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Sample records for willebrand factor type

  1. Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor

    Science.gov (United States)

    De Meyer, Simon F.; Vanhoorelbeke, Karen; Chuah, Marinee K.; Pareyn, Inge; Gillijns, Veerle; Hebbel, Robert P.; Collen, Désiré; Deckmyn, Hans; VandenDriessche, Thierry

    2006-01-01

    Von Willebrand disease (VWD) is an inherited bleeding disorder, caused by quantitative (type 1 and 3) or qualitative (type 2) defects in von Willebrand factor (VWF). Gene therapy is an appealing strategy for treatment of VWD because it is caused by a single gene defect and because VWF is secreted into the circulation, obviating the need for targeting specific organs or tissues. However, development of gene therapy for VWD has been hampered by the considerable length of the VWF cDNA (8.4 kb [kilobase]) and the inherent complexity of the VWF protein that requires extensive posttranslational processing. In this study, a gene-based approach for VWD was developed using lentiviral transduction of blood-outgrowth endothelial cells (BOECs) to express functional VWF. A lentiviral vector encoding complete human VWF was used to transduce BOECs isolated from type 3 VWD dogs resulting in high-transduction efficiencies (95.6% ± 2.2%). Transduced VWD BOECs efficiently expressed functional vector-encoded VWF (4.6 ± 0.4 U/24 hour per 106 cells), with normal binding to GPIbα and collagen and synthesis of a broad range of multimers resulting in phenotypic correction of these cells. These results indicate for the first time that gene therapy of type 3 VWD is feasible and that BOECs are attractive target cells for this purpose. PMID:16478886

  2. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

    International Nuclear Information System (INIS)

    Hill-Eubanks, D.C.; Parker, C.G.; Lollar, P.

    1989-01-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. The authors isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO 4 /PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated 125 I-fVIII to function as a cofactor in the activation of factor X by factor IXa, they found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated by light-chain cleavage to dissociate the complex and heavy-chain cleavage to activate the cofactor function

  3. Pseudo (Platelet-type von Willebrand disease in pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Grover Neetu

    2013-01-01

    Full Text Available Abstract Background Pseudo (platelet-type-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD. Case presentation We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient’s platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration

  4. Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms.

    Science.gov (United States)

    Albánez, S; Ogiwara, K; Michels, A; Hopman, W; Grabell, J; James, P; Lillicrap, D

    2016-05-01

    Essentials von Willebrand factor (VWF) and factor VIII (FVIII) levels are modulated by age and ABO status. The effect of aging and ABO blood type on VWF and FVIII was assessed in 207 normal individuals. Aging and ABO blood type showed combined and bidirectional influences on VWF and FVIII levels. Aging and ABO blood type influence VWF levels through both secretion and clearance mechanisms. Background The effect of aging and ABO blood type on plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII) have been widely reported; however, a comprehensive analysis of their combined effect has not been performed and the mechanisms responsible for the age-related changes have not been determined. Objectives To assess the influence of aging and ABO blood type on VWF and FVIII levels, and to evaluate the contribution of VWF secretion and clearance to the age-related changes. Methods A cross-sectional observational study was performed in a cohort of 207 normal individuals, whose levels of VWF, FVIII, VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio and blood type A antigen content on VWF (A-VWF) were quantified. Results Aging and ABO blood type exerted interrelated effects on VWF and FVIII plasma levels, because the age-related increase in both proteins was significantly higher in type non-O individuals (β = 0.011 vs. 0.005). This increase with age in non-O subjects drove the differences between blood types in VWF levels, as the mean difference increased from 0.13 U/mL in the young to 0.57 U/mL in the old. Moreover, A-VWF was associated with both VWF antigen (β = 0.29; 95% confidence interval [CI], 0.09, 0.50) and VWF clearance (β = -0.15; 95% CI, -0.25, -0.06). We also documented an effect of ABO blood type on VWF secretion with aging, as old individuals with blood type non-O showed higher levels of VWFpp (mean difference 0.29 U/mL). Conclusions Aging and ABO blood type have an interrelated effect on VWF and FVIII levels, where the effect of one is significantly

  5. A study of the effect of ethamsylate (Dicynene) on the bleeding time, von Willebrand factor level and fibrinolysis in patients with von Willebrand's disease.

    Science.gov (United States)

    Hutton, R A; Hales, M; Kernoff, P B

    1988-12-22

    Nine patients with clinically moderate or severe Type I von Willebrand's disease were treated for 2 weeks with ethamsylate (2 g/day in four equal doses) and with a matched placebo in a randomised double-blind trial. Template bleeding time, von Willebrand factor activity (ristocetin co-factor) and antigen, euglobulin lysis time and type I tissue plasminogen activator inhibitor were determined before and at the end of each treatment period. None of these parameters showed any significant change attributable to ethamsylate. Thus, despite the fact that five patients thought subjectively that their bleeding symptoms improved during ethamsylate treatment compared to only one while on placebo, we obtained no evidence that the drug was of benefit to patients with von Willebrand's disease.

  6. Differential effects of the loss of intrachain- versus interchain-disulfide bonds in the cystine-knot domain of von Willebrand factor on the clinical phenotype of von Willebrand disease

    NARCIS (Netherlands)

    Tjernberg, Pernilla; Vos, Hans L.; Spaargaren-van Riel, Caroline C.; Luken, Brenda M.; Voorberg, Jan; Bertina, Rogier M.; Eikenboom, Jeroen C. J.

