs cultured on Fn and R-pept after 2 h incubation, while the shape of cells cultured on Coll and RGD substrates indicated that they might experience stress condition in early hours of culture. Investigation of adhesion behavior, as well as proliferation pattern, suggests R-peptide as a promising bio-active molecule to be used for surface modification of substrate in supporting and inducing cell adhesion and proliferation. - Highlights: • Bioactive molecules modified surface is a strategy to design biomimicry scaffold. • Bi-functional Tat-derived peptide (R-pept) enhanced MSCs adhesion and proliferation. • R-pept showed similar influences to fibronectin on FA formation and attachment.

Quantifying Cardiometabolic Risk Using Modifiable Non–Self-Reported Risk Factors

Science.gov (United States)

Marino, Miguel; Li, Yi; Pencina, Michael J.; D’Agostino, Ralph B.; Berkman, Lisa F.; Buxton, Orfeu M.

2014-01-01

Background Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. Purpose To develop and validate a cumulative general cardiometabolic risk score that focuses on non–self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut off points for risk categories. Methods We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14–year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender–specific Cox proportional hazards models were considered to evaluate the effects of non–self-reported modifiable risk factors (blood pressure, total cholesterol, high–density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10–year general cardiometabolic risk score functions and evaluated its predictive performance in 2012–2013. Results HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit χ2=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). Conclusions This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk based on modifiable risk factors that can motivate an individual’s commitment to prevention and intervention. PMID:24951039

Quantifying cardiometabolic risk using modifiable non-self-reported risk factors.

Science.gov (United States)

Marino, Miguel; Li, Yi; Pencina, Michael J; D'Agostino, Ralph B; Berkman, Lisa F; Buxton, Orfeu M

2014-08-01

Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. To develop and validate a cumulative general cardiometabolic risk score that focuses on non-self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut-off points for risk categories. We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14-year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender-specific Cox proportional hazards models were considered to evaluate the effects of non-self-reported modifiable risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10-year general cardiometabolic risk score functions and evaluated its predictive performance in 2012-2013. HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit chi-square=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk on the basis of modifiable risk factors that can motivate an individual's commitment to prevention and intervention. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

A review of lifestyle, smoking and other modifiable risk factors for osteoporotic fractures

DEFF Research Database (Denmark)

Abrahamsen, Bo; Brask-Lindemann, Dorthe; Rubin, Katrine Hass

2014-01-01

Although many strong risk factors for osteoporosis-such as family history, fracture history and age-are not modifiable, a number of important risk factors are potential targets for intervention. Thus, simple, non-pharmacological intervention in patients at increased risk of osteoporotic fractures...... could include reduction of excessive alcohol intake, smoking cessation, adequate nutrition, patient education, daily physical activity and a careful review of medications that could increase the risk of falls and fractures. There remains, however, an unmet need for high-quality intervention studies...

Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco.

Science.gov (United States)

Wojtukiewicz, Marek Z; Sierko, Ewa; Skalij, Piotr; Kamińska, Magda; Zimnoch, Lech; Brekken, Ralf A; Thorpe, Philip E

2016-01-01

Doxorubicin and docetaxel-based chemotherapy regimens used in breast cancer patients are associated with high risk of febrile neutropenia (FN). Granulocyte colony-stimulating factors (G-CSF) are recommended for both treating and preventing chemotherapy-induced neutropenia. Increased thrombosis incidence in G-CSF treated patients was reported; however, the underlying mechanisms remain unclear. The principal activator of blood coagulation in cancer is tissue factor (TF). It additionally contributes to cancer progression and stimulates angiogenesis. The main proangiogenic factor is vascular endothelial growth factor (VEGF). The aim of the study was to evaluate granulocyte-colony stimulating factor receptor (G-CSFR), tissue factor (TF) expression and vascular endothelial growth factor receptor (VEGF-R) bound VEGF in human breast cancer in loco. G-CSFR, TF and VEGFR bound VEGF (VEGF: VEGFR) were assessed in 28 breast cancer tissue samples. Immunohistochemical (IHC) methodologies according to ABC technique and double staining IHC procedure were employed utilizing antibodies against G-CSFR, TF and VEGF associated with VEGFR (VEGF: VEGFR). Expression of G-CSFR was demonstrated in 20 breast cancer tissue specimens (71%). In 6 cases (21%) the expression was strong (IRS 9-12). Strong expression of TF was observed in all investigated cases (100%). Moreover, expression of VEGF: VEGFR was visualized in cancer cells (IRS 5-8). No presence of G-CSFR, TF or VEGF: VEGFR was detected on healthy breast cells. Double staining IHC studies revealed co-localization of G-CSFR and TF, G-CSFR and VEGF: VEGFR, as well as TF and VEGF: VEGFR on breast cancer cells and ECs. The results of the study indicate that GCSFR, TF and VEGF: VEGFR expression as well as their co-expression might influence breast cancer biology, and may increase thromboembolic adverse events incidence.

O6-methylguanine DNA methyltransferase in human fetal tissues: fetal and maternal factors

International Nuclear Information System (INIS)

D'Ambrosio, S.M.; Samuel, M.J.; Dutta-Choudhury, T.A.; Wani, A.A.

1986-01-01

O 6 -Methylguanine methyltransferase (O 6 -MT) was measured and compared in extracts of 7 human fetal tissues obtained from 21 different fetal specimens as a function of fetal age and race, and maternal smoking and drug usage. Activity was determined from the proteinase-K solubilized radioactivity transferred from the DNA to the O 6 -MT. S9 homogenates were incubated with a heat depurinated [ 3 H]-methylnitrosourea alkylated DNA. Liver exhibited the highest activity followed by kidney, lung, small intestine, large intestine, skin and brain. Each of the tissues exhibited a 3- to 5-fold level of interindividual variation of O 6 -MT. There did not appear to be any significant difference of O 6 -MT in the tissues obtained from mothers who smoked cigarettes during pregnancy. Also, fetal race and age did not appear to account for the level of variation of O 6 -MT. The fetal tissues obtained from an individual using phenobarbital and smoking exhibited 4-fold increases in O 6 -MT activity. The tissues obtained from another individual on kidney dialysis were 2- to 3-fold higher than the normal population. These data suggest that the variation in human O 6 -MT can not be explained by racial or smoking factors, but may be modulated by certain drugs

Variability of individual normal tissue radiation sensitivity. An international empirical evaluation of endogenous and exogenous

International Nuclear Information System (INIS)

Zimmermann, J.S.; Kumpf, L.; Kimmig, B.

1998-01-01

Background: The variability of normal-tissue response is of major concern for radiation therapy. Multiple endogenous and exogenous factors are qualitatively known to alter the acute and late tissue response. Which of them are regarded most important by the European radiation oncologists and what is, empirically, their quantitative influence on the acute or late tissue tolerance? Methods: In August 1997, we sent a questionnaire to 255 European radiation oncology departments. Among others, the questionnaire asked for endogenous and exogenous factors modifying the tissue response to radiation therapy and their quantitative influence on the acute and late radiation morbidity (TD5/5). Fifty-five questionnaires (21.5%) were answered. Results: Empirically, the most important endogenous factors to modify the acute tissue tolerance are (a) metabolic/other diseases with macro- or microangiopathia (17 answers [a]/32% mean decrease of tissue tolerance), (b) collagen diseases (9 a/37%) and (c) immune diseases (5 a/53%). As endogenous response modifiers for the TD5/5 are recognized (a) metabolic or other diseases leading to marcro- or microangiopathia (15 a/31%), (b) collagen diseases (11 a/38%) and (c) immune diseases (2 a/50%). Inflammations from any reason are assumed to alter the acute tissue tolerance by (6 a/26%) and the TD5/5 by (10 a/24%). Exogenous modifiers of the acute tissue response mentioned are (a) smoking (34 a/44%), (b) alcohol (23 a/45%), (c) nutrition/diets (16 a/45%), (d) hygiene (9 a/26%) and (e) medical therapies (10 a/37%). Exogenous factors assumed to influence the TD5/5 are (a) smoking (22 a/40%), (b) alcohol (15 a/38%), (c) nutrition/diets (9 a/48%), (d) hygiene (5 a/34%) and (e) medical therapies (10 a/30%). Conclusions: Exogenous factors are regarded more important by number and extent on the acute and late tissue response than endogenous modifiers. Both may have an important influence on the individual expression of normal tissue response. (orig

Modifiable Cardiovascular Disease Risk Factors among Indigenous Populations

Directory of Open Access Journals (Sweden)

Adam A. Lucero

2014-01-01

Full Text Available Objective. To identify modifiable cardio-metabolic and lifestyle risk factors among indigenous populations from Australia (Aboriginal Australians/Torres Strait Islanders, New Zealand (Māori, and the United States (American Indians and Alaska Natives that contribute to cardiovascular disease (CVD. Methods. National health surveys were identified where available. Electronic databases identified sources for filling missing data. The most relevant data were identified, organized, and synthesized. Results. Compared to their non-indigenous counterparts, indigenous populations exhibit lower life expectancies and a greater prevalence of CVD. All indigenous populations have higher rates of obesity and diabetes, hypertension is greater for Māori and Aboriginal Australians, and high cholesterol is greater only among American Indians/Alaska Natives. In turn, all indigenous groups exhibit higher rates of smoking and dangerous alcohol behaviour as well as consuming less fruits and vegetables. Aboriginal Australians and American Indians/Alaska Natives also exhibit greater rates of sedentary behaviour. Conclusion. Indigenous groups from Australia, New Zealand, and the United States have a lower life expectancy then their respective non-indigenous counterparts. A higher prevalence of CVD is a major driving force behind this discrepancy. A cluster of modifiable cardio-metabolic risk factors precede CVD, which, in turn, is linked to modifiable lifestyle risk factors.

Neutron kerma factors, and water equivalence of some tissue substitutes

International Nuclear Information System (INIS)

Singh, V. P.; Badiger, N. M.; Vega C, H. R.

2014-08-01

The kerma factors and kerma relative to air and water of 24 compounds used as tissue substitutes were calculated for neutron energy from 2.53 x 10 -8 up to 29 MeV. The kerma ratio of the tissue substitutes relative to air and water were calculated by the ratio of kerma factors of the tissue substitute to air and water respectively. The water equivalence of the selected tissue substitutes was observed above neutron energies 100 eV. Kerma ratio relative to the air for Poly-vinylidene fluoride and Teflon are found to be nearest to unity in very low energy (up to 1 eV) and above 63 eV respectively. It was found that the natural rubber as a water equivalent tissue substitute compound. The results of the kerma factors in our investigation shows a very good agreement with those published in ICRU-44. We found that at higher neutron energies, the kerma factors and kerma ratios of the selected tissue substitute compounds are approximately same, but differences are large for energies below 100 eV. (Author)

Monte Carlo study of voxel S factor dependence on tissue density and atomic composition

Energy Technology Data Exchange (ETDEWEB)

Amato, Ernesto, E-mail: eamato@unime.it [University of Messina, Department of Biomedical Sciences and of Morphologic and Functional Imaging, Section of Radiological Sciences, via Consolare Valeria, 1, I-98125 Messina (Italy); Italiano, Antonio [INFN – Istituto Nazionale di Fisica Nucleare, Gruppo Collegato di Messina (Italy); Baldari, Sergio [University of Messina, Department of Biomedical Sciences and of Morphologic and Functional Imaging, Section of Radiological Sciences, via Consolare Valeria, 1, I-98125 Messina (Italy)

2013-11-21

Voxel dosimetry is a common approach to the internal dosimetry of non-uniform activity distributions in nuclear medicine therapies with radiopharmaceuticals and in the estimation of the radiation hazard due to internal contamination of radionuclides. Aim of the present work is to extend our analytical approach for the calculation of voxel S factors to materials different from the soft tissue. We used a Monte Carlo simulation in GEANT4 of a voxelized region of each material in which the source of monoenergetic electrons or photons was uniformly distributed within the central voxel, and the energy deposition was scored over the surrounding 11×11×11 voxels. Voxel S factors were obtained for the following standard ICRP materials: Adipose tissue, Bone cortical, Brain, Lung, Muscle skeletal and Tissue soft with 1 g cm{sup −3} density. Moreover, we considered the standard ICRU materials: Bone compact and Muscle striated. Voxel S factors were represented as a function of the “normalized radius”, defined as the ratio between the source–target voxel distance and the voxel side. We found that voxel S factors and related analytical fit functions are mainly affected by the tissue density, while the material composition gives only a slight contribution to the difference between data series, which is negligible for practical purposes. Our results can help in broadening the dosimetric three-dimensional approach based on voxel S factors to other tissues where diagnostic and therapeutic radionuclides can be taken up and radiation can propagate.

Monte Carlo study of voxel S factor dependence on tissue density and atomic composition

International Nuclear Information System (INIS)

Amato, Ernesto; Italiano, Antonio; Baldari, Sergio

2013-01-01

Voxel dosimetry is a common approach to the internal dosimetry of non-uniform activity distributions in nuclear medicine therapies with radiopharmaceuticals and in the estimation of the radiation hazard due to internal contamination of radionuclides. Aim of the present work is to extend our analytical approach for the calculation of voxel S factors to materials different from the soft tissue. We used a Monte Carlo simulation in GEANT4 of a voxelized region of each material in which the source of monoenergetic electrons or photons was uniformly distributed within the central voxel, and the energy deposition was scored over the surrounding 11×11×11 voxels. Voxel S factors were obtained for the following standard ICRP materials: Adipose tissue, Bone cortical, Brain, Lung, Muscle skeletal and Tissue soft with 1 g cm −3 density. Moreover, we considered the standard ICRU materials: Bone compact and Muscle striated. Voxel S factors were represented as a function of the “normalized radius”, defined as the ratio between the source–target voxel distance and the voxel side. We found that voxel S factors and related analytical fit functions are mainly affected by the tissue density, while the material composition gives only a slight contribution to the difference between data series, which is negligible for practical purposes. Our results can help in broadening the dosimetric three-dimensional approach based on voxel S factors to other tissues where diagnostic and therapeutic radionuclides can be taken up and radiation can propagate

Could Sirtuin Activities Modify ALS Onset and Progression?

Science.gov (United States)

Tang, Bor Luen

2017-10-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a complex etiology. Sirtuins have been implicated as disease-modifying factors in several neurological disorders, and in the past decade, attempts have been made to check if manipulating Sirtuin activities and levels could confer benefit in terms of neuroprotection and survival in ALS models. The efforts have largely focused on mutant SOD1, and while limited in scope, the results were largely positive. Here, the body of work linking Sirtuins with ALS is reviewed, with discussions on how Sirtuins and their activities may impact on the major etiological mechanisms of ALS. Moving forward, it is important that the potentially beneficial effect of Sirtuins in ALS disease onset and progression are assessed in ALS models with TDP-43, FUS, and C9orf72 mutations.

Antitumor Effect of Selenium and Modified Pectin Nano Particles and Gamma Radiation on Ehrilch Solid Tumor in Female Mice

International Nuclear Information System (INIS)

Mansour, S. Z.; Anis, L.M.; EI- Batal, A.I.

2010-01-01

Selenium nano particle (Nano- Se) is a novel Se species with novel biological activities with low toxicity. The aim of the present work was to evaluate the antitumor activity of a novel Nano- Se compound with or without gamma irradiation of female mice. Selenium size- controlled Nano-Se was prepared by a simple method by adding modified pectin to the selenious acid and ascorbic acid. The antitumor activity of Selenium and Modified Pectin Nano Particles (Se-Mp- NPs) were evaluated against Ehrilch ascites carcinoma (In vitro) and Ehrilch solid tumor model (In vivo). The antioxidant states of the novel compound were assessed measuring parameters in blood and tumor tissue of female mice. Malonaldehydoyl (MDA) end product of lipid peroxidation was evaluated in plasma and tumor tissue. Glutathione -S- transferase (GST) and cytochrome P450 (Cyto P450) were determined in tumor tissue homogenate. Tumor necrosis factor alpha (TNF- a) concentration and interleukin 10 (IL- 10) concentrations was evaluated in plasma of female mice. The effect of tumor inoculation and different treatments on liver enzymes (ALT and AST) and kidney Function (urea and creatinine) were detected in the plasma of animals. Apoptosis was shown and estimated in tumor tissue of animals histopathological of tumor in different groups of mice were examined. Ehrilch solid tumor induced a significant increase in MDA content, GSH-Px and GST activities level and in the amount of metabolites of CYP 450. Moreover, a significant decrease was observed in GSH content, SOD activity level in the tumor tissue, INF- a concentration, IL- 10 concentration in the plasma. Also, a significant alteration in kidney and liver functions was occurred as compared to control group. The results showed a significant antitumor activity of selenium and Modified Pectin Nano Particles (Se-Mp- NPs) at the concentration 2.25 μg / ml was 70%

Isolation of cDNA clones coding for human tissue factor: primary structure of the protein and cDNA

International Nuclear Information System (INIS)

Spicer, E.K.; Horton, R.; Bloem, L.

1987-01-01

Tissue factor is a membrane-bound procoagulant protein that activates the extrinsic pathway of blood coagulation in the presence of factor VII and calcium. λ Phage containing the tissue factor gene were isolated from a human placental cDNA library. The amino acid sequence deduced from the nucleotide sequence of the cDNAs indicates that tissue factor is synthesized as a higher molecular weight precursor with a leader sequence of 32 amino acids, while the mature protein is a single polypeptide chain composed of 263 residues. The derived primary structure of tissue factor has been confirmed by comparison to protein and peptide sequence data. The sequence of the mature protein suggests that there are three distinct domains: extracellular, residues 1-219; hydrophobic, residues 220-242; and cytoplasmic, residues 243-263. Three potential N-linked carbohydrate attachment sites occur in the extracellular domain. The amino acid sequence of tissue factor shows no significant homology with the vitamin K-dependent serine proteases, coagulation cofactors, or any other protein in the National Biomedical Research Foundation sequence data bank (Washington, DC)

p27{sup Kip1} inhibits tissue factor expression

Energy Technology Data Exchange (ETDEWEB)

Breitenstein, Alexander, E-mail: alexander.breitenstein@usz.ch [Cardiology, University Heart Center, University Hospital Zurich (Switzerland); Cardiovascular Research, Physiology Institute, University of Zurich (Switzerland); Center for Integrative Human Physiology (ZHIP), University of Zurich (Switzerland); Akhmedov, Alexander; Camici, Giovanni G.; Lüscher, Thomas F.; Tanner, Felix C. [Cardiology, University Heart Center, University Hospital Zurich (Switzerland); Cardiovascular Research, Physiology Institute, University of Zurich (Switzerland); Center for Integrative Human Physiology (ZHIP), University of Zurich (Switzerland)

2013-10-04

Highlights: •p27{sup Kip1}regulates the expression of tissue factor at the transcriptional level. •This inhibitory effect of p27{sup Kip1} is independently of its cell regulatory action. •The current study provides new insights into a pleiotrophic function of p27{sup Kip1}. -- Abstract: Background: The cyclin-dependent kinase inhibitor (CDKI) p27{sup Kip1} regulates cell proliferation and thus inhibits atherosclerosis and vascular remodeling. Expression of tissue factor (TF), the key initator of the coagulation cascade, is associated with atherosclerosis. Yet, it has not been studied whether p27{sup Kip1} influences the expression of TF. Methods and results: p27{sup Kip1} overexpression in human aortic endothelial cells was achieved by adenoviral transfection. Cells were rendered quiescent for 24 h in 0.5% fetal-calf serum. After stimulation with TNF-α (5 ng/ml), TF protein expression and activity was significantly reduced (n = 4; P < 0.001) in cells transfected with p27{sup Kip1}. In line with this, p27{sup Kip1} overexpression reduced cytokine-induced TF mRNA expression (n = 4; P < 0.01) and TF promotor activity (n = 4; P < 0.05). In contrast, activation of the MAP kinases p38, ERK and JNK was not affected by p27{sup Kip1} overexpression. Conclusion: This in vitro study suggests that p27{sup Kip1} inhibits TF expression at the transcriptional level. These data indicate an interaction between p27{sup Kip1} and TF in important pathological alterations such as atherosclerosis and vascular remodeling.

A role of active brown adipose tissue in cancer cachexia?

Directory of Open Access Journals (Sweden)

Emiel Beijer

2012-06-01

Full Text Available Until a few years ago, adult humans were not thought to have brown adipose tissue (BAT. Now, this is a rapidly evolving field of research with perspectives in metabolic syndromes such as obesity and new therapies targeting its bio-energetic pathways. White, brown and socalled brite adipose fat seem to be able to trans-differentiate into each other, emphasizing the dynamic nature of fat tissue for metabolism. Human and animal data in cancer cachexia to date provide some evidence for BAT activation, but its quantitative impact on energy expenditure and weight loss is controversial. Prospective clinical studies can address the potential role of BAT in cancer cachexia using 18F-fluorodeoxyglucose positron emission tomography-computed tomography scanning, with careful consideration of co-factors such as diet, exposure to the cold, physical activity and body mass index, that all seem to act on BAT recruitment and activity.

Factors promoting increased rate of tissue regeneration: the zebrafish fin as a tool for examining tissue engineering design concepts.

Science.gov (United States)

Boominathan, Vijay P; Ferreira, Tracie L

2012-12-01

Student interest in topics of tissue engineering is increasing exponentially as the number of universities offering programs in bioengineering are on the rise. Bioengineering encompasses all of the STEM categories: Science, Technology, Engineering, and Math. Inquiry-based learning is one of the most effective techniques for promoting student learning and has been demonstrated to have a high impact on learning outcomes. We have designed program outcomes for our bioengineering program that require tiered activities to develop problem solving skills, peer evaluation techniques, and promote team work. While it is ideal to allow students to ask unique questions and design their own experiments, this can be difficult for instructors to have reagents and supplies available for a variety of activities. Zebrafish can be easily housed, and multiple variables can be tested on a large enough group to provide statistical value, lending them well to inquiry-based learning modules. We have designed a laboratory activity that takes observation of fin regeneration to the next level: analyzing conditions that may impact regeneration. Tissue engineers seek to define the optimum conditions to grow tissue for replacement parts. The field of tissue engineering is likely to benefit from understanding natural mechanisms of regeneration and the factors that influence the rate of regeneration. We have outlined the results of varying temperature on fin regeneration and propose other inquiry modules such as the role of pH in fin regeneration. Furthermore, we have provided useful tools for developing critical thinking and peer review of research ideas, assessment guidelines, and grading rubrics for the activities associated with this exercise.

Correction factors to convert microdosimetry measurements in silicon to tissue in 12C ion therapy.

Science.gov (United States)

Bolst, David; Guatelli, Susanna; Tran, Linh T; Chartier, Lachlan; Lerch, Michael L F; Matsufuji, Naruhiro; Rosenfeld, Anatoly B

2017-03-21

Silicon microdosimetry is a promising technology for heavy ion therapy (HIT) quality assurance, because of its sub-mm spatial resolution and capability to determine radiation effects at a cellular level in a mixed radiation field. A drawback of silicon is not being tissue-equivalent, thus the need to convert the detector response obtained in silicon to tissue. This paper presents a method for converting silicon microdosimetric spectra to tissue for a therapeutic 12 C beam, based on Monte Carlo simulations. The energy deposition spectra in a 10 μm sized silicon cylindrical sensitive volume (SV) were found to be equivalent to those measured in a tissue SV, with the same shape, but with dimensions scaled by a factor κ equal to 0.57 and 0.54 for muscle and water, respectively. A low energy correction factor was determined to account for the enhanced response in silicon at low energy depositions, produced by electrons. The concept of the mean path length [Formula: see text] to calculate the lineal energy was introduced as an alternative to the mean chord length [Formula: see text] because it was found that adopting Cauchy's formula for the [Formula: see text] was not appropriate for the radiation field typical of HIT as it is very directional. [Formula: see text] can be determined based on the peak of the lineal energy distribution produced by the incident carbon beam. Furthermore it was demonstrated that the thickness of the SV along the direction of the incident 12 C ion beam can be adopted as [Formula: see text]. The tissue equivalence conversion method and [Formula: see text] were adopted to determine the RBE 10 , calculated using a modified microdosimetric kinetic model, applied to the microdosimetric spectra resulting from the simulation study. Comparison of the RBE 10 along the Bragg peak to experimental TEPC measurements at HIMAC, NIRS, showed good agreement. Such agreement demonstrates the validity of the developed tissue equivalence correction factors and of

Development of a GAL4-VP16/UAS trans-activation system for tissue specific expression in Medicago truncatula.

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Amélie Sevin-Pujol

Full Text Available Promoters with tissue-specific activity are very useful to address cell-autonomous and non cell autonomous functions of candidate genes. Although this strategy is widely used in Arabidopsis thaliana, its use to study tissue-specific regulation of root symbiotic interactions in legumes has only started recently. Moreover, using tissue specific promoter activity to drive a GAL4-VP16 chimeric transcription factor that can bind short upstream activation sequences (UAS is an efficient way to target and enhance the expression of any gene of interest. Here, we developed a collection of promoters with different root cell layers specific activities in Medicago truncatula and tested their abilities to drive the expression of a chimeric GAL4-VP16 transcription factor in a trans-activation UAS: β-Glucuronidase (GUS reporter gene system. By developing a binary vector devoted to modular Golden Gate cloning together with a collection of adapted tissue specific promoters and coding sequences we could test the activity of four of these promoters in trans-activation GAL4/UAS systems and compare them to "classical" promoter GUS fusions. Roots showing high levels of tissue specific expression of the GUS activity could be obtained with this trans-activation system. We therefore provide the legume community with new tools for efficient modular Golden Gate cloning, tissue specific expression and a trans-activation system. This study provides the ground work for future development of stable transgenic lines in Medicago truncatula.

In vitro evidence of a tissue factor-independent mode of action of recombinant factor VIIa in hemophilia.

Science.gov (United States)

Augustsson, Cecilia; Persson, Egon

2014-11-13

Successful competition of activated factor VII (FVIIa) with zymogen factor VII (FVII) for tissue factor (TF) and loading of the platelet surface with FVIIa are plausible driving forces behind the pharmacological effect of recombinant FVIIa (rFVIIa) in hemophilia patients. Thrombin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which potentially could reduce the effective (r)FVIIa:TF complex concentration and thereby attenuate factor Xa production. However, (auto)activation of FVII apparently counteracted the negative effect of zymogen binding; a small impact was observed at endogenous concentrations of FVII and FVIIa but was virtually absent at pharmacological amounts of rFVIIa. Moreover, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the range where a physiological level of FVII was capable to downregulate thrombin generation. These data strongly suggest that rFVIIa acts independently of TF in hemophilia therapy and that FVII displacement by rFVIIa is a negligible mechanistic component. © 2014 by The American Society of Hematology.

Chemically modified carboxypeptidase Y with increased amidase activity

International Nuclear Information System (INIS)

Breddam, K.

1984-01-01

Treatment of carboxypeptidase Y with 14 C-iodoacetamide caused a drastic reduction in the peptidase activity towards FA-Phe-Leu-OH while the esterase activity towards FA-Phe-OMe, the amidase activity towards FA-Phe-NH 2 and the peptidyl amino acid amide hydrolase activity towards FA-Phe-Gly-NH 2 were much less affected. The loss of peptidase activity could be correlated with the incorporation of a single equivalent of reagent and it was demonstrated that the site of reaction was a methionyl residue, thus forming a sulfonium derivative. Analogous methionyl modifications were performed: carboxypeptidase Y modified with phenacylbromide hydrolysed substrates with bulky leaving groups in the P position, i.e. -OEt, -OBzl, -Gly-NH 2 ,-Gly-OH, and -Leu-OH, at reduced rates while substrates with small groups in that position, i.e. -OMe and -NH 2 , were hydrolysed with increased rates. These results indicate that the methionyl residue modified by phenacylbromide is located in the S binding site of the enzyme. Similar results were obtained with carboxypeptidase Y modified with m-nitrophen- acylbromide and p-nitrophenacylbromide. The increase in amidase activity and decrease in peptidyl amino acid amide hydrolase activity of carboxypeptidase Y following modification with phenacylbromide, m-nitrophenacylbromide, and p-nitrophenacylbromide was exploited in deamidation of peptide amides. These modified enzymes deamidated peptide amides with the exception of those containing a C-terminal glycyl or seryl residue in yields of 80-100% which is significantly higher than with unmodified carboxypeptidase Y. (author)

Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 7

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Maeda, Tomoho; Yoshida, Shoji; Yamamoto, Yoichi; Morita, Masaru

1983-01-01

We have already reported the remarkable effect of the active specific immunotherapy utilizing cryopreserved tumor cells and infiltrating mononuclear cells prepared from a lowdose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the effect of a biological response modifier, PSK combined with this active specific immunotherapy was investigated. Twelve-week-aged female C3H/He mice transplanted with MM46 tumor cells were received local radiotherapy with the dose of 3,000 rads by high energy electron beam on the fifth day after tumor inoculation. This active specific immunotherapy was performed on the twelveth day, and daily dose of 200 mg/kg of PSK was injected intraperitoneally from the sixth day to the tenth day. The more inhibition of the tumor growth was observed in the group which received this active specific immunotherapy combined with a biological response modifier, PSK compared with that received this active specific immunotherapy alone. (author)

Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 5

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Imanaka, Kazufumi; Gose, Kyuhei; Imajo, Yoshinari; Kimura, Shuji

1982-01-01

We have already reported the remarkable effect of the active specific immunotherapy utilizing cryopreserved tumor cells and infiltrating mononuclear cells prepared from a low-dose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the effect of a biological response modifier, OK-432 combined with this active specific immunotherapy was investigated. Twelve-week-aged female C3H/He mice transplanted with MM46 tumor cells were received local radiotherapy with the dose of 3,000 rads by high energy electron beam on the sixth day after inoculation. This active specific immunotherapy was performed on the thirteenth day, and daily dose of 1.0 KE of OK-432 was injected intraperitoneally from the thirteenth day to the seventeenth day. The inhibition of the tumor growth was observed in the group which received this active specific immunotherapy combined with a biological response modifier, OK-432 compared with that received this active specific immunotherapy alone. (author)

Modifiable Risk factors of Hypertension and Socio‑demographic ...

African Journals Online (AJOL)

, Hypertension, Modifiable risk factors, Oghara ... to 140/90 mmHg is the most common Non Communicable .... In the first part, data on socio‑demographic variables of the ... blood pressure, and it was measured using sphygmomanometer.

Influences of lifestyle factors on cardiac autonomic nervous system activity over time

NARCIS (Netherlands)

Hu, Mandy Xian; Lamers, Femke; de Geus, Eco J C; Penninx, Brenda W J H

Physical activity, alcohol use and smoking might affect cardiovascular disease through modifying autonomic nervous system (ANS) activity. We investigated: 1) whether there are consistent relationships between lifestyle factors and cardiac ANS activity over time, and 2) whether 2-year changes in

The Adsorption Mechanism of Modified Activated Carbon on Phenol

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Lin J. Q.

2016-01-01

Full Text Available Modified activated carbon was prepared by thermal treatment at high temperature under nitrogen flow. The surface properties of the activated carbon were characterized by Boehm titration, BET and point of zero charge determination. The adsorption mechanism of phenol on modified activated carbon was explained and the adsorption capacity of modified activated carbon for phenol when compared to plain activated carbon was evaluated through the analysis of adsorption isotherms, thermodynamic and kinetic properties. Results shows that after modification the surface alkaline property and pHpzc value of the activated carbon increase and the surface oxygen-containing functional groups decrease. The adsorption processes of the plain and modified carbon fit with Langmuir isotherm equation well, and the maximum adsorption capacity increase from 123.46, 111.11, 103.09mg/g to 192.31, 178.57, 163,93mg/g under 15, 25 and 35°C after modification, respectively. Thermodynamic parameters show that the adsorption of phenol on activated carbon is a spontaneously exothermic process of entropy reduction, implying that the adsorption is a physical adsorption. The adsorption of phenol on activated carbon follows the pseudo-second-order kinetics (R2>0.99. The optimum pH of adsorption is 6~8.

The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice

NARCIS (Netherlands)

Defour, Merel; Dijk, Wieneke; Ruppert, Philip; Nascimento, Emmani B.M.; Schrauwen, Patrick; Kersten, Sander

2018-01-01

Objective: Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue (BAT), a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPARα) in cold-induced

Modified stress intensity factor as a crack growth parameter applicable under large scale yielding conditions

International Nuclear Information System (INIS)

Yasuoka, Tetsuo; Mizutani, Yoshihiro; Todoroki, Akira

2014-01-01

High-temperature water stress corrosion cracking has high tensile stress sensitivity, and its growth rate has been evaluated using the stress intensity factor, which is a linear fracture mechanics parameter. Stress corrosion cracking mainly occurs and propagates around welded metals or heat-affected zones. These regions have complex residual stress distributions and yield strength distributions because of input heat effects. The authors previously reported that the stress intensity factor becomes inapplicable when steep residual stress distributions or yield strength distributions occur along the crack propagation path, because small-scale yielding conditions deviate around those distributions. Here, when the stress intensity factor is modified by considering these distributions, the modified stress intensity factor may be used for crack growth evaluation for large-scale yielding. The authors previously proposed a modified stress intensity factor incorporating the stress distribution or yield strength distribution in front of the crack using the rate of change of stress intensity factor and yield strength. However, the applicable range of modified stress intensity factor for large-scale yielding was not clarified. In this study, the range was analytically investigated by comparison with the J-integral solution. A three-point bending specimen with parallel surface crack was adopted as the analytical model and the stress intensity factor, modified stress intensity factor and equivalent stress intensity factor derived from the J-integral were calculated and compared under large-scale yielding conditions. The modified stress intensity was closer to the equivalent stress intensity factor when compared with the stress intensity factor. If deviation from the J-integral solution is acceptable up to 2%, the modified stress intensity factor is applicable up to 30% of the J-integral limit, while the stress intensity factor is applicable up to 10%. These results showed that

Growth factor effects on costal chondrocytes for tissue engineering fibrocartilage

Science.gov (United States)

Johns, D.E.; Athanasiou, K.A.

