首页> 外国专利> METHOD FOR LABELLING WITH RADIONUCLIDES MURINE OR HUMAN, MONOCLONAL OR POLYCLONAL ANTI-TUMOUR NECROSIS FACTOR ANTIBODIES ASSOCIATED WITH DISEASES WITH PHYSIOPATHOGENESIS INVOLVING TUMOR NECROSIS FACTOR; REAGENT FOR IN VIVO AND/OR IN VITRO DIAGNOSIS ON THE BASIS OF MURINE OR HUMAN, MONOCLONAL OR POLYCLONAL ANTI-TUMOR NECROSIS FACTOR ANTIBODIES LINKED TO RADIONUCLIDES; METHODS FOR DIAGNOSING IN VITRO AND/OR IN VIVO DISEASES WITH PHYSIOPATHOGENESIS INVOLVING THE TUMOUR NECROSIS FACTOR, USING THE THUS OBTAINED REAGENT, AND KIT CONTAINING SAID REAGENT FOR DIAGNOSING DISEASES WITH PHYSIOPATHOGENESIS INVOLVING THE TUMOUR NECROSIS FACTOR

METHOD FOR LABELLING WITH RADIONUCLIDES MURINE OR HUMAN, MONOCLONAL OR POLYCLONAL ANTI-TUMOUR NECROSIS FACTOR ANTIBODIES ASSOCIATED WITH DISEASES WITH PHYSIOPATHOGENESIS INVOLVING TUMOR NECROSIS FACTOR; REAGENT FOR IN VIVO AND/OR IN VITRO DIAGNOSIS ON THE BASIS OF MURINE OR HUMAN, MONOCLONAL OR POLYCLONAL ANTI-TUMOR NECROSIS FACTOR ANTIBODIES LINKED TO RADIONUCLIDES; METHODS FOR DIAGNOSING IN VITRO AND/OR IN VIVO DISEASES WITH PHYSIOPATHOGENESIS INVOLVING THE TUMOUR NECROSIS FACTOR, USING THE THUS OBTAINED REAGENT, AND KIT CONTAINING SAID REAGENT FOR DIAGNOSING DISEASES WITH PHYSIOPATHOGENESIS INVOLVING THE TUMOUR NECROSIS FACTOR

机译：用放射性核素标记鼠或人，单克隆或多克隆抗肿瘤坏死因子抗体与涉及肿瘤坏死因子的光致病性疾病相关的抗体的方法;根据与放射性核素相连的鼠或人，单克隆或多克隆抗肿瘤坏死因子抗体对活体和/或活体诊断的试剂;诊断与肿瘤致病因素有关的，具有病理病理性疾病的和/或体内疾病的方法，使用上述获得的试剂，并包含用于诊断疾病的诊断性疾病的试剂盒。肿瘤坏死因子

展开▼

页面导航

摘要

著录项

相似文献

摘要

The present invention relates to a method for labelling with radionuclides murine or human, monoclonal or polyclonal anti-tumour necrosis factor antibodies, to a reagent for in vivo and/or in vitro diagnosis on the basis of murine or human, monoclonal or polyclonal anti-tumor necrosis factor antibodies labelled with radionuclides, and to the diagnostic use thereof; to the method for diagnosing in vitro and/or in vivo diseases with physiopathogenesis involving the tumour necrosis factor, and to the kit for diagnosing diseases with physiopathogenesis involving the tumour necrosis factor, using the said reagent. 展开▼

机译：本发明涉及一种用放射性核素标记鼠或人，单克隆或多克隆抗肿瘤坏死因子抗体的方法，用于体内和/或体外的试剂基于用放射性核素标记的鼠或人，单克隆或多克隆抗肿瘤坏死因子抗体进行诊断，及其诊断用途;诊断涉及具有肿瘤坏死因子的生理病理的体外和/或体内疾病的方法，以及涉及涉及肿瘤坏死因子的生理病理的疾病的诊断试剂盒，使用所述试剂。 展开▼

著录项

公开/公告号WO2012054997A1

专利类型

公开/公告日2012-05-03

原文格式PDF

申请/专利权人 UNIVERSIDADE FEDERAL DO RIO DE JANEIRO;GUTFILEN BIANCA;BARBOSA DA FONSECA LEA MIRIAN;LOPES DE SOUZA SERGIO AUGUSTO;PROENCA LOBO LOPES FLAVIA PAIVA;
展开▼