    2006-01-01

    Von Willebrand factor (VWF) contains a large number of cysteine residues, which all form disulfide bonds. Mutations of cysteines located in the cystine-knot (CK) domain of VWF have been identified in both qualitative type 2A (IID) and quantitative type 3 von Willebrand disease (VWD). Our objective

  7. Diagnosis and management of von Willebrand disease: guidelines for primary care.

    Science.gov (United States)

    Yawn, Barbara; Nichols, William L; Rick, Margaret E

    2009-12-01

    Von Willebrand disease is an inherited condition characterized by deficiency of von Willebrand factor, which is essential in hemostasis. The National Heart, Lung, and Blood Institute has released new evidence-based guidelines for the diagnosis and management of the disease. There are three major subtypes of von Willebrand disease, classified as partial quantitative deficiency (low levels) of von Willebrand factor (type 1), qualitative deficiency (type 2), or virtually complete deficiency (type 3). Diagnosis is usually made by reviewing the patient's personal and family history of bleeding and by clinical evaluation for more common reasons for bleeding, supplemented with laboratory tests. Assessment may be used to determine bleeding risk before surgery and other invasive procedures, and to diagnose reasons for unexplained hemorrhaging. Von Willebrand factor levels of 30 IU per dL or lower are required for the definite diagnosis of inherited von Willebrand disease. Persons with levels of 30 to 50 IU per dL may not have the disease, but may need agents to increase von Willebrand factor levels during invasive procedures or childbirth. Treatment is tailored to the subtype of the disease: increasing plasma concentration of von Willebrand factor by releasing endogenous stores with desmopressin or replacing nonexistent or ineffective von Willebrand factor by using human plasma-derived, viral-inactivated concentrates; treatment is often combined with hemostatic agents that have mechanisms other than increasing von Willebrand factor. Regular prophylaxis is seldom required, and treatment is initiated before planned invasive procedures or in response to bleeding.

  8. Doença de von Willebrand e anestesia Enfermedad de von Willebrand y anestesia Von Willebrand's disease and anesthesia

    Directory of Open Access Journals (Sweden)

    Fabiano Timbó Barbosa

    2007-06-01

    íodo perioperatorio. CONTENIDO: Se definieron las características de la enfermedad de von Willebrand en cuanto a las fisiopatologías, la clasificación, al diagnóstico laboratorial, al tratamiento actual y a los cuidados con el manejo del paciente en el período perioperatorio. CONCLUSIONES: La enfermedad de von Willebrand es el disturbio hemorrágico hereditario más común, sin embargo ella está subdiagnosticada por la complejidad de la propia enfermedad. La correcta clasificación del paciente, el uso apropiado de la desmopresina y la transfusión del factor de von Willebrand son medidas fundamentales para la realización del procedimiento anestésico exitoso.BACKGROUND AND OBJECTIVES: von Willebrand's disease is secondary to a mutation on chromosome 12, and is characterized by a qualitative and quantitative deficiency of the von Willebrand's factor. The diversity of the mutations is responsible for several different clinical manifestations, enabling the classification of several types and subtypes. The coagulopathy is manifested basically through a platelet dysfunction associated with a reduction in the serum levels of factor VIII. The objective of this review was to present the perioperative care of patients with von Willebrand's disease. CONTENTS: The physiopathology, classification, laboratorial diagnosis, and current treatment of von Willebrand's disease, as well as the perioperative management of these patients are discussed. CONCLUSIONS: von Willebrand's disease is the most common hereditary coagulopathy, but it is underdiagnosed due to the complexity of the disease itself. The right classification, proper use of desmopressin, and transfusion of von Willebrand's factor are fundamental for a successful anesthesia.

  9. Von Willebrand factor regulation of blood vessel formation.

    Science.gov (United States)

    Randi, Anna M; Smith, Koval E; Castaman, Giancarlo

    2018-06-04

    Several important physiological processes, from permeability to inflammation to haemostasis, take place at the vessel wall and are regulated by endothelial cells (EC). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for Von Willebrand Factor (VWF), a large glycoprotein best known for its critical role in haemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularisation, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth endothelial cells (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel Palade bodies (WPB), such as Angiopoietin-2 and Galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor (VEGF) signalling. Recent studies suggest that the roles of VWF may be tissue-specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding due to vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high molecular weight multimers in regulating angiogenesis, and the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome. Copyright © 2018 American Society of Hematology.

  10. Associations Between Diabetic Retinopathy and Plasma Levels of High-sensitive C-reactive Protein or Von Willebrand Factor in Long-term Type 1 Diabetic Patients

    DEFF Research Database (Denmark)

    Laursen, Jonas Vejvad Nørskov; Hoffmann, Stine Skovbo; Green, Anders

    2013-01-01

    .27 IU/ml (0.79-2.07 IU/ml), respectively. No or minimal DR (ETDRS-levels 10-20) was found in 16.4%, mild DR (ETDRS-level 35) in 19.4%, moderate DR (ETDRS-levels 43-47) in 11.0%, and 53.2% had proliferative diabetic retinopathy (PDR) corresponding to ETDRS-level 60 or more. In an age- and sex......Purpose: To evaluate high-sensitive C-reactive protein (hs-CRP) and von Willebrand factor as possible plasma markers of diabetic retinopathy in a population-based cohort of type 1 diabetic patients. Materials and Methods: This was a cross-sectional study of 201 type 1 diabetic patients from...... a population-based cohort from Fyn County, Denmark. Plasma levels of hs-CRP and von Willebrand factor antigen were measured and related to the level of diabetic retinopathy (DR) as evaluated by dilated nine-field 45 degree monoscopic fundus photos captured by Topcon TRC-NWS6 and graded according to the Early...

  11. No evidence for a direct effect of von Willebrand factor's ABH blood group antigens on von Willebrand factor clearance

    NARCIS (Netherlands)

    Groeneveld, D J; van Bekkum, T; Cheung, K L; Dirven, R J; Castaman, G; Reitsma, P H; van Vlijmen, B; Eikenboom, J

    BACKGROUND: One of the major determinants of von Willebrand factor (VWF) plasma levels is ABO blood group status, and individuals with blood group O have ~ 25% lower plasma levels. The exact mechanism behind this relationship remains unknown, although effects on clearance have been postulated.

  12. Active Von Willebrand Factor, thrombocytopenia and thrombosis

    NARCIS (Netherlands)

    Hulstein, J.J.J.