2010-01-01

Tissue engineered fibrocartilage could become a feasible option for replacing tissues like the knee meniscus or temporomandibular joint disc. This study employed five growth factors insulin-like growth factor-I, transforming growth factor-β1, epidermal growth factor, platelet-derived growth factor-BB, and basic fibroblast growth factor in a scaffoldless approach with costal chondrocytes, attempting to improve biochemical and mechanical properties of engineered constructs. Samples were quantitatively assessed for total collagen, glycosaminoglycans, collagen type I, collagen type II, cells, compressive properties, and tensile properties at two time points. Most treated constructs were worse than the no growth factor control, suggesting a detrimental effect, but the IGF treatment tended to improve the constructs. Additionally, the 6wk time point was consistently better than 3wks, with total collagen, glycosaminoglycans, and aggregate modulus doubling during this time. Further optimization of the time in culture and exogenous stimuli will be important in making a more functional replacement tissue. PMID:18597118

Gene therapy with growth factors for periodontal tissue engineering–A review

Science.gov (United States)

Gupta, Shipra; Mahendra, Aneet

2012-01-01

The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. A challenge faced by periodontal therapy is the predictable regeneration of periodontal tissues lost as a consequence of disease. Growth factors are critical to the development, maturation, maintenance and repair of oral tissues as they establish an extra-cellular environment that is conducive to cell and tissue growth. Tissue engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. The aim of this paper is to review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Various such materials have been formulated into devices that can be used as vehicles for delivery of cells, growth factors and DNA. Different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral and tooth supporting structure. Key words: Periodontal disease, gene therapy, regeneration, tissue repair, growth factors, tissue engineering. PMID:22143705

A virtual surgical training system that simulates cutting of soft tissue using a modified pre-computed elastic model.

Science.gov (United States)

Toe, Kyaw Kyar; Huang, Weimin; Yang, Tao; Duan, Yuping; Zhou, Jiayin; Su, Yi; Teo, Soo-Kng; Kumar, Selvaraj Senthil; Lim, Calvin Chi-Wan; Chui, Chee Kong; Chang, Stephen

2015-08-01

This work presents a surgical training system that incorporates cutting operation of soft tissue simulated based on a modified pre-computed linear elastic model in the Simulation Open Framework Architecture (SOFA) environment. A precomputed linear elastic model used for the simulation of soft tissue deformation involves computing the compliance matrix a priori based on the topological information of the mesh. While this process may require a few minutes to several hours, based on the number of vertices in the mesh, it needs only to be computed once and allows real-time computation of the subsequent soft tissue deformation. However, as the compliance matrix is based on the initial topology of the mesh, it does not allow any topological changes during simulation, such as cutting or tearing of the mesh. This work proposes a way to modify the pre-computed data by correcting the topological connectivity in the compliance matrix, without re-computing the compliance matrix which is computationally expensive.

Risk Factors for Pressure Ulcers Including Suspected Deep Tissue Injury in Nursing Home Facility Residents: Analysis of National Minimum Data Set 3.0.

Science.gov (United States)

Ahn, Hyochol; Cowan, Linda; Garvan, Cynthia; Lyon, Debra; Stechmiller, Joyce

2016-04-01

To provide information on risk factors associated with pressure ulcers (PrUs), including suspected deep tissue injury (sDTI), in nursing home residents in the United States. This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Examine the literature related to risk factors for the development of PrUs.2. Compare risk factors associated with the prevalence of PrUs and sDTI from the revised Minimum Data Set 3.0 2012 using a modified Defloor's conceptual model of PrUs as a theoretical framework. This study aims to characterize and compare risk factors associated with pressure ulcers (PrUs), including suspected deep tissue injury (sDTI), in nursing home (NH) residents in the United States. Secondary analysis of the 2012 Minimum Data Set (MDS 3.0). Medicare- or Medicaid-certified NHs in the United States. Nursing home residents (n = 2,936,146) 18 years or older with complete PrU data, who received comprehensive assessments from January to December 2012. Pressure ulcer by stage was the outcome variable. Explanatory variables (age, gender, race and ethnicity, body mass index, skin integrity, system failure, disease, infection, mobility, and cognition) from the MDS 3.0 were aligned with the 4 elements of Defloor's conceptual model: compressive forces, shearing forces, tissue tolerance for pressure, and tissue tolerance for oxygen. Of 2,936,146 NH residents who had complete data for PrU, 89.9% had no PrU; 8.4% had a Stage 2, 3, or 4 or unstagable PrU; and 1.7% had an sDTI. The MDS variables corresponding to the 4 elements of Defloor's model were significantly predictive of both PrU and sDTI. Black residents had the highest risk of any-stage PrU, and Hispanic residents had the highest risk of sDTI. Skin integrity, system failure, infection, and disease risk factors had larger effect sizes for sDTI than for other PrU stages

Modifiable Lifestyle Risk Factors and Incident Diabetes in African Americans.

Science.gov (United States)

Joseph, Joshua J; Echouffo-Tcheugui, Justin B; Talegawkar, Sameera A; Effoe, Valery S; Okhomina, Victoria; Carnethon, Mercedes R; Hsueh, Willa A; Golden, Sherita H

2017-11-01

The associations of modifiable lifestyle risk factors with incident diabetes are not well investigated in African Americans (AAs). This study investigated the association of modifiable lifestyle risk factors (exercise, diet, smoking, TV watching, and sleep-disordered breathing burden) with incident diabetes among AAs. Modifiable lifestyle risk factors were characterized among 3,252 AAs in the Jackson Heart Study who were free of diabetes at baseline (2000-2004) using baseline questionnaires and combined into risk factor categories: poor (0-3 points), average (4-7 points), and optimal (8-11 points). Incidence rate ratios (IRR) for diabetes (fasting glucose ≥126 mg/dL, physician diagnosis, use of diabetes drugs, or glycosylated hemoglobin A1c ≥6.5%) were estimated using Poisson regression modeling adjusting for age, sex, education, occupation, systolic blood pressure, and BMI. Outcomes were collected 2005-2012 and data analyzed in 2016. Over 7.6 years, there were 560 incident diabetes cases (mean age=53.3 years, 64% female). An average or optimal compared to poor risk factor categorization was associated with a 21% (IRR=0.79, 95% CI=0.62, 0.99) and 31% (IRR=0.69, 95% CI=0.48, 1.01) lower risk of diabetes. Among participants with BMI <30, IRRs for average or optimal compared to poor categorization were 0.60 (95% CI=0.40, 0.91) and 0.53 (95% CI=0.29, 0.97) versus 0.90 (95% CI=0.67, 1.21) and 0.83 (95% CI=0.51, 1.34) among participants with BMI ≥30. A combination of modifiable lifestyle factors are associated with a lower risk of diabetes among AAs, particularly among those without obesity. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Cellular organization of pre-mRNA splicing factors in several tissues. Changes in the uterus by hormone action.

Science.gov (United States)

George-Téllez, R; Segura-Valdez, M L; González-Santos, L; Jiménez-García, L F

2002-05-01

In the mammalian cell nucleus, splicing factors are distributed in nuclear domains known as speckles or splicing factor compartments (SFCs). In cultured cells, these domains are dynamic and reflect transcriptional and splicing activities. We used immunofluorescence and confocal microscopy to monitor whether splicing factors in differentiated cells display similar features. Speckled patterns are observed in rat hepatocytes, beta-cells, bronchial and intestine epithelia and also in three cell types of the uterus. Moreover, the number, distribution and sizes of the speckles vary among them. In addition, we studied variations in the circular form (shape) of speckles in uterine cells that are transcriptionally modified by a hormone action. During proestrus of the estral cycle, speckles are irregular in shape while in diestrus I they are circular. Experimentally, in castrated rats luminal epithelial cells show a pattern where speckles are dramatically rounded, but they recover their irregular shape rapidly after an injection of estradiol. The same results were observed in muscle and gland epithelial cells of the uterus. We concluded that different speckled patterns are present in various cells types in differentiated tissues and that these patterns change in the uterus depending upon the presence or absence of hormones such as estradiol.

Is Physical Activity Able to Modify Oxidative Damage in Cardiovascular Aging?

Directory of Open Access Journals (Sweden)

Graziamaria Corbi

2012-01-01

Full Text Available Aging is a multifactorial process resulting in damage of molecules, cells, and tissues. It has been demonstrated that the expression and activity of antioxidant systems (SOD, HSPs are modified in aging, with reduced cell ability to counteract the oxidant molecules, and consequent weak resistance to ROS accumulation. An important mechanism involved is represented by sirtuins, the activity of which is reduced by aging. Physical activity increases the expression and the activity of antioxidant enzymes, with consequent reduction of ROS. Positive effects of physical exercise in terms of antioxidant activity could be ascribable to a greater expression and activity of SOD enzymes, HSPs and SIRT1 activity. The antioxidant effects could increase, decrease, or not change in relation to the exercise protocol. Therefore, some authors by using a new approach based on the in vivo/vitro technique demonstrated that the highest survival and proliferation and the lowest senescence were obtained by performing an aerobic training. Therefore, the in vivo/vitro technique described could represent a good tool to better understand how the exercise training mediates its effects on aging-related diseases, as elderly with heart failure that represents a special population in which the exercise plays an important role in the improvement of cardiovascular function, quality of life, and survival.

Gemini Surfactant-Modified Activated Carbon for Remediation of Hexavalent Chromium from Water

Directory of Open Access Journals (Sweden)

Yingying Zhou

2018-01-01

Full Text Available Gemini surfactants, with double hydrophilic and hydrophobic groups, offer potentially orders of magnitude greater surface activity compared to similar single unit molecules. A cationic Gemini surfactant (Propyl didodecyldimethylammonium Bromide, PDDDAB and a conventional cationic surfactant (Dodecyltrimethylammonium Bromide, DTAB were used to pre-treat and generate activated carbon. The removal efficiency of the surfactant-modified activated carbon through adsorption of chromium(VI was investigated under controlled laboratory conditions. Fourier-transform infrared spectroscopy (FT-IR and scanning electron microscopy (SEM were used to investigate the surface changes of surfactant-modified activated carbon. The effect of important parameters such as adsorbent dosage, pH, ionic strength and contact time were also investigated. The chromium(VI was adsorbed more significantly on the Gemini surfactant-modified activated carbon than on the conventional surfactant-modified activated carbon. The correlation coefficients show the data best fit the Freundlich model, which confirms the monolayer adsorption of chromium(VI onto Gemini surfactant-modified activated carbon. From this assessment, the surfactant-modified (especially Gemini surfactant-modified activated carbon in this study showed promise for practical applications to treat water pollution.

Connective tissue growth factor is a substrate of ADAM28

International Nuclear Information System (INIS)

Mochizuki, Satsuki; Tanaka, Rena; Shimoda, Masayuki; Onuma, Junko; Fujii, Yutaka; Jinno, Hiromitsu; Okada, Yasunori

2010-01-01

Research highlights: → The hyper-variable region in the cysteine-rich domain of ADAM28 binds to C-terminal domain of CTGF. → ADAM28 cleaves CTGF alone and CTGF in the CTGF/VEGF 165 complex. → CTGF digestion by ADAM28 releases biologically active VEGF 165 from the complex. → ADAM28, CTGF and VEGF 165 are commonly co-expressed by carcinoma cells in human breast carcinoma tissues. → These suggest that ADAM28 promotes VEGF 165 -induced angiogenesis in the breast carcinomas by selective CTGF digestion in the CTGF/VEGF 165 complex. -- Abstract: ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinoma cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala 181 -Tyr 182 and Asp 191 -Pro 192 bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor 165 (VEGF 165 ), releasing biologically active VEGF 165 from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF 165 -induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF 165 complex.

Are school factors and urbanization supportive for being physically active and engaging in less screen-based activities?

NARCIS (Netherlands)

Kopcakova, Jaroslava; Dankulincova Veselska, Zuzana; Madarasova Geckova, Andrea; Klein, Daniel; van Dijk, Jitse P; Reijneveld, Sijmen A

The aim was to assess the association between physical activity and screen-based activities in adolescents and selected school factors and urbanization and whether these associations were modified by degree of urbanization. We obtained data regarding the fifth-ninth grade students from 130 schools

Variance Components Models for Physical Activity With Age as Modifier: A Comparative Twin Study in Seven Countries

NARCIS (Netherlands)

Vink, J.M.; Boomsma, D.I.; Medland, S.E.; Moor, H.M. de; Stubbe, J.H.; Corner, B.K.; Martin, N.G.; Skytthea, A.; Kyvik, K.O.; Rose, R..J.; Kujala, U.M.; Kaprio, J.; Harris, J.R.; Pedersen, N.L.; Cherkas, L.; Spector, T.D.; Geus, E.J.

2011-01-01

Physical activity is influenced by genetic factors whose expression may change with age. We employed an extension to the classical twin model that allows a modifier variable, age, to interact with the effects of the latent genetic and environmental factors. The model was applied to self-reported

Modified Active Videogame Play Results in Moderate-Intensity Exercise.

Science.gov (United States)

Monedero, Javier; McDonnell, Adam C; Keoghan, Melissa; O'Gorman, Donal J

2014-08-01

Large proportions of the population do not meet current American College of Sports Medicine physical activity recommendations, and innovative approaches are required. Most active videogames do not require a significant amount of energy expenditure. The purpose of this study was to determine if modifying an active videogame increased exercise intensity to meet current physical activity recommendations. After completing a maximal oxygen uptake test, participants did a familiarization session on a separate day. Thirteen healthy participants 24.2±3.4 years of age played (1) a sedentary videogame, (2) an active videogame, and (3) a modified active videogame designed to increase physical activity for 46 minutes in a randomized order on separate days. Oxygen uptake, heart rate, heart rate reserve, percentage of maximal heart rate, metabolic equivalents of task, and energy expenditure were significantly higher during the modified active videogame trial than during the active videogame or sedentary videogame trials and also between the active videogame and sedentary videogame. A simple modification to an existing active videogame was sufficient to reach moderate exercise intensity. Active videogames could provide an important option for increasing daily physical activity and reducing sedentary time.

In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. possible implications for measurements in vivo after heparin therapy

DEFF Research Database (Denmark)

Bladbjerg, E-M; Larsen, L F; Ostergaard, P

2000-01-01

The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII......:C, activated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after infusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 healthy subjects. Additionally, we conducted in vitro experiments...

Toxicity of fluoride to aquatic species and evaluation of toxicity modifying factors.

Science.gov (United States)

Pearcy, Krysta; Elphick, James; Burnett-Seidel, Charlene

2015-07-01

The present study was performed to investigate the toxicity of fluoride to a variety of freshwater aquatic organisms and to establish whether water quality variables contribute substantively to modifying its toxicity. Water hardness, chloride, and alkalinity were tested as possible toxicity modifying factors for fluoride using acute toxicity tests with Hyalella azteca and Oncorhynchus mykiss. Chloride appeared to be the major toxicity modifying factor for fluoride in these acute toxicity tests. The chronic toxicity of fluoride was evaluated with a variety of species, including 3 fish (Pimephales promelas, O. mykiss, and Salvelinus namaycush), 3 invertebrates (Ceriodaphnia dubia, H. azteca, and Chironomus dilutus), 1 plant (Lemna minor), and 1 alga (Pseudokirchneriella subcapitata). Hyalella azteca was the most sensitive species overall, and O. mykiss was the most sensitive species of fish. The role of chloride as a toxicity modifying factor was inconsistent between species in the chronic toxicity tests. © 2015 SETAC.

Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells.

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Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

2015-01-01

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors.

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Bhardwaj, Nandana; Devi, Dipali; Mandal, Biman B

2015-02-01

Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modifiable risk factors for prescription medicine sharing behaviours.

Science.gov (United States)

Beyene, Kebede; Aspden, Trudi; McNeill, Rob; Sheridan, Janie

2018-04-06

Prescription medicine sharing has been defined as giving one's own medicine to someone else (lending) or taking someone else's medicine (borrowing). Medicines can be shared for non-medical purposes (recreational sharing or drug abuse) or for their intended therapeutic benefits (non-recreational sharing, e.g. sharing antibiotics to self-treat); the latter is the focus of this research. Limited research evidence is available about modifiable risk factors for non-recreational medicine sharing and addressing this issue was the main aim of this research. An online, cross-sectional survey design was used. The study population comprised a convenience sample of 233 adults, who were primarily recruited through patient support groups across New Zealand. Principal component analysis was used to develop scales assessing attitudes toward medicine lending and borrowing. Logistic regression was used to examine the relationship between explanatory (demographics, medical conditions, and attitudes towards medicine sharing) and outcome (medicine sharing behaviours) variables. Half of the study participants reported ever borrowing/lending medicines, and approximately a third of participants reported borrowing/lending in the past year. Modifiable risk factors associated with an increased risk of medicine borrowing behaviour were having more difficulty with accessing medicine ('access-related issue'), stronger 'emotional beliefs about borrowing', and greater 'concern about missing doses.' Greater 'concern for the wellbeing of others' and stronger 'beliefs about the benefits and safety of lending' were associated with an increased risk of medicine lending behaviour. Those with a higher 'perceived risk of harm' were less likely to borrow or lend medicines. This research expands the current knowledge of medicine sharing by examining underlying behavioural factors which predict sharing behaviours and that can be modified by interventions. This research suggests using multifaceted

Tissue and plasma enzyme activities in juvenile green iguanas.

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Wagner, R A; Wetzel, R

1999-02-01

To determine activities of intracellular enzymes in 8 major organs in juvenile green iguanas and to compare tissue and plasma activities. 6 green iguanas iguanas, but high values may not always indicate overt muscle disease. The AMS activity may be specific for the pancreas, but the wide range of plasma activity would likely limit its diagnostic usefulness. Activities of AST and LDH may reflect tissue damage or inflammation, but probably do not reflect damage to specific tissues or organs.

The Modified Risk Factors of Health Heads of the Medical Organizations

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O. L. Zadvornaya

2017-01-01

Full Text Available Purpose: study and evaluation of modifiable potential risk factors of health of heads of medical organizations in terms of structural and technological modernization of the health system, the growing need for highly qualified management personnel. Efficiency of activity of medical associations largely due to the level of health managers, allowing to solve problems of activities of medical organizations in the modern fastchanging environmental conditions. Based on international experience and our own research the authors identified features of the state of health of heads of medical organizations, and the degree of exposure to risk factors for no communicable diseases; considered approaches to assess motivation and psychological readiness to promote the health and potential of managerial personnel in the formation of health-saving behavior. Methods: in the present study, the following methods were used: systemic approach, content analysis, methods of social diagnosis (questionnaires, interviews, comparative analysis, method of expert evaluations, and method of statistical processing of information. Results: reviewed and proposed approaches to use preventive measures prevention of risk factors of non-communicable diseases healthcare leaders, forming health-preserving behavior. Conclusions and Relevance: in modern scientific studies on the health of medical workers, including heads of medical institutions, defined the modern methodological approaches to formation of health-saving behavior and maintaining healthy lifestyle health care workers. Despite the high awareness of heads of medical organizations in the area of influence of risk factors on health, accessibility of medical care for the diagnosis and correction of risk factors of chronic no communicable diseases, risk factors of health among healthcare leaders have sufficient prevalence. Health-promoting behavior model is not a conscious lifestyle leader and formed as a reaction if you have

Activity of recombinant factor VIIa under different conditions in vitro

DEFF Research Database (Denmark)

Bladbjerg, Else-Marie; Jespersen, Jørgen

2008-01-01

Recombinant activated factor VII (NovoSeven; Novo Nordisk A/S, Måløv, Denmark) is an effective drug for treatment of bleeding in patients with haemophilia A or B and inhibitors. Little is known about physiological conditions influencing the efficacy of recombinant activated factor VII. We...... investigated the in-vitro effects of pH, temperature, and haemodilution on the activity of recombinant activated factor VII. Samples from eight healthy volunteers were spiked with recombinant activated factor VII (final concentration 1.7 microg/ml) and adjusted to pH 6.0, 6.5, 7.0, and 7.4 or analysed at 30......, 33, 37, and 40 degrees C, or diluted 0, 10, 20, 40, and 60% with dextran before analysis. Samples were analysed as rotational thromboelastometry in whole blood (clotting time, clot formation time, and maximum clot firmness) with and without Innovin (tissue factor), and as factor VII coagulant...

A Chemically Modified Curcumin (CMC 2.24) Inhibits Nuclear Factor κB Activation and Inflammatory Bone Loss in Murine Models of LPS-Induced Experimental Periodontitis and Diabetes-Associated Natural Periodontitis.

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Elburki, Muna S; Rossa, Carlos; Guimarães-Stabili, Morgana R; Lee, Hsi-Ming; Curylofo-Zotti, Fabiana A; Johnson, Francis; Golub, Lorne M

2017-08-01

The purpose of this study was to assess the effect of a novel chemically modified curcumin (CMC 2.24) on NF-κB and MAPK signaling and inflammatory cytokine production in two experimental models of periodontal disease in rats. Experimental model I: Periodontitis was induced by repeated injections of LPS into the gingiva (3×/week, 3 weeks); control rats received vehicle injections. CMC 2.24, or the vehicle, was administered by daily oral gavage for 4 weeks. Experimental model II: Diabetes was induced in adult male rats by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC 2.24, or the vehicle, was administered by oral gavage daily for 3 weeks to the diabetics. Hemimaxillae and gingival tissues were harvested, and bone loss was assessed radiographically. Gingival tissues were pooled according to the experimental conditions and processed for the analysis of matrix metalloproteinases (MMPs) and bone-resorptive cytokines. Activation of p38 MAPK and NF-κB signaling pathways was assessed by western blot. Both LPS and diabetes induced an inflammatory process in the gingival tissues associated with excessive alveolar bone resorption and increased activation of p65 (NF-κB) and p38 MAPK. In both models, the administration of CMC 2.24 produced a marked reduction of inflammatory cytokines and MMPs in the gingival tissues, decreased bone loss, and decreased activation of p65 (NF-κB) and p38 MAPK. Inhibition of these cell signaling pathways by this novel tri-ketonic curcuminoid (natural curcumin is di-ketonic) may play a role in its therapeutic efficacy in locally and systemically associated periodontitis.

Active Noise Control Using Modified FsLMS and Hybrid PSOFF Algorithm

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Ranjan Walia

2018-04-01

Full Text Available Active noise control is an efficient technique for noise cancellation of the system, which has been defined in this paper with the aid of Modified Filtered-s Least Mean Square (MFsLMS algorithm. The Hybrid Particle Swarm Optimization and Firefly (HPSOFF algorithm are used to identify the stability factor of the MFsLMS algorithm. The computational difficulty of the modified algorithm is reduced when compared with the original Filtered-s Least Mean Square (FsLMS algorithm. The noise sources are removed from the signal and it is compared with the existing FsLMS algorithm. The performance of the system is established with the normalized mean square error for two different types of noises. The proposed method has also been compared with the existing algorithms for the same purposes.

Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

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van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

2012-10-01

The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

Science.gov (United States)

Gaut, Carrie; Sugaya, Kiminobu

2015-01-01

Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

Tissue factor-dependent blood coagulation is enhanced following delivery irrespective of the mode of delivery

NARCIS (Netherlands)

Boer, K.; den Hollander, I. A.; Meijers, J. C. M.; Levi, M. [=Marcel M.

2007-01-01

BACKGROUND: The risk of thrombosis is clearly increased in the postpartum period. Mice with a targeted deletion of the transmembrane domain of tissue factor (TF) develop serious activation of blood coagulation and widespread thrombosis after delivery. OBJECTIVE AND METHODS: We hypothesized that TF,

Connective tissue growth factor is activated by gastrin and involved in gastrin-induced migration and invasion.

Science.gov (United States)

Bhandari, Sabin; Bakke, Ingunn; Kumar, J; Beisvag, Vidar; Sandvik, Arne K; Thommesen, Liv; Varro, Andrea; Nørsett, Kristin G

2016-06-17

Connective tissue growth factor (CTGF) has been reported in gastric adenocarcinoma and in carcinoid tumors. The aim of this study was to explore a possible link between CTGF and gastrin in gastric epithelial cells and to study the role of CTGF in gastrin induced migration and invasion of AGS-GR cells. The effects of gastrin were studied using RT-qPCR, Western blot and assays for migration and invasion. We report an association between serum gastrin concentrations and CTGF abundancy in the gastric corpus mucosa of hypergastrinemic subjects and mice. We found a higher expression of CTGF in gastric mucosa tissue adjacent to tumor compared to normal control tissue. We showed that gastrin induced expression of CTGF in gastric epithelial AGS-GR cells via MEK, PKC and PKB/AKT pathways. CTGF inhibited gastrin induced migration and invasion of AGS-GR cells. We conclude that CTGF expression is stimulated by gastrin and involved in remodeling of the gastric epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

Biological Activity Alterations of Human Amniotic Membrane Pre and Post Irradiation Tissue Banking.

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Nemr, Waleed; Bashandy, A S; Araby, Eman; Khamiss, O

Innate immunity of Human Amniotic Membrane (HAM) and its highly active secretome that rich with various types of growth factors and anti-inflammatory substances proposed it as a promising material for many medical studies and applications. This study evaluate the biological activity of cultivated HAM pre and post tissue banking process in which freeze-dried HAM was sterilized by 25 KGray (kGy) dose of γ radiation. The HAM's antimicrobial activity, viability, growth of isolated human amniotic epithelial cells (HAECs), hematopoietic stimulation of co-cultivated murine bone marrow cells (mammalian model), scaffold efficiency for fish brain building up (non-mammalian model) and self re-epithelialization after trypsin denuding treatment were examined as supposed biological activity features. Native HAM revealed viability indications and was active to kill all tested microorganisms; 6 bacterial species (3 Gram-positive and 3 Gram-negative) and Candida albicans as a pathogenic fungus. Also, HAM activity promoted colony formation of murine hematopoietic cells, Tilapia nilotica brain fragment building-up and self re-epithelialization after trypsin treatment. In contrary, radiation-based tissue banking of HAM caused HAM cellular death and consequently lacked almost all of examined biological activity features. Viable HAM was featured with biological activity than fixed HAM prepared by irradiation tissue banking.

Modification of the activity of lymphocytes by xenotransplantation of thyroid gland tissue and by the transfer factor of immune reactivity in the case of radiation-induced hypothyrosis

International Nuclear Information System (INIS)

Goleva, O.G.; Paster, Yi.P.; Lyubchenko, T.A.; Kholodna, L.S.; Paster, Je.U.; Donyich, S.F.; Grodzins'kij, D.M.

1999-01-01

Transplantation of a thyroid tissue is one of the possible methods for the curing of functional disorders of thyroid gland that appear due to the influence of insufficient environmental conditions on organism. By the micro method of lymphocyte blast transformation reaction, the functional activity of Wistar rat's splenocytes is studied. In the case of radiation-induced hypothyrosis before and after xenotransplantation of the organic cell culture of thyroid gland of newborn pigs, the opportunities for correction of immunological disorders with the help of transfer factor preparations are investigated. The transfer factor is a low-molecular weight leukocyte extract (≤ 10kD) with immuno modulating activities. The reducing of self and PHA-stimulated proliferation of rat's splenocytes with [J131]-induced hypothyrosis is found. Bovine and human transfer factor preparations activate the proliferation of splenocytes from animals with hypothyrosis and animals with xenotransplantation

COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

International Nuclear Information System (INIS)

Asting, Annika Gustafsson; Carén, Helena; Andersson, Marianne; Lönnroth, Christina; Lagerstedt, Kristina; Lundholm, Kent

2011-01-01

Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue

COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

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Lagerstedt Kristina

2011-06-01

Full Text Available Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4 showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3 were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

Activity of pyrimidine degradation enzymes in normal tissues

NARCIS (Netherlands)

van Kuilenburg, A. B. P.; van Lenthe, H.; van Gennip, A. H.

2006-01-01

In this study, we measured the activity of dihydropyrimidine dehydrogenase (DPD), dihydropyrimidinase (DHP) and beta-ureidopropionase (beta-UP), using radiolabeled substrates, in 16 different tissues obtained at autopsy from a single patient. The activity of DPD could be detected in all tissues

Tissue localization of human trefoil factors 1, 2, and 3

DEFF Research Database (Denmark)

Madsen, Jens; Nielsen, Ole; Tornøe, Ida

2007-01-01

Trefoil factors (TTFs) are small, compact proteins coexpressed with mucins in the gastrointestinal tract. Three trefoil factors are known in mammals: TFF1, TFF2, and TFF3. They are implicated to play diverse roles in maintenance and repair of the gastrointestinal channel. We compared the expression...... pattern of the three trefoil factors analyzing mRNA from a panel of 20 human tissues by conventional reverse transcriptase (RT) PCR and, in addition, by real-time PCR. These findings were supported by immunohistochemical analysis of paraffin-embedded human tissues using rabbit polyclonal antibodies raised...... against these factors. TFF1 showed highest expression in the stomach and colon, whereas TFF2 and TFF3 showed highest expression in stomach and colon, respectively. All three TFFs were found in the ducts of pancreas. Whereas TFF2 was found to be restricted to these two tissues, the structurally more...

Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

Science.gov (United States)

Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

2013-07-01

Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

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Halima Rakhila

Full Text Available Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2, cell adhesion (αv and β3 integrins, survival (B-cell lymphoma-2 and angiogenic (vascular endothelial cell growth factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.

Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

Science.gov (United States)

Rakhila, Halima; Girard, Karine; Leboeuf, Mathieu; Lemyre, Madeleine; Akoum, Ali

2014-01-01

Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF) appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO) mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT) mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2), cell adhesion (αv and β3 integrins), survival (B-cell lymphoma-2) and angiogenic (vascular endothelial cell growth) factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.

Transcription factor binding sites prediction based on modified nucleosomes.

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Mohammad Talebzadeh

Full Text Available In computational methods, position weight matrices (PWMs are commonly applied for transcription factor binding site (TFBS prediction. Although these matrices are more accurate than simple consensus sequences to predict actual binding sites, they usually produce a large number of false positive (FP predictions and so are impoverished sources of information. Several studies have employed additional sources of information such as sequence conservation or the vicinity to transcription start sites to distinguish true binding regions from random ones. Recently, the spatial distribution of modified nucleosomes has been shown to be associated with different promoter architectures. These aligned patterns can facilitate DNA accessibility for transcription factors. We hypothesize that using data from these aligned and periodic patterns can improve the performance of binding region prediction. In this study, we propose two effective features, "modified nucleosomes neighboring" and "modified nucleosomes occupancy", to decrease FP in binding site discovery. Based on these features, we designed a logistic regression classifier which estimates the probability of a region as a TFBS. Our model learned each feature based on Sp1 binding sites on Chromosome 1 and was tested on the other chromosomes in human CD4+T cells. In this work, we investigated 21 histone modifications and found that only 8 out of 21 marks are strongly correlated with transcription factor binding regions. To prove that these features are not specific to Sp1, we combined the logistic regression classifier with the PWM, and created a new model to search TFBSs on the genome. We tested the model using transcription factors MAZ, PU.1 and ELF1 and compared the results to those using only the PWM. The results show that our model can predict Transcription factor binding regions more successfully. The relative simplicity of the model and capability of integrating other features make it a superior method

Osseointegration improvement by plasma electrolytic oxidation of modified titanium alloys surfaces.

Science.gov (United States)

Echeverry-Rendón, Mónica; Galvis, Oscar; Quintero Giraldo, David; Pavón, Juan; López-Lacomba, José Luis; Jiménez-Piqué, Emilio; Anglada, Marc; Robledo, Sara M; Castaño, Juan G; Echeverría, Félix

2015-02-01

Titanium (Ti) is a material frequently used in orthopedic applications, due to its good mechanical properties and high corrosion resistance. However, formation of a non-adherent fibrous tissue between material and bone drastically could affect the osseointegration process and, therefore, the mechanical stability of the implant. Modifications of topography and configuration of the tissue/material interface is one of the mechanisms to improve that process by manipulating parameters such as morphology and roughness. There are different techniques that can be used to modify the titanium surface; plasma electrolytic oxidation (PEO) is one of those alternatives, which consists of obtaining porous anodic coatings by controlling parameters such as voltage, current, anodizing solution and time of the reaction. From all of the above factors, and based on previous studies that demonstrated that bone cells sense substrates features to grow new tissue, in this work commercially pure Ti (c.p Ti) and Ti6Al4V alloy samples were modified at their surface by PEO in different anodizing solutions composed of H2SO4 and H3PO4 mixtures. Treated surfaces were characterized and used as platforms to grow osteoblasts; subsequently, cell behavior parameters like adhesion, proliferation and differentiation were also studied. Although the results showed no significant differences in proliferation, differentiation and cell biological activity, overall results showed an important influence of topography of the modified surfaces compared with polished untreated surfaces. Finally, this study offers an alternative protocol to modify surfaces of Ti and their alloys in a controlled and reproducible way in which biocompatibility of the material is not compromised and osseointegration would be improved.

Modifiable Factors Associated with Cognitive Impairment in 1,143 Japanese Outpatients: The Project in Sado for Total Health (PROST

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Kaori Kitamura

2016-08-01

Full Text Available Background/Aims: Evidence on modifiable factors associated with cognitive impairment in Japanese patients is scarce. This study aimed to determine modifiable factors for cognitive impairment in a Japanese hospital-based population. Methods: Subjects of this cross-sectional study were 1,143 patients of Sado General Hospital (Niigata, Japan registered in the Project in Sado for Total Health (PROST between June 2008 and September 2014. We assessed disease history, body mass index (BMI, leisure time physical activity, walking time, smoking and drinking habits, and consumption of vegetables, fruits, and green tea as predictors, with cognitive impairment defined by the Mini-Mental State Examination (score Results: The mean subject age was 68.9 years, and the prevalence of cognitive impairment was 21.5%. Multivariate analysis revealed that age (p Conclusions: Modifiable factors, such as low BMI, low fruit consumption, and low green tea consumption, are associated with cognitive impairment. Longitudinal studies will be needed to confirm these findings.

Tissue factor pathway inhibitor 2 is found in skin and its C-terminal region encodes for antibacterial activity.

Science.gov (United States)

Papareddy, Praveen; Kalle, Martina; Sørensen, Ole E; Lundqvist, Katarina; Mörgelin, Matthias; Malmsten, Martin; Schmidtchen, Artur

2012-01-01

Tissue factor pathway inhibitor 2 (TFPI-2) is a matrix-associated serine protease inhibitor with an enigmatic function in vivo. Here, we describe that TFPI-2 is present in fibrin of wounds and also expressed in skin, where it is up-regulated upon wounding. Neutrophil elastase cleaved TFPI-2, and a C-terminal fragment was found to bind to bacteria. Similarly, a prototypic peptide representing this C-terminal part, EDC34, bound to bacteria and bacterial lipopolysaccharide, and induced bacterial permeabilization. The peptide also induced leakage in artificial liposomes, and displayed a random coil conformation upon interactions with liposomes as well as lipopolysaccharide. EDC34 was antibacterial against both Gram-negative and Gram-positive bacteria in physiological buffer conditions. The results demonstrate that the C-terminus of TFPI-2 encodes for antimicrobial activity, and may be released during wounding.

Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

Directory of Open Access Journals (Sweden)

Rinaldo Florencio-Silva

2015-01-01

Full Text Available Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines and systemic (e.g., calcitonin and estrogens factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

Plasmin-dependent proteolysis of tissue factor pathway inhibitor in a mouse model of endotoxemia.