申请/专利号WO2011BR00392

发明设计人 GUTFILEN BIANCA;BARBOSA DA FONSECA LEA MIRIAN;LOPES DE SOUZA SERGIO AUGUSTO;PROENCA LOBO LOPES FLAVIA PAIVA;
展开▼

申请日2011-10-26

分类号A61K51/10;A61K103/10;A61K39/395;

国家 WO

入库时间 2022-08-21 17:16:19

相似文献

专利

外文文献

中文文献

1. 亲和层析纯化抗肿瘤坏死因子α单克隆抗体的方法 [P] . 中国专利： CN105294861B . 2019.02.19

2. 亲和层析纯化抗肿瘤坏死因子α单克隆抗体的方法 [P] . 中国专利： CN105294861A . 2016-02-03

3. process of radionuclide labeling of murine or human, monoclonal or polyclonal anti-tumor necrosis factor associated with diseases whose pathophysiology involves tumor necrosis factor; reagent for diagnosis "in vivo" and / or "in vitro" based on murine or human antibodies, monoclonal or polyclonal anti-tumor necrosis factor associated with radionuclides; diagnostic methods "in vitro" and / or "in vivo" of diseases whose physiotopagenia involves tumor necrosis factor using the reagent thus obtained and kit for diagnosing diseases whose pathophysiology involves tumor necrosis factor based on said reagent [P] . BRPI1003970B1 . 2020-05-05

机译：与病理生理涉及肿瘤坏死因子的疾病相关的鼠类或人，单克隆或多克隆抗肿瘤坏死因子的放射性核素标记过程;基于鼠或人抗体，与放射性核素有关的单克隆或多克隆抗肿瘤坏死因子的“体内”和/或“体外”诊断试剂;使用如此获得的试剂的生理失常涉及肿瘤坏死因子的疾病的“体外”和/或“体内”诊断方法以及基于所述试剂的病理生理涉及肿瘤坏死因子的疾病的诊断试剂盒

4. radionuclide labeling process for murine or human monoclonal or polyclonal anti-tumor necrosis factor-associated antibodies to diseases whose pathophysiology involves tumor necrosis factor; "in vivo" and / or "in vitro" diagnostic reagent based on murine or human, monoclonal or polyclonal anti-tumor necrosis factor-associated antibodies to radionuclides; "In vitro" and / or "in vivo" diagnostic methods for diseases whose pathophysiology involves tumor necrosis factor using the reagent thus obtained and a kit for the diagnosis of diseases whose pathophysiology involves tumor necrosis factor based on said reagent [P] . BRPI1003970A2 . 2012-06-12

机译：鼠或人单克隆或多克隆抗肿瘤坏死因子相关抗体对病理生理学涉及肿瘤坏死因子的疾病的放射性核素标记过程;基于鼠或人，单克隆或多克隆抗肿瘤坏死因子相关抗体的“体内”和/或“体外”诊断试剂;使用如此获得的试剂对病理生理涉及肿瘤坏死因子的疾病的“体外”和/或“体内”诊断方法，以及基于所述试剂的病理生理涉及肿瘤坏死因子的疾病的试剂盒

5. METHOD FOR LABELLING WITH RADIONUCLIDES SOMATOSTATIN ANALOGUES ASSOCIATED WITH DISEASES WITH PHYSIOPATHOGENESIS INVOLVING SOMATOSTATIN RECEPTORS, REAGENT FOR IN VIVO AND/OR IN VITRO DIAGNOSIS ON THE BASIS OF SOMATOSTATIN ANALOGUES LINKED TO RADIONUCLIDES, METHOD FOR DIAGNOSING IN VITRO OR IN VIVO DISEASES WITH PHYSIOPATHOGENESIS INVOLVING SOMATOSTATIN RECEPTORS, USING THE THUS OBTAINED REAGENT, AND KIT CONTAINING SAID REAGENT FOR DIAGNOSING DISEASES WITH PHYSIOPATHOGENESIS INVOLVING SOMATOSTATIN [P] . 世界知识产权组织专利： WO2012054998A1 . 2012-05-03