    2006-01-01

    Platelets and von Willebrand factor (VWF) are unable to interact in circulation. To induce an interaction, a conversion of VWF to a platelet-binding conformation is required. At higher shear stresses, the first step in thrombus formation is binding of VWF to the subendothelium. This results in

  13. DEEP VEIN THROMBOSIS IN PATIENT WITH VON WILLEBRAND DISEASE

    Directory of Open Access Journals (Sweden)

    V. A. Elykomov

    2016-01-01

    Full Text Available Objective: to identify the possible factors of thrombogenic risk and ways of its prevention in patients with von Willebrand disease.Case description. Patient X., 42 years old, who suffers from von Willebrand disease type 3 with 5-years of age. Asked on reception to the traumatologist in the polyclinic of the Regional Hospital with pain in the left hip joint. Recommended planned operative treatment in the Altai Regional Clinical Hospital. Preoperative preparation included the infusion of concentrate of von Willebrand factor and coagulation factor VIII. Operation – cement total arthroplasty of the left hip joint. In the postoperative period analgesic treatment, elastic compression of the lower extremities, iron supplements, also conducted infusion of concentrate of von Willebrand factor and coagulation factor VIII for 20 days and thromboprophylactic with dabigatran. On the 3rd day after the operation the patient revealed deep vein thrombosis of the femoral segment (floating clot.Results. The patient was operated for emergency indications in the Department of endovascular surgery – installation of venous cava filter “Volan”. Dabigatran is cancelled, appointed clexane for 3 months. In our clinical example the patient lacked risk factors of pulmonary embolism as obesity, age, smoking, prolonged immobilization, estrogen therapy. Overdose of factor VIII were not observed – the level of factor did not exceed 135 % on transfusions. At the same time, the patient was found polymorphisms in the genes ITGA2, FGB, MTHFR, MTR – heterozygote, MTRR – mutant homozygote, which may indicate the genetic factors of thrombogenic risk. Also a significant risk factor was massive surgical intervention (total hip replacement. Despite preventive measures (elastic compression, thromboprophylactic dabigatran, early activation we cannot to avoid thrombotic complications.Conclusion. This article presents a case demonstrating a thrombotic complication in patients

  14. Insulin resistance is accompanied by increased von Willebrand factor levels in nondiabetic women: a study of offspring of type 2 diabetic subjects compared to offspring of nondiabetic subjects

    DEFF Research Database (Denmark)

    Foss, Anne-Catherine; Vestbo, Else; Frøland, Anders

    2002-01-01

    OBJECTIVES: To examine whether levels of von Willebrand factor (vWF), fibrinogen and fibronectin are related to a parental history of type 2 diabetes and to determine possible explanatory factors for high versus low vWF and fibrinogen. DESIGN: Cross-sectional study. SUBJECTS, MAIN OUTCOME MEASURE...

  15. Labor management in a patient with on willebrand

    International Nuclear Information System (INIS)

    Saaqib, S.

    2007-01-01

    von Willebrand disease (VWD) is an inherited bleeding disorder involving a deficiency or abnormal function of a blood clotting protein called von Willebrand factor (VWF). Deficiency of VWF, therefore, shows primarily in organs with small blood vessels such as the skin, the gastrointestinal tract and the uterus. This case report describes management of a patient presenting with type II von Willebrand disease in labor. She had history of lifethreatening hemorrhage from an operation for deviated nasal septum and had a risk of severe postpartum hemorrhage (PPH) within 48 hours of delivery, which was avoided by appropriate planning and timely management. (author)

  16. Value of Von Willebrand Factor as a Predictor for Osteoporosis Development in Women with Hypothyroidism

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    I.V. Pankiv

    2015-08-01

    Full Text Available The paper presents the study of the value of von Willebrand factor as a marker of endothelial dysfunction for osteoporosis development and for prediction of risk of its formation in women with hypothyroidism. Postmenopausal women with hypothyroidism have significant increase of von Willebrand factor at lumbar osteopenia. High concentrations of von Willebrand factor in women with hypothyroidism follows to consider it as a predictor for osteoporosis development. Increased level of С-reactive protein belongs to the unfavorable prognostic signs in relation to the decline of bone mineral density for patients with primary hypothyroidism.

  17. Von Willebrand's disease: case report and review of literature.

    Science.gov (United States)

    Echahdi, Hanae; El Hasbaoui, Brahim; El Khorassani, Mohamed; Agadr, Aomar; Khattab, Mohamed

    2017-01-01

    Von Willebrand Disease (VWD) is the most common human inherited bleeding disorder due to a defect of Von Willebrand Factor (VWF), which a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels < 50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50IU/dL). Von willebrand factor is a complex multimeric protein with two functions: it forms a bridge between the platelets and areas of vascular damage and it binds to and stabilizes factor VIII, which is necessary for the clotting cascade. By taking a clinical history of bleeding (mucocutaneous bleeding symptoms suggestive of a primary haemostatic disorder, a quantitative or qualitative abnormality of VWF is possible) it is important to think about VWD and to make the appropriate diagnosis. If the VWD is suspected diagnostic tests should include an activated partial thromboplastin time, bleeding time, factor VIII: C Ristocetin cofactor and vWF antigen. Additional testing of ristocetin induced plattlet adhesion (RIPA) the multimeric structure and collagen binding test and genanalysis allow diagnosing the different types of von. Willebrand Disease. The treatment of choice in mild forms is the synthetic agent desmopressin. In patients with severe type 1, type 2B, 2N and type 3 or in people who do not response to desmopressin, the appropriate treatment is a factor VIII concentrate that is rich of VWF. We report a case of infant in 27-month-old boy who had been referred due to haemorrhagic shock. His birth histories, his familie's social history and developmental milestones were unremarkable. He was born at full term with no antenatal or perinatal complications. Prior to

  18. Elevated levels of plasma von Willebrand factor and the risk of macro- and microvascular disease in type 2 diabetic patients with microalbuminuria

    DEFF Research Database (Denmark)

    Gaede, P; Vedel, P; Parving, H H

    2001-01-01

    BACKGROUND: The purpose of this study was to examine the concept suggesting that microalbuminuria in combination with high levels of plasma von Willebrand factor is a stronger predictor for cardiovascular disease and microvascular complications than microalbuminuria alone in type 2 diabetic...... patients. METHODS: One hundred and sixty patients with type 2 diabetes mellitus and persistent microalbuminuria were followed for an average of 3.8 (SD 0.3) years. 70% of the patients were treated with angiotensin converting enzyme (ACE)-inhibitors. Patients in this subanalysis were divided into two groups...... nephropathy or progression in diabetic retinopathy than microalbuminuria alone in patients with type 2 diabetes and persistent microalbuminuria....