Science.gov (United States)

Lupu, C; Herlea, O; Tang, H; Lijnen, R H; Lupu, F

2013-01-01

The development of a procoagulant state in sepsis, owing to aberrant expression of tissue factor (TF) and a sharp decrease in the level of its major inhibitor, TF pathway inhibitor (TFPI), could lead to microthrombotic organ failure. The mechanism for the decline in TFPI activity in the lung could involve plasmin-mediated cleavage of the inhibitor. To investigate the effect of plasmin generation on lung-associated TFPI activity, in normal conditions and during infusion of endotoxin (lipopolysaccharide [LPS]) in mice. Plasmin generation and TFPI activity were assayed in the lungs of mice deficient in tissue-type plasminogen (Plg) activator (t-PA) or Plg, at 2 h after LPS or saline injection. The sharp loss of lung-associated TFPI activity at 2 h after LPS challenge paralleled the abrupt increase in plasmin generation. TFPI activity was significantly retained in both t-PA(-/-) and Plg(-/-) mice, which are unable to generate plasmin. The increased plasmin generation during the early stages of sepsis could cleave/inactivate TFPI and thus lead to thrombotic complications. © 2012 International Society on Thrombosis and Haemostasis.

Modifiable factors associated with caregiver burden among family caregivers of terminally ill Korean cancer patients.

Science.gov (United States)

Yoon, Seok-Joon; Kim, Jong-Sung; Jung, Jin-Gyu; Kim, Sung-Soo; Kim, Samyong

2014-05-01

Higher caregiver burden is associated with poor quality of life among family caregivers. However, in Korea, very few studies have examined factors associated with caregiver burden. The present study investigated factors associated with caregiver burden among family caregivers of terminally ill Korean cancer patients, particularly modifiable factors as a potential target of intervention strategies. A cross-sectional study using self-administered questionnaires was performed. Sixty-four family caregivers of terminally ill cancer patients who were admitted to the hospice-palliative care unit of a university hospital in South Korea were included. To identify caregiver burden, the Caregiver Reaction Assessment scale (CRA) was used in this study. Time spent in providing care per day, number of visits per week from other family members, family functioning, and a positive subscale, self-esteem, of the CRA were deemed as modifiable factors. Other sociodemographic, caregiving characteristics of the subjects were non-modifiable factors. Longer time spent providing care per day, fewer weekly visits from other family members, poor family functioning, and low self-esteem were considered as modifiable factors associated with caregiver burden. Low monthly income and the spouse being the family caregiver were non-modifiable factors. Our study has practical significance in that it identifies modifiable factors that can be used to devise intervention strategies. Developing and applying such intervention strategies for alleviating the factors associated with high caregiver burden could be important for improving the quality of life of both patients and their families.

Development of the removal technology for toxic heavy metal ions by surface-modified activated carbon

International Nuclear Information System (INIS)

Park, Geun Il; Song, Kee Chan; Kim, Kwang Wook; Kim, In Tae; Cho, Il Hoon; Kim, Joon Hyung

2001-01-01

Adsorption capacities of both radionuclides(uranium, cobalt) and toxic heavy metals (lead, cadmium and chromium) using double surface-modified activated carbon in wide pH ranges are extensively evaluated. Surface-modified activated carbons are classified as AC(as-received carbon), OAC(single surface-modified carbon with nitric acid solution) and OAC-Na(double surface-modified carbon with various alkali solutions). It is established that optimal condition for the second surface modification of OAC is to use the mixed solution of both NaOH and NaCl with total concentration of 0.1 N based on adsorption efficiencies of uranium and cobalt. Variations of adsorption efficiencies in pH ranges of 2∼10 and the adsorption capacities in batch adsorber and fixed bed for removal of both radionuclides and toxic heavy metals using OAC-Na were shown to be superior to that of the AC and OAC even in a low pH range. Capacity factors of OAC-Na for the removal of various metal ions are also excellent to that of AC or OAC. Quantitative analysis of capacity factors for each ions showed that adsorption capacity of OAC-Na increased by 30 times for uranium, 60 times for cobalt, 9 times for lead, 30 times for cadmium, 3 times for chromium compared to that of AC at pH 5, respectively. Adsorption capacity of OAC-Na is comparable to that of XAD-16-TAR used as commercial ion exchange resin

Modifiable risk factors and colorectal adenomas among those at high risk of colorectal cancer

NARCIS (Netherlands)

Botma, A.

2011-01-01

Epidemiological studies have identified several modifiable risk factors for colorectal neoplasms in the general population. However, associations between modifiable risk factors, including body mass index (BMI), smoking, alcohol consumption and dietary patterns, and colorectal neoplasms in two

Tissue Factor and Tissue Factor Pathway Inhibitor in the Wound-Healing Process After Neurosurgery.

Science.gov (United States)

Ślusarz, Robert; Głowacka, Mariola; Biercewicz, Monika; Barczykowska, Ewa; Haor, Beata; Rość, Danuta; Gadomska, Grażyna

2016-03-01

The aim of the study was to assess the concentrations of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the blood of patients with a postoperative wound after neurosurgery. Participants included 20 adult patients who underwent neurosurgery because of degenerative spine changes. The concentration of TF and TFPI in the patients' blood serum was measured 3 times: before surgery, during the first 24 hr after surgery, and between the 5th and 7th days after surgery. The control group comprised 20 healthy volunteers similar to the patient group with respect to gender and age. A statistically significant difference was observed between TF concentration at all three measurement time points in the research group and TF concentration in the control group (p = .018, p = .010, p = .001). A statistically significant difference was found between TFPI concentration at the second time point in the research group and TFPI concentration in the control group (p = .041). No statistically significant within-subject difference was found between TF concentrations before and after surgery. A statistically significant within-subject difference was found between TFPI concentrations within 24 hr after surgery and 5-7 days after surgery (p = .004). High perioperative concentrations of TF indicate not only the presence of thrombophilia but also the importance of TF in the wound-healing process. Perioperative changes in TFPI concentrations are related to its compensatory influence on hemostasis in thrombophilic conditions. © The Author(s) 2015.

Peritumoral adipose tissue as a source of inflammatory and angiogenic factors in colorectal cancer.

Science.gov (United States)

Amor, S; Iglesias-de la Cruz, M C; Ferrero, E; García-Villar, O; Barrios, V; Fernandez, N; Monge, L; García-Villalón, A L; Granado, M

2016-02-01

Obesity is a risk factor for the development of human colorectal cancer (CC). The aim of this work is to report the inflammatory and angiogenic scenario in lean (BMI  30 kg/m2) patients with and without CC and to assess the role of peritumoral adipose tissue in CC-induced inflammation. Patients were divided in four experimental groups: obese patients with CC (OB-CC), lean patients with CC (LEAN-CC), obese patients without CC (OB), and lean patients without CC (LEAN). Plasma levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-4, IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in OB-CC patients. Peritumoral adipose tissue (TF) explants and cultured mature adipocytes secreted higher amounts of nitrites and nitrates than did control and non-tumoral (NTF) adipose tissue both alone and in response to lipopolysaccharide (LPS). Nitrite and nitrate secretion was also increased in TF explants from OB-CC patients compared with that from LEAN-CC patients. Gene expression of adiponectin, tumor necrosis factor alpha (TNF-α), insulin-like growth factor type I (IGF-I), cyclooxygenase-2 (COX-2), and peroxisome proliferator-activated receptor γ (PPAR-γ) was increased in TF explants from CC patients. LPS increased the gene expression of IL-6, IL-10, TNF-α, vascular endothelial growth factor (VEGF), and COX-2 in OB and in TF explants from OB-CC patients. COX-2 and PPAR-γ inhibition further increased LPS-induced release of nitrites and nitrates in TF explants and adipocytes from OB-CC patients. In conclusion, OB-CC patients have increased plasma levels of pro-inflammatory and angiogenic factors. TF from OB-CC patients shows an increased secretion of inflammatory markers compared with both TF from LEAN-CC and non-tumoral adipose tissue (AT) through a COX-2- and PPAR-γ-independent mechanism.

Kinetics of the Factor XIa catalyzed activation of human blood coagulation Factor IX

International Nuclear Information System (INIS)

Walsh, P.N.; Bradford, H.; Sinha, D.; Piperno, J.R.; Tuszynski, G.P.

1984-01-01

The kinetics of activation of human Factor IX by human Factor XIa was studied by measuring the release of a trichloroacetic acid-soluble tritium-labeled activation peptide from Factor IX. Initial rates of trichloroacetic acid-soluble 3 H-release were linear over 10-30 min of incubation of Factor IX (88 nM) with CaCl 2 (5 mM) and with pure (greater than 98%) Factor XIa (0.06-1.3 nM), which was prepared by incubating human Factor XI with bovine Factor XIIa. Release of 3 H preceded the appearance of Factor IXa activity, and the percentage of 3 H released remained constant when the mole fraction of 3 H-labeled and unlabeled Factor IX was varied and the total Factor IX concentration remained constant. A linear correlation (r greater than 0.98, P less than 0.001) was observed between initial rates of 3 H-release and the concentration of Factor XIa, measured by chromogenic assay and by radioimmunoassay and added at a Factor IX:Factor XIa molar ratio of 70-5,600. Kinetic parameters, determined by Lineweaver-Burk analysis, include K/sub m/ (0.49 microM) of about five- to sixfold higher than the plasma Factor IX concentration, which could therefore regulate the reaction. The catalytic constant (k/sub cat/) (7.7/s) is approximately 20-50 times higher than that reported by Zur and Nemerson for Factor IX activation by Factor VIIa plus tissue factor. Therefore, depending on the relative amounts of Factor XIa and Factor VIIa generated in vivo and other factors which may influence reaction rates, these kinetic parameters provide part of the information required for assessing the relative contributions of the intrinsic and extrinsic pathways to Factor IX activation, and suggest that the Factor XIa catalyzed reaction is physiologically significant

Young age as a modifying factor in sports concussion management: what is the evidence?

Science.gov (United States)

Foley, Cassidy; Gregory, Andrew; Solomon, Gary

2014-01-01

In 2008, the Concussion in Sport Group (CISG) published its third consensus statement and introduced 10 'modifying' factors that were presumed clinically to influence the investigation and management of concussions in sports. Young age was listed as one of the modifying factors. In some cases, these modifiers were thought to be predictive of prolonged or persistent symptoms. These same modifying factors were retained in the fourth iteration of the CISG consensus statement (2013), although mention was made of possible limitations of their efficacy. The CISG statements provided several empirical references regarding young age as a modifying factor. We reviewed the published sports concussion literature with the purpose of determining empirical studies that support or refute the inclusion of young age as a modifier of concussive injury in sports. We performed a systematic review of the PubMed database utilizing the keywords concussion, sports, mild traumatic brain injury, youth, adolescents, and children. English language studies were extracted by the authors and summarized for review. Multiple empirical studies were found indicating that younger athletes may take longer to recover from a sports-related concussion (SRC) than their older peers. However, studies did not indicate that younger athletes were at more risk for prolonged recovery (>4 wk). Empirical evidence supports the inclusion of young age as a modifying factor in sports concussion. However, the difference in recovery time seems relatively small (a few days) and young age does not predict prolonged recovery (>4 wk). The findings support the inclusion of young age as a specific modifier in the treatment of SRC and have implications for the clinical management of this common injury.

Factor Xa stimulates fibroblast procollagen production, proliferation, and calcium signaling via PAR1 activation

International Nuclear Information System (INIS)

Blanc-Brude, Olivier P.; Archer, Fabienne; Leoni, Patricia; Derian, Claudia; Bolsover, Steven; Laurent, Geoffrey J.; Chambers, Rachel C.

2005-01-01

Fibroblast proliferation and procollagen production are central features of tissue repair and fibrosis. In addition to its role in blood clotting, the coagulation cascade proteinase thrombin can contribute to tissue repair by stimulating fibroblasts via proteolytic activation of proteinase-activated receptor-1 (PAR 1 ). During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa. We have previously shown that factor Xa upregulates fibroblast proliferation via production of autocrine PDGF. In this study, we further examined the effects of factor Xa on fibroblast function and aimed to identify its signaling receptor. We showed that factor Xa stimulates procollagen promoter activity and protein production by human and mouse fibroblasts. This effect was independent of PDGF and thrombin production, but dependent on factor Xa proteolytic activity. We also showed that PAR 1 -deficient mouse fibroblasts did not upregulate procollagen production, mobilize cytosolic calcium, or proliferate in response to factor Xa. Desensitization techniques and PAR 1 -specific agonists and inhibitors were used to demonstrate that PAR 1 mediates factor Xa signaling in human fibroblasts. This is the first report that factor Xa stimulates extracellular matrix production. In contrast with endothelial cells and vascular smooth muscle cells, fibroblasts appear to be the only cell type in which the effects of factor Xa are mediated mainly via PAR 1 and not PAR 2 . These findings are critical for our understanding of tissue repair and fibrotic mechanisms, and for the design of novel approaches to inhibit the profibrotic effects of the coagulation cascade without compromising blood hemostasis

Peroxisome proliferator-activated receptor-gamma agonists suppress tissue factor overexpression in rat balloon injury model with paclitaxel infusion.

Directory of Open Access Journals (Sweden)

Jun-Bean Park

Full Text Available The role and underlying mechanisms of rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ agonist, on myocardial infarction are poorly understood. We investigated the effects of this PPAR-γ agonist on the expression of tissue factor (TF, a primary molecule for thrombosis, and elucidated its underlying mechanisms. The PPAR-γ agonist inhibited TF expression in response to TNF-α in human umbilical vein endothelial cells, human monocytic leukemia cell line, and human umbilical arterial smooth muscle cells. The overexpression of TF was mediated by increased phosphorylation of mitogen-activated protein kinase (MAPK, which was blocked by the PPAR-γ agonist. The effective MAPK differed depending on each cell type. Luciferase and ChIP assays showed that transcription factor, activator protein-1 (AP-1, was a pivotal target of the PPAR-γ agonist to lower TF transcription. Intriguingly, two main drugs for drug-eluting stent, paclitaxel or rapamycin, significantly exaggerated thrombin-induced TF expression, which was also effectively blocked by the PPAR-γ agonist in all cell types. This PPAR-γ agonist did not impair TF pathway inhibitor (TFPI in three cell types. In rat balloon injury model (Sprague-Dawley rats, n = 10/group with continuous paclitaxel infusion, the PPAR-γ agonist attenuated TF expression by 70±5% (n = 4; P<0.0001 in injured vasculature. Taken together, rosiglitazone reduced TF expression in three critical cell types involved in vascular thrombus formation via MAPK and AP-1 inhibitions. Also, this PPAR-γ agonist reversed the paclitaxel-induced aggravation of TF expression, which suggests a possibility that the benefits might outweigh its risks in a group of patients with paclitaxel-eluting stent implanted.

Endocrine factors influencing radiation injury to central nervous tissue

International Nuclear Information System (INIS)

Aristizabal, S.A.; Boone, M.L.; Laguna, J.F.

1979-01-01

Corticosteroids have been shown experimentally to lower the tolerance of various normal tissues (lung, kidney, intestine) to irradiation. Pre-existing hypertension also modified the effect of irradiation on the rat spinal cord and brain. Hypercorticism and hypertension co-exist in patients with Cushing's disease. Although these patients are often approached therapeutically by irradiation, no reports concerning differences in the radiation sensitivity of nervous tissue between normal subjects (non-functioning pituitary adenomas) and those with hormonal imbalance and/or hypertension appear to be available. A comprehensive review of the literature revealed 14 patients with radiation damage to brain or to optic pathways following moderate doses for pituitary adenomas. Seven of the 14 patients (50%) had Cushing's disease. This apparent higher incidence of radiation injury is significant if we consider that less than 5% of all patients receiving irradiation for pituitary adenomas have Cushing's disease

PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

Science.gov (United States)

Karakan, Tarkan; Kerem, Mustafa; Cindoruk, Mehmet; Engin, Doruk; Alper, Murat; Akın, Okan

2013-01-01

Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.

Do methodological differences account for the current controversy on tissue factor expression in platelets?

Science.gov (United States)

Brambilla, Marta; Rossetti, Laura; Zara, Chiara; Canzano, Paola; Giesen, Peter L A; Tremoli, Elena; Camera, Marina

2018-06-01

Tissue factor (TF), the key activator of the blood coagulation cascade and of thrombus formation, is also expressed by circulating human platelets. Despite the documented in-depth characterization of platelet TF carried out in the past 15 years, some authors still fail to identify TF in platelets, especially when assessment in platelet-rich plasma (PRP) or washed platelets is carried out. This study aims to extend the characterization of the subset of TF-positive platelets in PRP from healthy subjects and to verify how different centrifugation forces, used to prepare the PRP, could affect the analysis of TF-positive platelets. Data indicate that large-size platelets express significantly higher amount of TF compared to small-size cells, in terms of both TF protein and TF mRNA. Upon stimulation, large platelets readily expose on the cell membrane TF, which is functionally active, i.e., able to generate factor Xa (FXa) as well as thrombin. By contrast, TF activity in small platelets is almost completely quenched by tissue factor pathway inhibitor (TFPI), becoming indeed detectable only after treatment with an anti-TFPI antibody. Our data highlight that particular attention must be paid to the preparation and collection of the PRP since such preanalytical variables may influence the platelet recovery and in turn affect subsequent analysis, whether it is flow cytometry, functional activity tests, proteome, or transcriptome analysis. Indeed, the TF-positive subset of large platelets can easily be lost if centrifugation protocols are not optimized, thus erroneously leading to a false-negative result.

Is There an Economical Running Technique? A Review of Modifiable Biomechanical Factors Affecting Running Economy.

Science.gov (United States)

Moore, Isabel S

2016-06-01

Running economy (RE) has a strong relationship with running performance, and modifiable running biomechanics are a determining factor of RE. The purposes of this review were to (1) examine the intrinsic and extrinsic modifiable biomechanical factors affecting RE; (2) assess training-induced changes in RE and running biomechanics; (3) evaluate whether an economical running technique can be recommended and; (4) discuss potential areas for future research. Based on current evidence, the intrinsic factors that appeared beneficial for RE were using a preferred stride length range, which allows for stride length deviations up to 3 % shorter than preferred stride length; lower vertical oscillation; greater leg stiffness; low lower limb moment of inertia; less leg extension at toe-off; larger stride angles; alignment of the ground reaction force and leg axis during propulsion; maintaining arm swing; low thigh antagonist-agonist muscular coactivation; and low activation of lower limb muscles during propulsion. Extrinsic factors associated with a better RE were a firm, compliant shoe-surface interaction and being barefoot or wearing lightweight shoes. Several other modifiable biomechanical factors presented inconsistent relationships with RE. Running biomechanics during ground contact appeared to play an important role, specifically those during propulsion. Therefore, this phase has the strongest direct links with RE. Recurring methodological problems exist within the literature, such as cross-comparisons, assessing variables in isolation, and acute to short-term interventions. Therefore, recommending a general economical running technique should be approached with caution. Future work should focus on interdisciplinary longitudinal investigations combining RE, kinematics, kinetics, and neuromuscular and anatomical aspects, as well as applying a synergistic approach to understanding the role of kinetics.

Treatment of Ebola Virus Infection With a Recombinant Inhibitor of Factor Vlla/Tissue Factor: A Study in Rhesus Monkeys

National Research Council Canada - National Science Library

Geisbert, Thomas W; Hensley, Lisa E; Jahrling, Peter B; Larsen, Tom; Geisbert, Joan B

2003-01-01

Infection with the Ebola virus induces overexpression of the procoagulant tissue factor in primate monocytes and macrophages, suggesting that inhibition of the tissue-factor pathway could ameliorate...

Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

Science.gov (United States)

Koizume, Shiro; Miyagi, Yohei

2015-01-01

Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

DEFF Research Database (Denmark)

Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie

2000-01-01

Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples...... that triglyceride-rich lipoproteins may activate prokallikrein. Neither plasma triglycerides nor kallikrein and activated FVII were statistically associated. This may suggest that additional factors are involved in the postprandial FVII activation. No clear evidence for a role of tissue factor expression...... by monocytes, factor XII or insulin in postprandial FVII activation was observed. Tissue factor pathway inhibitor and prothrombin fragment 1+2, a marker of thrombin generation, were not affected postprandially after either the high-fat or the low-fat meals. Our findings indicate that triglyceride...

Receptor for advanced glycation end products - membrane type1 matrix metalloproteinase axis regulates tissue factor expression via RhoA and Rac1 activation in high-mobility group box-1 stimulated endothelial cells.

Directory of Open Access Journals (Sweden)

Koichi Sugimoto

Full Text Available BACKGROUND: Atherosclerosis is understood to be a blood vessel inflammation. High-mobility group box-1 (HMGB-1 plays a key role in the systemic inflammation. Tissue factor (TF is known to lead to inflammation which promotes thrombus formation. Membrane type1 matrix metalloprotease (MT1-MMP associates with advanced glycation endproducts (AGE triggered-TF protein expression and phosphorylation of NF-κB. However, it is still unclear about the correlation of MT1-MMP and HMBG-1-mediated TF expression. In this study, we investigated the molecular mechanisms of TF expression in response to HMGB-1 stimulation and the involvement of MT1-MMP in endothelial cells. METHODS AND RESULTS: Pull-down assays and Western blotting revealed that HMGB-1 induced RhoA/Rac1 activation and NF-kB phosphorylation in cultured human aortic endothelial cells. HMGB-1 increased the activity of MT1-MMP, and inhibition of RAGE or MT1-MMP by siRNA suppressed HMGB-1-induced TF upregulation as well as HMGB-1-triggered RhoA/Rac1 activation and NF-kB phosphorylation. CONCLUSIONS: The present study showed that RAGE/MT1-MMP axis modified HMBG-1-mediated TF expression through RhoA and Rac1 activation and NF-κB phosphorylation in endothelial cells. These results suggested that MT1-MMP was involved in vascular inflammation and might be a good target for treating atherosclerosis.

A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

DEFF Research Database (Denmark)

Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik

2007-01-01

Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD......) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation...... in the presence of TF or an active-site inhibitor. Based on MD simulations, a key switch of the TF-induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural...

Effect of tissue and plasma factors on kidney proliferation.

Science.gov (United States)

Inda, A M; García, A L; Errecalde, A L; Badrán, A F

1997-04-01

Liver extract, plasma from intact mice, ES2 tumour extract and plasma from tumour bearing mice has an inhibiting effect on the mitotic activity of hepatocytes and duodenal enterocytes. In the present experiments, the effect of these treatments on the mitotic activity of renal tubular cells was studied. C3HS 28 day-old male mice, standardized for periodicity analysis were used. The determination of normal mitotic circadian curve of the renocytes was done. A second batch of mice were injected with 0.01 ml/gr of either liver extract, plasma from intact mice, ES2 tumour extract or plasma from tumour bearing mice, at 16:00 hours and controlled at 08:00, 12:00 and 16:00 hs during 2 consecutive days post treatment. Colchicine (2 micrograms/gr) was injected 4 hours before killing. Kidneys were processed for histology and mitotic index determinations. Results were expressed as colchicine metaphases per 1000 nuclei, and showed that mitotic activity values of treated animals were significantly lower than those of controls. In conclusion, mitotic activity inhibition of renocytes may be due to some non specific plasmatic and/or tissue factors.

Does food store access modify associations between intrapersonal factors and fruit and vegetable consumption?

Science.gov (United States)

Thornton, L E; Lamb, K E; Tseng, M; Crawford, D A; Ball, K

2015-08-01

Existing theoretical frameworks suggest that healthy eating is facilitated by an individual's ability, motivation and environmental opportunities. It is plausible, although largely untested, that the importance of factors related to ability and motivation differ under varied environmental conditions. This study aimed to determine whether the magnitude of associations between fruit and vegetable consumption and intrapersonal factors (ability and motivation) were modified by differences in access to stores selling these items (environmental opportunities). Cross-sectional analysis of 4335 women from socioeconomically disadvantaged neighbourhoods in the state of Victoria, Australia. Self-reported fruit and vegetable consumption was assessed against a number of ability- and motivation-related factors. To examine whether associations were modified by store access, interactions with access to supermarkets and greengrocers within 2 km of participants' households were tested. Of the two factors related to ability and seven factors related to motivation, almost all were associated with fruit and vegetable consumption. In general, associations were not modified by store access suggesting that these factors were not tempered by environmental opportunities. This study provides little support for the hypothesis that the importance of intra-personal factors to fruit and vegetable consumption is modified by food store access. Further research on this topic is required to inform behaviour change interventions.

Human tissue factor: cDNA sequence and chromosome localization of the gene

International Nuclear Information System (INIS)

Scarpati, E.M.; Wen, D.; Broze, G.J. Jr.; Miletich, J.P.; Flandermeyer, R.R.; Siegel, N.R.; Sadler, J.E.

1987-01-01

A human placenta cDNA library in λgt11 was screened for the expression of tissue factor antigens with rabbit polyclonal anti-human tissue factor immunoglobulin G. Among 4 million recombinant clones screened, one positive, λHTF8, expressed a protein that shared epitopes with authentic human brain tissue factor. The 1.1-kilobase cDNA insert of λHTF8 encoded a peptide that contained the amino-terminal protein sequence of human brain tissue factor. Northern blotting identified a major mRNA species of 2.2 kilobases and a minor species of ∼ 3.2 kilobases in poly(A) + RNA of placenta. Only 2.2-kilobase mRNA was detected in human brain and in the human monocytic U937 cell line. In U937 cells, the quantity of tissue factor mRNA was increased several fold by exposure of the cells to phorbol 12-myristate 13-acetate. Additional cDNA clones were selected by hybridization with the cDNA insert of λHTF8. These overlapping isolates span 2177 base pairs of the tissue factor cDNA sequence that includes a 5'-noncoding region of 75 base pairs, an open reading frame of 885 base pairs, a stop codon, a 3'-noncoding region of 1141 base pairs, and a poly(a) tail. The open reading frame encodes a 33-kilodalton protein of 295 amino acids. The predicted sequence includes a signal peptide of 32 or 34 amino acids, a probable extracellular factor VII binding domain of 217 or 219 amino acids, a transmembrane segment of 23 acids, and a cytoplasmic tail of 21 amino acids. There are three potential glycosylation sites with the sequence Asn-X-Thr/Ser. The 3'-noncoding region contains an inverted Alu family repetitive sequence. The tissue factor gene was localized to chromosome 1 by hybridization of the cDNA insert of λHTF8 to flow-sorted human chromosomes

Placental Growth Factor Promotes Ovarian Cancer Cell Invasion via ZEB2

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Ning Song

2016-01-01

Full Text Available Background/Aims: The aggressive manner of ovarian cancer (OVC cells accounts for the majority of its lethality. Recently, we have shown that placental growth factor (PLGF promotes metastases of OVC cells through miR-543-regulated MMP7. In the current study, we analyzed the effects of PLGF on another cell invasion associated protein, ZEB2, in OVC cells. Methods: The PLGF and ZEB2 levels in OVC tissues were compared to the paired adjacent non-tumor ovary tissue. We modified ZEB2 levels in OVC cells, and examined its effects on PLGF mRNA and protein levels by RT-qPCR and by Western blot, respectively. We also modified PLGF levels in OVC cells, and examined its effects on ZEB2 mRNA and protein levels by RT-qPCR and by Western blot, respectively. Then, we examined the cell invasiveness in PLGF-modified OVC cells in a transwell cell invasion assay. Finally, we used specific signal pathway inhibitors to treat PLGF-modified OVC cells and examined the effects on ZEB2 activation. Results: PLGF and ZEB2 levels were both significantly increased in OVC tissues, compared to the paired adjacent non-tumor ovary tissue. The PLGF and ZEB2 levels were strongly correlated. ZEB2 modification did not alter PLGF levels. Overexpression of PLGF in OVC cells significantly increased ZEB2 levels and cell invasiveness, while PLGF depletion in OVC cells significantly decreased ZEB2 levels and cell invasiveness. Application of a specific MAPK-p38 inhibitor, but not application of specific inhibitors for MAPK-p42/p44, PI3k/Akt, or JNK signaling pathways, to PLGF-overexpressing OVC cells substantially abolished the PLGF-induced ZEB2 activation. Conclusion: PLGF enhances OVC cell invasion through MAPK-p38-dependent activation of ZEB2.

Effect of cystamine on rat tissue GSH level and glutathione reductase activity

International Nuclear Information System (INIS)

Kovarova, H.; Pulpanova, J.

1979-01-01

Reduced glutathione (GSH) level and glutathione reductase activity were determined by means of the spectrophotometric method in various rat tissues after i.p. administration of cystamine (50 mg/kg and 20 mg/kg). GSH amount dropped in the spleen and kidney at 10 and 20 min; following this interval, an increase of GSH level was observed in the liver at 20-30 min, in the spleen and kidney at 60 min after the treatment with a radioprotective cystamine dose (50 mg/kg). The changes in GSH level induced by a non-radioprotective cystamine dose (20 mg/kg) had an opposite tendency. The activity of glutathione reductase was decreased in all tissues studied. As to the mechanism of the radioprotective action, both the inactivation of glutathione reductase activity and the changes in GSH level seem to be the factors contributing to the radioprotective effect of cystamine by strengthening the cellular radioresistance. (orig.) 891 MG/orig. 892 RKD [de

[Effective productions of plant secondary metabolites having antitumor activity by plant cell and tissue cultures].

Science.gov (United States)

Taniguchi, Shoko

2005-06-01

Methods for the effective production of plant secondary metabolites with antitumor activity using plant cell and tissue cultures were developed. The factors in tannin productivity were investigated using culture strains producing different types of hydrolyzable tannins, i.e., gallotannins (mixture of galloylglucoses), ellagi-, and dehydroellagitannins. Production of ellagi- and dehydroellagitannins was affected by the concentrations and ratio of nitrogen sources in the medium. The formation of oligomeric ellagitannins in shoots of Oenothera tetraptera was correlated with the differentiation of tissues. Cultured cells of Eriobotrya japonica producing ursane- and oleanane-type triterpenes with antitumor activities were also established.

Modifiable worker risk factors contributing to workplace absence: a stakeholder-centred best-evidence synthesis of systematic reviews.

Science.gov (United States)

Wagner, Shannon; White, Marc; Schultz, Izabela; Murray, Eleanor; Bradley, Susan M; Hsu, Vernita; McGuire, Lisa; Schulz, Werner

2014-01-01

A challenge facing stakeholders is the identification and translation of relevant high quality research to inform policy and practice. This study engaged academic and community stakeholders in conducting a best evidence-synthesis to identify modifiable risk and protective worker factors across health conditions impacting work-related absence. To identify modifiable worker disability risk and protective factors across common health conditions impacting work-related absence. We searched Medline, Embase, CINHAL, The Cochrane Library, PsycINFO, BusinessSourceComplete, and ABI/Inform from 2000 to 2011. Quantitative, qualitative, or mixed methods systematic reviews of work-focused population were considered for inclusion. Two or more reviewers independently reviewed articles for inclusion and methodological screening. The search strategy, expert input and grey literature identified 2,467 unique records. One hundred and forty-two full text articles underwent comprehensive review. Twenty-four systematic reviews met eligibility criteria. Modifiable worker factors found to have consistent evidence across two or more health conditions included emotional distress, negative enduring psychology/personality factors, negative health and disability perception, decreased physical activity, lack of family support, poor general health, increased functional disability, increased pain, increased fatigue and lack of motivation to return to work. Systematic reviews are limited by availability of high quality studies, lack of consistency of methodological screening and reporting, and variability of outcome measures used.

Over-expression of thymosin β4 in granulomatous lung tissue with active pulmonary tuberculosis.

Science.gov (United States)

Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Yoo, Young-Bin; Chun, Bong-Kwon; Oak, Chul-Ho; Cha, Hee-Jae

2014-05-01

Recent studies have shown that thymosin β4 (Tβ4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1α (HIF-1α) protein. Pulmonary tuberculosis (TB), a type of granulomatous disease, is accompanied by intense angiogenesis and VEGF levels have been reported to be elevated in serum or tissue inflamed by pulmonary tuberculosis. We investigated the expression of Tβ4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1α to compare their Tβ4 expression patterns in patients' tissues and in the tissue microarray of TB patients. Tβ4 was highly expressed in both granulomas and surrounding lymphocytes in nascent granulomatous lung tissue, but was expressed only surrounding tissues of necrotic or caseous necrotic regions. The expression pattern of HIF-1α was similar to that of Tβ4. VEGF was expressed in both granulomas and blood vessels surrounding granulomas. The expression pattern of VEGF co-localized with CD31 (platelet endothelial cell adhesion molecule, PECAM-1), a blood endothelial cell marker, and partially co-localized with Tβ4. However, the expression of Tβ4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing Tβ4. We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of Tβ4 was significantly higher in patients with pulmonary tuberculosis than in normal controls. These data suggest that Tβ4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1α- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of Tβ4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Periodontal tissue damage in smokers

Directory of Open Access Journals (Sweden)

Hutojo Djajakusuma

2006-09-01

Full Text Available Dental plaque is the primary etiological factor in periodontal diseases. However, there are many factors that can modify how an individual periodontal tissue will respond to the accumulation of dental plaque. Among such risk factors, there is increasing evidence that smoking tobacco products alters the expression and rate of progression of periodontal diseases. The aim of this study was to find out the loss of periodontal tissue adhesion in smokers by measuring pocket depth using probe, and by measuring alveolar bone damage using Bone Loss Score (BLS radiographic methods on teeth 12, 11, 21, 22, 32, 31, 41, 42. Based on T Test statistical analysis, there were significant differences in pocket depth damage of alveolar bone in smokers and non smokers. In conclusion there were increasing pocket depth and alveolar bone damage in smokers.

Autocrine effect of DHT on FGF signaling and cell proliferation in LNCaP cells: role of heparin/heparan-degrading enzymes.

Science.gov (United States)

Kassen, A E; Sensibar, J A; Sintich, S M; Pruden, S J; Kozlowski, J M; Lee, C

2000-07-01

LNCaP cells are androgen-sensitive human prostate cancer cells. They are characterized by a bell-shaped growth curve in response to increasing doses of dihydrotestosterone (DHT) in culture. At a low concentration of DHT (0.1 nM), these cells show an increase in proliferation, but their growth is arrested at a high concentration (100 nM) of DHT. Results of our previous study demonstrated that the inhibitory effect of DHT at a high concentration was mediated through the action of TGF-beta1. The objective of the present study was to elucidate the mechanism of the proliferative effect of DHT in LNCaP cells. METHODS AND RESULTS DHT stimulated LNCaP proliferation only when cells were cultured in the presence of serum. In serum-free cultures, the characteristic DHT-induced proliferation was not observed. The addition of neutralizing antibody against FGF-2 (basic fibroblast growth factor) was able to inhibit this DHT-induced proliferation. These results suggest that the proliferative effect of DHT was mediated through the action of FGF-2. However, results of the reverse transcriptase polymerase chain reaction indicated that LNCaP cells did not express FGF-2 message. As a result, the source of FGF-2 in these cultures must be the serum supplemented in the culture media. FGF-2 can bind to heparin sulfate chains within the extracellular matrix (ECM). In cultures treated with exogenous heparin, the proliferative effect of DHT was abolished. These results led to the development of the hypothesis that DHT treatment mediates the release of FGF-2 entrapped in the ECM through increased heparinase activity. The addition of heparinase to cultures of LNCaP cells, in the absence of DHT, was able to stimulate cell proliferation. Moreover, 0.1 nM DHT caused a significant increase in heparinase activity. These results provide a possible mechanism for DHT action in LNCaP cells. In the absence of DHT, FGF-2 in culture was trapped in the extracellular matrix and was not available to interact

Extracellular histones induce tissue factor expression in vascular endothelial cells via TLR and activation of NF-κB and AP-1.