机译：与涉及生长抑素受体，活体和/或体外诊断的物理病理学疾病有关的，涉及生理病理的疾病的放射性核素类似物标记的方法，使用该获得的试剂，诊断含有生长抑素受体的，患有物理病因的体外或体内疾病的方法，并使用包含该试剂的试剂盒诊断患有生长激素的病原体

1. Reduction of circulating secretory phospholipase A2 levels by anti-tumor necrosis factor chimeric monoclonal antibody in patients with severe Crohn's disease. Relation between tumor necrosis factor and secretory phospholipase A2 in healthy humans and [J] . van-Dullemen HM, Wolbink GJ, Wever PC, Scandinavian journal of gastroenterology. . 1998,第10期

2. Biosimilars in immune-mediated inflammatory diseases: initial lessons from the first approved biosimilar anti-tumour necrosis factor monoclonal antibody [J] . Isaacs J. D., Cutolo M., Keystone E. C., Journal of Internal Medicine . 2016,第1期

3. Biosimilars in immune-mediated inflammatory diseases: initial lessons from the first approved biosimilar anti-tumour necrosis factor monoclonal antibody [J] . Isaacs J. D., Cutolo M., Keystone E. C., Journal of Internal Medicine . 2016,第1期

4. A Novel Humanized Single-Chain Variable-Fragment Antibody Against the Tumor Necrosis Factor-Alpha [C] . Davoud Farajzadeh, Siavoush Dastmalchi PEGS . 2014

5. Intracellular Signal Transduction Mechanisms Regulating the Activation of Human Bronchial Epithelial Cells by Interleukin-17A, Interleukin-27, Tumor Necrosis Factor-alpha and Human Basophils in Inflammatory Diseases [D] . Cao, Ju 2010

6. Tumour necrosis factor and anti-tumour necrosis factor approach to inflammatory demyelinating diseases of the central nervous system [O] . K. Selmaj 2000