  19. Binding of von Willebrand factor to collagen type III: role of specific amino acids in the collagen binding domain of vWF and effects of neighboring domains

    NARCIS (Netherlands)

    van der Plas, R. M.; Gomes, L.; Marquart, J. A.; Vink, T.; Meijers, J. C.; de Groot, P. G.; Sixma, J. J.; Huizinga, E. G.

    2000-01-01

    Binding of von Willebrand Factor (vWF) to sites of vascular injury is the first step of hemostasis. Collagen types I and III are important binding sites for vWF. We have previously determined the three-dimensional structure of the collagen binding A3 domain of vWF (Huizinga et al., Structure 1997;

  20. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis

    Czech Academy of Sciences Publication Activity Database

    Abdelmagid, N.; Bereczky-Veress, B.; Atanur, S.; Musilová, Alena; Zídek, Václav; Saba, L.; Warnecke, A.; Khademi, M.; Studahl, M.; Aurelius, E.; Hjalmarsson, A.; Garcia-Dias, A.; Denis, C. V.; Bergström, T.; Sköldenberg, B.; Kockum, I.; Aitman, T.; Hübner, N.; Olsson, T.; Pravenec, Michal; Diez, M.

    2016-01-01

    Roč. 11, č. 5 (2016), e0155832 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) 7E10067; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 Keywords : Von Willebrand Factor gene * Herpes simplex encephalitis * rat * humans Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.806, year: 2016

  1. Von Willebrand's disease in the German shepherd dog : clinical communication

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    R.G. Lobetti

    2000-07-01

    Full Text Available Two litters of Germanshepherd dogs were evaluated for a haemorrhagic tendency that was characterised by excessive bleeding from the umbilicus at birth, haemorrhage and haematoma formation at vaccination, excessive bruising, and lameness due to haemarthrosis. Platelet counts, clotting times and Von Willebrand's factor (VWF assays were assessed in all dogs. Factor VIII determination was performed in 1 puppy and its parents. Based on the clotting times and VWF assay, 6 puppies (4 male and 2 female showed type I Von Willebrand's disease (VWD, 5 (4 male and 1 female possible type II VWD, and 4 were unaffected. One puppy with possible type II VWD had very low factor VIII activity; its sire had a normal factor activity, whereas the dam was in the low-normal range. This article reports type I and possible type II VWD in 2 related litters of German shepherd dogs, the latter being rare in German shepherd dogs.

  2. The Molecular Genetics of von Willebrand Disease

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    Ergül Berber

    2012-12-01

    Full Text Available Quantitative and/or qualitative deficiency of von Willebrand factor (vWF is associated with the most common inherited bleeding disease von Willebrand disease (vWD. vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD.

  3. The molecular genetics of von Willebrand disease.

    Science.gov (United States)

    Berber, Ergül

    2012-12-01

    Quantitative and/or qualitative deficiency of von Willebrand factor (vWF) is associated with the most common inherited bleeding disease von Willebrand disease (vWD). vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD. None declared.

  4. Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy : results from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    Holm, Elena; Abshire, Thomas C; Bowen, Joel; Álvarez, M Teresa; Bolton-Maggs, Paula; Carcao, Manuel; Federici, Augusto B; Gill, Joan Cox; Halimeh, Susan; Kempton, Christine; Key, Nigel S; Kouides, Peter; Lail, Alice; Landorph, Andrea; Leebeek, Frank; Makris, Michael; Mannucci, Pier; Mauser-Bunschoten, Eveline P; Nugent, Diane; Valentino, Leonard A; Winikoff, Rochelle; Berntorp, Erik

    Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed

  5. Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise

    NARCIS (Netherlands)

    J.E. van Loon (Janine ); M.A.H. Sonneveld (Michelle); S.F.E. Praet (Stephan); M.P.M. de Maat (Moniek); F.W.G. Leebeek (Frank)

    2014-01-01

    textabstractBackground: Physical stress triggers the endothelium to release von Willebrand Factor (VWF) from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the

  6. Evaluation of von Willebrand factor during pregnancy, lactation and oestrous cycle in bitches affected and unaffected by von Willebrand disease.

    Science.gov (United States)

    Mattoso, C R S; Takahira, R K; Beier, S L; Araujo, J P; Corrente, J E

    2013-06-01

    Plasmatic concentrations of von Willebrand Factor (vWF) increase during pregnancy in humans and dogs; however the mechanism of such increase is still not well defined. The aims of this study were: (i) to evaluate changes in vWF concentration during pregnancy and during the subsequent oestrous cycle in bitches affected and unaffected by von Willebrand Disease (vWD); (ii) to correlate the vWF levels and cortisol levels in both groups. Seven vWD affected (GI) and nine unaffected (GII) bitches were used. The animals were assessed during pregnancy, parturition, lactation and non-gestational oestrous cycle in 11 moments (Pregnancy 1, Pregnancy 2, Parturition, Lactation 1, Lactation 2, Lactation 3, Anestrus, Proestrus, Oestrus, Diestrus 1, and Diestrus 2). The following tests were performed; measurement of von Willebrand factor antigen (vWF:Ag), albumin and cortisol. In both groups, vWF concentration remained stable during the non-gestational oestrous cycle, but increased during pregnancy, with the highest value observed at parturition. Increases of 70% and 124% in vWF were seen in GI and GII, respectively, compared to anestrus. No correlation was found between vWF and cortisol. Values of vWF:Ag changed during pregnancy, with a peak at parturition, both in vWD affected and unaffected animals. Values of vWF were not altered in the different phases of the oestrous cycle following pregnancy in both groups. Evaluation of vWF during pregnancy can cause false negative results for vWD, but assessment can be performed at any point in the oestrous cycle of non-pregnant bitches. © 2012 Blackwell Verlag GmbH.