Science.gov (United States)

Yang, Xinyu; Li, Lin; Liu, Jin; Lv, Ben; Chen, Fangping

2016-01-01

Extracellular histones have been recognized recently as proinflammatory mediators; they are released from dying cells in response to inflammatory challenge, contributing to endothelial cell dysfunction, thrombin formation, organ failure, and death during sepsis. Clinical studies suggest that the plasma concentration of the histone-DNA complex is correlated with the severity of DIC and is a poor independent prognostic marker in sepsis. In addition, platelet activation stimulates thrombus formation. Whether histones contribute to procoagulant activity in other ways remains elusive. In this study, we confirmed that histones induce tissue factor (TF) expression in a concentration- and time-dependent manner in vascular endothelial cells (ECs) and macrophages. However, histones did not affect TF pathway inhibitor expression. Moreover, blocking the cell surface receptors TLR4 and TLR2 with specific neutralizing antibodies significantly reduced histone-induced TF expression. Furthermore, histones enhanced the nuclear translocation of NF-κB (c-Rel/p65) and AP-1 expression in a time-dependent manner in ECs. Mutating NF-κB and AP-1 significantly reduced histone-induced TF expression. Altogether, our experiments suggest that histone induces TF expression in ECs via cell surface receptors TLR4 and TLR2, simultaneously depending on the activation of the transcription factors NF-κB and AP-1. Copyright © 2015 Elsevier Ltd. All rights reserved.

Factors modifying sensitivity to carcinogens and the problem of threshold in carcinogenesis

International Nuclear Information System (INIS)

Anisimov, V.N.

1983-01-01

Maximum allowable concentrations of chemical carcinogens and dose rates of ionizing radiation have been under extensive study both experimentally and epidemiologically. The problem of the carcinogenic hazards of low-level radiation is a very difficult one: in epidemiological studies it is hard to take into account the many factors (e.g. diseases, diet, genetic peculiarities) that may affect sensitivity to radiation; in experimental studies it is hard to extrapolate with accuracy from one species to another or from the individual threshold to that of the whole population. Age, enzyme activity, sex, and DNA repair capability also modify sensitivity to radiation; when factors such as these are better understood it is expected that epidemiological studies will give a solution that allows estimation of the carcinogenic risk from low-level radiation and hence establishment of a threshold dose. (author)

Differences in modifiable feeding factors by overweight status in Latino infants.

Science.gov (United States)

Cartagena, Diana; McGrath, Jacqueline M; Masho, Saba W

2016-05-01

Obesity prevalence remains disproportionally high for young American children from low-socioeconomic and ethnic minorities. Modifiable feeding factors may lead to infant overfeeding and an increased risk for obesity. This study explored differences in modifiable feeding factors by overweight status (>85% weight-for-length) in the first year of life of Latino infants. Data were obtained from a cross-sectional pilot study of 62 low-income immigrant Latina mothers and their infants (ages 4-12 months). Measures included maternal feeding practices, feeding pattern, infant's 24-hour dietary recall, and maternal perception of infant weight. Chi-square and t-tests were used for comparisons between healthy weight and overweight infants. Birth weight z-scores did not significantly differ by weight status. Overweight status was not associated with maternal feeding practices, feeding pattern or infant dietary intake. A trend toward significance was seen in the maternal perception of infant weight. Overweight infants were similar to healthy weight infants in their birth weight z-scores and supports the premise that modifiable feeding factors are in play and thus targeted early feeding interventions may prove effective in decreasing obesity risk in Latinos. Copyright © 2015 Elsevier Inc. All rights reserved.

Use of fibroblast growth factor 2 for expansion of chondrocytes and tissue engineering

Science.gov (United States)

Vunjak-Novakovic, Gordana (Inventor); Martin, Ivan (Inventor); Freed, Lisa E. (Inventor); Langer, Robert (Inventor)

2003-01-01

The present invention provides an improved method for expanding cells for use in tissue engineering. In particular the method provides specific biochemical factors to supplement cell culture medium during the expansion process in order to reproduce events occurring during embryonic development with the goal of regenerating tissue equivalents that resemble natural tissues both structurally and functionally. These specific biochemical factors improve proliferation of the cells and are capable of de-differentiation mature cells isolated from tissue so that the differentiation potential of the cells is preserved. The bioactive molecules also maintain the responsiveness of the cells to other bioactive molecules. Specifically, the invention provides methods for expanding chondrocytes in the presence of fibroblast growth factor 2 for use in regeneration of cartilage tissue.

Heat stress differentially modifies ethylene biosynthesis and signaling in pea floral and fruit tissues.

Science.gov (United States)

Savada, Raghavendra P; Ozga, Jocelyn A; Jayasinghege, Charitha P A; Waduthanthri, Kosala D; Reinecke, Dennis M

2017-10-01

Ethylene biosynthesis is regulated in reproductive tissues in response to heat stress in a manner to optimize resource allocation to pollinated fruits with developing seeds. High temperatures during reproductive development are particularly detrimental to crop fruit/seed production. Ethylene plays vital roles in plant development and abiotic stress responses; however, little is known about ethylene's role in reproductive tissues during development under heat stress. We assessed ethylene biosynthesis and signaling regulation within the reproductive and associated tissues of pea during the developmental phase that sets the stage for fruit-set and seed development under normal and heat-stress conditions. The transcript abundance profiles of PsACS [encode enzymes that convert S-adenosyl-L-methionine to 1-aminocyclopropane-1-carboxylic acid (ACC)] and PsACO (encode enzymes that convert ACC to ethylene), and ethylene evolution were developmentally, environmentally, and tissue-specifically regulated in the floral/fruit/pedicel tissues of pea. Higher transcript abundance of PsACS and PsACO in the ovaries, and PsACO in the pedicels was correlated with higher ethylene evolution and ovary senescence and pedicel abscission in fruits that were not pollinated under control temperature conditions. Under heat-stress conditions, up-regulation of ethylene biosynthesis gene expression in pre-pollinated ovaries was also associated with higher ethylene evolution and lower retention of these fruits. Following successful pollination and ovule fertilization, heat-stress modified PsACS and PsACO transcript profiles in a manner that suppressed ovary ethylene evolution. The normal ethylene burst in the stigma/style and petals following pollination was also suppressed by heat-stress. Transcript abundance profiles of ethylene receptor and signaling-related genes acted as qualitative markers of tissue ethylene signaling events. These data support the hypothesis that ethylene biosynthesis is

Validity of the modified Reynolds equation for incompressible active lubrication

DEFF Research Database (Denmark)

Cerda Varela, Alejandro Javier; Santos, Ilmar

2016-01-01

The modified Reynolds equation for active lubrication has been the cornerstone around which the theoretical investigations regarding actively lubricated bearings have evolved over the years. Introduced originally in 1994, it enables to calculate in a simplified manner the bearing pressure field...... as a function of servovalve controlled pressurized oil injection. This article deals with a preliminary critical review of the simplificatory assumptions that are introduced into the modified Reynolds equation in order to model the phenomena taking place in the interface between the injection nozzle...... and the bearing clearance. The analysis is performed by means of direct comparison of the results of the modified Reynolds equation model versus benchmark CFD calculations, applied to a geometry representative of the system analyzed. The results show that the modified Reynolds equation mathematical simplicity...

In situ monitoring of myenteric neuron activity using acetylcholinesterase-modified AlGaN/GaN solution-gate field-effect transistors.

Science.gov (United States)

Müntze, Gesche Mareike; Pouokam, Ervice; Steidle, Julia; Schäfer, Wladimir; Sasse, Alexander; Röth, Kai; Diener, Martin; Eickhoff, Martin

2016-03-15

The response characteristics of acetylcholinesterase-modified AlGaN/GaN solution-gate field-effect transistors (AcFETs) are quantitatively analyzed by means of a kinetic model. The characterization shows that the covalent enzyme immobilization process yields reproducible AcFET characteristics with a Michaelis constant KM of (122 ± 4) μM for the immobilized enzyme layer. The increase of KM by a factor of 2.4 during the first four measurement cycles is attributed to partial denaturation of the enzyme. The AcFETs were used to record the release of acetylcholine (ACh) by neuronal tissue cultivated on the gate area upon stimulation by rising the extracellular K(+) concentration. The neuronal tissue constituted of isolated myenteric neurons from four to 12 days old Wistar rats, or sections from the muscularis propria containing the myenteric plexus from adult rats. For both cases the AcFET response was demonstrated to be related to the activity of the immobilized acetylcholinesterase using the reversible acetylcholinesterase blocker donepezil. A concentration response curve of this blocking agent revealed a half maximal inhibitory concentration of 40 nM which is comparable to values measured by complementary in vitro methods. Copyright © 2015 Elsevier B.V. All rights reserved.

Nutritional status induces divergent variations of GLUT4 protein content, but not lipoprotein lipase activity, between adipose tissues and muscles in adult cattle.

Science.gov (United States)

Bonnet, Muriel; Faulconnier, Yannick; Hocquette, Jean-François; Bocquier, François; Leroux, Christine; Martin, Patrice; Chilliard, Yves

2004-10-01

Metabolic adaptations to variations in food supply are incompletely understood in ruminant animal adipose tissue (AT) and muscle. To explore this, we studied lipid metabolism and glucose transport potential in one internal and one external AT, as well as in one oxidative and one glycolytic muscle from control, 7 d underfed and 21 d refed adult cows. Refeeding increased (+79 to +307 %) the activities of enzymes involved in de novo lipogenesis (fatty acid synthase, malic enzyme, glucose-6-phosphate dehydrogenase) in perirenal and subcutaneous AT; underfeeding did not modify these variables. Underfeeding decreased the activities of lipoprotein lipase (LPL) in perirenal AT (-70 %) and cardiac muscle (-67 %), but did not modify the activities in subcutaneous AT and longissimus thoracis. Refeeding increased LPL activities in all tissues (+40 to +553 %) to levels comparable with (cardiac muscle) or greater than (AT, longissimus thoracis) those observed in control cows. Such variations in perirenal and cardiac muscle LPL activities did not result from variations in LPL mRNA levels, but suggest a post-transcriptional regulation of LPL in these nutritional conditions. Underfeeding did not modify GLUT4 contents in perirenal AT and muscles, while refeeding increased it only in perirenal AT (+250 %). Our present results contrast with previous results in rats, where LPL is regulated in opposite directions in AT and muscles, and GLUT4 is generally increased by fasting and decreased by refeeding in skeletal muscles. The present results highlight the bovine specificity of the response, which probably arises in part from peculiarities of ruminant animals for nutrient digestion and absorption.

Little change of modifiable risk factors 1 year after stroke: a pilot study

DEFF Research Database (Denmark)

Hornnes, Nete; Larsen, Klaus; Boysen, Gudrun

2010-01-01

Recurrent stroke accounts for about 25% of admissions for acute stroke. For the prevention of recurrent cerebro and cardiovascular disease, stroke patients are advised to change modifiable stroke risk factors before discharge from stroke units.......Recurrent stroke accounts for about 25% of admissions for acute stroke. For the prevention of recurrent cerebro and cardiovascular disease, stroke patients are advised to change modifiable stroke risk factors before discharge from stroke units....

Synthesis and characterization of cycloaliphatic hydrophilic polyurethanes, modified with L-ascorbic acid, as materials for soft tissue regeneration

Energy Technology Data Exchange (ETDEWEB)

Kucinska-Lipka, J., E-mail: juskucin@pg.gda.pl [Gdank University of Technology, Faculty of Chemistry, Department of Polymer Technology, Narutowicza St. 11/12, 80-233 Gdansk (Poland); Gubanska, I.; Strankowski, M. [Gdank University of Technology, Faculty of Chemistry, Department of Polymer Technology, Narutowicza St. 11/12, 80-233 Gdansk (Poland); Cieśliński, H.; Filipowicz, N. [Gdansk University of Technology, Faculty of Chemistry, Department of Microbiology, Narutowicza St. 11/12, 80-233 Gdansk (Poland); Janik, H. [Gdank University of Technology, Faculty of Chemistry, Department of Polymer Technology, Narutowicza St. 11/12, 80-233 Gdansk (Poland)

2017-06-01

In this paper we described synthesis and characteristic of obtained hydrophilic polyurethanes (PURs) modified with ascorbic acid (commonly known as vitamin C). Such materials may find an application in the biomedical field, for example in the regenerative medicine of soft tissues, according to ascorbic acid wide influence on tissue regeneration Flora (2009), Szymańska-Pasternak et al. (2011), Taikarimi and Ibrahim (2011), Myrvik and Volk (1954), Li et al. (2001), Cursino et al. (2005) . Hydrophilic PURs were obtained with the use of amorphous α,ω-dihydroxy(ethylene-butylene adipate) (dHEBA) polyol, 1,4-butanediol (BDO) chain extender and aliphatic 4,4′-methylenebis(cyclohexyl isocyanate) (HMDI). HMDI was chosen as a nontoxic diisocyanate, suitable for biomedical PUR synthesis. Modification with L-ascorbic acid (AA) was performed to improve obtained PUR materials biocompatibility. Chemical structure of obtained PURs was provided and confirmed by Fourier transform infrared spectroscopy (FTIR) and Proton nuclear magnetic resonance spectroscopy ({sup 1}HNMR). Differential scanning calorimetry (DSC) was used to indicate the influence of ascorbic acid modification on such parameters as glass transition temperature, melting temperature and melting enthalpies of obtained materials. To determine how these materials may potentially behave, after implementation in tissue, degradation behavior of obtained PURs in various chemical environments, which were represented by canola oil, saline solution, distilled water and phosphate buffered saline (PBS) was estimated. The influence of AA on hydrophilic-hydrophobic character of obtained PURs was established by contact angle study. This experiment revealed that ascorbic acid significantly improves hydrophilicity of obtained PUR materials and the same cause that they are more suitable candidates for biomedical applications. Good hemocompatibility characteristic of studied PUR materials was confirmed by the hemocompatibility test

Synthesis and characterization of cycloaliphatic hydrophilic polyurethanes, modified with L-ascorbic acid, as materials for soft tissue regeneration

International Nuclear Information System (INIS)

Kucinska-Lipka, J.; Gubanska, I.; Strankowski, M.; Cieśliński, H.; Filipowicz, N.; Janik, H.

2017-01-01

In this paper we described synthesis and characteristic of obtained hydrophilic polyurethanes (PURs) modified with ascorbic acid (commonly known as vitamin C). Such materials may find an application in the biomedical field, for example in the regenerative medicine of soft tissues, according to ascorbic acid wide influence on tissue regeneration Flora (2009), Szymańska-Pasternak et al. (2011), Taikarimi and Ibrahim (2011), Myrvik and Volk (1954), Li et al. (2001), Cursino et al. (2005) . Hydrophilic PURs were obtained with the use of amorphous α,ω-dihydroxy(ethylene-butylene adipate) (dHEBA) polyol, 1,4-butanediol (BDO) chain extender and aliphatic 4,4′-methylenebis(cyclohexyl isocyanate) (HMDI). HMDI was chosen as a nontoxic diisocyanate, suitable for biomedical PUR synthesis. Modification with L-ascorbic acid (AA) was performed to improve obtained PUR materials biocompatibility. Chemical structure of obtained PURs was provided and confirmed by Fourier transform infrared spectroscopy (FTIR) and Proton nuclear magnetic resonance spectroscopy ( 1 HNMR). Differential scanning calorimetry (DSC) was used to indicate the influence of ascorbic acid modification on such parameters as glass transition temperature, melting temperature and melting enthalpies of obtained materials. To determine how these materials may potentially behave, after implementation in tissue, degradation behavior of obtained PURs in various chemical environments, which were represented by canola oil, saline solution, distilled water and phosphate buffered saline (PBS) was estimated. The influence of AA on hydrophilic-hydrophobic character of obtained PURs was established by contact angle study. This experiment revealed that ascorbic acid significantly improves hydrophilicity of obtained PUR materials and the same cause that they are more suitable candidates for biomedical applications. Good hemocompatibility characteristic of studied PUR materials was confirmed by the hemocompatibility test with

Air pollution upregulates endothelial cell procoagulant activity via ultrafine particle-induced oxidant signaling and tissue factor expression.

Science.gov (United States)

Snow, S J; Cheng, W; Wolberg, A S; Carraway, M S

2014-07-01

Air pollution exposure is associated with cardiovascular events triggered by clot formation. Endothelial activation and initiation of coagulation are pathophysiological mechanisms that could link inhaled air pollutants to vascular events. Here we investigated the underlying mechanisms of increased endothelial cell procoagulant activity following exposure to soluble components of ultrafine particles (soluble UF). Human coronary artery endothelial cells (HCAEC) were exposed to soluble UF and assessed for their ability to trigger procoagulant activity in platelet-free plasma. Exposed HCAEC triggered earlier thrombin generation and faster fibrin clot formation, which was abolished by an anti-tissue factor (TF) antibody, indicating TF-dependent effects. Soluble UF exposure increased TF mRNA expression without compensatory increases in key anticoagulant proteins. To identify early events that regulate TF expression, we measured endothelial H2O2 production following soluble UF exposure and identified the enzymatic source. Soluble UF exposure increased endothelial H2O2 production, and antioxidants attenuated UF-induced upregulation of TF, linking the procoagulant responses to reactive oxygen species (ROS) formation. Chemical inhibitors and RNA silencing showed that NOX-4, an important endothelial source of H2O2, was involved in UF-induced upregulation of TF mRNA. These data indicate that soluble UF exposure induces endothelial cell procoagulant activity, which involves de novo TF synthesis, ROS production, and the NOX-4 enzyme. These findings provide mechanistic insight into the adverse cardiovascular effects associated with air pollution exposure. Published by Oxford University Press on behalf of Toxicological Sciences 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Growth differentiation factor-15 (GDF-15) suppresses in vitro angiogenesis through a novel interaction with connective tissue growth factor (CCN2).

Science.gov (United States)

Whitson, Ramon J; Lucia, Marshall Scott; Lambert, James R

2013-06-01

Growth differentiation factor-15 (GDF-15) and the CCN family member, connective tissue growth factor (CCN2), are associated with cardiac disease, inflammation, and cancer. The precise role and signaling mechanism for these factors in normal and diseased tissues remains elusive. Here we demonstrate an interaction between GDF-15 and CCN2 using yeast two-hybrid assays and have mapped the domain of interaction to the von Willebrand factor type C domain of CCN2. Biochemical pull down assays using secreted GDF-15 and His-tagged CCN2 produced in PC-3 prostate cancer cells confirmed a direct interaction between these proteins. To investigate the functional consequences of this interaction, in vitro angiogenesis assays were performed. We demonstrate that GDF-15 blocks CCN2-mediated tube formation in human umbilical vein endothelial (HUVEC) cells. To examine the molecular mechanism whereby GDF-15 inhibits CCN2-mediated angiogenesis, activation of αV β3 integrins and focal adhesion kinase (FAK) was examined. CCN2-mediated FAK activation was inhibited by GDF-15 and was accompanied by a decrease in αV β3 integrin clustering in HUVEC cells. These results demonstrate, for the first time, a novel signaling pathway for GDF-15 through interaction with the matricellular signaling molecule CCN2. Furthermore, antagonism of CCN2 mediated angiogenesis by GDF-15 may provide insight into the functional role of GDF-15 in disease states. Copyright © 2012 Wiley Periodicals, Inc.

Extremity Regeneration of Soft Tissue Injury Using Growth Factor-Impregnated Gels

Science.gov (United States)

2017-10-01

vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). Repeated injections of growth factor-alginate material are... Vascularized endothelial growth factor (VEGF) Insulin-like growth factor-1 (IGF-1) Alginate gel Ischemia-reperfusion Large animal model...operative complications including skin necrosis and seroma development. The IACUC protocol was reevaluated and modified thought multiple discussions

Computer modeling the boron compound factor in normal brain tissue

International Nuclear Information System (INIS)

Gavin, P.R.; Huiskamp, R.; Wheeler, F.J.; Griebenow, M.L.

1993-01-01

The macroscopic distribution of borocaptate sodium (Na 2 B 12 H 11 SH or BSH) in normal tissues has been determined and can be accurately predicted from the blood concentration. The compound para-borono-phenylalanine (p-BPA) has also been studied in dogs and normal tissue distribution has been determined. The total physical dose required to reach a biological isoeffect appears to increase directly as the proportion of boron capture dose increases. This effect, together with knowledge of the macrodistribution, led to estimates of the influence of the microdistribution of the BSH compound. This paper reports a computer model that was used to predict the compound factor for BSH and p-BPA and, hence, the equivalent radiation in normal tissues. The compound factor would need to be calculated for other compounds with different distributions. This information is needed to design appropriate normal tissue tolerance studies for different organ systems and/or different boron compounds

Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 9

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Maeda, Tomoho; Yoshida, Shoji

1983-01-01

We have already reported the remarkable effect of an active specific immunotherapy using cryopreserved tumor cells and infiltrating mononuclear cells prepared from a low-dose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the effect of a biological response modifier, OK-432 combined with the active specific immunotherapy was investigated. Twelve-week-aged female C3H/He mice transplanted with MM 46 tumor cells were received local radiotherapy with a dose of 3,000 rads by high energy electron beams on the fifth day after inoculation. The tumor cells and infiltrating mononuclear cells cryopreserved for two months were thawed and treated with mitomycin-C at concentration of 20 μg/10 7 cells at 37 0 C for 30 min. Then, these cells were injected subcutaneously into the left hind paws as a mitomycin C-treated, cryopreserved active specific immunotherapy on the thirteenth day, and daily dose of 1 KE of OK-432 was injected intraperitoneally from the sixth to the tenth days. The inhibition of the tumor growth was similarly observed in the group which received this active specific immunotherapy combined with a biological response modifier, OK-432. (author)

Stroke Prevention: Managing Modifiable Risk Factors

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Silvia Di Legge

2012-01-01

Full Text Available Prevention plays a crucial role in counteracting morbidity and mortality related to ischemic stroke. It has been estimated that 50% of stroke are preventable through control of modifiable risk factors and lifestyle changes. Antihypertensive treatment is recommended for both prevention of recurrent stroke and other vascular events. The use of antiplatelets and statins has been shown to reduce the risk of recurrent stroke and other vascular events. Angiotensin-converting enzyme inhibitors (ACEIs and angiotensin II receptor blockers (ARBs are indicated in stroke prevention because they also promote vascular health. Effective secondary-prevention strategies for selected patients include carotid revascularization for high-grade carotid stenosis and vitamin K antagonist treatment for atrial fibrillation. The results of recent clinical trials investigating new anticoagulants (factor Xa inhibitors and direct thrombin inhibitors clearly indicate alternative strategies in stroke prevention for patients with atrial fibrillation. This paper describes the current landscape and developments in stroke prevention with special reference to medical treatment in secondary prevention of ischemic stroke.

Demographic, genetic, and environmental factors that modify disease course.

Science.gov (United States)

Marrie, Ruth Ann

2011-05-01

As with susceptibility to disease, it is likely that multiple factors interact to influence the phenotype of multiple sclerosis and long-term disease outcomes. Such factors may include genetic factors, socioeconomic status, comorbid diseases, and health behaviors, as well as environmental exposures. An improved understanding of the influence of these factors on disease course may reap several benefits, such as improved prognostication, allowing us to tailor disease management with respect to intensity of disease-modifying therapies and changes in specific health behaviors, in the broad context of coexisting health issues. Such information can facilitate appropriately adjusted comparisons within and between populations. Elucidation of these factors will require careful study of well-characterized populations in which the roles of multiple factors are considered simultaneously. Copyright © 2011 Elsevier Inc. All rights reserved.

Increased and correlated expression of connective tissue growth factor and transforming growth factor beta 1 in surgically removed periodontal tissues with chronic periodontitis.

Science.gov (United States)

Mize, T W; Sundararaj, K P; Leite, R S; Huang, Y

2015-06-01

Both gingival tissue destruction and regeneration are associated with chronic periodontitis, although the former overwhelms the latter. Studies have shown that transforming growth factor beta 1 (TGF-β1), a growth factor largely involved in tissue regeneration and remodeling, is upregulated in chronic periodontitis. However, the gingival expression of connective tissue growth factor (CTGF or CCN2), a TGF-β1-upregulated gene, in patients with periodontitis remains undetermined. Although both CTGF/CCN2 and TGF-b1 increase the production of extracellular matrix, they have many different biological functions. Therefore, it is important to delineate the impact of periodontitis on gingival CTGF/CCN2 expression. Periodontal tissue specimens were collected from seven individuals without periodontitis (group 1) and from 14 with periodontitis (group 2). The expression of CTGF and TGFβ1 mRNAs were quantified using real-time PCR. Analysis using the nonparametric Mann-Whitney U-test showed that the levels of expression of both CTGF/CCN2 and TGFβ1 mRNAs were significantly increased in individuals with periodontitis compared with individuals without periodontitis. Furthermore, analysis using a nonparametric correlation (Spearman r) test showed a positive correlation between TGFβ1 and CTGF/CCN2 mRNAs. The gingival expression levels of CTGF/CCN2 and TGFβ1 mRNAs in individuals with periodontitis are upregulated and correlated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Type I iodothyronine 5′-deiodinase mRNA and activity is increased in adipose tissue of obese subjects

Czech Academy of Sciences Publication Activity Database

Ortega, F.J.; Jílková, Zuzana; Moreno-Navarrete, J.M.; Pavelka, S.; Rodriguez-Hermosa, J.I.; Kopecký, Jan; Fernández-Real, J.M.

2012-01-01

Roč. 36, č. 2 (2012), s. 320-324 ISSN 0307-0565 R&D Projects: GA MŠk(CZ) OC08008 Institutional research plan: CEZ:AV0Z50110509 Keywords : adipose tissue * thyroid hormones * deiodinases * tissue expression * enzyme activity Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 5.221, year: 2012

Backbone modified TBA analogues endowed with antiproliferative activity.

Science.gov (United States)

Esposito, Veronica; Russo, Annapina; Amato, Teresa; Varra, Michela; Vellecco, Valentina; Bucci, Mariarosaria; Russo, Giulia; Virgilio, Antonella; Galeone, Aldo

2017-05-01

The thrombin binding aptamer (TBA) is endowed with antiproliferative properties but its potential development is counteracted by the concomitant anticoagulant activity. Five oligonucleotides (ODNs) based on TBA sequence (GGTTGGTGTGGTTGG) and containing l-residues or both l-residues and inversion of polarity sites have been investigated by NMR and CD techniques for their ability to form G-quadruplex structures. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay), and their resistance in fetal bovine serum have been tested. CD and NMR data suggest that the investigated ODNs are able to form right- and left-handed G-quadruplex structures. All ODNs do not retain the anticoagulant activity characteristic of TBA but are endowed with a significant antiproliferative activity against two cancerous cell lines. Their resistance in biological environment after six days is variable, depending on the ODN. A comparison between results and literature data suggests that the antiproliferative activity of the TBA analogues investigated could depends on two factors: a) biological pathways and targets different from those already identified or proposed for other antiproliferative G-quadruplex aptamers, and b) the contribution of the guanine-based degradation products. Modified TBA analogues containing l-residues and inversion of polarity sites lose the anticoagulant activity but gain antiproliferative properties against two cancer cell lines. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016 Elsevier B.V. All rights reserved.

Tissue factor/FVIIa activates Bcl-2 and prevents doxorubicin-induced apoptosis in neuroblastoma cells

International Nuclear Information System (INIS)

Fang, Jun; Gu, Lubing; Zhu, Ningxi; Tang, Hao; Alvarado, Carlos S; Zhou, Muxiang

2008-01-01

Tissue factor (TF) is a transmembrane protein that acts as a receptor for activated coagulation factor VII (FVIIa), initiating the coagulation cascade. Recent studies demonstrate that expression of tumor-derived TF also mediates intracellular signaling relevant to tumor growth and apoptosis. Our present study investigates the possible mechanism by which the interaction between TF and FVIIa regulates chemotherapy resistance in neuroblastoma cell lines. Gene and siRNA transfection was used to enforce TF expression in a TF-negative neuroblastoma cell line and to silence endogenous TF expression in a TF-overexpressing neuroblastoma line, respectively. The expression of TF, Bcl-2, STAT5, and Akt as well as the phosphorylation of STAT5 and Akt in gene transfected cells or cells treated with JAK inhibitor and LY294002 were determined by Western blot assay. Tumor cell growth was determined by a clonogenic assay. Cytotoxic and apoptotic effect of doxorubicin on neuroblastoma cell lines was analyzed by WST assay and annexin-V staining (by flow cytometry) respectively. Enforced expression of TF in a TF-negative neuroblastoma cell line in the presence of FVIIa induced upregulation of Bcl-2, leading to resistance to doxorubicin. Conversely, inhibition of endogenous TF expression in a TF-overexpressing neuroblastoma cell line using siRNA resulted in down-regulation of Bcl-2 and sensitization to doxorubicin-induced apoptosis. Additionally, neuroblastoma cells expressing high levels of either endogenous or transfected TF treated with FVIIa readily phosphorylated STAT5 and Akt. Using selective pharmacologic inhibitors, we demonstrated that JAK inhibitor I, but not the PI3K inhibitor LY294002, blocked the TF/FVIIa-induced upregulation of Bcl-2. This study shows that in neuroblastoma cell lines overexpressed TF ligated with FVIIa produced upregulation of Bcl-2 expression through the JAK/STAT5 signaling pathway, resulting in resistance to apoptosis. We surmise that this TF

Modified silk fibroin scaffolds with collagen/decellularized pulp for bone tissue engineering in cleft palate: Morphological structures and biofunctionalities

International Nuclear Information System (INIS)

Sangkert, Supaporn; Meesane, Jirut; Kamonmattayakul, Suttatip; Chai, Wen Lin

2016-01-01

Cleft palate is a congenital malformation that generates a maxillofacial bone defect around the mouth area. The creation of performance scaffolds for bone tissue engineering in cleft palate is an issue that was proposed in this research. Because of its good biocompatibility, high stability, and non-toxicity, silk fibroin was selected as the scaffold of choice in this research. Silk fibroin scaffolds were prepared by freeze-drying before immerging in a solution of collagen, decellularized pulp, and collagen/decellularized pulp. Then, the immersed scaffolds were freeze-dried. Structural organization in solution was observed by Atomic Force Microscope (AFM). The molecular organization of the solutions and crystal structure of the scaffolds were characterized by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD), respectively. The weight increase of the modified scaffolds and the pore size were determined. The morphology was observed by a scanning electron microscope (SEM). Mechanical properties were tested. Biofunctionalities were considered by seeding osteoblasts in silk fibroin scaffolds before analysis of the cell proliferation, viability, total protein assay, and histological analysis. The results demonstrated that dendrite structure of the fibrils occurred in those solutions. Molecular organization of the components in solution arranged themselves into an irregular structure. The fibrils were deposited in the pores of the modified silk fibroin scaffolds. The modified scaffolds showed a beta-sheet structure. The morphological structure affected the mechanical properties of the silk fibroin scaffolds with and without modification. Following assessment of the biofunctionalities, the modified silk fibroin scaffolds could induce cell proliferation, viability, and total protein particularly in modified silk fibroin with collagen/decellularized pulp. Furthermore, the histological analysis indicated that the cells could adhere in modified silk fibroin

Radioprotector modifying influence upon the ion transport ATPase activities

International Nuclear Information System (INIS)

Dvoretsky, A.I.; Egorova, E.G.; Ananieva, T.V.; Kulikova, I.A.

1993-01-01

The effects of aminothiol and biogenic amine radioprotectors (β-mercaptoethylamine, AET, serotonin, dopamine, histamine) on the basic ion transport enzymes, such as Na, K-ATP ase and Mg, Ca-ATPase activities were investigated in the tissues of numerous organs, with different radiosensitivity in the wistar rats. Experimental results showed that intraperitoneal injection of the used radioprotectors caused preliminary inhibition of the Na, K-ATPase activity in tissues from organs with different radioresistance, but had no influence on the Mg, Ca-ATPase activity in membranes of erythrocytes and rat brain cells. (2 tabs.)

Unruptured Cerebral Aneurysm Detected after Intravenous Tissue Plasminogen Activator for Stroke

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Yukihiro Yoneda

2009-06-01

Full Text Available Therapeutic guidelines of intravenous thrombolysis with tissue plasminogen activator (tPA for hyperacute ischemic stroke are very strict. Because of potential higher risk of bleeding complications, the presence of unruptured cerebral aneurysm is a contraindication for systemic thrombolysis with tPA. According to the standard CT criteria, a 66-year-old woman who suddenly developed aphasia and hemiparesis received intravenous tPA within 3 h after ischemic stroke. Magnetic resonance angiography during tPA infusion was performed and the presence of a small unruptured cerebral aneurysm was suspected at the anterior communicating artery. Delayed cerebral angiography confirmed an aneurysm with a size of 7 mm. The patient did not experience any adverse complications associated with the aneurysm. Clinical experiences of this kind of accidental off-label thrombolysis may contribute to modify the current rigid tPA guidelines for stroke.

Biological effects of several extreme space flight factors (acceleration, magnetically activated water) on mouse natural or modified radiosensitivity

International Nuclear Information System (INIS)

Datsov, E.R.

1979-01-01

Irradiated and Adeturon-protected mice were used to assess biological effects of several static (magnetically-activated water - MW) and dynamic (acceleration) factors of space flight. The study shows that increased gravitation, 20 G, 5 min, generated by a small radius centrifuge, increases static ability to work, while the number of peripheral blood cells decreases. Continuous exposure of mice to MW induces a decrease in dynamic ability to work, in comparison with the physiological controls, without substantial changes in other indices. Extreme factors in space flight (acceleration MW, radiation, radiation protector), alone or in combination, decrease the animal's growth rate. After administration of 200 mg/kg Adeturone, mouse dynamic ability to work increases, while its capabilities for adaptation and training are lowered, and pronounced leucocytosis is observed. MW, acceleration, or Adeturone pre-treatment of mice increases their survival and dynamic ability to work, following exposure to 600 R, when compared to irradiated animals, but decreases their capabilities for adaptation and training. Acceleration and Adeturone protect peripheral blood from radiation injury, while MW alone intensifies radiation cytopenia. Irradiation does not significantly modify the static ability to work, upon preceding exposure to MW or acceleration. In this case, Adeturone exerts protective effect. ME and Adeturone combined action results in increased survival rate and mean duration of life of irradiated animals, as compared to their single administration. Acceleration reduces MW, Adeturone and MW + Adeturone effect on survival. Peripheral blood parameters do not correlate with survival rates. Combined pre-treatment with two or three of the factors studied increases dynamic ability to work following irradiation, and in many cases the static ability as well. The combination of Adeturone and MW was the only one with negative effect on the static ability to work. (A.B.)