7. Poster session 2Morphogenetic mechanisms290MiR-133 regulates retinoic acid pathway during early cardiac chamber specification291Bmp2 regulates atrial differentiation through miR-130 during early heart looping formationDevelopmental genetics294Association of deletion allele of insertion/deletion polymorphism in alpha 2B adrenoceptor gene and hypertension with or without type 2 diabetes mellitus295Association of G1359A polymorphism of the endocannabinoid type 1 receptor (CNR1) with coronary artery disease (CAD) with type 2 diabetes mellitusCell growth, differentiation and stem cells - Vascular298Gamma-secretase inhibitor prevents proliferation and migration of ductus arteriosus smooth muscle cells: a role of Notch signaling in postnatal closure of ductus arteriosus299Mesenchymal stromal-like cells (MLCs) derived from induced pluripotent stem (iPS) cells: a promising therapeutic option to promote neovascularization300Sonic Hedgehog promotes mesenchymal stem cell differentiation to vascular smooth muscle cells in cardiovacsular disease301Proinflammatory cytokine secretion and epigenetic modification in endothelial cells treated LPS-GinfivalisCell death and apoptosis - Vascular304Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipidsTranscriptional control and RNA species - Vascular307MicroRNA-34a role in vascular calcification308Local delivery of a miR-146a inhibitor utilizing a clinically applicable approach attenuates neointima formation after vascular injury309Long noncoding RNA landscape of hypoxic endothelial cells310Specific circulating microRNAs levels associate with hypertension, hyperglycemia and dysfunctional HDL in acute coronary syndrome patientsCytokines and cellular inflammation - Vascular313Phosphodiesterase5A up-regulation in vascular endothelium under pro-inflammatory conditions: a newly disclosed anti-inflammatory activity for the omega-3polyunsaturated aatty acid docosahexaenoic acid314Cardiovascular risk modifying with extra-low dose anticytokine drugs in rhematoid arthritis315Conversion of human M-CSF macrophages into foam cells reduces their proinflammatory responses to classical M1-polarizing activation316Lymphocytic myocarditis coincides with increased plaque inflammation and plaque hemorrhage in coronary arteries, facilitating myocardial infarction317Serum osteoprotegerin level predictsdeclined numerous of circulating endothelial- derived and mononuclear-derived progenitor cells in patients with metabolic syndromeGrowth factors and neurohormones - Vascular320Effect of gastrin-releasing peptide (GRP) on vascular inflammationSignal transduction - Heart323A new synthetic peptide regulates hypertrophy in vitro through means of the inhibition of nfkb324Inducible fibroblast-specific knockout of p38 alpha map kinase is cardioprotective in a mouse model of isoproterenol-induced cardiac hypertrophy325Regulation of beta-adrenoceptor-evoked inotropic responses by inhibitory G protein, adenylyl cyclase isoforms 5 and 6 and phosphodiesterases326Binding to RGS3 and stimulation of M2 muscarinic acetylcholine receptors modulates the substrate specificity of p190RhoGAP in cardiac myocytes327Cardiac regulation of post-translational modifications, parylation and deacetylation in LMNA dilated cardiomyopathy mouse model328Beta-adrenergic regulation of the b56delta/pp2a holoenzyme in cardiac myocytes through b56delta phosphorylation at serine 573Nitric oxide and reactive oxygen species - Vascular331Oxidative stress-induced miR-200c disrupts the regulatory loop among SIRT1, FOXO1 and eNOS332Antioxidant therapy prevents oxidative stress-induced endothelial dysfunction and Enhances Wound Healing333Morphological and biochemical characterization of red blood cell in coronary artery diseaseCytoskeleton and mechanotransduction - Heart336Novel myosin activator, JSH compounds, increased myocardial contractility without chronotropic effect in ratsExtracellular matrix and fibrosis - Vascular339Ablation of Toll-like receptor 9 causes cardiac rupture after myocardial infarction by attenuating proliferation and differentiation of cardiac fibroblasts340Altered vascular remodeling in the mouse hind limb ischemia model in Factor VII activating protease (FSAP) deficiencyVasculogenesis, angiogenesis and arteriogenesis343Pro-angiogenic effects of proly-hydroxylase inhibitors and their potential for use in a novel strategy of therapeutic angiogenesis for coronary total occlusion344Nrf2 drives angiogenesis in transcription-independent manner: new function of the master regulator of oxidative stress response345Angiogenic gene therapy, despite efficient vascular growth, is not able to improve muscle function in normoxic or chronically ischemic rabbit hindlimbs -role of capillary arterialization and shunting346Effect of PAR-1 inhibition on collateral vessel growth in the murine hind limb model347Quaking is a key regulator of endothelial cell differentiation, neovascularization and angiogenesis348"Emerging angiogenesis" in the chick chorioallantoic membrane (CAM). An in vivo study349Exosomes from cardiomyocyte progenitor cells and mesenchymal stem cells stimulate angiogenesis in vitro and in vivo via EMMPRINEndothelium352Reciprocal regulation of GRK2 and bradykinin receptor stimulation modulate Ca2+ intracellular level in endothelial cells353The roles of bone morphogenetic proteins 9 and 10 in endothelial inflammation and atherosclerosis354The contribution of GPR55 to the L-alpha-lysophosphatidylinositol-induced vasorelaxation in isolated human pulmonary arteries355The endothelial protective ACE inhibitor Zofenoprilat exerts anti-inflammatory activities through H2S production356A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction357Endothelial progenitor cells to apoptotic endothelial cell-derived microparticles ration differentiatesas preserved from reduced ejection fractionheart failure358Proosteogenic genes are activated in endothelial cells of patients with thoracic aortic aneurysm359Endothelin ETB receptors mediate relaxing responses to insulin in pericardial resistance arteries from patients with cardiovascular disease (CVD)Smooth muscle and pericytes362CX3CR1 positive myeloid cells regulate vascular smooth muscle tone by inducing calcium oscillations via activation of IP3 receptors363A novel function of PI3Kg on cAMP regulation, role in arterial wall hyperplasia through modulation of smooth muscle cells proliferation364NRP1 and NRP2 play important roles in the development of neointimal hyperplasia in vivo365Azithromycin induces autophagy in aortic smooth muscle cellsCoagulation, thrombosis and platelets368The real time in vivo evaluation of platelet-dependent aldosterone prothrombotic action in mice369Development of a method for in vivo detection of active thrombi in mice370The antiplatelet effects of structural analogs of the taurine chloramine371The influence of heparin anticoagulant drugs on functional state of human platelets372Regulation of platelet aggregation and adenosine diphosphate release by d dimer in acute coronary