  7. Von Willebrand protein binds to extracellular matrices independently of collagen.

    OpenAIRE

    Wagner, D D; Urban-Pickering, M; Marder, V J

    1984-01-01

    Von Willebrand protein is present in the extracellular matrix of endothelial cells where it codistributes with fibronectin and types IV and V collagen. Bacterial collagenase digestion of endothelial cells removed fibrillar collagen, but the pattern of fibronectin and of von Willebrand protein remained undisturbed. Exogenous von Willebrand protein bound to matrices of different cells, whether rich or poor in collagen. von Willebrand protein also decorated the matrix of cells grown in the prese...

  8. Von Willebrand disease protects against arterial thrombosis

    NARCIS (Netherlands)

    Sanders, Y.V.; Eikenboom, J.C.; De Wee, E.M.; Van Der Bom, J.G.; Cnossen, M.H.; Degenaar-Dujardin, M.E.; Fijnvandraat, K.; Kamphuisen, P.W.; Laros-Van Gorkum, B.A.; Meijer, K.; Mauser -Bunschoten, E.P.; Leebee k, F.W.

    Background and Aims: Von Willebrand disease (VWD) is caused by reduced levels of or dysfunctional von Willebrand factor (VWF) and is characterized by a bleeding tendency. It is well known that individuals with high VWF levels have a higher risk for arterial thrombosis. Although it has never been

  9. [Homocysteine and von Willebrand factor in chronic alcoholism].

    Science.gov (United States)

    Koriakin, A M; Epifantseva, N N; Dadyka, I V; Gorbatovskiĭ, Ia A

    2010-04-01

    The levels of homocysteine (HC) and von Willebrand factor (VWF) as cardiovascular risk factors were studied in patients with Stage II chronic alcoholism. Forty-one men with Stage II chronic alcoholism without clinical signs of somatic and infectious diseases were examined. Their median age was 37 (range 32-40) years; the alcoholization period was 12 (range 8-17) years. Plasma HC and VWF (amount and activity) levels were determined. In 63.4% of chronic alcoholic patients, HC levels was twice as high as in the controls; in 80.6%, both the content and activity of VWF were increased. There was no correlation between the levels of HC and VWF. Vascular endothelial damage concurrent with hyperhomocysteinemia increases a cardiovascular risk in patients with Stage II chronic alcoholism.

  10. Expression of von Willebrand factor and caldesmon in the placental tissues of pregnancies complicated with intrauterine growth restriction.

    Science.gov (United States)

    Göksever Çelik, Hale; Uhri, Mehmet; Yildirim, Gökhan

    2017-11-02

    The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues. A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits. The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction.

  11. von Willebrand factor, Jedi knight of the bloodstream.

    Science.gov (United States)

    Springer, Timothy A

    2014-08-28

    When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use "the Force" to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned. © 2014 by The American Society of Hematology.

  12. An ELISA for the quantitation of von Willebrand Factor

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Overgaard, Martin; Diederichsen, Axel Cosmus Pyndt

    2013-01-01

    for measurement of von Willebrand factor-osteoprotegerin complex (VWF:OPG) in human plasma. Furthermore, the significance of VWF:OPG complex as a marker of cardiovascular disease (CVD) was evaluated. PATIENTS/METHODS: A sandwich ELISA for quantification of VWF:OPG was developed using a polyclonal rabbit anti...... with and without documented coronary calcification (total n=118). RESULTS AND CONCLUSIONS: The assay detected VWF:OPG complexes in human plasma, while no significant signal was observed when testing solutions containing VWF or recombinant OPG alone. Importantly, the ELISA assay was able to detect in vitro formed...

  13. Single molecule force spectroscopy data and BD- and MD simulations on the blood protein von Willebrand factor

    Directory of Open Access Journals (Sweden)

    Sandra Posch

    2016-09-01

    Full Text Available We here give information for a deeper understanding of single molecule force spectroscopy (SMFS data through the example of the blood protein von Willebrand factor (VWF. It is also shown, how fitting of rupture forces versus loading rate profiles in the molecular dynamics (MD loading-rate range can be used to demonstrate the qualitative agreement between SMFS and MD simulations. The recently developed model by Bullerjahn, Sturm, and Kroy (BSK was used for this demonstration. Further, Brownian dynamics (BD simulations, which can be utilized to estimate the lifetimes of intramolecular VWF interactions under physiological shear, are described. For interpretation and discussion of the methods and data presented here, we would like to directly point the reader to the related research paper, “Mutual A domain interactions in the force sensing protein von Willebrand Factor” (Posch et al., 2016 [1]. Keywords: Atomic force microscopy, Single molecule force spectroscopy, Molecular dynamics simulation, Brownian dynamics simulation, von Willebrand factor

  14. Interference from lupus anticoagulant on von Willebrand factor measurement in splenic marginal zone lymphoma

    DEFF Research Database (Denmark)

    Vinholt, Pernille J; Nybo, Mads

    2015-01-01

    We present a case concerning a patient with splenic marginal zone lymphoma (SMZL) and isolated prolonged activated partial thromboplastin time (aPTT) caused by lupus anticoagulant. Von Willebrand factor (VWF) activity and antigen were immeasurable by latex particle immunoturbidimetric assays...