Characterizing Stressors and Modifiable Health Risk Factors Among Homeless Smokers: An Exploratory Pilot Study.

Science.gov (United States)

Kendzor, Darla E; Reitzel, Lorraine R; Businelle, Michael S

2015-10-01

This pilot study was conducted to explore the associations between stressors related to homelessness and modifiable health risk factors (poor diet, insufficient physical activity, and overweight/obesity) and to provide direction for future research. Participants (N = 57) were homeless adults enrolled in a smoking cessation program. Analyses were conducted to characterize the sample as well as the relations between relevant stressors (discrimination, chronic stress, and fear and mistrust) and health risk factors. Inadequate daily consumption of fruits, vegetables, and fiber was common. High-fat diet and insufficient physical activity were also prevalent, and the majority of participants were overweight/obese. Participants commonly endorsed discrimination, fear of victimization, mistrust of others, and several other stressors. Greater endorsement of stressors was associated with a high-fat diet. Results suggest that lifestyle interventions and policy changes may be warranted in homeless shelters to attenuate the potential effects of stressors on high-fat dietary consumption among smokers. © 2015 Society for Public Health Education.

Transcriptomic Analysis of Intestinal Tissues from Two 90-Day Feeding Studies in Rats Using Genetically Modified MON810 Maize Varieties.

Science.gov (United States)

Sharbati, Jutta; Bohmer, Marc; Bohmer, Nils; Keller, Andreas; Backes, Christina; Franke, Andre; Steinberg, Pablo; Zeljenková, Dagmar; Einspanier, Ralf

2017-01-01

Background: Global as well as specific expression profiles of selected rat tissues were characterized to assess the safety of genetically modified (GM) maize MON810 containing the insecticidal protein Cry1Ab. Gene expression was evaluated by use of Next Generation Sequencing (NGS) as well as RT-qPCR within rat intestinal tissues based on mandatory 90-day rodent feeding studies. In parallel to two 90-day feeding studies, the transcriptional response of rat tissues was assessed as another endpoint to enhance the mechanistic interpretation of GM feeding studies and/or to facilitate the generation of a targeted hypothesis. Rats received diets containing 33% GM maize (MON810) or near-isogenic control maize. As a site of massive exposure to ingested feed the transcriptomic response of ileal and colonic tissue was profiled via RT-qPCR arrays targeting apoptosis, DNA-damage/repair, unfolded protein response (UPR). For global RNA profiling of rat ileal tissue, we applied NGS. Results: No biological response to the GM-diet was observed in male and in female rat tissues. Transcriptome wide analysis of gene expression by RNA-seq confirmed these findings. Nevertheless, gene ontology (GO) analysis clearly associated a set of distinctly regulated transcripts with circadian rhythms. We confirmed differential expression of circadian clock genes using RT-qPCR and immunoassays for selected factors, thereby indicating physiological effects caused by the time point of sampling. Conclusion: Prediction of potential unintended effects of GM-food/feed by transcriptome based profiling of intestinal tissue presents a novel approach to complement classical toxicological testing procedures. Including the detection of alterations in signaling pathways in toxicity testing procedures may enhance the confidence in outcomes of toxicological trials. In this study, no significant GM-related changes in intestinal expression profiles were found in rats fed GM-maize MON810. Relevant alterations of

Indian values of tissue weighting factors for internal dosimetry

International Nuclear Information System (INIS)

Mehta, S.K.

1995-01-01

In the present work the induced cancer component of detriment by the relative risk (RR) as well as US National Institute of Health (NIH) models using Indian organ based baseline cancer data and the all-causes mortality of the Indian population has been estimated. The Indian values of tissue weighting factors (W T ) have been worked out by the ICRP-60 methodology. The Indian values of detriment from the exposure of principal organs stomach, lung, colon and bone marrow are factors of 1.5 to 2.5 lower than the corresponding ICRP values. The Indian values of W T differ significantly from the ICRP five population average values. A tissue weighting factor of 0.08 for breast, colon, lung and stomach for the Indian population is more appropriate than the ICRP assigned factors of 0.05, 0.12, 0.12 and 0.12 respectively for these organs. For gonads, the appropriate Indian factor is 0.29 instead of the ICRP value of 0.20. The use of appropriate Indian values of W T is advocated for the Indian population in special investigation cases requiring regulatory intervention. (author). 11 refs., 11 figs., 4 tabs

Factors affecting the tissues composition of pork belly.

Science.gov (United States)

Duziński, K; Knecht, D; Lisiak, D; Janiszewski, P

2015-11-01

Bellies derived from the commercial population of pig carcasses are diverse in terms of tissue composition. Knowledge of the factors influencing it and the expected results, permits quick and easy evaluation of raw material. The study was designed to determine the factors affecting the tissues composition of pork bellies and to estimate their lean meat content. The research population (n=140 pig carcasses) was divided into groups according to sex (gilts, barrows), half-carcass mass (meat content class: S (⩾60%), E (55% to 60%), U (50% to 55%), R (meat content affected the growth of the fat and skin mass in a linear way. No differences were observed between class S and E in terms of belly muscle mass. A 0.37% higher share of belly in the half-carcass was found for barrows (Pmeat content in bellies, suggesting they may be used directly in the production line.

Moojenactivase, a novel pro-coagulant PIIId metalloprotease isolated from Bothrops moojeni snake venom, activates coagulation factors II and X and induces tissue factor up-regulation in leukocytes.

Science.gov (United States)

Sartim, Marco A; Costa, Tassia R; Laure, Helen J; Espíndola, Milena S; Frantz, Fabiani G; Sorgi, Carlos A; Cintra, Adélia C O; Arantes, Eliane C; Faccioli, Lucia H; Rosa, José C; Sampaio, Suely V

2016-05-01

Coagulopathies following snakebite are triggered by pro-coagulant venom toxins, in which metalloproteases play a major role in envenomation-induced coagulation disorders by acting on coagulation cascade, platelet function and fibrinolysis. Considering this relevance, here we describe the isolation and biochemical characterization of moojenactivase (MooA), a metalloprotease from Bothrops moojeni snake venom, and investigate its involvement in hemostasis in vitro. MooA is a glycoprotein of 85,746.22 Da, member of the PIIId group of snake venom metalloproteases, composed of three linked disulfide-bonded chains: an N-glycosylated heavy chain, and two light chains. The venom protease induced human plasma clotting in vitro by activating on both blood coagulation factors II (prothrombin) and X, which in turn generated α-thrombin and factor Xa, respectively. Additionally, MooA induced expression of tissue factor (TF) on the membrane surface of peripheral blood mononuclear cells (PBMC), which led these cells to adopt pro-coagulant characteristics. MooA was also shown to be involved with production of the inflammatory mediators TNF-α, IL-8 and MCP-1, suggesting an association between MooA pro-inflammatory stimulation of PBMC and TF up-regulation. We also observed aggregation of washed platelets when in presence of MooA; however, the protease had no effect on fibrinolysis. Our findings show that MooA is a novel hemostatically active metalloprotease, which may lead to the development of coagulopathies during B. moojeni envenomation. Moreover, the metalloprotease may contribute to the development of new diagnostic tools and pharmacological approaches applied to hemostatic disorders.

A prospective investigation of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene carriers

International Nuclear Information System (INIS)

Guinan, Emer M; Hussey, Juliette; McGarrigle, Sarah A; Healy, Laura A; O’Sullivan, Jacintha N; Bennett, Kathleen; Connolly, Elizabeth M

2013-01-01

Breast cancer is the most common female cancer worldwide. The lifetime risk of a woman being diagnosed with breast cancer is approximately 12.5%. For women who carry the deleterious mutation in either of the BRCA genes, BRCA1 or BRCA2, the risk of developing breast or ovarian cancer is significantly increased. In recent years there has been increased penetrance of BRCA1 and BRCA2 associated breast cancer, prompting investigation into the role of modifiable risk factors in this group. Previous investigations into this topic have relied on participants recalling lifetime weight changes and subjective methods of recording physical activity. The influence of obesity-related biomarkers, which may explain the link between obesity, physical activity and breast cancer risk, has not been investigated prospectively in this group. This paper describes the design of a prospective cohort study investigating the role of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene mutation carriers. Participants will be recruited from breast cancer family risk clinics and genetics clinics. Lifestyle risk factors that will be investigated will include body composition, metabolic syndrome and its components, physical activity and dietary intake. PBMC telomere length will be measured as a potential predictor of breast cancer occurrence. Measurements will be completed on entry to the study and repeated at two years and five years. Participants will also be followed annually by questionnaire to track changes in risk factor status and to record cancer occurrence. Data will be analysed using multiple regression models. The study has an accrual target of 352 participants. The results from this study will provide valuable information regarding the role of modifiable lifestyle risk factors for breast cancer in women with a deleterious mutation in the BRCA gene. Additionally, the study will attempt to identify potential blood biomarkers which may be predictive

Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

Shu-Ling; Wu; Dong-Mei; Zhan; Shu-Hong; Xi; Xiang-Lian; He

2014-01-01

AIM:To investigate the role of tissue plasminogen activator(t-PA) and plasminogen activator inhibitor(PAI)in proliferative diabetic retinopathy(PDR) and to discuss the correlations among t-PA, PAI and vascular endothelial growth factor(VEGF) expressions.METHODS:A total of 36 vitreous samples were collected from 36 patients with PDR(PDR group), and 17 vitreous samples from 17 patients with idiopathic macular hole were used as control. The concentrations of t-PA, PAI and VEGF in samples were determined by ELISA method. The correlations among t-PA, PAI and VEGF expressions were discussed.RESULTS:The concentrations of t-PA, PAI and VEGF in the PDR group were significantly higher than those in the control group(P <0.001). The t-PA and PAI expressions were highly correlated with the VEGF expression(P <0.001).CONCLUSION:In addition to VEGF, a variety of bioactive substances, such as t-PA and PAI, are involved in the pathogenesis involved in the angiogenesis of PDR.VEGF can activate t-PA expression, resulting in collagen tissue degradation and angiogenesis. VEGF may also activate the mechanism for endogenous anti-neovascularization.

Immunolocalization of transforming growth factor alpha in normal human tissues

DEFF Research Database (Denmark)

Christensen, M E; Poulsen, Steen Seier

1996-01-01

anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

C-terminal peptides of tissue factor pathway inhibitor are novel host defense molecules.

Science.gov (United States)

Papareddy, Praveen; Kalle, Martina; Kasetty, Gopinath; Mörgelin, Matthias; Rydengård, Victoria; Albiger, Barbara; Lundqvist, Katarina; Malmsten, Martin; Schmidtchen, Artur

2010-09-03

Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation, but may, via its C terminus, also modulate cell surface, heparin, and lipopolysaccharide interactions as well as participate in growth inhibition. Here we show that C-terminal TFPI peptide sequences are antimicrobial against the gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungi Candida albicans and Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen for the "classic" human antimicrobial peptide LL-37. The killing of E. coli, but not P. aeruginosa, by the C-terminal peptide GGLIKTKRKRKKQRVKIAYEEIFVKNM (GGL27), was enhanced in human plasma and largely abolished in heat-inactivated plasma, a phenomenon linked to generation of antimicrobial C3a and activation of the classic pathway of complement activation. Furthermore, GGL27 displayed anti-endotoxic effects in vitro and in vivo in a mouse model of LPS shock. Importantly, TFPI was found to be expressed in the basal layers of normal epidermis, and was markedly up-regulated in acute skin wounds as well as wound edges of chronic leg ulcers. Furthermore, C-terminal fragments of TFPI were associated with bacteria present in human chronic leg ulcers. These findings suggest a new role for TFPI in cutaneous defense against infections.

The influence of different pathogens on the lysozyme activity into tissues of rat oral cavity

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A. P. Levitsky

2017-08-01

Full Text Available Aim: To determine action of the different pathogens on the lysozyme activity into tissues of oral cavity and serum. Methods: The lysozyme activities was determined into oral mucosa cheek, tongue gum and serum of 158 white rats (11 series experiments. The pathogens were used: atropine, protamine sulfat, indometacyn, bee poison, hydrasine sulfat, cytostatic cyclofosfan, lincomycin, lipopolysaccharide, composition of antibiotic and omeprasol for ACBT Results: The  whole of pathogens decreased lysozyme activity (mean in 1,6-2,5 times into oral tissues and on 16 % into serum. The specific lowering of lysozyme activities (Δ%/mg pathogen was low most for lipopolysaccharide, especially after oral application usage (exceeding was in tens times. Conclusion: The lysozyme activity lowering may play significant role in pathogenesis of stomatologic diseases/ Lipopolysaccharide (LPS send lysozyme activity lowering most especially after oral application. Probably, the antilysozyme action of pathogens realize by LPS. The stomatogenic factor in pathogenesis and profilactic of noninfection diseases is important.

Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

Science.gov (United States)

Chen, Guobao; Lv, Yonggang

2015-01-01

Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

The effect of a single lethal X-irradiation exposure on the activity of lipoprotein lipase in the tissues of the rat

International Nuclear Information System (INIS)

Sedlakova, A.; Ahlers, I.; Praslicka, M.

1979-01-01

Wistar male rats, both fed and fasting for 16 h prior to irradiation, were exposed to a single lethal X-ray dose of 387 mC/kg (1500R). The activity of lipoprotein lipase in white adipose (epididymal) tissue and heart muscle and the concentration of serum triglycerides were determined at 1, 6, 24, 48, and 72 h after irradiation. In the early time periods, at 1 and 6 h after exposure, the activity of lipoprotein lipase decreased in adipose tissue and increased in heart muscle of the irradiated fed rats; in fasting rats it decreased in heart muscle at 1 h after exposure. The concentration of serum triglycerides increased at 1 h and decreased at 6 h after exposure in fed rats. In these rats, alterations in serum triglycerides correlated with changes in lipoprotein lipase activity in adipose tissue. Alterations observed at the later time periods were more dependent on the time interval between irradiation and the analysis. Lipoprotein lipase activity increased with time after irradiation up to the maximal values at 72 h. Fasting prior to and after irradiation substantially modified the response of animals to radiation. (author)

Cell-State Transitions Regulated by SLUG Are Critical for Tissue Regeneration and Tumor Initiation

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Sarah Phillips

2014-05-01

Full Text Available Perturbations in stem cell activity and differentiation can lead to developmental defects and cancer. We use an approach involving a quantitative model of cell-state transitions in vitro to gain insights into how SLUG/SNAI2, a key developmental transcription factor, modulates mammary epithelial stem cell activity and differentiation in vivo. In the absence of SLUG, stem cells fail to transition into basal progenitor cells, while existing basal progenitor cells undergo luminal differentiation; together, these changes result in abnormal mammary architecture and defects in tissue function. Furthermore, we show that in the absence of SLUG, mammary stem cell activity necessary for tissue regeneration and cancer initiation is lost. Mechanistically, SLUG regulates differentiation and cellular plasticity by recruiting the chromatin modifier lysine-specific demethylase 1 (LSD1 to promoters of lineage-specific genes to repress transcription. Together, these results demonstrate that SLUG plays a dual role in repressing luminal epithelial differentiation while unlocking stem cell transitions necessary for tumorigenesis.

Regulation of the Incorporation of Tissue Factor into Microparticles by Serine Phosphorylation of the Cytoplasmic Domain of Tissue Factor*

Science.gov (United States)

Collier, Mary E. W.; Ettelaie, Camille

2011-01-01

The mechanisms that regulate the incorporation and release of tissue factors (TFs) into cell-derived microparticles are as yet unidentified. In this study, we have explored the regulation of TF release into microparticles by the phosphorylation of serine residues within the cytoplasmic domain of TF. Wild-type and mutant forms of TF, containing alanine and aspartate substitutions at Ser253 and Ser258, were overexpressed in coronary artery and dermal microvascular endothelial cells and microparticle release stimulated with PAR2 agonist peptide (PAR2-AP). The release of TF antigen and activity was then monitored. In addition, the phosphorylation state of the two serine residues within the released microparticles and the cells was monitored for 150 min. The release of wild-type TF as procoagulant microparticles peaked at 90 min and declined thereafter in both cell types. The TF within these microparticles was phosphorylated at Ser253 but not at Ser258. Aspartate substitution of Ser253 resulted in rapid release of TF antigen but not activity, whereas TF release was reduced and delayed by alanine substitution of Ser253 or aspartate substitution of Ser258. Alanine substitution of Ser258 prolonged the release of TF following PAR2-AP activation. The release of TF was concurrent with phosphorylation of Ser253 and was followed by dephosphorylation at 120 min and phosphorylation of Ser258. We propose a sequential mechanism in which the phosphorylation of Ser253 through PAR2 activation results in the incorporation of TF into microparticles, simultaneously inducing Ser258 phosphorylation. Phosphorylation of Ser258 in turn promotes the dephosphorylation of Ser253 and suppresses the release of TF. PMID:21310953

Impact of geriatric factors on surgical and prognostic outcomes in elderly patients with soft-tissue sarcoma.

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Tsuda, Yusuke; Ogura, Koichi; Kobayashi, Eisuke; Hiruma, Toru; Iwata, Shintaro; Asano, Naofumi; Kawai, Akira; Chuman, Hirokazu; Ishii, Takeshi; Morioka, Hideo; Kobayashi, Hiroshi; Kawano, Hirotaka

2017-05-01

Patients aged ≥65 years requiring surgery for soft-tissue sarcoma are a concern in an aging society. We aimed to reveal the association of clinical/geriatric factors with survival period or postoperative events in such patients who underwent surgery. We enrolled patients aged ≥65 years who underwent surgery for localized soft-tissue sarcoma at five institutions. We retrospectively collected clinical/geriatric factors and laboratory data, and analyzed their association with outcomes using univariate and multivariate analyses. Among the 202 patients included, mean age at presentation was 73 years. Surgical margin was R0 in 139 patients (69%). The Eastern Cooperative Oncology Group performance status was ≥2 in 15 (7%). Thirty patients (15%) showed thinness (body mass index sarcoma-specific survival (hazard ratio for R1 vs. R0, 3.17; P = 0.001) and event-free survival (hazard ratio for R1 vs. R0, 2.56; P sarcoma-specific survival (hazard ratio for ≥2 vs. 0 or 1, 2.15; P = 0.038), and higher sensitivity-modified Glasgow prognostic score was significantly associated with poor event-free survival (hazard ratio for ≥1 vs. 0, 1.74; P = 0.046). Severe thinness (body mass index sarcoma patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Potentially modifiable factors contributing to sepsis-associated encephalopathy.

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Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

2017-08-01

Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia 10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

Effect of Amelogenin Coating of a Nano-Modified Titanium Surface on Bioactivity

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Chisato Terada

2018-04-01

Full Text Available The interactions between implants and host tissues depend on several factors. In particular, a growing body of evidence has demonstrated that the surface texture of an implant influences the response of the surrounding cells. The purpose of this study is to develop new implant materials aiming at the regeneration of periodontal tissues as well as hard tissues by coating nano-modified titanium with amelogenin, which is one of the main proteins contained in Emdogain®. We confirmed by quartz crystal microbalance evaluation that amelogenin is easy to adsorb onto the nano-modified titanium surface as a coating. Scanning electron microscopy, scanning probe microscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy analyses confirmed that amelogenin coated the nano-modified titanium surface following alkali-treatment. In vitro evaluation using rat bone marrow and periodontal ligament cells revealed that the initial adhesion of both cell types and the induction of hard tissue differentiation such as cementum were improved by amelogenin coating. Additionally, the formation of new bone in implanted surrounding tissues was observed in in vivo evaluation using rat femurs. Together, these results suggest that this material may serve as a new implant material with the potential to play a major role in the advancement of clinical dentistry.

Association of intraoperative tissue oxygenation with suspected risk factors for tissue hypoxia.

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Spruit, R J; Schwarte, L A; Hakenberg, O W; Scheeren, T W L

2013-10-01

Tissue hypoxia may cause organ dysfunction, but not much is known about tissue oxygenation in the intraoperative setting. We studied microcirculatory tissue oxygen saturation (StO₂) to determine representative values for anesthetized patients undergoing urological surgery and to test the hypothesis that StO₂ is associated with known perioperative risk factors for morbidity and mortality, conventionally monitored variables, and hypotension requiring norepinephrine. Using near-infrared spectroscopy, we measured StO₂ on the thenar eminence in 160 patients undergoing open urological surgery under general anesthesia (FiO2 0.35-0.4), and calculated its correlations with age, risk level for general perioperative complications and mortality (high if age ≥70 and procedure is radical cystectomy), mean arterial pressure (MAP), hemoglobin concentration (Hb), central venous oxygen saturation (ScvO₂), and norepinephrine use. The time averaged StO₂ was 86 ± 6 % (mean ± SD). In the multivariate analysis, Hb [standardized coefficient (SC) 0.21, p = 0.003], ScvO₂ (SC 0.53, p SStO₂ was partly dependent on MAP only when this was below 65 mmHg (lowest MAP SC 0.20, p = 0.006, MAP area under the curve <65 mmHg SC 0.03, p = 0.02). Finally, StO₂ was slightly lower in patients requiring norepinephrine (85 ± 6 vs. 89 ± 6 %, p = 0.001). Intraoperative StO₂ in urological patients was comparable to that of healthy volunteers breathing room air as reported in the literature and correlated with known perioperative risk factors. Further research should investigate its association with outcome and the effect of interventions aimed at optimizing StO₂.

Activation of the connective tissue growth factor (CTGF-transforming growth factor β 1 (TGF-β 1 axis in hepatitis C virus-expressing hepatocytes.

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Tirumuru Nagaraja

Full Text Available BACKGROUND: The pro-fibrogenic cytokine connective tissue growth factor (CTGF plays an important role in the development and progression of fibrosis in many organ systems, including liver. However, its role in the pathogenesis of hepatitis C virus (HCV-induced liver fibrosis remains unclear. METHODS: In the present study, we assessed CTGF expression in HCV-infected hepatocytes using replicon cells containing full-length HCV genotype 1 and the infectious HCV clone JFH1 (HCV genotype 2 by real-time PCR, Western blot analysis and confocal microscopy. We evaluated transforming growth factor β1 (TGF-β1 as a key upstream mediator of CTGF production using neutralizing antibodies and shRNAs. We also determined the signaling molecules involved in CTGF production using various immunological techniques. RESULTS: We demonstrated an enhanced expression of CTGF in two independent models of HCV infection. We also demonstrated that HCV induced CTGF expression in a TGF-β1-dependent manner. Further dissection of the molecular mechanisms revealed that CTGF production was mediated through sequential activation of MAPkinase and Smad-dependent pathways. Finally, to determine whether CTGF regulates fibrosis, we showed that shRNA-mediated knock-down of CTGF resulted in reduced expression of fibrotic markers in HCV replicon cells. CONCLUSION: Our studies demonstrate a central role for CTGF expression in HCV-induced liver fibrosis and highlight the potential value of developing CTGF-based anti-fibrotic therapies to counter HCV-induced liver damage.

Estimation of anisotropy factor spectrum for determination of optical properties in biological tissues

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Iwamoto, Misako; Honda, Norihiro; Ishii, Katsunori; Awazu, Kunio

2017-07-01

Spectroscopic setup for measuring anisotropy factor g spectrum of biological tissues was constructed. g of chicken liver tissue was lower than chicken breast tissue. High absorption of hemoglobin can have an influence on g spectrum.

Clustering of modifiable biobehavioral risk factors for chronic disease in US adults: a latent class analysis.

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Leventhal, Adam M; Huh, Jimi; Dunton, Genevieve F

2014-11-01

Examining the co-occurrence patterns of modifiable biobehavioral risk factors for deadly chronic diseases (e.g. cancer, cardiovascular disease, diabetes) can elucidate the etiology of risk factors and guide disease-prevention programming. The aims of this study were to (1) identify latent classes based on the clustering of five key biobehavioral risk factors among US adults who reported at least one risk factor and (2) explore the demographic correlates of the identified latent classes. Participants were respondents of the National Epidemiologic Survey of Alcohol and Related Conditions (2004-2005) with at least one of the following disease risk factors in the past year (N = 22,789), which were also the latent class indicators: (1) alcohol abuse/dependence, (2) drug abuse/dependence, (3) nicotine dependence, (4) obesity, and (5) physical inactivity. Housing sample units were selected to match the US National Census in location and demographic characteristics, with young adults oversampled. Participants were administered surveys by trained interviewers. Five latent classes were yielded: 'obese, active non-substance abusers' (23%); 'nicotine-dependent, active, and non-obese' (19%); 'active, non-obese alcohol abusers' (6%); 'inactive, non-substance abusers' (50%); and 'active, polysubstance abusers' (3.7%). Four classes were characterized by a 100% likelihood of having one risk factor coupled with a low or moderate likelihood of having the other four risk factors. The five classes exhibited unique demographic profiles. Risk factors may cluster together in a non-monotonic fashion, with the majority of the at-risk population of US adults expected to have a high likelihood of endorsing only one of these five risk factors. © Royal Society for Public Health 2013.

Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: involvement of tissue factor, inducible NO synthase and nuclear factor (NF)-κB.

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Sun, Qi; Chen, Ling; Gao, Mengyu; Jiang, Wenwen; Shao, Fangxian; Li, Jingjing; Wang, Jun; Kou, Junping; Yu, Boyang

2012-01-01

Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0 mg/kg 1 h prior to LPS challenge (30 mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-κB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis. Copyright © 2011 Elsevier B.V. All rights reserved.

Factors that influence soft tissue thickness over the greater trochanter: application to understanding hip fractures.

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Levine, Iris C; Minty, Lauren E; Laing, Andrew C

2015-03-01

Fall-related hip injuries are a concern for the growing population of older adults. Evidence suggests that soft tissue overlying the greater trochanter attenuates the forces transmitted to the proximal femur during an impact, reducing mechanical risk of hip fracture. However, there is limited information about the factors that influence trochanteric soft tissue thickness. The current study used ultrasonography and electromyography to determine whether trochanteric soft tissue thickness could be quantified reproducibly and whether it was influenced by: (1) gender; (2) hip postures associated with potential falling configurations in the sagittal plane (from 30° of extension to 60° of flexion, at 15° intervals), combined adduction-flexion, and combined adduction-extension; and (3) activation levels of the tensor fascia lata (TFL) and gluteus medius (GM) muscles. Our results demonstrated that soft tissue thickness can be measured reliably in nine hip postures and three muscle activation conditions (for all conditions, ICC >0.98). Mean (SD) thickness in quiet stance was 2.52 cm. Thickness was 27.0% lower for males than females during quiet stance. It was 16.4% greater at maximum flexion than quiet standing, 27.2% greater at maximum extension, and 12.5% greater during combined adduction-flexion. However, there was no significant difference between combined adduction-extension and quiet standing. Thickness was not affected by changes in muscle activity. Forces applied to the femoral neck during a lateral fall decrease as trochanteric soft tissue thickness increases; gender and postural configuration at impact could influence the loads applied to the proximal femur (and thus hip fracture risk) during falls on the hip. © 2014 Wiley Periodicals, Inc.

Photocatalytic Activity and Characterization of Carbon-Modified Titania for Visible-Light-Active Photodegradation of Nitrogen Oxides

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Chun-Hung Huang

2012-01-01

Full Text Available A variety of carbon-modified titania powders were prepared by impregnation method using a commercial available titania powder, Hombikat UV100, as matrix material while a range of alcohols from propanol to hexanol were used as precursors of carbon sources. Rising the carbon number of alcoholic precursor molecule, the modified titania showed increasing visible activities of NOx photodegradation. The catalyst modified with cyclohexanol exhibited the best activities of 62%, 62%, 59%, and 54% for the total NOx removal under UV, blue, green, and red light irradiation, respectively. The high activity with long wavelength irradiation suggested a good capability of photocatalysis in full visible light spectrum. Analysis of UV-visible spectrum indicated that carbon modification promoted visible light absorption and red shift in band gap. XPS spectroscopic analysis identified the existence of carbonate species (C=O, which increased with the increasing carbon number of precursor molecule. Photoluminescence spectra demonstrated that the carbonate species suppressed the recombination rate of electron-hole pair. As a result, a mechanism of visible-light-active photocatalyst was proposed according to the formation of carbonate species on carbon-modified TiO2.

Diet and lifestyle factors associated with miRNA expression in colorectal tissue

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Slattery ML

2016-12-01

Full Text Available Martha L Slattery,1 Jennifer S Herrick,1 Lila E Mullany,1 John R Stevens,2 Roger K Wolff1 1Department of Internal Medicine, The University of Utah, Salt Lake City, 2Department of Mathematics and Statistics, Utah State University, Logan, UT, USA Abstract: MicroRNAs (miRNAs are small non-protein-coding RNA molecules that regulate gene expression. Diet and lifestyle factors have been hypothesized to be involved in the regulation of miRNA expression. In this study it was hypothesized that diet and lifestyle factors are associated with miRNA expression. Data from 1,447 cases of colorectal cancer to evaluate 34 diet and lifestyle variables using miRNA expression in normal colorectal mucosa as well as for differential expression between paired carcinoma and normal tissue were used. miRNA data were obtained using an Agilent platform. Multiple comparisons were adjusted for using the false discovery rate q-value. There were 250 miRNAs differentially expressed between carcinoma and normal colonic tissue by level of carbohydrate intake and 198 miRNAs differentially expressed by the level of sucrose intake. Of these miRNAs, 166 miRNAs were differentially expressed for both carbohydrate intake and sucrose intake. Ninety-nine miRNAs were differentially expressed by the level of whole grain intake in normal colonic mucosa. Level of oxidative balance score was associated with 137 differentially expressed miRNAs between carcinoma and paired normal rectal mucosa. Additionally, 135 miRNAs were differentially expressed in colon tissue based on recent NSAID use. Other dietary factors, body mass index, waist and hip circumference, and long-term physical activity levels did not alter miRNA expression after adjustment for multiple comparisons. These results suggest that diet and lifestyle factors regulate miRNA level. They provide additional support for the influence of carbohydrate, sucrose, whole grains, NSAIDs, and oxidative balance score on colorectal cancer risk

Activity and immunohistochemical localization of porphobilinogen deaminase in rat tissues

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Jørgensen, P E; Erlandsen, E J; Poulsen, Steen Seier

2000-01-01

the activity and the immunohistochemical localization of PBGD in the following tissues of wistar female rats: brain, heart, submandibular gland, liver, kidney, pancreas, ovary, stomach, duodenum, jejunum, ileum, colon and musculature. The PBGD activity varied considerably among the tissues. It was highest...

A network of epigenetic modifiers and DNA repair genes controls tissue-specific copy number alteration preference.

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Cramer, Dina; Serrano, Luis; Schaefer, Martin H

2016-11-10

Copy number alterations (CNAs) in cancer patients show a large variability in their number, length and position, but the sources of this variability are not known. CNA number and length are linked to patient survival, suggesting clinical relevance. We have identified genes that tend to be mutated in samples that have few or many CNAs, which we term CONIM genes (COpy Number Instability Modulators). CONIM proteins cluster into a densely connected subnetwork of physical interactions and many of them are epigenetic modifiers. Therefore, we investigated how the epigenome of the tissue-of-origin influences the position of CNA breakpoints and the properties of the resulting CNAs. We found that the presence of heterochromatin in the tissue-of-origin contributes to the recurrence and length of CNAs in the respective cancer type.

Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors.

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Orgeur, Mickael; Martens, Marvin; Leonte, Georgeta; Nassari, Sonya; Bonnin, Marie-Ange; Börno, Stefan T; Timmermann, Bernd; Hecht, Jochen; Duprez, Delphine; Stricker, Sigmar

2018-03-29

Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development. © 2018. Published by The Company of Biologists Ltd.

Activation of the ERK1/2 Signaling Pathway during the Osteogenic Differentiation of Mesenchymal Stem Cells Cultured on Substrates Modified with Various Chemical Groups

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Bing Bai

2013-01-01

Full Text Available The current study examined the influence of culture substrates modified with the functional groups –OH, –COOH, –NH2, and –CH3 using SAMs technology, in conjunction with TAAB control, on the osteogenic differentiation of rabbit BMSCs. The CCK-8 assay revealed that BMSCs exhibited substrate-dependent cell viability. The cells plated on –NH2- and –OH-modified substrates were well spread and homogeneous, but those on the –COOH- and –CH3-modified substrates showed more rounded phenotype. The mRNA expression of BMSCs revealed that –NH2-modified substrate promoted the mRNA expression and osteogenic differentiation of the BMSCs. The contribution of ERK1/2 signaling pathway to the osteogenic differentiation of BMSCs cultured on the –NH2-modified substrate was investigated in vitro. The –NH2-modified substrate promoted the expression of integrins; the activation of FAK and ERK1/2. Inhibition of ERK1/2 activation by PD98059, a specific inhibitor of the ERK signaling pathway, blocked ERK1/2 activation in a dose-dependent manner, as revealed for expression of Cbfα-1 and ALP. Blockade of ERK1/2 phosphorylation in BMSCs by PD98059 suppressed osteogenic differentiation on chemical surfaces. These findings indicate a potential role for ERK in the osteogenic differentiation of BMSCs on surfaces modified by specific chemical functional groups, indicating that the microenvironment affects the differentiation of BMSCs. This observation has important implications for bone tissue engineering.

Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

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Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

2017-06-01

During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation

Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

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Herrera Maria

2006-04-01

Full Text Available Abstract Background Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG in vitro. Methods and results TG was quantified by time parameters: lag time (LT and time to peak (TTP, and by amount of TG: peak of TG (PTG and area under thrombin formation curve after 35 minutes (AUC→35min in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA, ADP, and collagen (Col. In addition, the effects of recombinant activated FVII (rFVIIa alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p 35min were significantly increased (p 35min (but not PTG when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. Conclusion Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis.

Variance components models for physical activity with age as modifier: a comparative twin study in seven countries

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Vink, Jacqueline M; Boomsma, Dorret I; Medland, Sarah E

2011-01-01

-reported data from twins aged 19 to 50 from seven countries that collaborated in the GenomEUtwin project: Australia, Denmark, Finland, Norway, Netherlands, Sweden and United Kingdom. Results confirmed the importance of genetic influences on physical activity in all countries and showed an age-related decrease......Physical activity is influenced by genetic factors whose expression may change with age. We employed an extension to the classical twin model that allows a modifier variable, age, to interact with the effects of the latent genetic and environmental factors. The model was applied to self...... into account when exploring the genetic and environmental contribution to physical activity. It also suggests that the power of genome-wide association studies to identify the genetic variants contributing to physical activity may be larger in young adult cohorts....