syndrome (in vitro study)Oxygen sensing, ischaemia and reperfusion375Sirtuin 5 mediates brain injury in a mouse model of cerebral ischemia-reperfusion376Abscisic acid: a new player in cardiomyocyte protection from ischaemia?377Protective effects of ultramicronized palmitoylethanolamide (PEA-um) in myocardial ischaemia and reperfusion injury in vivo378Identification of stem cell-derived cardiomyocytes using cardiac specific markers and additional testing of these cells in simulated ischemia/reperfusion system379Single-dose intravenous metformin treatment could afford significant protection of the injured rat kidney in an experimental model of ischemia-reperfusion380Cardiotoxicity of long acting muscarinic receptor antagonists used for chronic obstructive pulmonary disease381Dependence antioxidant potential on the concentration of amino acids382The impact of ischemia-reperfusion on physiological parameters,apoptosis and ultrastructure of rabbit myocardium with experimental aterosclerosisMitochondria and energetics385MicroRNA-1 dependent regulation of mitochondrial calcium uniporter (MCU) in normal and hypertrophied hearts386Mitochondrial homeostasis and cardioprotection: common targets for desmin and aB-crystallin387Overexpression of mitofusin-2 (Mfn2) and associated mitochondrial dysfunction in the diabetic heart388NO-dependent prevention of permeability transition pore (MPTP) opening by H2S and its regulation of Ca2+ accumulation in rat heart mitochondria389G protein coupled receptor kinase 2 (GRK2) is fundamental in recovering mitochondrial morphology and function after exposure to ionizing radiation (IR)Gender issues392Sex differences in pulmonary vascular control; focus on the nitric oxide pathwayAging395Heart failure with preserved ejection fraction develops when feeding western diet to senescence-accelerated mice396Cardiovascular markers as predictors of cognitive decline in elderly hypertensive patients397Changes in connexin43 in old rats with volume overload chronic heart failureGenetics and epigenetics400Calcium content in the aortic valve is associated with 1G>2G matrix metalloproteinase 1 polymorphism401Neuropeptide receptor gene s (NPSR1) polymorphism and sleep disturbances402Endothelin-1 gene Lys198Asn polymorphism in men with essential hypertension complicated and uncomplicated with chronic heart failure403Association of common polymorphisms of the lipoprotein lipase and pon1 genes with the metabolic syndrome in a sample of community participantsGenomics, proteomics, metabolomics, lipidomics and glycomics405Gene expression quantification using multiplexed color-coded probe pairs to determine RNA content in sporadic cardiac myxoma406Large-scale phosphorylation study of the type 2 diabetic heart subjected to ischemia / reperfusion injury407Transcriptome-based identification of new anti-inflammatory properties of the olive oil hydroxytyrosol in vascular endothelial cell under basal and proinflammatory conditions408Gene polymorphisms combinations and risk of myocardial infarctionComputer modelling, bioinformatics and big data411Comparison of the repolarization reserve in three state-of-the-art models of the human ventricular action potentialMetabolism, diabetes mellitus and obesity414Endothelial monocyte-activating polypeptide-II improves heart function in type -I Diabetes mellitus415Admission glucose level is independent predictor of impaired left ventricular function in patients with acute myocardial infarction: a two dimensional speckle-tracking echocardiography study416Association between biochemical markers of lipid profile and inflammatory reaction and stiffness of the vascular wall in hypertensive patients with abdominal obesity417Multiple common co-morbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress and myocardial stiffening418Investigating the cardiovascular effects of antiretroviral drugs in a lean and high fat/sucrose diet rat model of obesity419Statins in the treatment of non-alcoholic steatohepatitis (NASH). Our experience from a 2-year prospective study in Constanta County, Romania420Epicardial adipose tissue as a predictor of cardiovascular outcome in patients with ACS undergoing PCI?Arterial and pulmonary hypertension423Dependence between heart rhythm disorers and ID polymorphism of ACE gene in hypertensive patients424Molecular mechanisms underlying the beneficial effects of Urocortin 2 in pulmonary arterial hypertension425Inhibition of TGf-b axis and action of renin-angiotensin system in human ascending aorta aneurysms426Early signs of microcirculation and macrocirculation abnormalities in prehypertension427Vascular smooth muscle cell-expressed Tie-2 controls vascular tone428Cardiac and vascular remodelling in the development of chronic thrombo-embolic pulmonary hypertension in a novel swine modelBiomarkers431Arrhythmogenic cardiomyopathy: a new, non invasive biomarker432Can circulating microRNAs distinguish type 1 and type 2 myocardial infarction?433Design of a high-throughput multiplex proteomics assay to identify left ventricular diastolic dysfunction in diabetes434Monocyte-derived and P-selectin-carrying microparticles are differently modified by a low fat diet in patients with cardiovascular risk factors who will and who will not develop a cardiovascular event435Red blood cell distribution width assessment by polychromatic interference microscopy of thin films in chronic heart failure436Invasive and noninvasive evaluation of quality of radiofrequency-induced cardiac denervation in patients with atrial fibrillation437The effect of therapeutic hypothermia on the level of brain derived neurotrophic factor (BDNF) in sera following cardiopulmonary resustitation438Novel biomarkers to predict outcome in patients with heart failure and severe aortic stenosis439Biological factors linking depression and anxiety to cardiovascular disease440Troponins and myoglobin dynamic at coronary arteries graftingInvasive, non-invasive and molecular imaging443Diet composition effects on the genetic typing of the mouse ob mutation: a micro-ultrasound characterization of cardiac function, macro and micro circulation and liver steatosis444Characterization of pig coronary and rabbit aortic lesions using IV-OCT quantitative analysis: correlations with histologyGene therapy and cell therapy447Enhancing the survival and angiogenic potential of mouse atrial mesenchymal cells448VCAM-1 expression in experimental myocardial infarction and its relation to bone marrow-derived mononuclear cell retentionTissue engineering451Advanced multi layered scaffold that increases the maturity of stem cell-derived human cardiomyocytes452Response of engineered heart tissue to simulated ischemia/reperfusion in the presence of acute hyperglycemic conditions453Serum albumin hydrogels prevent de-differentiation of neonatal cardiomyocytes454A novel paintbrush technique for transfer of low viscosity ultraviolet light curable cyan methacrylate on saline immersed in-vitro sheep heart [O] . V Garcia-Martinez, C Lopez Sanchez, W Hamed, 2016