  15. Of von Willebrand factor and platelets.

    Science.gov (United States)

    Bryckaert, Marijke; Rosa, Jean-Philippe; Denis, Cécile V; Lenting, Peter J

    2015-01-01

    Hemostasis and pathological thrombus formation are dynamic processes that require multiple adhesive receptor-ligand interactions, with blood platelets at the heart of such events. Many studies have contributed to shed light on the importance of von Willebrand factor (VWF) interaction with its platelet receptors, glycoprotein (GP) Ib-IX-V and αIIbβ3 integrin, in promoting primary platelet adhesion and aggregation following vessel injury. This review will recapitulate our current knowledge on the subject from the rheological aspect to the spatio-temporal development of thrombus formation. We will also discuss the signaling events generated by VWF/GPIb-IX-V interaction, leading to platelet activation. Additionally, we will review the growing body of evidence gathered from the recent development of pathological mouse models suggesting that VWF binding to GPIb-IX-V is a promising target in arterial and venous pathological thrombosis. Finally, the pathological aspects of VWF and its impact on platelets will be addressed.

  16. Translational Medicine Advances in von Willebrand Disease

    Science.gov (United States)

    Lillicrap, David

    2014-01-01

    Following the recognition of von Willebrand disease (VWD) in 1926 and the cloning of the gene for von Willebrand factor (VWF) in 1985, significant advances have been made in our fundamental knowledge of both the disease and the protein. Some of this new knowledge has also begun to impact the clinical management of VWD. First, the progressive increase in our understanding of the molecular genetic basis of VWD has resulted in rational applications of molecular testing to complement the current range of phenotypic tests for VWD. These molecular genetic strategies are most effectively directed at the prenatal diagnosis of type 3 VWD and confirmatory testing for types 2B and 2N disease. In contrast, the use of molecular testing to clarify the diagnosis of type 1 VWD is of marginal benefit, at best. In terms of VWD therapies, a new recombinant VWF concentrate has recently completed successful clinical trials and is now awaiting more widespread application. There have even been some pre-clinical successes with VWF gene transfer although the clinical rationale for this therapeutic strategy needs careful consideration. Much more remains to be learnt about the biology of VWF and further translational advances for the enhancement of VWD care will inevitably be realized. PMID:23809112

  17. Characterization of a novel mutation in the von Willebrand factor propeptide in a distinct subtype of recessive von Willebrand disease

    DEFF Research Database (Denmark)

    Lanke, Elsa; Kristoffersson, Ann-Charlotte; Philips, Malou

    2008-01-01

    von Willebrand factor (VWF) is a plasma protein that consists of a series of multimers of which the high-molecular-weight VWF multimers are the most potent in platelet adhesion and aggregation. The propeptide of the VWF (VWFpp) is known to be essential in the process of multimer assembly. Genetic...... mutation in the VWFpp abolishes multimerization of VWF. The mutation probably disrupts the normal configuration of the VWFpp, which is essential for correct orientation of the protomers and ultimately multimerization. The mutant amino acid is located in a region that is highly conserved across several...

  18. Diagnosis and management of von Willebrand disease: a developing country perspective.

    Science.gov (United States)

    Nair, Sukesh Chandran; Viswabandya, Auro; Srivastava, Alok

    2011-07-01

    Special challenges exist in the management of patients with von Willebrand disease (VWD) because of limitations in diagnostic facilities and therapeutic options. However, even within these limitations, it is possible to establish comprehensive services for this condition. Our data show that among 202 patients with VWD, 107 were type 3, 62 were type 1, and the others different categories of type 2. Basic tests such as bleeding time and activated partial thromboplastin time with factor (F)VIII coagulant are able to diagnose most of those with severe disease. We have been able to adapt the specific tests such as von Willebrand factor (VWF) ristocetin cofactor and VWF antigen from the tedious batched manual methods to cost-effective automated methods on advanced coagulometers. Discriminatory tests such as VWF collagen binding, VWF:FVIIIB, ristocetin-induced platelet agglutination (RIPA) are done in batches. Therapeutic options and for the treatment of bleeding include desmopressin, cryoprecipitate, and intermediate purity VWF-containing clotting factor concentrates. Tranexamic acid is also widely used as well as hormonal therapy for menorrhagia. We have also shown that modest doses of intermediate purity FVIII (Koate DVI; Talecris Biotherapeutics, Raleigh, NC, USA) at 35 IU/kg preoperatively and 10 to 20 IU/kg after that are sufficient for surgical hemostasis in these patients. © Thieme Medical Publishers.

  19. A 12.3-kb Duplication Within the VWF Gene in Pigs Affected by Von Willebrand Disease Type 3

    Directory of Open Access Journals (Sweden)

    Stefanie Lehner

    2018-02-01

    Full Text Available Von Willebrand Disease (VWD type 3 is a serious and sometimes fatal hereditary bleeding disorder. In pigs, the disease has been known for decades, and affected animals are used as models for the human disease. Due to the recessive mode of inheritance of VWD type 3, severe bleeding is typically seen in homozygous individuals. We sequenced the complete porcine VWF (Von Willebrand Factor complementary DNA (cDNA and detected a tandem duplication of exons 17 and 18, causing a frameshift and a premature termination codon (p.Val814LeufsTer3 in the affected pig. Subsequent next generation sequencing on genomic DNA proved the existence of a 12.3-kb tandem duplication associated with VWD. This duplication putatively originates from porcine Short Interspersed Nuclear Elements (SINEs located within VWF introns 16 and 18 with high identity. The premature termination truncates the VWF open reading frame by a large part, resulting in an almost entire loss of the mature peptide. It is therefore supposed to account for the severe VWD type 3. Our results further indicate the presence of strong, nonsense-mediated decay in VWF messenger RNA (mRNA containing the duplication, which was supported by the almost complete absence of the complete VWF protein in immunohistochemistry analysis of the VWD-affected pig. In the past, differentiation of wild-type and heterozygous pigs in this VWD colony had to rely on clinical examinations and additional laboratory methods. The present study provides the basis to distinguish both genotypes by performing a rapid and simple genetic analysis.