Design of a modified endoscope illuminator for spectral imaging of colorectal tissues

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Browning, Craig M.; Mayes, Samuel; Rich, Thomas C.; Leavesley, Silas J.

2017-02-01

The gold standard for locating colonic polyps is a white light endoscope in a colonoscopy, however, polyps smaller than 5 mm can be easily missed. Modified procedures such as narrow band imaging have shown only marginal increases in detection rates. Spectral imaging is a potential solution to improve the sensitivity and specificity of colonoscopies by providing the ability to distinguish molecular fluorescence differences in tissues. The goal of this work is to implement a spectral endoscopic light source to acquire spectral image data of colorectal tissues. A beta-version endoscope light source was developed, by retrofitting a white light endoscope light source (Olympus, CLK-4) with 16 narrow band LEDs. This redesigned, beta-prototype uses high-power LEDs with a minimum output of 500 mW to provide sufficient spectral output (0.5 mW) through the endoscope. A mounting apparatus was designed to provide sufficient heat dissipation. Here, we report recent results of our tests to characterize the intensity output through the light source and endoscope to determine the flat spectral output for imaging and intensity losses through the endoscope. We also report preliminary spectral imaging data from transverse pig colon that demonstrates the ability to result in working practical spectral data. Preliminary results of this revised prototype spectral endoscope system demonstrate that there is sufficient power to allow the imaging process to continue and potentially determine spectral differences in cancerous and normal tissue from imaging ex vivo pairs. Future work will focus on building a spectral library for the colorectal region and refining the user interface the system for in vivo use.

Immobilization of lipases on alkyl silane modified magnetic nanoparticles: effect of alkyl chain length on enzyme activity.

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Jiqian Wang

Full Text Available BACKGROUND: Biocatalytic processes often require a full recycling of biocatalysts to optimize economic benefits and minimize waste disposal. Immobilization of biocatalysts onto particulate carriers has been widely explored as an option to meet these requirements. However, surface properties often affect the amount of biocatalysts immobilized, their bioactivity and stability, hampering their wide applications. The aim of this work is to explore how immobilization of lipases onto magnetite nanoparticles affects their biocatalytic performance under carefully controlled surface modification. METHODOLOGY/PRINCIPAL FINDINGS: Magnetite nanoparticles, prepared through a co-precipitation method, were coated with alkyl silanes of different alkyl chain lengths to modulate their surface hydrophobicity. Candida rugosa lipase was then directly immobilized onto the modified nanoparticles through hydrophobic interaction. Enzyme activity was assessed by catalytic hydrolysis of p-nitrophenyl acetate. The activity of immobilized lipases was found to increase with increasing chain length of the alkyl silane. Furthermore, the catalytic activities of lipases immobilized on trimethoxyl octadecyl silane (C18 modified Fe(3O(4 were a factor of 2 or more than the values reported from other surface immobilized systems. After 7 recycles, the activities of the lipases immobilized on C18 modified nanoparticles retained 65%, indicating significant enhancement of stability as well through hydrophobic interaction. Lipase immobilized magnetic nanoparticles facilitated easy separation and recycling with high activity retaining. CONCLUSIONS/SIGNIFICANCE: The activity of immobilized lipases increased with increasing alkyl chain length of the alkyl trimethoxy silanes used in the surface modification of magnetite nanoparticles. Lipase stability was also improved through hydrophobic interaction. Alkyl silane modified magnetite nanoparticles are thus highly attractive carriers for

Immobilization of lipases on alkyl silane modified magnetic nanoparticles: effect of alkyl chain length on enzyme activity.

Science.gov (United States)

Wang, Jiqian; Meng, Gang; Tao, Kai; Feng, Min; Zhao, Xiubo; Li, Zhen; Xu, Hai; Xia, Daohong; Lu, Jian R

2012-01-01

Biocatalytic processes often require a full recycling of biocatalysts to optimize economic benefits and minimize waste disposal. Immobilization of biocatalysts onto particulate carriers has been widely explored as an option to meet these requirements. However, surface properties often affect the amount of biocatalysts immobilized, their bioactivity and stability, hampering their wide applications. The aim of this work is to explore how immobilization of lipases onto magnetite nanoparticles affects their biocatalytic performance under carefully controlled surface modification. Magnetite nanoparticles, prepared through a co-precipitation method, were coated with alkyl silanes of different alkyl chain lengths to modulate their surface hydrophobicity. Candida rugosa lipase was then directly immobilized onto the modified nanoparticles through hydrophobic interaction. Enzyme activity was assessed by catalytic hydrolysis of p-nitrophenyl acetate. The activity of immobilized lipases was found to increase with increasing chain length of the alkyl silane. Furthermore, the catalytic activities of lipases immobilized on trimethoxyl octadecyl silane (C18) modified Fe(3)O(4) were a factor of 2 or more than the values reported from other surface immobilized systems. After 7 recycles, the activities of the lipases immobilized on C18 modified nanoparticles retained 65%, indicating significant enhancement of stability as well through hydrophobic interaction. Lipase immobilized magnetic nanoparticles facilitated easy separation and recycling with high activity retaining. The activity of immobilized lipases increased with increasing alkyl chain length of the alkyl trimethoxy silanes used in the surface modification of magnetite nanoparticles. Lipase stability was also improved through hydrophobic interaction. Alkyl silane modified magnetite nanoparticles are thus highly attractive carriers for enzyme immobilization enabling efficient enzyme recovery and recycling.

5α-reductase activity in rat adipose tissue

International Nuclear Information System (INIS)

Zyirek, M.; Flood, C.; Longcope, C.

1987-01-01

We measured the 5 α-reductase activity in isolated cell preparations of rat adipose tissue using the formation of [ 3 H] dihydrotestosterone from [ 3 H] testosterone as an endpoint. Stromal cells were prepared from the epididymal fat pad, perinephric fat, and subcutaneous fat of male rats and from perinephric fat of female rats. Adipocytes were prepared from the epididymal fat pad and perinephric fat of male rats. Stromal cells from the epididymal fat pad and perinephric fat contained greater 5α-reductase activity than did the adipocytes from these depots. Stromal cells from the epididymal fat pad contained greater activity than those from perinephric and subcutaneous depots. Perinephric stromal cells from female rats were slightly more active than those from male rats. Estradiol (10 -8 M), when added to the medium, caused a 90% decrease in 5α-reductase activity. Aromatase activity was minimal, several orders of magnitude less than 5α-reductase activity in each tissue studied

Glucose Oxidation on Gold-modified Copper Electrode

Energy Technology Data Exchange (ETDEWEB)

Lim, Jieun; Pyo, Sung Gyu; Son, Hyungbin; Kim, Sookil [Chung-Ang Univ., Seoul (Korea, Republic of); Ahn, Sang Hyun; Son, Hyungbin [Korea Institute of Science and Technology, Seoul (Korea, Republic of)

2013-09-15

The activities of Au-modified Cu electrodes toward glucose oxidation are evaluated according to their fabrication conditions and physico-chemical properties. The Au-modified Cu electrodes are fabricated by the galvanic displacement of Au on a Cu substrate and the characteristics of the Au particles are controlled by adjusting the displacement time. From the glucose oxidation tests, it is found that the Au modified Cu has superior activity to the pure Au or Cu film, which is evidenced by the negative shift in the oxidation potential and enhanced current density during the electrochemical oxidation. Though the activity of the Au nanoparticles is a contributing factor, the enhanced activity of the Au-modified Cu electrode is due to the increased oxidation number of Cu through the electron transfer from Cu to more electronegative Au. The depletion of electron in Cu facilitates the oxidation of glucose. The stability of the Au-modified Cu electrode was also studied by chronoamperometry.

Oxidative stress and antioxidant activity in orbital fibroadipose tissue in Graves' ophthalmopathy.

Science.gov (United States)

Hondur, Ahmet; Konuk, Onur; Dincel, Aylin Sepici; Bilgihan, Ayse; Unal, Mehmet; Hasanreisoglu, Berati

2008-05-01

To investigate the oxidative stress and antioxidant activity in the orbit in Graves' ophthalmopathy (GO). Orbital fibroadipose tissue samples were obtained from 13 cases during orbital fat decompression surgery. All cases demonstrated features of moderate or severe GO according to the European Group on Graves' Orbitopathy classification. The disease activity was evaluated with the Clinical Activity Score, and the clinical features of GO were evaluated with the Ophthalmopathy Index. Orbital fibroadipose tissue samples of 8 patients without any thyroid or autoimmune disease were studied as controls. In the tissue samples, lipid hydroperoxide level was examined to determine the level of oxidative stress; glutathione level to determine antioxidant level; superoxide dismutase, glutathione reductase, and glutathione peroxidase activities to determine antioxidant activity. Lipid hydroperoxide level and all three antioxidant enzyme activities were found to be significantly elevated, while glutathione level significantly diminished in tissue samples from GO cases compared to controls (p < 0.05). Glutathione levels in tissue samples of GO cases showed negative correlation with Ophthalmopathy Index (r = -0.59, p < 0.05). The antioxidant activity in the orbit is enhanced in GO. However, the oxidative stress appears to be severe enough to deplete the tissue antioxidants and leads to oxidative tissue damage. This study may support the possible value of antioxidant treatment in GO.

Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade.

LENUS (Irish Health Repository)

Rooney, Terence

2012-02-01

OBJECTIVES: To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). METHODS: Patients with active RA entered a randomised study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 microg\\/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. RESULTS: Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFbeta) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor\\/TGFbeta, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. CONCLUSIONS: Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.

Natural radiation exposure modified by human activities

International Nuclear Information System (INIS)

Fujimoto, Kenzo

1995-01-01

We are now living in the radiation environment modified by our technology. It is usually called 'Technologically Enhanced Natural Radiation' and have been discussed in the UNSCEAR Reports as an important source of exposure. The terrestrial radionuclide concentrations as well as the intensity of cosmic rays are considered to have been constant after our ancestors came down from trees and started walking on their two feet. However, we have been changing our environment to be more comfortable for our life and consequently ambient radiation levels are nomore what used to be. In this paper exposures due to natural radiation modified by our following activities are discussed: housing, balneology, cave excursion, mountain climbing, skiing, swimming, smoking and usage of mineral water, well water, coal, natural gas, phosphate rocks and minerals. In the ICRP Publication No. 39, it is clearly mentioned that even natural radiation should be controlled as far as it is controllable. We have to pay more attention to our activities not to enhance the exposure due to unnecessary, avoidable radiation. (author)

Effect of Grinding at Modified Atmosphere or Vacuum on Browning, Antioxidant Capacities, and Oxidative Enzyme Activities of Apple.

Science.gov (United States)

Kim, Ah-Na; Lee, Kyo-Yeon; Kim, Hyun-Jin; Chun, Jiyeon; Kerr, William L; Choi, Sung-Gil

2018-01-01

This study evaluated the effects of grinding at atmospheric pressure (control), under vacuum (∼2.67 kPa), or with modified atmosphere (N 2 and CO 2 ) on the browning, antioxidant activity, phenolics, and oxidative enzyme activity of apples as a function of time. The control group was affected most, showing distinct browning and losing most of the antioxidant activity and concentrations of the main phenolic compounds. The modified atmosphere groups retained color, antioxidant activity, and phenolic compounds better than the control group. Least changes were obtained with vacuum grinding, particularly in terms of preventing enzymatic browning and oxidation of antioxidants apples. At 12 h after grinding, vacuum-ground apples retained total phenolic contents 5.32, 1.54, and 1.49 times higher than control, nitrogen gas, and carbon dioxide gas-ground samples, respectively. The oxidative enzyme activity, including that of polyphenol oxidase and peroxidase, decreased in the control and modified atmosphere group, but they were maintained in the samples ground under the vacuum. In this study, we found that grinding with modified atmosphere or vacuum conditions could effectively prevent browning as well as loss of phenolic compounds and antioxidant activity of ground apples. These results can help scientists and engineers build better grinding systems for retaining nutrient and quality factors of ground apples. In addition, these results may be useful to other fruit and vegetable industries that wish to retain fresh-like quality and nutritional value during grinding and storage. © 2017 Institute of Food Technologists®.

TALE factors poise promoters for activation by Hox proteins.

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Choe, Seong-Kyu; Ladam, Franck; Sagerström, Charles G

2014-01-27

Hox proteins form complexes with TALE cofactors from the Pbx and Prep/Meis families to control transcription, but it remains unclear how Hox:TALE complexes function. Examining a Hoxb1b:TALE complex that regulates zebrafish hoxb1a transcription, we find maternally deposited TALE proteins at the hoxb1a promoter already during blastula stages. These TALE factors recruit histone-modifying enzymes to promote an active chromatin profile at the hoxb1a promoter and also recruit RNA polymerase II (RNAPII) and P-TEFb. However, in the presence of TALE factors, RNAPII remains phosphorylated on serine 5 and hoxb1a transcription is inefficient. By gastrula stages, Hoxb1b binds together with TALE factors to the hoxb1a promoter. This triggers P-TEFb-mediated transitioning of RNAPII to the serine 2-phosphorylated form and efficient hoxb1a transcription. We conclude that TALE factors access promoters during early embryogenesis to poise them for activation but that Hox proteins are required to trigger efficient transcription. Copyright © 2014 Elsevier Inc. All rights reserved.

Fell-Muir lecture: connective tissue growth factor (CCN2) – a pernicious and pleiotropic player in the development of kidney fibrosis

Science.gov (United States)

Mason, Roger M

2013-01-01

Connective tissue growth factor (CTGF, CCN2) is a member of the CCN family of matricellular proteins. It interacts with many other proteins, including plasma membrane proteins, modulating cell function. It is expressed at low levels in normal adult kidney cells but is increased in kidney diseases, playing important roles in inflammation and in the development of glomerular and interstitial fibrosis in chronic disease. This review reports the evidence for its expression in human and animal models of chronic kidney disease and summarizes data showing that anti-CTGF therapy can successfully attenuate fibrotic changes in several such models, suggesting that therapies targeting CTGF and events downstream of it in renal cells may be useful for the treatment of human kidney fibrosis. Connective tissue growth factor stimulates the development of fibrosis in the kidney in many ways including activating cells to increase extracellular matrix synthesis, inducing cell cycle arrest and hypertrophy, and prolonging survival of activated cells. The relationship between CTGF and the pro-fibrotic factor TGFβ is examined and mechanisms by which CTGF promotes signalling by the latter are discussed. No specific cellular receptors for CTGF have been discovered but it interacts with and activates several plasma membrane proteins including low-density lipoprotein receptor-related protein (LRP)-1, LRP-6, tropomyosin-related kinase A, integrins and heparan sulphate proteoglycans. Intracellular signalling and downstream events triggered by such interactions are reviewed. Finally, the relationships between CTGF and several anti-fibrotic factors, such as bone morphogenetic factor-4 (BMP4), BMP7, hepatocyte growth factor, CCN3 and Oncostatin M, are discussed. These may determine whether injured tissue heals or progresses to fibrosis. PMID:23110747

Population attributable risk of modifiable risk factors associated with invasive breast cancer in women aged 45-69 years in Queensland, Australia.

Science.gov (United States)

Wilson, Louise F; Page, Andrew N; Dunn, Nathan A M; Pandeya, Nirmala; Protani, Melinda M; Taylor, Richard J

2013-12-01

To quantify the population attributable risk of key modifiable risk factors associated with breast cancer incidence in Queensland, Australia. Population attributable fractions (PAFs) for high body mass index (BMI), use of hormone replacement therapy (HRT), alcohol consumption and inadequate physical activity were calculated, using prevalence data from a representative survey of women attending mammographic screening at BreastScreen Queensland in 2008 and relative risk estimates sourced from published literature. Attributable cancers were calculated using 'underlying' breast cancer incidence data for 2008 based on Poisson regression models, adjusting for the inflation of incidence due to the effects of mammographic screening. Attributable burden of breast cancer due to high body mass index (BMI), use of hormone replacement therapy (HRT), alcohol consumption and inadequate physical activity. In Queensland women aged 45-69 years, an estimated 12.1% (95% CI: 11.6-12.5%) of invasive breast cancers were attributable to high BMI in post-menopausal women who have never used HRT; 2.8% (95% CI: 2.7-2.9%) to alcohol consumption; 7.6% (95% CI: 7.4-7.9%) to inadequate physical activity in post-menopausal women and 6.2% (95% CI: 5.5-7.0%) to current use of HRT after stratification by BMI and type of HRT used. Combined, just over one quarter (26.0%; 95% CI: 25.4-26.6%) of all invasive breast cancers in Queensland women aged 45-69 years in 2008 were attributable to these modifiable risk factors. There is benefit in targeting prevention strategies to modify lifestyle behaviours around BMI, physical activity, HRT use and alcohol consumption, as a reduction in these risk factors could decrease invasive breast cancer incidence in the Queensland population. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Characterization of fatty acid modifying enzyme activity in staphylococcal mastitis isolates and other bacteria

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Lu Thea

2012-06-01

Full Text Available Abstract Background Fatty acid modifying enzyme (FAME has been shown to modify free fatty acids to alleviate their bactericidal effect by esterifying fatty acids to cholesterol or alcohols. Although it has been shown in previous studies that FAME is required for Staphylococcus aureus survival in skin abscesses, FAME is poorly studied compared to other virulence factors. FAME activity had also been detected in coagulase-negative staphylococci (CNS. However, FAME activity was only surveyed after a bacterial culture was grown for 24 h. Therefore if FAME activity was earlier in the growth phase, it would not have been detected by the assay and those strains would have been labeled as FAME negative. Results Fifty CNS bovine mastitis isolates and several S. aureus, Escherichia coli, and Streptococcus uberis strains were assayed for FAME activity over 24 h. FAME activity was detected in 54% of CNS and 80% S. aureus strains surveyed but none in E. coli or S. uberis. While some CNS strains produced FAME activity comparable to the lab strain of S. aureus, the pattern of FAME activity varied among strains and across species of staphylococci. All CNS that produced FAME activity also exhibited lipase activity. Lipase activity relative to colony forming units of these CNS decreased over the 24 h growth period. No relationship was observed between somatic cell count in the milk and FAME activity in CNS. Conclusions Some staphylococcal species surveyed produced FAME activity, but E. coli and S. uberis strains did not. All FAME producing CNS exhibited lipase activity which may indicate that both these enzymes work in concert to alter fatty acids in the bacterial environment.

Transcriptomic Analysis of Intestinal Tissues from Two 90-Day Feeding Studies in Rats Using Genetically Modified MON810 Maize Varieties

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Jutta Sharbati

2017-12-01

Full Text Available Background: Global as well as specific expression profiles of selected rat tissues were characterized to assess the safety of genetically modified (GM maize MON810 containing the insecticidal protein Cry1Ab. Gene expression was evaluated by use of Next Generation Sequencing (NGS as well as RT-qPCR within rat intestinal tissues based on mandatory 90-day rodent feeding studies. In parallel to two 90-day feeding studies, the transcriptional response of rat tissues was assessed as another endpoint to enhance the mechanistic interpretation of GM feeding studies and/or to facilitate the generation of a targeted hypothesis. Rats received diets containing 33% GM maize (MON810 or near-isogenic control maize. As a site of massive exposure to ingested feed the transcriptomic response of ileal and colonic tissue was profiled via RT-qPCR arrays targeting apoptosis, DNA-damage/repair, unfolded protein response (UPR. For global RNA profiling of rat ileal tissue, we applied NGS.Results: No biological response to the GM-diet was observed in male and in female rat tissues. Transcriptome wide analysis of gene expression by RNA-seq confirmed these findings. Nevertheless, gene ontology (GO analysis clearly associated a set of distinctly regulated transcripts with circadian rhythms. We confirmed differential expression of circadian clock genes using RT-qPCR and immunoassays for selected factors, thereby indicating physiological effects caused by the time point of sampling.Conclusion: Prediction of potential unintended effects of GM-food/feed by transcriptome based profiling of intestinal tissue presents a novel approach to complement classical toxicological testing procedures. Including the detection of alterations in signaling pathways in toxicity testing procedures may enhance the confidence in outcomes of toxicological trials. In this study, no significant GM-related changes in intestinal expression profiles were found in rats fed GM-maize MON810. Relevant

Oral heparin results in the appearance of heparin fragments in the plasma of rats

International Nuclear Information System (INIS)

Larsen, A.K.; Lund, D.P.; Langer, R.; Folkman, J.

1986-01-01

We have previously shown that angiogenesis inhibition and tumor regression can be accomplished by combinations of heparin or heparin fragments with cortisone. Oral heparin was also effective in combination with cortisone. We now show that a single oral dose of [ 35 S]heparin or [ 3 H]heparin (15,000 units/kg) results in continuous release of radioactive material into the bloodstream for at least 12 hr. This is associated with the presence of anti-factor Xa activity at a level of approximately equal to 0.1 unit/ml. The radioactive material is identified as oligo-, di-, and monosaccharides by its behavior in chromatographic systems, its possession of anti-factor Xa activity, and the effect of treatment with bacterial heparinase. The heparin fragments are extensively metabolized to fragments without anti-factor Xa activity that are readily subject to urinary excretion

Knowledge of modifiable risk factors of Coronary Atherosclerotic Heart Disease (CASHD among a sample in India

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Ku Melvin

2009-02-01

Full Text Available Abstract Background The prevalence of Coronary Atherosclerotic Heart Disease (CASHD is increasing in India. Several modifiable risk factors contribute directly to this disease burden. Public knowledge of such risk factors among the urban Indian population is largely unknown. This investigation attempts to quantify knowledge of modifiable risk factors of CASHD as sampled among an Indian population at a large metropolitan hospital. Methods A hospital-based, cross sectional study was conducted at All India Institute of Medical Sciences (AIIMS, a major tertiary care hospital in New Delhi, India. Participants (n = 217 recruited from patient waiting areas in the emergency room were provided with standardized questionnaires to assess their knowledge of modifiable risk factors of CASHD. The risk factors specifically included smoking, hypertension, elevated cholesterol levels, diabetes mellitus and obesity. Identifying 3 or less risk factors was regarded as a poor knowledge level, whereas identifying 4 or more risk factors was regarded as a good knowledge level. A multiple logistic regression model was used to isolate independent demographic markers predictive of a participant's level of knowledge. Results 41% of the sample surveyed had a good level of knowledge. 68%, 72%, 73% and 57% of the population identified smoking, obesity, hypertension, and high cholesterol correctly, respectively. 30% identified diabetes mellitus as a modifiable risk factor of CASHD. In multiple logistic regression analysis independent demographic predictors of a good knowledge level with a statistically significant (p Conclusion An Indian population in a hospital setting shows a lack of knowledge pertaining to modifiable risk factors of CASHD. By isolating demographic predictors of poor knowledge, such as current smokers and persons who do not exercise regularly, educational interventions can be effectively targeted and implemented as primary and secondary prevention strategies

Surface-modified bacterial nanofibrillar PHB scaffolds for bladder tissue repair.

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Karahaliloğlu, Zeynep; Demirbilek, Murat; Şam, Mesut; Sağlam, Necdet; Mızrak, Alpay Koray; Denkbaş, Emir Baki

2016-01-01

The aim of the study is in vitro investigation of the feasibility of surface-modified bacterial nanofibrous poly [(R)-3-hydroxybutyrate] (PHB) graft for bladder reconstruction. In this study, the surface of electrospun bacterial PHB was modified with PEG- or EDA via radio frequency glow discharge method. After plasma modification, contact angle of EDA-modified PHB scaffolds decreased from 110 ± 1.50 to 23 ± 0.5 degree. Interestingly, less calcium oxalate stone deposition was observed on modified PHB scaffolds compared to that of non-modified group. Results of this study show that surface-modified scaffolds not only inhibited calcium oxalate growth but also enhanced the uroepithelial cell viability and proliferation.

The use of simultaneous chemical precipitation in modified activated ...

African Journals Online (AJOL)

The use of simultaneous chemical precipitation in modified activated sludge systems exhibiting biological excess phosphate removal: Part 6: Modelling of simultaneous chemical-biological P removal - review of existing models.

Expression of cyclooxygenase-1 and cyclooxygenase-2, syndecan-1 and connective tissue growth factor in benign and malignant breast tissue from premenopausal women.

Science.gov (United States)

Fahlén, M; Zhang, H; Löfgren, L; Masironi, B; von Schoultz, E; von Schoultz, B; Sahlin, L

2017-05-01

Stromal factors have been identified as important for tumorigenesis and metastases of breast cancer. From 49 premenopausal women, samples were collected from benign or malignant tumors and the seemingly normal tissue adjacent to the tumor. The factors studied, with real-time polymerase chain reaction (PCR) and immunohistochemistry, were cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), syndecan-1 (S-1) and connective tissue growth factor (CTGF). COX-1 and S-1 mRNA levels were higher in the malignant tumors than in normal and benign tissues. The COX-2 mRNA level was lower in the malignant tumor than in the normal tissue, while CTGF mRNA did not differ between the groups. COX-1 immunostaining was higher in stroma from malignant tumors than in benign tissues, whereas COX-2 immunostaining was higher in the malignant tissue. Glandular S-1 immunostaining was lower in malignant tumors compared to benign and normal tissues, and the opposite was found in stroma. Conclusively, mRNA levels of COX-1 and COX-2 were oppositely regulated, with COX-1 being increased in the malignant tumor while COX-2 was decreased. S-1 protein localization switched from glandular to stromal cells in malignant tissues. Thus, these markers are, in premenopausal women, localized and regulated differently in normal/benign breast tissue as compared to the malignant tumor.

Tissue bionics: examples in biomimetic tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Green, David W [Bone and Joint Research Group, Developmental Origins of Health and Disease, General Hospital, University of Southampton, SO16 6YD (United Kingdom)], E-mail: Hindoostuart@googlemail.com

2008-09-01

Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

Tissue bionics: examples in biomimetic tissue engineering

International Nuclear Information System (INIS)

Green, David W

2008-01-01

Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic

Chitosan/γ-poly(glutamic acid) scaffolds with surface-modified albumin, elastin and poly-l-lysine for cartilage tissue engineering.

Science.gov (United States)

Kuo, Yung-Chih; Ku, Hao-Fu; Rajesh, Rajendiran

2017-09-01

Cartilage has limited ability to self-repair due to the absence of blood vessels and nerves. The application of biomaterial scaffolds using biomimetic extracellular matrix (ECM)-related polymers has become an effective approach to production of engineered cartilage. Chitosan/γ-poly(glutamic acid) (γ-PGA) scaffolds with different mass ratios were prepared using genipin as a cross-linker and a freeze-drying method, and their surfaces were modified with elastin, human serum albumin (HSA) and poly-l-lysine (PLL). The scaffolds were formed through a complex between NH 3 + of chitosan and COO - of γ-PGA, confirmed by Fourier transform infrared spectroscopy, and exhibited an interconnected porous morphology in field emission scanning electron microscopy analysis. The prepared chitosan/γ-PGA scaffolds, at a 3:1 ratio, obtained the required porosity (90%), pore size (≥100μm), mechanical strength (compressive strength>4MPa, Young's modulus>4MPa) and biodegradation (30-60%) for articular cartilage tissue engineering applications. Surface modification of the scaffolds showed positive indications with improved activity toward cell proliferation (deoxyribonucleic acid), cell adhesion and ECM (glycoaminoglycans and type II collagen) secretion of bovine knee chondrocytes compared with unmodified scaffolds. In caspase-3 detection, elastin had a higher inhibitory effect on chondrocyte apoptosis in vitro, followed by HSA, and then PLL. We concluded that utilizing chitosan/γ-PGA scaffolds with surface active biomolecules, including elastin, HSA and PLL, can effectively promote the growth of chondrocytes, secrete ECM and improve the regenerative ability of cartilaginous tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

Some growth factors in neoplastic tissues of brain tumors of different histological structure

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O. I. Kit

2016-01-01

Full Text Available Introduction. Pathologic angiogenesis is typical for angiogenic diseases including tumor growth. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, transforming growth factor alpha and beta (which are also known as “triggers” of angiogenesis, and other factors (Gacche, Meshram, 2013; Nijaguna et al., 2015 play a special role in its development. Evaluation of the important mechanisms of angiogenesis in physiological and pathological conditions remains to be a subject of heightened interest for the past 30 years. It is known that VEGF A is the main trigger of growing blood vessels into the tumor tissue. This is specific mitogen signal for endothelial cells that triggers the mechanisms of cell division and migration. VEGF-induced tumor vasculature has a number of structural and functional features that provide growth and progression of tumors, including increased permeability of blood vessels and their chaotic arrangement.Objective: to study in comparative aspect the level of certain growth factors in the following tissues: glioblastomas, brain metastasis of the breast cancer, meningiomas as well as corresponding peritumoral areas.Materials and methods. Tissue samples were obtained from 56 patients admitted to the surgical treatment in Rostov Research Institute of Oncology: 24 patients had glioblastomas, 19 patients had brain metastasis of the breast cancer, 13 patients with meningiomas without peritumoral edema. Histological control was carried out in all cases. Age of patients ranged from 35 to 72 years. The level of growth factor was detected in the samples of tumor tissue and regions immediately adjacent to the tumor foci (peritumoral area by the method of immunoassay and using standard test systems. The following growth factor were detected: VEGF-A and its receptors VEGF-R1 (BenderMedSystem, Austria, VEGF-C and its receptor VEGF-R3 (BenderMedSystem, Austria, EGF (Biosource, USA, IFR-1 and IFR-2 (Mediagnost, USA, TGF

[Clinical effect modified Chevron osteotomy combined with lateral tissue loosening in treating mild-moderate hallux valgus through internal signal approach].

Science.gov (United States)

Chen, Xue-Qiang; Wu, Qun-Feng; Dong, Wei-Qin; Yu, Li-Xin; Li, Xiong-Feng

2018-03-25

To explore clinical effect of modified Chevron osteotomy combined with lateral tissue loosening for the treatment of mild-moderate hallux valgus through internal signal approach. From July 2015 to June 2016, 26 patients with mild-moderate hallux valgus treated with modified Chevron osteotomy combined with lateral tissue loosening through internal signal approach, including 2 males and 24 females aged from 45 to 65 years old with an average of(54.6±4.8) years old;the courses of diseases ranged from 1 to 5 months with an average of (7.5±3.3) months. Hallux valgus angle(HVA), inter metatarsal angle(IMA) were measured at 12 months after operation, and AOFAS score was applied to evaluate clinical effect before and after operation. All incisions were healed at stage I. No incision occurred infection, metatarsal necrosis and recurrence of hallux valgus deformity. Two patients occurred skin numbness caused by musculocutaneous nerve injury. Twenty-six patients were followed up from 6 to 12 months with an average of(9.12±2.06) months. HVA, IMA were(30.01±3.71)°, (14.00±1.50)° before operation and(9.41±4.16)°, (7.00±0.60)° after operation, which had significant difference. There was statistical significance in AOFAS score before operation 54.77±9.59 and after operation 92.73±5.47, and 19 cases obtained excellent results and 7 moderate. Modified Chevron osteotomy combined with full thread headless pressure screw fixation and lateral tissue loosening for the treatment of mild-moderate hallux valgus has advantages of excellent exposure, simple operation, stable fixation, rapid recovery. Akin osteotomy with internal capsulorrhaphy were used with lateral loosening and could recover soft tissue balance between lateral and internal, and could receive satisfied clinical effects. Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.

Modifiable risk factors for Alzheimer disease and subjective memory impairment across age groups.

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Chen, Stephen T; Siddarth, Prabha; Ercoli, Linda M; Merrill, David A; Torres-Gil, Fernando; Small, Gary W

2014-01-01

Previous research has identified modifiable risk factors for Alzheimer's disease (AD) in older adults. Research is limited on the potential link between these risk factors and subjective memory impairment (SMI), which may precede AD and other dementias. Examination of these potential relationships may help identify those at risk for AD at a stage when interventions may delay or prevent further memory problems. The objective of this study was to determine whether risk factors for AD are associated with SMI among different age groups. Trained interviewers conducted daily telephone surveys (Gallup-Healthways) of a representative community sample of 18,614 U.S. respondents, including 4,425 younger (age 18 to 39 years), 6,365 middle-aged (40 to 59 years), and 7,824 older (60 to 99 years) adults. The surveyors collected data on demographics, lifestyles, and medical information. Less education, smoking, hypertension, diabetes, less exercise, obesity and depression, and interactions among them, were examined for associations with SMI. Weighted logistic regressions and chi-square tests were used to calculate odds ratios and confidence intervals for SMI with each risk factor and pairwise interactions across age groups. Depression, less education, less exercise, and hypertension were significantly associated with SMI in all three age groups. Several interactions between risk factors were significant in younger and middle-aged adults and influenced their associations with SMI. Frequency of SMI increased with age and number of risk factors. Odds of having SMI increased significantly with just having one risk factor. These results indicate that modifiable risk factors for AD are also associated with SMI, suggesting that these relationships occur in a broad range of ages and may be targeted to mitigate further memory problems. Whether modifying these risk factors reduces SMI and the eventual incidence of AD and other dementias later in life remains to be determined.

Modifiable risk factors for Alzheimer disease and subjective memory impairment across age groups.

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Stephen T Chen

Full Text Available INTRODUCTION: Previous research has identified modifiable risk factors for Alzheimer's disease (AD in older adults. Research is limited on the potential link between these risk factors and subjective memory impairment (SMI, which may precede AD and other dementias. Examination of these potential relationships may help identify those at risk for AD at a stage when interventions may delay or prevent further memory problems. The objective of this study was to determine whether risk factors for AD are associated with SMI among different age groups. METHOD: Trained interviewers conducted daily telephone surveys (Gallup-Healthways of a representative community sample of 18,614 U.S. respondents, including 4,425 younger (age 18 to 39 years, 6,365 middle-aged (40 to 59 years, and 7,824 older (60 to 99 years adults. The surveyors collected data on demographics, lifestyles, and medical information. Less education, smoking, hypertension, diabetes, less exercise, obesity and depression, and interactions among them, were examined for associations with SMI. Weighted logistic regressions and chi-square tests were used to calculate odds ratios and confidence intervals for SMI with each risk factor and pairwise interactions across age groups. RESULTS: Depression, less education, less exercise, and hypertension were significantly associated with SMI in all three age groups. Several interactions between risk factors were significant in younger and middle-aged adults and influenced their associations with SMI. Frequency of SMI increased with age and number of risk factors. Odds of having SMI increased significantly with just having one risk factor. CONCLUSIONS: These results indicate that modifiable risk factors for AD are also associated with SMI, suggesting that these relationships occur in a broad range of ages and may be targeted to mitigate further memory problems. Whether modifying these risk factors reduces SMI and the eventual incidence of AD and other

Beneficial effects of a N-terminally modified GIP agonist on tissue-level bone material properties.