8. Interdependence of the Radioprotective Effects of Human Recombinant Interleukin 1alpha, Tumor Necrosis Factor alpha, Granulocyte Colony-Stimulating Factor, and Murine Recombinant Granulocyte-Macrophage Colony-Stimulating Factor [R] . Neta, R., Oppenheim, J. J., Douches, S. D. 1988

1. Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases [J] . Ulrike Billmeier ,Walburga Dieterich ,Markus F Neurath . 世界胃肠病学杂志：英文版 . 2016,第42期

2. What is left when anti-tumour necrosis factor therapy in inflammatory bowel diseases fails? [J] . Ian C Lawrance . 世界胃肠病学杂志：英文版 . 2014,第5期

3. Strategies for overcoming anti-tumor necrosis factor drug antibodies in inflammatory bowel disease:Case series and review of literature [J] . Mansi M Kothari ,Douglas L Nguyen ,Nimisha K Parekh . 世界胃肠药理与治疗学杂志：英文版（电子版） . 2017,第3期

4. Withdrawal of anti-tumour necrosis factor α therapy in inflammatory bowel disease [J] . Konstantinos Papamichael ,Severine Vermeire . 世界胃肠病学杂志：英文版 . 2015,第16期

5. Growth and bone health in paediatric patients with Crohn's disease receiving subcutaneous tumor necrosis factor antibody [J] . Judith Pichler ,Wolf Dietrich Huber ,Christoph Aufricht . 世界胃肠病学杂志：英文版 . 2015,第21期

6. 抗肿瘤坏死因子-α单克隆抗体对哮喘豚鼠气道炎症抑制作用的研究 [C] . 昝双江 ,朱立勤 ,杨文杰 . 第六次全国中西医结合变态反应学术大会 . 2013

7. 抗肿瘤坏死因子-α单克隆抗体对大鼠脑缺血再灌注损伤的作用 [A] . 陈金 . 2008