  20. Establishment and characterization of a new and stable collagen-binding assay for the assessment of von Willebrand factor activity

    Science.gov (United States)

    Ni, Y; Nesrallah, J; Agnew, M; Geske, F J; Favaloro, E J

    2013-01-01

    Introduction Laboratory diagnosis of von Willebrand disease (VWD) requires determination of both von Willebrand factor (VWF) protein levels and activity. Current VWF activity tests include the ristocetin cofactor assay and the collagen-binding assay (VWF:CB). The goal of this investigation is to characterize a new collagen-binding assay and to determine its effectiveness in identifying VWD. Methods Analytical studies were carried out to characterize the performance of a new VWF:CB ELISA. Additionally, samples from a normal population were tested as were well-characterized type 1 and type 2 VWD samples. Results Repeatability and within-laboratory precision studies resulted in coefficients of variation (CVs) of ≤11%. A linear range of 1–354% (0.01–3.54 IU/mL) was determined, along with a limit of detection and a lower limit of quantitation of 1.6% and 4.0% (0.016 and 0.04 IU/mL), respectively. Samples tested from apparently healthy individuals resulted in a normal range of 54–217% (0.54–2.17 IU/mL). Known VWD type 1 and type 2 samples were also analyzed by the ELISA, with 99% of samples having VWF:CB below the normal reference range and an estimated 96% sensitivity and 87% specificity using a VWF collagen-binding/antigen cutoff ratio of 0.50. Conclusion This new VWF:CB ELISA provides an accurate measure of collagen-binding activity that aids in the diagnosis and differentiation of type 1 from type 2 VWD. PMID:23107512

  1. Profile of von Willebrand factor antigen and von Willebrand factor propeptide in an overall TIA and ischaemic stroke population and amongst subtypes.

    Science.gov (United States)

    Tobin, W O; Kinsella, J A; Kavanagh, G F; O'Donnell, J S; McGrath, R T; Tierney, S; Egan, B; Feeley, T M; Coughlan, T; Collins, D R; O'Neill, D; Murphy, Sjx; Lim, S J; Murphy, R P; McCabe, Djh

    2017-04-15

    Von Willebrand factor propeptide (VWF:Ag II) is proposed to be a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). Simultaneous data on VWF:Ag and VWF:Ag II profiles are very limited following TIA and ischaemic stroke. In this prospective, observational, case-control study, plasma VWF:Ag and VWF:Ag II levels were quantified in 164 patients≤4weeks of TIA or ischaemic stroke (baseline), and then ≥14days (14d) and ≥90days (90d) later, and compared with those from 27 healthy controls. TIA and stroke subtyping was performed according to the TOAST classification. The relationship between VWF:Ag and VWF:Ag II levels and platelet activation status was assessed. 'Unadjusted' VWF:Ag and VWF:Ag II levels were higher in patients at baseline, 14d and 90d than in controls (p≤0.03). VWF:Ag levels remained higher in patients than controls at baseline (p≤0.03), but not at 14d or 90d after controlling for differences in age or hypertension, and were higher in patients at baseline and 90d after controlling for smoking status (p≤0.04). 'Adjusted' VWF:Ag II levels were not higher in patients than controls after controlling for age, hypertension or smoking (p≥0.1). Patients with symptomatic carotid stenosis (N=46) had higher VWF:Ag and VWF:Ag II levels than controls at all time-points (p≤0.002). There was no significant correlation between platelet activation status and VWF:Ag or VWF:Ag II levels. VWF:Ag and VWF:Ag II levels are increased in an overall TIA and ischaemic stroke population, especially in patients with recently symptomatic carotid stenosis. VWF:Ag II was not superior to VWF:Ag at detecting acute endothelial activation in this cohort and might reflect timing of blood sampling in our study. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Dynamics of von Willebrand factor reactivity in sickle cell disease during vaso-occlusive crisis and steady state

    NARCIS (Netherlands)

    Sins, J. W. R.; Schimmel, M.; Luken, B. M.; Nur, E.; Zeerleder, S. S.; van Tuijn, C. F. J.; Brandjes, D. P. M.; Kopatz, W. F.; Urbanus, R. T.; Meijers, J. C. M.; Biemond, B. J.; Fijnvandraat, K.

    2017-01-01

    Background: Endothelial activation plays a central role in the pathophysiology of vaso-occlusion in sickle cell disease (SCD), facilitating adhesive interactions with circulating blood cells. Upon activation, various adhesive molecules are expressed, including von Willebrand factor (VWF). Increased

  3. Nordic Haemophilia Council's practical guidelines on diagnosis and management of von Willebrand disease

    DEFF Research Database (Denmark)

    Lassila, Riitta; Holme, Pål André; Landorph, Andrea

    2011-01-01

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder characterized by spontaneous or tissue injury-related, mostly mucocutaneous, bleeding events. VWD affects both males and females and is caused by quantitative or qualitative deficiency of Von Willebrand factor. The diagno......Von Willebrand disease (VWD) is the most common inherited bleeding disorder characterized by spontaneous or tissue injury-related, mostly mucocutaneous, bleeding events. VWD affects both males and females and is caused by quantitative or qualitative deficiency of Von Willebrand factor...... subtyping may also be problematic. This article summarizes the guidelines of the Nordic Haemophilia Council (NHC), which are intended to serve as a practical tool and provide the standards for diagnosing and treating VWD patients. The complete Nordic Guidelines on VWD are available at the NHC Web site (http://nordhemophilia.org)....

  4. Paciente portadora de doença de von Willebrand submetida a cirurgia da valva mitral: uma estratégia para o controle da coagulopatia Patient with von Willebrand disease undergoing mitral valve repair: a strategy for the control of the coagulopathy

    Directory of Open Access Journals (Sweden)

    Ally Nader Roquetti Saroute

    2007-01-01

    Full Text Available Relatamos o caso de uma mulher de 60 anos portadora da doença de von Willebrand tipo I, submetida a cirurgia da valva mitral. A paciente necessitou de cuidados especiais em razão da coagulopatia e foi necessária a utilização de concentrado de fator VIII (VIIIf e fator de von Willebrand (vWf antes, durante e depois da cirurgia. Não houve complicações durante e após a cirurgia. Nove meses depois, a paciente encontra-se assintomática. A correção para valores adequados de VIIIf e vWf permitiu a realização da cirurgia com segurança.We report a case of a 60 year-old woman with von Willebrand disease type I that was submitted to a mitral valve repair. The patient needed special care due coagulopathy and needed VIII factor (VIIIf and von Willebrand factor (vWf, before, during and after surgery. There was no complication during or after surgery. Patient is asymptomatic nine months postoperatively. The correction of VIIIf and vWf allowed the realization of a safety surgery.