Science.gov (United States)

Mabilleau, Guillaume; Mieczkowska, Aleksandra; Irwin, Nigel; Simon, Yannick; Audran, Maurice; Flatt, Peter R; Chappard, Daniel

2014-06-01

Bone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4) precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed, with N-AcGIP being the most promising. The aims of the present study were to investigate the effects of N-AcGIP on bone at the micro-level using trabecular and cortical microstructural morphology, and at the tissue-level in rats. Copenhagen rats were randomly assigned into control or N-AcGIP-treated groups and received daily injection for 4 weeks. Bone microstructural morphology was assessed by microCT and dynamic histomorphometry and tissue-level properties by nanoindentation, qBEI and infra-red microscopy. Four week treatment with N-AcGIP did not alter trabecular or cortical microstructural morphology. In addition, no significant modifications of mechanical response and properties at the tissue-level were observed in trabecular bone. However, significant augmentations in maximum load (12%), hardness (14%), indentation modulus (13%) and dissipated energy (16%) were demonstrated in cortical bone. These beneficial modifications of mechanical properties at the tissue-level were associated with increased mineralization (22%) and collagen maturity (13%) of the bone matrix. Taken together, the results support a beneficial role of GIP, and particularly stable analogs such as N-AcGIP, on tissue material properties of bone. Copyright © 2014 Elsevier Inc. All rights reserved.

Revised age-dependent doses to members of the public from intake of radionuclides using the new tissue weighting factors

International Nuclear Information System (INIS)

Jain, S.C.; Gupta, M.M.; Nagaratnam, A.; Reddy, A.R.; Mehta, S.C.

1992-01-01

ICRP 56 gave age-dependent dose coefficients to members of the public from intake of most radiologically significant radionuclides that might be released to the environment due to various human activities. It has computed effective dose equivalent (now called effective dose) from these dose coefficients utilising the tissue weighting factors as given by ICRP 26. The recent ICRP 1990 recommendations have revised the tissue weighting factors based on new information on risk estimates of fatal cancer and hereditary disorders. This change in the tissue weighting factors will subsequently affect the computation of effective dose due to intake of various radio-nuclides considered by ICRP 56. The revised effective doses for ingested as well as inhaled radionuclides have been worked out and compared from corresponding earlier values. No change was found in the case of tritiated water, organically bound tritium and 14 C. For the majority of the radionuclides, the revised effective dose was within ± 20% of the earlier values. Larger variations in effective dose were noted for radionuclides which deposit preferentially in one or two organs. (author)

Is the role of the environment in carcinogenesis overestimated. [Individual health status, modifying factor

Energy Technology Data Exchange (ETDEWEB)

Calabrese, E J

1979-01-01

The dominant role of the physical and chemical environment in the development of cancer is challenged. Analyses of the etiology of skin, bladder, respiratory and gastric cancers are presented which demonstrate the considerable extent to which one's health status may modify the initiation and promotion of environmentally asociated cancers. It is concluded that although environmental factors may initiate and/or promote 85 to 90 percent of all cancers this is misleading since it neglects the critical role of the individual's health status as a factor modifying carcinogenesis.

A specific colorimetric assay for measuring transglutaminase 1 and factor XIII activities.

Science.gov (United States)

Hitomi, Kiyotaka; Kitamura, Miyako; Alea, Mileidys Perez; Ceylan, Ismail; Thomas, Vincent; El Alaoui, Saïd

2009-11-15

Transglutaminase (TGase) is an enzyme that catalyzes both isopeptide cross-linking and incorporation of primary amines into proteins. Eight TGases have been identified in humans, and each of these TGases has a unique tissue distribution and physiological significance. Although several assays for TGase enzymatic activity have been reported, it has been difficult to establish an assay for discriminating each of these different TGase activities. Using a random peptide library, we recently identified the preferred substrate sequences for three major TGases: TGase 1, TGase 2, and factor XIII. In this study, we use these substrates in specific tests for measuring the activities of TGase 1 and factor XIII.

Irbesartan increased PPARγ activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

International Nuclear Information System (INIS)

Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo; Horiuchi, Masatsugu

2011-01-01

Research highlights: → Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. → Irbesartan decreased white adipose tissue weight without affecting body weight. → DNA-binding for PPARγ was increased in white adipose tissue in vivo by irbesartan. → Irbesartan increased adipocyte number in white adipose tissue. → Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPARγ agonistic action of an AT 1 receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPARγ in white adipose tissue and the DNA-binding activity of PPARγ in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPARγ and improved adipose tissue dysfunction including insulin resistance.

The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure.

Science.gov (United States)

Li, Gang; Song, Xueqing; Xia, Jiyi; Li, Jing; Jia, Peng; Chen, Pengyuan; Zhao, Jian; Liu, Bin

2017-01-01

The aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure. Methods and results Plasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices. Plasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.

Immediately modifiable risk factors attributable to colorectal cancer in Malaysia.

Science.gov (United States)

Naing, Cho; Lai, Pei Kuan; Mak, Joon Wah

2017-08-04

This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population. Gender specific population-attributable fractions (PAFs) for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions). Exposure prevalence were sourced from a large-scale national representative survey. Risk estimates of the relationship between the exposure of interest and colorectal cancer were obtained from published meta-analyses. The overall PAF was then estimated, using the 2013 national cancer incidence data from the Malaysian Cancer Registry. Overall, the mean incidence rate for colorectal cancer in Malaysia from 2008 to 2013 was 21.3 per 100,000 population, with the mean age of 61.6 years (±12.7) and the majority were men (56.6%). Amongst 369 colorectal cancer cases in 2013, 40 cases (20 men, 20 women), 10 cases (9 men, 1 woman) or 20 cases (16 men,4 women) would be prevented, if they had done physical exercises, could reduce their body weight to normal level or avoided alcohol consumption, assuming that these factors are causally related to colorectal cancer. It was estimated that 66 (17.8%;66/369) colorectal cancer cases (42 men, 24 women) who had all these three risk factors for the last 10 years would have been prevented, if they could control these three risk factors through effective preventive measures. Findings suggest that approximately 18% of colorectal cancer cases in Malaysia would be prevented through appropriate preventive measures such as doing regular physical exercises, reducing their body weight to normal level and avoiding alcohol consumption, if these factors are causally related to colorectal cancer. Scaling-up nationwide public health campaigns tailored to increase physical activity, controlling body weight within normal

Impact of pre-analytical factors on the proteomic analysis of formalin-fixed paraffin-embedded tissue.

Science.gov (United States)

Thompson, Seonaid M; Craven, Rachel A; Nirmalan, Niroshini J; Harnden, Patricia; Selby, Peter J; Banks, Rosamonde E

2013-04-01

Formalin-fixed paraffin-embedded (FFPE) tissue samples represent a tremendous potential resource for biomarker discovery, with large numbers of samples in hospital pathology departments and links to clinical information. However, the cross-linking of proteins and nucleic acids by formalin fixation has hampered analysis and proteomic studies have been restricted to using frozen tissue, which is more limited in availability as it needs to be collected specifically for research. This means that rare disease subtypes cannot be studied easily. Recently, improved extraction techniques have enabled analysis of FFPE tissue by a number of proteomic techniques. As with all clinical samples, pre-analytical factors are likely to impact on the results obtained, although overlooked in many studies. The aim of this review is to discuss the various pre-analytical factors, which include warm and cold ischaemic time, size of sample, fixation duration and temperature, tissue processing conditions, length of storage of archival tissue and storage conditions, and to review the studies that have considered these factors in more detail. In those areas where investigations are few or non-existent, illustrative examples of the possible importance of specific factors have been drawn from studies using frozen tissue or from immunohistochemical studies of FFPE tissue. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Normal tissue complication probability (NTCP), the clinician,s perspective

International Nuclear Information System (INIS)

Yeoh, E.K.

2011-01-01

Full text: 3D radiation treatment planning has enabled dose distributions to be related to the volume of normal tissues irradiated. The dose volume histograms thus derived have been utilized to set NTCP dose constraints to facilitate optimization of treatment planning. However, it is not widely appreciated that a number of important variables other than DYH's which determine NTCP in the individual patient. These variables will be discussed under the headings of patient and treatment related as well as tumour related factors. Patient related factors include age, co-morbidities such as connective tissue disease and diabetes mellitus, previous tissue/organ damage, tissue architectural organization (parallel or serial), regional tissue/organ and individual tissue/organ radiosensitivities as well as the development of severe acute toxicity. Treatment related variables which need to be considered include dose per fraction (if not the conventional 1.8012.00 Gy/fraction, particularly for IMRT), number of fractions and total dose, dose rate (particularly if combined with brachytherapy) and concurrent chemotherapy or other biological dose modifiers. Tumour related factors which impact on NTCP include infiltration of normal tissue/organ usually at presentation leading to compromised function but also with recurrent disease after radiation therapy as well as variable tumour radiosensitivities between and within tumour types. Whilst evaluation of DYH data is a useful guide in the choice of treatment plan, the current state of knowledge requires the clinician to make an educated judgement based on a consideration of the other factors.

Modifiable Coronary Heart Disease Risk Factors in the Population Aged 20-49 Years

Directory of Open Access Journals (Sweden)

Francisco Carlos Valladares Mas

2014-04-01

Full Text Available Background: evidence provided by the Framingham Heart Study established the critical role of risk factors in the development of coronary heart disease. Over half a century later, current detection and control are still inadequate. Objective: to identify modifiable risk factors of coronary heart disease in individuals aged 20 to 49 years. Methods: a descriptive, cross-sectional study was conducted in 276 individuals from the doctor’s office No. 1 of the Fabio di Celmo Community Teaching Polyclinic in Cienfuegos. Patients were examined in the clinic visit and/or whole family visit. The studied variables included age, sex, skin color, risk factors (excess weight/obesity, physical inactivity, smoking, hypertension, diabetes, dyslipidemia and psychosocial factors, which were obtained from the medical interview, physical examination, laboratory tests (total cholesterol and triglycerides and review of individual medical records and family history. Results: risk factors most frequently identified were excess weight/obesity (42.4 %, physical inactivity (34.4 % and smoking (20.3 %. Presence of these risk factors increased with age, showing differences in the distribution by sex and was associated with psychosocial factors. Their coexistence and progress with age was significant. Conclusion: prevalence of modifiable risk factors for coronary heart disease in a young population was high, with frequent association, predominating factors related to unhealthy lifestyles.

Recombinant nematode anticoagulant protein c2, an inhibitor of tissue factor/factor VIIa, attenuates coagulation and the interleukin-10 response in human endotoxemia

NARCIS (Netherlands)

de Pont, A. C. J. M.; Moons, A. H. M.; de Jonge, E.; Meijers, J. C. M.; Vlasuk, G. P.; Rote, W. E.; Büller, H. R.; van der Poll, T.; Levi, M. [=Marcel M.

2004-01-01

The tissue factor-factor (F)VIIa complex (TF/FVIIa) is responsible for the initiation of blood coagulation under both physiological and pathological conditions. Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of TF/FVIIa. mechanistically distinct from tissue factor

Modifiable Risk Factors and Interventions for Childhood Obesity Prevention within the First 1,000 Days.

Science.gov (United States)

Dattilo, Anne M

2017-01-01

Worldwide, the prevalence of childhood obesity has increased, amounting to 42 million overweight or obese children, and there is increasing evidence that the origins are within the first 1,000 days: the period of conception through 2 years. Antecedents of early childhood obesity are multifactorial, and associations of varying strength have been documented for genetic/epigenetic, biologic, dietary, environmental, social, and behavioral influences. Modifiable factors in pregnancy and early infancy associated with childhood obesity include maternal overweight/obesity, maternal smoking, gestational weight gain, infant and young child feeding, caregiver responsive feeding practices, as well as sleep duration, and physical activity. Promising obesity prevention interventions include those beginning during the first 1,000 days, using a multicomponent approach, with roots in nutrition education theories or behavior change communication that can continue over time. However, the limited number of completed interventions to date (within pediatric clinics or in home-based or community settings) may not be scalable to the magnitude needed for sustainable obesity prevention. Scale-up interventions that can be maintained for the durations needed, addressing infant and young child feeding and other modifiable risk factors associated with childhood obesity are needed. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

Monitoring of treatment with vitamin K antagonists: recombinant thromboplastins are more sensitive to factor VII than tissue-extract thromboplastins.

Science.gov (United States)

Biedermann, J S; van den Besselaar, A M H P; de Maat, M P M; Leebeek, F W G; Kruip, M J H A

2017-03-01

Essentials Differences in sensitivity to factor VII (FVII) have been suggested between thromboplastins. FVII-induced International Normalized Ratio (INR) changes differ between commercial reagents. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Thromboplastin choice may affect FVII-mediated INR stability. Background Differences regarding sensitivity to factor VII have been suggested for recombinant human and tissue-extract thromboplastins used for International Normalized Ratio (INR) measurement, but the evidence is scarce. Differences in FVII sensitivity are clinically relevant, as they can affect INR stability during treatment with vitamin K antagonists (VKAs). Objectives To determine whether commercial thromboplastins react differently to changes in FVII. Methods We studied the effect of addition of FVII on the INR in plasma by using three tissue-extract (Neoplastin C1+, Hepato Quick, and Thromborel S) and three recombinant human (Recombiplastin 2G, Innovin, and CoaguChek XS) thromboplastins. Three different concentrations of purified human FVII (0.006, 0.012 and 0.062 μg mL -1 plasma), or buffer, were added to five certified pooled plasmas of patients using VKAs (INR of 1.5-3.5). Changes in FVII activity were measured with two bioassays (Neoplastin and Recombiplastin), and relative INR changes were compared between reagents. Results After addition of 0.062 μg mL -1 FVII, FVII activity in the pooled plasmas increased by approximately 20% (Neoplastin) or 32% (Recombiplastin) relative to the activity in pooled normal plasma. All thromboplastins showed dose-dependent INR decreases. The relative INR change in the pooled plasmas significantly differed between the six thromboplastins. No differences were observed among recombinant or tissue-extract thromboplastins. Pooled results indicated that the FVII-induced INR change was greater for recombinant than for tissue-extract thromboplastins. Conclusions Differences

EAMJ Modifiable 10.indd

African Journals Online (AJOL)

2010-02-02

Feb 2, 2010 ... MODIFIABLE FACTORS ASSOCIATED WITH ACTIVE PULMONARY TUBERCULOSIS IN A KENYAN PRISON. A. S. Amwayi, MBChB, MSc., ... University of Agriculture and Technology, P.O. Box 62000- 0200, Nairobi, Kenya and E. M. Muchiri, MSc, PhD., Division ..... Diabetes and low BMI. 223452.81.

Driving factors behind carbon dioxide emissions in China: A modified production-theoretical decomposition analysis

International Nuclear Information System (INIS)

Wang, Qunwei; Chiu, Yung-Ho; Chiu, Ching-Ren

2015-01-01

Research on the driving factors behind carbon dioxide emission changes in China can inform better carbon emission reduction policies and help develop a low-carbon economy. As one of important methods, production-theoretical decomposition analysis (PDA) has been widely used to understand these driving factors. To avoid the infeasibility issue in solving the linear programming, this study proposed a modified PDA approach to decompose carbon dioxide emission changes into seven drivers. Using 2005–2010 data, the study found that economic development was the largest factor of increasing carbon dioxide emissions. The second factor was energy structure (reflecting potential carbon), and the third factor was low energy efficiency. Technological advances, energy intensity reductions, and carbon dioxide emission efficiency improvements were the negative driving factors reducing carbon dioxide emission growth rates. Carbon dioxide emissions and driving factors varied significantly across east, central and west China. - Highlights: • A modified PDA used to decompose carbon dioxide emission changes into seven drivers. • Two models were proposed to ameliorate the infeasible occasions. • Economic development was the largest factor of increasing CO_2 emissions in China.

Preparation and Evaluation of Dexamethasone (DEX/Growth and Differentiation Factor-5 (GDF-5 Surface-Modified Titanium Using β-Cyclodextrin-Conjugated Heparin (CD-Hep for Enhanced Osteogenic Activity In Vitro and In Vivo

Directory of Open Access Journals (Sweden)

Dae Hyeok Yang

2017-08-01

Full Text Available The most ideal implant models in the dental and orthopedic fields to minimize the failure rate of implantation involve the improvement of osseointegration with host bone. Therefore, a focus of this study is the preparation of surface-modified titanium (Ti samples of disc and screw types using dexamethasone (DEX and/or growth and differentiation factor-5 (GDF-5, as well as the evaluation of their efficacies on bone formation in vitro and in vivo. X-ray photoelectron spectroscopy (XPS, scanning electron microscopy (SEM and contact angle measurement were used to evaluate the surface chemical composition, surface morphology and wettability, respectively. The results showed that implant surfaces were successfully modified with DEX and/or GDF-5, and had rough surfaces along with hydrophilicity. DEX, GDF-5 or DEX/GDF-5 on the surface-modified samples were rapidly released within one day and released for 28 days in a sustained manner. The proliferation and bone formation of MC3T3-E1 cells cultured on pristine and surface-modified implants in vitro were examined by cell counting kit-8 (CCK-8 assay, as well as the measurements of alkaline phosphatase (ALP activity and calcium deposition, respectively. MC3T3-E1 cells cultured on DEX/GDF-5–Ti showed noticeable ALP activity and calcium deposition in vitro. Active bone formation and strong osseointegration occurred at the interface between DEX/GDF-5–Ti and host bone, as evaluated by micro computed-tomography (micro CT analysis. Surface modification using DEX/GDF-5 could be a good method for advanced implants for orthopaedic and dental applications.

Protein adsorption capability on polyurethane and modified-polyurethane membrane for periodontal guided tissue regeneration applications

Energy Technology Data Exchange (ETDEWEB)

Sheikh, Zeeshan [Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, 150 College Street, Toronto, ON M5S 3E2 (Canada); School of Engineering and Materials Science, Queen Mary, University of London, Mile End Rd, London, E1 4NS (United Kingdom); Khan, Abdul Samad, E-mail: draskhan@ciitlahore.edu.pk [Interdisciplinary Research Centre in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Roohpour, Nima [Oral Care R& D, GSK St., Georges Ave., Weybridge KT13 8PA (United Kingdom); Glogauer, Michael [Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, 150 College Street, Toronto, ON M5S 3E2 (Canada); Rehman, Ihtesham u [Department of Materials Science and Engineering, The Kroto Research Institute, North Campus, University of Sheffield, Broad Lane, Sheffield S3 7HQ (United Kingdom)

2016-11-01

Periodontal disease if left untreated can result in creation of defects within the alveolar ridge. Barrier membranes are frequently used with or without bone replacement graft materials for achieving periodontal guided tissue regeneration (GTR). Surface properties of barrier membranes play a vital role in their functionality and clinical success. In this study polyetherurethane (PEU) membranes were synthesized by using 4,4′-methylene-diphenyl diisocyanate (MDI), polytetramethylene oxide (PTMO) and 1,4-butane diol (BDO) as a chain extender via solution polymerization. Hydroxyl terminated polydimethylsiloxane (PDMS) due to having inherent surface orientation towards air was used for surface modification of PEU on one side of the membranes. This resulting membranes had one surface being PEU and the other being PDMS coated PEU. The prepared membranes were treated with solutions of bovine serum albumin (BSA) in de-ionized water at 37 °C at a pH of 7.2. The surface protein adsorptive potential of PEU membranes was observed using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), Raman spectroscopy and Confocal Raman spectroscopy. The contact angle measurement, tensile strength and modulus of prepared membranes were also evaluated. PEU membrane (89.86 ± 1.62°) exhibited less hydrophobic behavior than PEU-PDMS (105.87 ± 3.16°). The ultimate tensile strength and elastic modulus of PEU (27 ± 1 MPa and 14 ± 2 MPa) and PEU-PDMS (8 ± 1 MPa and 26 ± 1 MPa) membranes was in required range. The spectral analysis revealed adsorption of BSA proteins on the surface of non PDMS coated PEU surface. The PDMS modified PEU membranes demonstrated a lack of BSA adsorption. The non PDMS coated side of the membrane which adsorbs proteins could potentially be used facing towards the defect attracting growth factors for periodontal tissue regeneration. Whereas, the PDMS coated side could serve as an occlusive barrier for preventing gingival epithelial

Protein adsorption capability on polyurethane and modified-polyurethane membrane for periodontal guided tissue regeneration applications

International Nuclear Information System (INIS)

Sheikh, Zeeshan; Khan, Abdul Samad; Roohpour, Nima; Glogauer, Michael; Rehman, Ihtesham u

2016-01-01

Periodontal disease if left untreated can result in creation of defects within the alveolar ridge. Barrier membranes are frequently used with or without bone replacement graft materials for achieving periodontal guided tissue regeneration (GTR). Surface properties of barrier membranes play a vital role in their functionality and clinical success. In this study polyetherurethane (PEU) membranes were synthesized by using 4,4′-methylene-diphenyl diisocyanate (MDI), polytetramethylene oxide (PTMO) and 1,4-butane diol (BDO) as a chain extender via solution polymerization. Hydroxyl terminated polydimethylsiloxane (PDMS) due to having inherent surface orientation towards air was used for surface modification of PEU on one side of the membranes. This resulting membranes had one surface being PEU and the other being PDMS coated PEU. The prepared membranes were treated with solutions of bovine serum albumin (BSA) in de-ionized water at 37 °C at a pH of 7.2. The surface protein adsorptive potential of PEU membranes was observed using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), Raman spectroscopy and Confocal Raman spectroscopy. The contact angle measurement, tensile strength and modulus of prepared membranes were also evaluated. PEU membrane (89.86 ± 1.62°) exhibited less hydrophobic behavior than PEU-PDMS (105.87 ± 3.16°). The ultimate tensile strength and elastic modulus of PEU (27 ± 1 MPa and 14 ± 2 MPa) and PEU-PDMS (8 ± 1 MPa and 26 ± 1 MPa) membranes was in required range. The spectral analysis revealed adsorption of BSA proteins on the surface of non PDMS coated PEU surface. The PDMS modified PEU membranes demonstrated a lack of BSA adsorption. The non PDMS coated side of the membrane which adsorbs proteins could potentially be used facing towards the defect attracting growth factors for periodontal tissue regeneration. Whereas, the PDMS coated side could serve as an occlusive barrier for preventing gingival epithelial

Modifiable Resilience Factors to Childhood Adversity for Clinical Pediatric Practice.

Science.gov (United States)

Traub, Flora; Boynton-Jarrett, Renée

2017-05-01

Childhood adversity is highly prevalent and associated with risk for poor health outcomes in childhood and throughout the life course. Empirical literature on resilience over the past 40 years has identified protective factors for traumatized children that improve health outcomes. Despite these empirical investigations of resilience, there is limited integration of these findings into proactive strategies to mitigate the impact of adverse childhood experiences. We review the state of resilience research, with a focus on recent work, as it pertains to protecting children from the health impacts of early adversity. We identify and document evidence for 5 modifiable resilience factors to improve children's long- and short-term health outcomes, including fostering positive appraisal styles in children and bolstering executive function, improving parenting, supporting maternal mental health, teaching parents the importance of good self-care skills and consistent household routines, and offering anticipatory guidance about the impact of trauma on children. We conclude with 10 recommendations for pediatric practitioners to leverage the identified modifiable resilience factors to help children withstand, adapt to, and recover from adversity. Taken together, these recommendations constitute a blueprint for a trauma-informed medical home. Building resilience in pediatric patients offers an opportunity to improve the health and well-being of the next generation, enhance national productivity, and reduce spending on health care for chronic diseases. Copyright © 2017 by the American Academy of Pediatrics.

Connective tissue growth factor immunohistochemical expression is associated with gallbladder cancer progression.

Science.gov (United States)

Garcia, Patricia; Leal, Pamela; Alvarez, Hector; Brebi, Priscilla; Ili, Carmen; Tapia, Oscar; Roa, Juan C

2013-02-01

Gallbladder cancer (GBC) is an aggressive neoplasia associated with late diagnosis, unsatisfactory treatment, and poor prognosis. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. Connective tissue growth factor (CTGF) is thought to play a role in the pathologic processes and is overexpressed in several human cancers, including GBC. No information is available about CTGF expression in early stages of gallbladder carcinogenesis. Objective.- To evaluate the expression level of CTGF in benign and malignant lesions of gallbladder and its correlation with clinicopathologic features and GBC prognosis. Connective tissue growth factor protein was examined by immunohistochemistry on tissue microarrays containing tissue samples of chronic cholecystitis (n = 51), dysplasia (n = 15), and GBC (n = 169). The samples were scored according to intensity of staining as low/absent and high CTGF expressers. Statistical analysis was performed using the χ(2) test or Fisher exact probability test with a significance level of P Connective tissue growth factor expression showed a progressive increase from chronic cholecystitis to dysplasia and then to early and advanced carcinoma. Immunohistochemical expression (score ≥2) was significantly higher in advanced tumors, in comparison with chronic cholecystitis (P < .001) and dysplasia (P = .03). High levels of CTGF expression correlated with better survival (P = .04). Our results suggest a role for CTGF in GBC progression and a positive association with better prognosis. In addition, they underscore the importance of considering the involvement of inflammation on GBC development.

Activation of SF1 Neurons in the Ventromedial Hypothalamus by DREADD Technology Increases Insulin Sensitivity in Peripheral Tissues.

Science.gov (United States)

Coutinho, Eulalia A; Okamoto, Shiki; Ishikawa, Ayako Wendy; Yokota, Shigefumi; Wada, Nobuhiro; Hirabayashi, Takahiro; Saito, Kumiko; Sato, Tatsuya; Takagi, Kazuyo; Wang, Chen-Chi; Kobayashi, Kenta; Ogawa, Yoshihiro; Shioda, Seiji; Yoshimura, Yumiko; Minokoshi, Yasuhiko

2017-09-01

The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, and this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology. Activation of SF1 neurons by an intraperitoneal injection of clozapine- N -oxide (CNO), a specific hM3Dq ligand, reduced food intake and increased energy expenditure in mice expressing hM3Dq in SF1 neurons. It also increased whole-body glucose utilization and glucose uptake in red-type skeletal muscle, heart, and interscapular brown adipose tissue, as well as glucose production and glycogen phosphorylase a activity in the liver, thereby maintaining blood glucose levels. During hyperinsulinemic-euglycemic clamp, such activation of SF1 neurons increased insulin-induced glucose uptake in the same peripheral tissues and tended to enhance insulin-induced suppression of glucose production by suppressing gluconeogenic gene expression and glycogen phosphorylase a activity in the liver. DREADD technology is thus an important tool for studies of the role of the brain in the regulation of insulin sensitivity in peripheral tissues. © 2017 by the American Diabetes Association.

Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)

DEFF Research Database (Denmark)

Erlandsson, Maria; Nielsen, Carsten Haagen; Jeppesen, Troels Elmer

2015-01-01

Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example......, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an 18F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[18F]fluorobenzoate, and the [18F]ASIS was purified on a PD-10 desalting...... column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [18F]ASIS to TF and to a specific anti-factor VII...

The role of metformin and resveratrol in the prevention of hypoxia-inducible factor 1α accumulation and fibrosis in hypoxic adipose tissue.

Science.gov (United States)

Li, Xiaole; Li, Jia; Wang, Lulu; Li, Aiyun; Qiu, Zhixia; Qi, Lian-Wen; Kou, Junping; Liu, Kang; Liu, Baolin; Huang, Fang

2016-06-01

Hypoxic activation of hypoxia-inducible factor 1α (HIF-1α) and fibrosis in adipose tissue contribute to adipose dysfunction. This study was designed to investigate the effects of metformin and resveratrol on the regulation of HIF-1α and fibrosis in hypoxic adipose tissue. Mice were fed a high-fat diet to induce hypoxia and fibrosis in adipose tissue; adipose tissue incubated in vitro in 1% O2 showed a similar change. The effects of metformin and resveratrol on hypoxia, HIF-1α accumulation, endoplasmic reticulum stress and gene expressions of extracellular matrix components and pro-inflammatory cytokines were examined. Oral administration of metformin or resveratrol prevented hypoxia and reduced HIF-1α accumulation with dephosphorylation of inositol-requiring enzyme 1α and eukaryotic initiation factor 2α, indicative of suppression of hypoxic HIF-1α activation and endoplasmic reticulum stress. Metformin and resveratrol down-regulated gene expressions of Col3α, Col6α, elastin and lysyl oxidase and thereby reduced collagen deposition in adipose tissue. The increased gene expressions of TNF-α, IL-6, monocyte chemoattractant protein 1 and F4/80 were also down-regulated by metformin and resveratrol. Metformin and resveratrol had similar effects in adipose tissue exposed to 1% O2 . Metformin reduced ATP production and prevented the reduction in oxygen tension in 3T3-L1 cells, suggesting that it prevented hypoxia by limiting oxygen consumption, whereas resveratrol reduced HIF-1α accumulation by promoting its proteasomal degradation via the regulation of AMPK/SIRT1. Hypoxia and fibrosis are early causes of adipose dysfunction in obesity. Both metformin and resveratrol effectively inhibited HIF-1α activation-induced fibrosis and inflammation in adipose tissue, although by different mechanisms. © 2016 The British Pharmacological Society.

Neoadjuvant chemoradiation (modified Eilber protocol) versus adjuvant radiotherapy in the treatment of extremity soft tissue sarcoma

International Nuclear Information System (INIS)

Lehane, Chris; Parasyn, Andrew; Ho, Frederick; Thompson, Stephen R.; Smee, Robert; Links, David; Crowe, Phil; Lewis, Craig; Friedlander, Michael; Williams, Janet

2016-01-01

Local control for extremity soft tissue sarcomas (STS) requires surgery combined with radiotherapy, usually given pre-operatively or post-operatively. The modified Eilber protocol, a neoadjuvant chemoradiation regimen, has been reported with excellent local control rates. This retrospective single-centre study compared outcomes for patients treated with the modified Eilber protocol with those treated with standard adjuvant radiotherapy. Twenty-nine patients were treated with modified Eilber protocol. Thirty-four patients received adjuvant radiotherapy. Three patients (10%) in the Eilber group and five patients (15%) in the Adjuvant group developed local recurrence (P = 0.87). Major acute wound complications were noted in four patients in each group (P = 0.55). One patient (3.4%) in the Eilber group developed Grade 3 or 4 late toxicities after 1 year compared with nine patients (27%) in the Adjuvant group (P = 0.02). Patients with a diagnosis of extremity STS were retrospectively reviewed from the Prince of Wales Hospital Sarcoma Database from 1995 to 2012. Sixty-three patients underwent curative surgery with either neoadjuvant Eilber chemoradiotherapy (Eilber) or adjuvant radiotherapy (Adjuvant). Neoadjuvant chemoradiation (Eilber protocol) provided similar rates of local control when compared with adjuvant radiotherapy. Acute wound complication rates were similar but there was less severe late toxicity in the Eilber group.

Potentially modifiable lifestyle factors, cognitive reserve, and cognitive function in later life: A cross-sectional study.

Directory of Open Access Journals (Sweden)

Linda Clare

2017-03-01

Full Text Available Potentially modifiable lifestyle factors may influence cognitive health in later life and offer potential to reduce the risk of cognitive decline and dementia. The concept of cognitive reserve has been proposed as a mechanism to explain individual differences in rates of cognitive decline, but its potential role as a mediating pathway has seldom been explored using data from large epidemiological studies. We explored the mediating effect of cognitive reserve on the cross-sectional association between lifestyle factors and cognitive function in later life using data from a population-based cohort of healthy older people.We analysed data from 2,315 cognitively healthy participants aged 65 y and over in the Cognitive Function and Ageing Study Wales (CFAS-Wales cohort collected in 2011-2013. Linear regression modelling was used to investigate the overall associations between five lifestyle factors-cognitive and social activity, physical activity, diet, alcohol consumption, and smoking-and cognition, adjusting for demographic factors and chronic conditions. Mediation analysis tested for indirect effects of the lifestyle factors on cognition via cognitive reserve. After controlling for age, gender, and the presence of chronic conditions, cognitive and social activity, physical activity, healthy diet, and light-to-moderate alcohol consumption were positively associated with cognitive function, together accounting for 20% (95% CI 17%-23% of variance in cognitive test scores. Cognitive reserve was an important mediator of this association, with indirect effects via cognitive reserve contributing 21% (95% CI 15%-27% of the overall effect on cognition. The main limitations of the study derive from the cross-sectional nature of the data and the challenges of accurately measuring the latent construct of cognitive reserve.Cross-sectional associations support the view that enhancing cognitive reserve may benefit cognition, and maintenance of cognitive health

Role of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in psychological stress and depression

OpenAIRE

Tsai, Shih-Jen

2017-01-01

Major depressive disorder is a common illness worldwide, but the pathogenesis of the disorder remains incompletely understood. The tissue-type plasminogen activator-plasminogen proteolytic cascade is highly expressed in the brain regions involved in mood regulation and neuroplasticity. Accumulating evidence from animal and human studies suggests that tissue-type plasminogen activator and its chief inhibitor, plasminogen activator inhibitor-1, are related to stress reaction and depression. Fur...

Application of Collagen Scaffold in Tissue Engineering: Recent Advances and New Perspectives

Directory of Open Access Journals (Sweden)

Chanjuan Dong

2016-02-01

Full Text Available Collagen is the main structural protein of most hard and soft tissues in animals and the human body, which plays an important role in maintaining the biological and structural integrity of the extracellular matrix (ECM and provides physical support to tissues. Collagen can be extracted and purified from a variety of sources and offers low immunogenicity, a porous structure, good permeability, biocompatibility and biodegradability. Collagen scaffolds have been widely used in tissue engineering due to these excellent properties. However, the poor mechanical property of collagen scaffolds limits their applications to some extent. To overcome this shortcoming, collagen scaffolds can be cross-linked by chemical or physical methods or modified with natural/synthetic polymers or inorganic materials. Biochemical factors can also be introduced to the scaffold to further improve its biological activity. This review will summarize the structure and biological characteristics of collagen and introduce the preparation methods and modification strategies of collagen scaffolds. The typical application of a collagen scaffold in tissue engineering (including nerve, bone, cartilage, tendon, ligament, blood vessel and skin will be further provided. The prospects and challenges about their future research and application will also be pointed out.

Tissue Factor–Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes

OpenAIRE

Koizume, Shiro; Miyagi, Yohei

2015-01-01

Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are...

The influence of tethered epidermal growth factor on connective tissue progenitor colony formation

OpenAIRE

Marcantonio, Nicholas A.; Boehm, Cynthia A.; Rozic, Richard J.; Au, Ada; Wells, Alan; Muschler, George F.; Griffith, Linda G.

2009-01-01

Strategies to combine aspirated marrow cells with scaffolds to treat connective tissue defects are gaining increasing clinical attention and use. In situations such as large defects where initial survival and proliferation of transplanted connective tissue progenitors (CTPs) are limiting, therapeutic outcomes might be improved by using the scaffold to deliver growth factors that promote the early stages of cell function in the graft. Signaling by the epidermal growth factor receptor (EGFR) pl...

Antimony (SbIII) reduces growth, declines photosynthesis, and modifies leaf tissue anatomy in sunflower (Helianthus annuus L.).

Science.gov (United States)

Vaculík, Marek; Mrázová, Anna; Lux, Alexander

2015-12-01

The role of antimony (Sb)--a non-essential trace metalloid--in physiological processes running in crops is still poorly understood. Present paper describes the effect of Sb tartrate (SbIII) on growth, Sb uptake, photosynthesis, photosynthetic pigments, and leaf tissue organization in young sunflower plants grown in hydroponics. We found that growth of below- and aboveground part was reduced with increasing concentration of Sb in the medium. Although Sb was mostly taken up by sunflower roots and only small part (1-2%) was translocated to the shoots, decline in photosynthesis, transpiration, and decreased content of photosynthetic pigments were observed. This indicates that despite relatively low mobility of Sb in root-shoot system, Sb in shoot noticeably modifies physiological status and reduced plant growth. Additionally, leaf anatomical changes indicated that Sb reduced the size of intercellular spaces and made leaf tissue more compact.

Trefoil factors in saliva and gingival tissues of patients with chronic periodontitis

DEFF Research Database (Denmark)

Chaiyarit, Ponlatham; Chayasadom, Anek; Wara-Aswapati, Nawarat

2012-01-01

BACKGROUND: Trefoil factors (TFFs) are secreted molecules that are involved in cytoprotection against tissue damage and the immune response. TFFs have been detected in saliva and oral tissues, but their clinical significance has never been investigated in patients with chronic periodontitis....... The objective of this study is to determine whether TFF expression in saliva and gingival tissues is associated with periodontal pathology. METHODS: Saliva and gingival tissue samples were collected from 25 non-periodontitis individuals and 25 patients with chronic periodontitis (CP). Enzyme...... observed in patients with CP (P = 0.003 and P periodontal pathology and number of Porphyromonas gingivalis...

Macroporous modified poly (vinyl alcohol) hydrogels with charged groups for tissue engineering: Preparation and in vitro evaluation

Energy Technology Data Exchange (ETDEWEB)

Drozdova, Maria G., E-mail: drozdovamg@gmail.com [Polymers for Biology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, Moscow 117997 (Russian Federation); Zaytseva-Zotova, Daria S. [Polymers for Biology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, Moscow 117997 (Russian Federation); Akasov, Roman A. [Polymers for Biology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, Moscow 117997 (Russian Federation); Sechenov First Moscow State Medical University, Institute for Regenerative Medicine, Trubetskaya str., 8/2, Moscow 119048 (Russian Federation); Golunova, Anna S.; Artyukhov, Alexander A. [D. Mendeleyev University of Chemical Technology of Russia, Miusskaya Square 9, Moscow 125047 (Russian Federation); Udartseva, Olga O.; Andreeva, Elena R. [Institute of Biomedical Problems of Russian Academy of Sciences, Khoroshevskoe Shosse 76a, Moscow 123007 (Russian Federation); Lisovyy, Denis E.; Shtilman, Michael I. [D. Mendeleyev University of Chemical Technology of Russia, Miusskaya Square 9, Moscow 125047 (Russian Federation); Markvicheva, Elena A. [Polymers for Biology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, Moscow 117997 (Russian Federation)

2017-06-01

Poly(vinyl alcohol) (PVA) hydrogels are widely employed for various biomedical applications, including tissue engineering, due to their biocompatibility, high water solubility, low protein adsorption, and chemical stability. However, non-charged surface of PVA-based hydrogels is not optimal for cell adhesion and spreading. Here, cross-linked macroporous hydrogels based on low molecular weight acrylated PVA (Acr-PVA) was synthesized by modification of the pendant alcohol groups on the PVA with glycidyl methacrylate (GMA). To enhance cell affinity, charged groups were introduced to the hydrogel composition. For this purpose, Acr-PVA was copolymerized with either negatively charged acrylic acid (AA) or positively charged 2-(diethylamino) ethyl methacrylate (DEAEMA) monomers. A surface charge of the obtained hydrogels was found to be in function of the co-monomer type and content. Confocal microscopy observations confirmed that adhesion and spreading of both mouse fibroblasts (L929) and human mesenchymal stem cells (hMSC) on the modified Acr-PVA-AA and Acr-PVA-DEAEMA hydrogels were better than those on the non-modified Acr-PVA hydrogel. The increase of DEAEMA monomer content from 5 to 15 mol% resulted in the enhancement of cell viability which was 1.5-fold higher for Acr-PVA-DEAEMA-15 hydrogel than that of the non-modified Acr-PVA hydrogel sample. - Highlights: • To enhance cell affinity, acrylated PVA hydrogel was modified with AA or DEAEMA monomers. • Cell adhesion and spreading were found to depend on the co-monomer type and content. • Proliferation of L929 fibroblasts and stem cells increased on the modified hydrogels.

Macroporous modified poly (vinyl alcohol) hydrogels with charged groups for tissue engineering: Preparation and in vitro evaluation

International Nuclear Information System (INIS)

Drozdova, Maria G.; Zaytseva-Zotova, Daria S.; Akasov, Roman A.; Golunova, Anna S.; Artyukhov, Alexander A.; Udartseva, Olga O.; Andreeva, Elena R.; Lisovyy, Denis E.; Shtilman, Michael I.; Markvicheva, Elena A.

2017-01-01

Poly(vinyl alcohol) (PVA) hydrogels are widely employed for various biomedical applications, including tissue engineering, due to their biocompatibility, high water solubility, low protein adsorption, and chemical stability. However, non-charged surface of PVA-based hydrogels is not optimal for cell adhesion and spreading. Here, cross-linked macroporous hydrogels based on low molecular weight acrylated PVA (Acr-PVA) was synthesized by modification of the pendant alcohol groups on the PVA with glycidyl methacrylate (GMA). To enhance cell affinity, charged groups were introduced to the hydrogel composition. For this purpose, Acr-PVA was copolymerized with either negatively charged acrylic acid (AA) or positively charged 2-(diethylamino) ethyl methacrylate (DEAEMA) monomers. A surface charge of the obtained hydrogels was found to be in function of the co-monomer type and content. Confocal microscopy observations confirmed that adhesion and spreading of both mouse fibroblasts (L929) and human mesenchymal stem cells (hMSC) on the modified Acr-PVA-AA and Acr-PVA-DEAEMA hydrogels were better than those on the non-modified Acr-PVA hydrogel. The increase of DEAEMA monomer content from 5 to 15 mol% resulted in the enhancement of cell viability which was 1.5-fold higher for Acr-PVA-DEAEMA-15 hydrogel than that of the non-modified Acr-PVA hydrogel sample. - Highlights: • To enhance cell affinity, acrylated PVA hydrogel was modified with AA or DEAEMA monomers. • Cell adhesion and spreading were found to depend on the co-monomer type and content. • Proliferation of L929 fibroblasts and stem cells increased on the modified hydrogels.

Synergistic and additive effects of hydrostatic pressure and growth factors on tissue formation.

Directory of Open Access Journals (Sweden)

Benjamin D Elder

2008-06-01

Full Text Available Hydrostatic pressure (HP is a significant factor in the function of many tissues, including cartilage, knee meniscus, temporomandibular joint disc, intervertebral disc, bone, bladder, and vasculature. Though studies have been performed in assessing the role of HP in tissue biochemistry, to the best of our knowledge, no studies have demonstrated enhanced mechanical properties from HP application in any tissue.The objective of this study was to determine the effects of hydrostatic pressure (HP, with and without growth factors, on the biomechanical and biochemical properties of engineered articular cartilage constructs, using a two-phased approach. In phase I, a 3x3 full-factorial design of HP magnitude (1, 5, 10 MPa and frequency (0, 0.1, 1 Hz was used, and the best two treatments were selected for use in phase II. Static HP at 5 MPa and 10 MPa resulted in significant 95% and 96% increases, respectively, in aggregate modulus (H(A, with corresponding increases in GAG content. These regimens also resulted in significant 101% and 92% increases in Young's modulus (E(Y, with corresponding increases in collagen content. Phase II employed a 3x3 full-factorial design of HP (no HP, 5 MPa static, 10 MPa static and growth factor application (no GF, BMP-2+IGF-I, TGF-beta1. The combination of 10 MPa static HP and TGF-beta1 treatment had an additive effect on both H(A and E(Y, as well as a synergistic effect on collagen content. This group demonstrated a 164% increase in H(A, a 231% increase in E(Y, an 85% increase in GAG/wet weight (WW, and a 173% increase in collagen/WW, relative to control.To our knowledge, this is the first study to demonstrate increases in the biomechanical properties of tissue from pure HP application, using a cartilage model. Furthermore, it is the only study to demonstrate additive or synergistic effects between HP and growth factors on tissue functional properties. These findings are exciting as coupling HP stimulation with growth

Combinatorial regulation of tissue specification by GATA and FOG factors

Science.gov (United States)

Chlon, Timothy M.; Crispino, John D.

2012-01-01

The development of complex organisms requires the formation of diverse cell types from common stem and progenitor cells. GATA family transcriptional regulators and their dedicated co-factors, termed Friend of GATA (FOG) proteins, control cell fate and differentiation in multiple tissue types from Drosophila to man. FOGs can both facilitate and antagonize GATA factor transcriptional regulation depending on the factor, cell, and even the specific gene target. In this review, we highlight recent studies that have elucidated mechanisms by which FOGs regulate GATA factor function and discuss how these factors use these diverse modes of gene regulation to control cell lineage specification throughout metazoans. PMID:23048181

Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation.

LENUS (Irish Health Repository)

Ni Ainle, Fionnuala

2009-08-20

Protamine sulfate is a positively charged polypeptide widely used to reverse heparin-induced anticoagulation. Paradoxically, prospective randomized trials have shown that protamine administration for heparin neutralization is associated with increased bleeding, particularly after cardiothoracic surgery with cardiopulmonary bypass. The molecular mechanism(s) through which protamine mediates this anticoagulant effect has not been defined. In vivo administration of pharmacologic doses of protamine to BALB\\/c mice significantly reduced plasma thrombin generation and prolonged tail-bleeding time (from 120 to 199 seconds). Similarly, in pooled normal human plasma, protamine caused significant dose-dependent prolongations of both prothrombin time and activated partial thromboplastin time. Protamine also markedly attenuated tissue factor-initiated thrombin generation in human plasma, causing a significant decrease in endogenous thrombin potential (41% +\\/- 7%). As expected, low-dose protamine effectively reversed the anticoagulant activity of unfractionated heparin in plasma. However, elevated protamine concentrations were associated with progressive dose-dependent reduction in thrombin generation. To assess the mechanism by which protamine mediates down-regulation of thrombin generation, the effect of protamine on factor V activation was assessed. Protamine was found to significantly reduce the rate of factor V activation by both thrombin and factor Xa. Protamine mediates its anticoagulant activity in plasma by down-regulation of thrombin generation via a novel mechanism, specifically inhibition of factor V activation.

Effect of Modifying Factors on Radiosensitive Biochemical Reactions

Energy Technology Data Exchange (ETDEWEB)

Romantsev, E. F.; Filippovich, I. V.; Zhulanova, Z. I.; Blokhina, V. D.; Trebenok, Z. A.; Kolesnikov, E. E.; Sheremetyevskaya, T. N.; Nikolsky, A. V.; Zymaleva, O. G. [Institute of Biophysics, USSR Ministry of Health, Moscow, USSR (Russian Federation)

1971-03-15

Some of the radioprotective aminothiols are now routine pharmacopoeial drugs and are used in clinics to decrease the radiation reaction which appears as a side effect during the radiotherapy of cancer. The action of effective modifying agents on radiosensitive biochemical reactions in the organisms of mammals, in principle, cannot be different from the same effects of the protectors on biochemical systems of the human organism. The effect of modifying agents is mediated by biochemical systems. The administration of radioprotective doses of MEA to rats before irradiation results in a significant normalization of the excretion in urine of degradation products of nucleic acids (so-called Dische-positive compounds), the excretion of which sharply rises after irradiation. The curve of the radioprotective effect of MEA (survival rate after administration of radioprotectors at different intervals of time) completely corresponds to curves of the accumulation of MEA which is bound (by mixed disulphide links) to the proteins of liver mitochondria, to proteins of the nuclear-sap, to the hyaloplasm of rat thymus and to the nuclear ribosomes of the spleen. After MEA administration the curve of the biosynthesis of deoxycytidine represents a mirror reflection of the curve of MEA bound to proteins of the thymus hyaloplasm by means of mixed disulphide links. The mechanism of action of such modifying factors as MEA in experiments on mammals is mediated to a great degree through the temporary formation of mixed disulphide links between the aminothiol and the protein component of enzymes in different biochemical systems. (author)

Validity and reliability of a modified english version of the physical activity questionnaire for adolescents.

Science.gov (United States)

Aggio, Daniel; Fairclough, Stuart; Knowles, Zoe; Graves, Lee

2016-01-01

Adaptation of physical activity self-report questionnaires is sometimes required to reflect the activity behaviours of diverse populations. The processes used to modify self-report questionnaires though are typically underreported. This two-phased study used a formative approach to investigate the validity and reliability of the Physical Activity Questionnaire for Adolescents (PAQ-A) in English youth. Phase one examined test content and response process validity and subsequently informed a modified version of the PAQ-A. Phase two assessed the validity and reliability of the modified PAQ-A. In phase one, focus groups (n = 5) were conducted with adolescents (n = 20) to investigate test content and response processes of the original PAQ-A. Based on evidence gathered in phase one, a modified version of the questionnaire was administered to participants (n = 169, 14.5 ± 1.7 years) in phase two. Internal consistency and test-retest reliability were assessed using Cronbach's alpha and intra-class correlations, respectively. Spearman correlations were used to assess associations between modified PAQ-A scores and accelerometer-derived physical activity, self-reported fitness and physical activity self-efficacy. Phase one revealed that the original PAQ-A was unrepresentative for English youth and that item comprehension varied. Contextual and population/cultural-specific modifications were made to the PAQ-A for use in the subsequent phase. In phase two, modified PAQ-A scores had acceptable internal consistency (α = 0.72) and test-retest reliability (ICC = 0.78). Modified PAQ-A scores were significantly associated with objectively assessed moderate-to-vigorous physical activity (r = 0.39), total physical activity (r = 0.42), self-reported fitness (r = 0.35), and physical activity self-efficacy (r = 0.32) (p ≤ 0.01). The modified PAQ-A had acceptable internal consistency and test-retest reliability. Modified PAQ-A scores

Antimicrobial activity of different tissues of snakehead fish Channa striatus (Bloch

Directory of Open Access Journals (Sweden)

Pravin Kumar N

2012-05-01

Full Text Available Objective: The aim of this study was to identify the presence of antimicrobial activity in different organs/tissues (gills, blood, skin, liver, intestine, kidney, tissue and ovary extract of snakehead fish Channa striatus. Methods: A total of 48 fractions from the organs and tissue extracts were obtained by solid-phase extraction and the fractions were assayed for antimicrobial activity. The screening of antimicrobial activity for all the fractions were tested against 8 human pathogens including Gram positive (Methicillin-resistant Staphylococcus aureus (MRSA, Staphylococcus aureus, Bacillus cereus and Gram negative bacteria (Salmonella enteritidis, Shigella flexneri, Acinetobacter baumanni, Escherichia coli, Klebsiella pneumoniae using the British Society for Antimicrobial Chemotherapy (BSAC standardized disc susceptibility test method. The activity was measured in terms of zone of inhibition in mm. Results: The results indicated that, among the 8 organs/tissues tested only blood and gills extract fractions (40 and 60 % ACN fraction showed inhibition against Escherichia coli and 60 % ACN fraction of gill extract showed inhibition against Salmonella enteritidis. Protein profile analysis by SDS-PAGE showed that antimicrobial activity of the partially purified blood and gill tissue extracts might be due to low molecular weight peptides. Conclusions: The present study showed that, gill and blood extracts of Channa striatus can be a potential source of an antimicrobial protein for specific human pathogens.

Morphology of the Interstitial Tissue of Active and Resting Testis of the Guinea Fowl

OpenAIRE

Dharani, Palanisamy; Kumary, S. Usha; Sundaram, Venkatesan; Joseph, Cecilia; Ramesh, Geetha

2017-01-01

SUMMARY: The morphology of the interstitial tissue of sexually active and resting testis of the guinea fowl were studied. Six adult health birds of active and resting phases of reproductive cycle were used for this study. The interstitial tissue consisted of loose connective tissue, interstitial cells (Leydig cells), few connective cells, blood vessels and adrenergic nerve fibres in the present study in both active and resting testes. The interstitial tissue was compact in sexually active tes...

Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial.

Science.gov (United States)

Scott, David L; Ibrahim, Fowzia; Farewell, Vern; O'Keeffe, Aidan G; Walker, David; Kelly, Clive; Birrell, Fraser; Chakravarty, Kuntal; Maddison, Peter; Heslin, Margaret; Patel, Anita; Kingsley, Gabrielle H

2015-03-13

To determine whether intensive combinations of synthetic disease modifying drugs can achieve similar clinical benefits at lower costs to high cost biologics such as tumour necrosis factor inhibitors in patients with active rheumatoid arthritis resistant to initial methotrexate and other synthetic disease modifying drugs. Open label pragmatic randomised multicentre two arm non-inferiority trial over 12 months. 24 rheumatology clinics in England. Patients with rheumatoid arthritis who were eligible for treatment with tumour necrosis factor inhibitors according to current English guidance were randomised to either the tumour necrosis factor inhibitor strategy or the combined disease modifying drug strategy. Biologic strategy: start tumour necrosis factor inhibitor; second biologic in six month for non-responders. Alternative strategy: start combination of disease modifying drugs; start tumour necrosis factor inhibitors after six months in non-responders. reduction in disability at 12 months measured with patient recorded heath assessment questionnaire (range 0.00-3.00) with a 0.22 non-inferiority margin for combination treatment versus the biologic strategy. quality of life, joint damage, disease activity, adverse events, and costs. Intention to treat analysis used multiple imputation methods for missing data. 432 patients were screened: 107 were randomised to tumour necrosis factor inhibitors and 101 started taking; 107 were randomised to the combined drug strategy and 104 started taking the drugs. Initial assessments were similar; 16 patients were lost to follow-up (seven with the tumour necrosis factor inhibitor strategy, nine with the combined drug strategy); 42 discontinued the intervention but were followed-up (19 and 23, respectively). The primary outcome showed mean falls in scores on the health assessment questionnaire of -0.30 with the tumour necrosis factor inhibitor strategy and -0.45 with the alternative combined drug strategy. The difference between

Factors influencing hydroquinone degradation in aqueous solution using a modified microelectrolysis method.

Science.gov (United States)

Li, Tong; Li, Tingting; Xiong, Houfeng; Zou, Donglei

2015-01-01

The discharge of hydroquinone (HQ), an important chemical raw material, to natural waters poses different ecological threats to aquatic organisms. In this study, we investigated the removal performance of traditional and modified microelectrolysis methods in aqueous solutions. The traditional microelectrolysis packing was modified by adding manganese (Mn), zinc (Zn), and copper (Cu) powder as additives. The factors affecting the removal performance of HQ, such as catalytic metal type, mass fraction of additive, reaction time, and initial pH, were examined. The results showed that the Mn modified packing exhibited the best performance compared to Zn and Cu powder. The removal rate of HQ using Mn modified packing can reach 94% after 4 h. In addition, 9% of Mn packing has a higher removal rate than other mass fractions. The acidic solution pH shows a more favorable degradation than a neutral and alkaline solution. The intermediates of HQ degradation by modified microelectrolysis were identified and then the pathway of HQ degradation was proposed. Our result indicates that Mn as catalytic metal holds promising potential to enhance HQ removal in water using the microelectrolysis method.

Overview of Twenty Years of Radiation and Tissue Banking Activity in Argentina

International Nuclear Information System (INIS)

Kairiyama, E.

2015-01-01

Radiation sterilization of human tissues in Argentina was a consequence of health care products sterilization by gamma radiation. Radiation technology was implemented in 1970 when the first multipurpose gamma facility was built at the Ezeiza Atomic Centre of CNEA. Organ and tissue transplantation is a well established effective therapy that saves lives and significantly improves the quality of life. Ionizing radiation is used for sterilization in order to provide clinically safe tissue for therapeutic purposes of implantation in every patient in need. Argentina radiation and tissue banking activity started in 1993 with the establishment of two tissue banks using radiation under the IAEA programme of technical cooperation, a skin bank and a bone one. Additionally to this start, other tissue banks have adopted tissue sterilization by irradiation. The compatible tissues sterilized with this methodology are mainly skin (frozen, glycerolized), bone (lyophilized, frozen), and amniotic membrane (glycerolized, frozen, dehydrated). The donation and transplant of human organ, tissue and cells is regulated and coordinated by the National Institute Unique Central Coordinator of Ablation and Implant (INCUCAI). In regards to radiation and nuclear safety, physical protection and nuclear non-proliferation issues are regulated and contorted by the Nuclear Regulatory Authority (ARN). Eight tissue banks use gamma radiation for sterilization of human tissues (6 musculoskeletal, 1 skin and 1 amniotic membrane). Argentina has participated actively in several IAEA projects regarding radiation and tissue banking program, and it has been selected by the IAEA to host the Regional Training Centre for the Latin American region. The following activities were implemented: regional training courses in Buenos Aires, face to face (five) and virtual (four) modalities; collaboration on several materials related to tissue banking and radiation sterilization of tissue allograft, codes of practice for

Efficacy of Chinese herbal medicine for stroke modifiable risk factors: a systematic review.

Science.gov (United States)

Peng, Wenbo; Lauche, Romy; Ferguson, Caleb; Frawley, Jane; Adams, Jon; Sibbritt, David

2017-01-01

The vast majority of stroke burden is attributable to its modifiable risk factors. This paper aimed to systematically summarise the evidence of Chinese herbal medicine (CHM) interventions on stroke modifiable risk factors for stroke prevention. A literature search was conducted via the MEDLINE, CINAHL/EBSCO, SCOPUS, and Cochrane Database from 1996 to 2016. Randomised controlled trials or cross-over studies were included. Risk of bias was assessed according to the Cochrane Risk of Bias tool. A total of 46 trials (6895 participants) were identified regarding the use of CHM interventions in the management of stroke risk factors, including 12 trials for hypertension, 10 trials for diabetes, eight trials for hyperlipidemia, seven trials for impaired glucose tolerance, three trials for obesity, and six trials for combined risk factors. Amongst the included trials with diverse study design, an intervention of CHM as a supplement to biomedicine and/or a lifestyle intervention was found to be more effective in lowering blood pressure, decreasing blood glucose level, helping impaired glucose tolerance reverse to normal, and/or reducing body weight compared to CHM monotherapy. While no trial reported deaths amongst the CHM groups, some papers do report moderate adverse effects associated with CHM use. However, the findings of such beneficial effects of CHM should be interpreted with caution due to the heterogeneous set of complex CHM studied, the various control interventions employed, the use of different participants' inclusion criteria, and low methodological quality across the published studies. The risk of bias of trials identified was largely unclear in the domains of selection bias and detection bias across the included studies. This study showed substantial evidence of varied CHM interventions improving the stroke modifiable risk factors. More rigorous research examining the use of CHM products for sole or multiple major stroke risk factors are warranted.

Use of focused ultrasonication in activity-based profiling of deubiquitinating enzymes in tissue

OpenAIRE

Nanduri, Bindu; Shack, Leslie A.; Rai, Aswathy N.; Epperson, William B.; Baumgartner, Wes; Schmidt, Ty B.; Edelmann, Mariola J.

2016-01-01

To develop a reproducible tissue-lysis method that retains enzyme function for activity-based protein profiling, we compared four different tissue lysis methods of bovine lung tissue: focused ultrasonication, standard sonication, mortar & pestle method, and homogenization combined with standard sonication. Focused ultrasonication and mortar & pestle methods were sufficiently effective for activity-based profiling of deubiquitinases in tissue and focused ultrasonication had also the fastest pr...

Modified friction factor correlation for CICC's based on a porous media analogy

Science.gov (United States)

Lewandowska, Monika; Bagnasco, Maurizio

2011-09-01

A modified correlation for the bundle friction factor in CICC's based on a porous media analogy is presented. The correlation is obtained by the analysis of the collected pressure drop data measured for 23 CICC's. The friction factors predicted by the proposed correlation are compared with those resulting from the pressure drop data for two CICC's measured recently using cryogenic helium in the SULTAN test facility at EPFL-CRPP.

Bone regeneration with active angiogenesis by basic fibroblast growth factor gene transfected mesenchymal stem cells seeded on porous beta-TCP ceramic scaffolds.

Science.gov (United States)

Guo, Xiaodong; Zheng, Qixin; Kulbatski, Iris; Yuan, Quan; Yang, Shuhua; Shao, Zengwu; Wang, Hong; Xiao, Baojun; Pan, Zhengqi; Tang, Shuo

2006-09-01

Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on combining gene transfer with tissue engineering techniques. Basic fibroblast growth factor (bFGF) is one of the most prominent osteogenic growth factors that has the potential to accelerate bone healing by promoting the proliferation and differentiation of mesenchymal stem cells (MSCs) and the regeneration of capillary vasculature. However, the short biological half-lives of growth factors may impose severe restraints on their clinical usefulness. Gene-based delivery systems provide a better way of achieving a sustained high concentration of growth factors locally in the defect and delivering a more biologically active product than that achieved by exogenous application of recombinant proteins. The objective of this experimental study was to investigate whether the bFGF gene modified MSCs could enhance the repair of large segmental bone defects. The pcDNA3-bFGF gene transfected MSCs were seeded on biodegradable porous beta tricalcium phosphate (beta-TCP) ceramics and allografted into the 15 mm critical-sized segmental bone defects in the radius of 18 New Zealand White rabbits. The pcDNA3 vector gene transfected MSCs were taken as the control. The follow-up times were 2, 4, 6, 8, 10 and 12 weeks. Scanning electron microscopic, roentgenographic, histologic and immunohistological studies were used to assess angiogenesis and bone regeneration. In vitro, the proliferation and differentiation of bFGF gene transfected MSCs were more active than that of the control groups. In vivo, significantly more new bone formation accompanied by abundant active capillary regeneration was observed in pores of the ceramics loaded with bFGF gene transfected MSCs, compared with control groups. Transfer of gene encoding bFGF to MSCs increases their osteogenic properties by enhancing capillary regeneration, thus providing a rich blood supply for new bone formation. This new b

Bone regeneration with active angiogenesis by basic fibroblast growth factor gene transfected mesenchymal stem cells seeded on porous {beta}-TCP ceramic scaffolds

Energy Technology Data Exchange (ETDEWEB)

Guo Xiaodong [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022 (China); Zheng Qixin [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022 (China); Kulbatski, Iris [Division of Cellular and Molecular Biology, Toronto Western Research Institute, University of Toronto, Toronto, Ontario M5T 2S8 (Canada); Yuan Quan [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022 (China); Yang Shuhua [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022 (China); Shao Zengwu [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022 (China); Wang Hong [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022 (China); Xiao Baojun [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022 (China); Pan Zhengqi [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022 (China); Tang Shuo [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022 (China)

2006-09-15

Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on combining gene transfer with tissue engineering techniques. Basic fibroblast growth factor (bFGF) is one of the most prominent osteogenic growth factors that has the potential to accelerate bone healing by promoting the proliferation and differentiation of mesenchymal stem cells (MSCs) and the regeneration of capillary vasculature. However, the short biological half-lives of growth factors may impose severe restraints on their clinical usefulness. Gene-based delivery systems provide a better way of achieving a sustained high concentration of growth factors locally in the defect and delivering a more biologically active product than that achieved by exogenous application of recombinant proteins. The objective of this experimental study was to investigate whether the bFGF gene modified MSCs could enhance the repair of large segmental bone defects. The pcDNA3-bFGF gene transfected MSCs were seeded on biodegradable porous {beta} tricalcium phosphate ({beta}-TCP) ceramics and allografted into the 15 mm critical-sized segmental bone defects in the radius of 18 New Zealand White rabbits. The pcDNA3 vector gene transfected MSCs were taken as the control. The follow-up times were 2, 4, 6, 8, 10 and 12 weeks. Scanning electron microscopic, roentgenographic, histologic and immunohistological studies were used to assess angiogenesis and bone regeneration. In vitro, the proliferation and differentiation of bFGF gene transfected MSCs were more active than that of the control groups. In vivo, significantly more new bone formation accompanied by abundant active capillary regeneration was observed in pores of the ceramics loaded with bFGF gene transfected MSCs, compared with control groups. Transfer of gene encoding bFGF to MSCs increases their osteogenic properties by enhancing capillary regeneration, thus providing a rich blood supply for new bone formation. This new

Bone regeneration with active angiogenesis by basic fibroblast growth factor gene transfected mesenchymal stem cells seeded on porous β-TCP ceramic scaffolds

International Nuclear Information System (INIS)

Guo Xiaodong; Zheng Qixin; Kulbatski, Iris; Yuan Quan; Yang Shuhua; Shao Zengwu; Wang Hong; Xiao Baojun; Pan Zhengqi; Tang Shuo

2006-01-01

Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on combining gene transfer with tissue engineering techniques. Basic fibroblast growth factor (bFGF) is one of the most prominent osteogenic growth factors that has the potential to accelerate bone healing by promoting the proliferation and differentiation of mesenchymal stem cells (MSCs) and the regeneration of capillary vasculature. However, the short biological half-lives of growth factors may impose severe restraints on their clinical usefulness. Gene-based delivery systems provide a better way of achieving a sustained high concentration of growth factors locally in the defect and delivering a more biologically active product than that achieved by exogenous application of recombinant proteins. The objective of this experimental study was to investigate whether the bFGF gene modified MSCs could enhance the repair of large segmental bone defects. The pcDNA3-bFGF gene transfected MSCs were seeded on biodegradable porous β tricalcium phosphate (β-TCP) ceramics and allografted into the 15 mm critical-sized segmental bone defects in the radius of 18 New Zealand White rabbits. The pcDNA3 vector gene transfected MSCs were taken as the control. The follow-up times were 2, 4, 6, 8, 10 and 12 weeks. Scanning electron microscopic, roentgenographic, histologic and immunohistological studies were used to assess angiogenesis and bone regeneration. In vitro, the proliferation and differentiation of bFGF gene transfected MSCs were more active than that of the control groups. In vivo, significantly more new bone formation accompanied by abundant active capillary regeneration was observed in pores of the ceramics loaded with bFGF gene transfected MSCs, compared with control groups. Transfer of gene encoding bFGF to MSCs increases their osteogenic properties by enhancing capillary regeneration, thus providing a rich blood supply for new bone formation. This new b

Intravenous recombinant tissue plasminogen activator for acute ischemic stroke: a feasibility and safety study

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Sadeghi-Hokmabadi E

2016-10-01

Full Text Available Elyar Sadeghi-Hokmabadi, Mehdi Farhoudi, Aliakbar Taheraghdam, Mazyar Hashemilar, Daryous Savadi-Osguei, Reza Rikhtegar, Kaveh Mehrvar, Ehsan Sharifipour, Parisa Youhanaee, Reshad Mirnour Neurosciences Research Center, Neurology Department, Tabriz University of Medical Sciences, Tabriz, East Azerbaijan, Iran Background: In developing countries, intravenous thrombolysis (IVT is available at a limited number of centers. This study aimed to assess the feasibility and safety of IVT at Tabriz Imam Reza Hospital. Methods: In a prospective study, over a 55-month period, any patient at the hospital for whom stroke code had been activated was enrolled in the study. Data on demographic characteristics, stroke risk factors, admission blood pressure, blood tests, findings of brain computed tomography (CT scans, time of symtom onset, time of arrival to the emergency department, time of stroke code activation, time of CT scan examination, and the time of recombinant tissue plasminogen activator administration were recorded. National Institutes of Health Stroke Scale assessments were performed before IVT bolus, at 36 hours, at either 7 days or discharge (which ever one was earlier, and at 3-month follow-up. Brain CT scans were done for all patients before and 24 hours after the treatment. Results: Stroke code was activated for 407 patients and IVT was done in 168 patients. The rate of functional independence (modified Rankin Scale [mRS] 0–1 at 3 months was 39.2% (62/158. The mortality rate at day 7 was 6% (10/168. Hemorrhagic transformation was noted in 16 patients (9.5%. Symptomatic intracranial hemorrhage occurred in 5 (3%, all of which were fatal. One case of severe urinary bleeding and one other fatal case of severe angioedema were observed. Conclusion: During the first 4–5 years of administration of IVT in the hospital, it was found to be feasible and safe, but to increase the efficacy, poststroke care should be more organized and a stroke center

Evaluation of functional nerve recovery after reconstruction with a poly (DL-lactide-epsilon-caprolactone) nerve guide, filled with modified denatured muscle tissue

NARCIS (Netherlands)

Meek, MF; Den Dunnen, WFA; Schakenraad, JM; Robinson, PH

1996-01-01

The aim of this study was to compare the speed of functional nerve recovery after reconstruction with a biodegradable p(DLLA-epsilon -CL) nerve guide, as filled with either modified denatured muscle tissue (MDMT) or phosphate-buffered saline (PBS). To evaluate both motor and sensory nerve recovery,

Risk factors for pedicled flap necrosis in hand soft tissue reconstruction: a multivariate logistic regression analysis.

Science.gov (United States)

Gong, Xu; Cui, Jianli; Jiang, Ziping; Lu, Laijin; Li, Xiucun

2018-03-01

Few clinical retrospective studies have reported the risk factors of pedicled flap necrosis in hand soft tissue reconstruction. The aim of this study was to identify non-technical risk factors associated with pedicled flap perioperative necrosis in hand soft tissue reconstruction via a multivariate logistic regression analysis. For patients with hand soft tissue reconstruction, we carefully reviewed hospital records and identified 163 patients who met the inclusion criteria. The characteristics of these patients, flap transfer procedures and postoperative complications were recorded. Eleven predictors were identified. The correlations between pedicled flap necrosis and risk factors were analysed using a logistic regression model. Of 163 skin flaps, 125 flaps survived completely without any complications. The pedicled flap necrosis rate in hands was 11.04%, which included partial flap necrosis (7.36%) and total flap necrosis (3.68%). Soft tissue defects in fingers were noted in 68.10% of all cases. The logistic regression analysis indicated that the soft tissue defect site (P = 0.046, odds ratio (OR) = 0.079, confidence interval (CI) (0.006, 0.959)), flap size (P = 0.020, OR = 1.024, CI (1.004, 1.045)) and postoperative wound infection (P < 0.001, OR = 17.407, CI (3.821, 79.303)) were statistically significant risk factors for pedicled flap necrosis of the hand. Soft tissue defect site, flap size and postoperative wound infection were risk factors associated with pedicled flap necrosis in hand soft tissue defect reconstruction. © 2017 Royal Australasian College of Surgeons.

Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

Energy Technology Data Exchange (ETDEWEB)

Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

2011-03-04

Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.