  5. PROTEOLYTIC PROCESSING OF VON WILLEBRAND FACTOR BY ADAMTS13 AND LEUKOCYTE PROTEASES

    Directory of Open Access Journals (Sweden)

    Stefano Lancellotti

    2013-09-01

    Full Text Available ADAMTS13 is a 190 kDa zinc protease encoded by a gene located on chromosome 9q34.   This protease specifically hydrolyzes von Willebrand factor (VWF multimers, thus causing VWF size reduction. ADAMTS13 belongs to the A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS family, involved in proteolytic processing of many matrix proteins. ADAMTS13 consists of numerous domains including a metalloprotease domain, a disintegrin domain, several thrombospondin type 1 (TSP1 repeats, a cysteine-rich domain, a spacer domain and 2 CUB (Complement c1r/c1s, sea Urchin epidermal growth factor, and Bone morphogenetic protein domains. ADAMTS13 cleaves a single peptide bond (Tyr1605-Met1606 in the central A2 domain of the VWF molecule. This proteolytic cleavage is essential to reduce the size of ultra-large VWF polymers, which, when exposed to high shear stress in the microcirculation, are prone to form with platelets clumps, which cause severe syndromes called thrombotic microangiopathies (TMAs. In this review, we a discuss the current knowledge of structure-function aspects of ADAMTS13 and its involvement in the pathogenesis of TMAs, b address the recent findings concerning proteolytic processing of VWF multimers by different proteases, such as the leukocyte-derived serine and metallo-proteases and c indicate the direction of future investigations

  6. Dynamics of von Willebrand factor reactivity in sickle cell disease during vaso-occlusive crisis and steady state

    NARCIS (Netherlands)

    Sins, J. W.R.; Schimmel, Marein; Luken, Brenda M.; Nur, Erfan; Zeerleder, S.; van Tuijn, Charlotte F. J.; Brandjes, Dees P. M.; Kopatz, W. F.; Urbanus, R. T.; Meijers, Joost C. M.; Biemond, B. J.; Fijnvandraat, K.

    2017-01-01

    Essentials The role of von Willebrand Factor (VWF) in the pathophysiology of sickle cell disease is unclear. We assessed markers of VWF during admission for vaso-occlusive crisis (VOC) and steady state. VWF reactivity was higher during VOC and was associated with inflammation and neutrophil

  7. Comparative analysis of von Willebrand factor profiles after implantation of left ventricular assist device and total artificial heart.

    Science.gov (United States)

    Reich, H J; Morgan, J; Arabia, F; Czer, L; Moriguchi, J; Ramzy, D; Esmailian, F; Lam, L; Dunhill, J; Volod, O

    2017-08-01

    Essentials Bleeding is a major source of morbidity during mechanical circulatory support. von Willebrand factor (VWF) multimer loss may contribute to bleeding. Different patterns of VWF multimer loss were seen with the two device types. This is the first report of total artificial heart associated VWF multimer loss. Background Bleeding remains a challenge during mechanical circulatory support and underlying mechanisms are incompletely understood. Functional von Willebrand factor (VWF) impairment because of loss of high-molecular-weight multimers (MWMs) produces acquired von Willebrand disease (VWD) after left ventricular assist device (LVAD). Little is known about VWF multimers with total artificial hearts (TAHs). Here, VWF profiles with LVADs and TAHs are compared using a VWD panel. Methods VWD evaluations for patients with LVAD or TAH (2013-14) were retrospectively analyzed and included: VWF activity (ristocetin cofactor, VWF:RCo), VWF antigen (VWF:Ag), ratio of VWF:RCo to VWF:Ag, and quantitative VWF multimeric analysis. Results Twelve patients with LVADs and 12 with TAHs underwent VWD evaluation. All had either normal (47.8%) or elevated (52.2%) VWF:RCo, normal (26.1%) or elevated (73.9%) VWF:Ag and 50.0% were disproportional (ratio ≤ 0.7). Multimeric analysis showed abnormal patterns in all patients with LVADs: seven with high MWM loss; five with highest MWM loss. With TAH, 10/12 patients had abnormal patterns: all with highest MWM loss. High MWM loss correlated with presence of LVAD and highest MWM loss with TAH. Increased low MWMs were detected in 22/24. Conclusion Using VWF multimeric analysis, abnormalities after LVAD or TAH were detected that would be missed with measurements of VWF level alone: loss of high MWM predominantly in LVAD, loss of highest MWM in TAH, and elevated levels of low MWM in both. This is the first study to describe TAH-associated highest MWM loss, which may contribute to bleeding. © 2017 International Society on Thrombosis and

  8. Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Robben, J H; Deen, P M T

    2010-01-01

    SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

  9. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

    Directory of Open Access Journals (Sweden)

    Jacqueline Stockley

    Full Text Available The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12 could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =, both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =. Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.

  10. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR) Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

    Science.gov (United States)

    Stockley, Jacqueline; Nisar, Shaista P; Leo, Vincenzo C; Sabi, Essa; Cunningham, Margaret R; Eikenboom, Jeroen C; Lethagen, Stefan; Schneppenheim, Reinhard; Goodeve, Anne C; Watson, Steve P; Mundell, Stuart J; Daly, Martina E

    2015-01-01

    The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12) could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =), both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N) was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =). Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.

  11. Association of ABO blood groups with von Willebrand factor, factor VIII and ADAMTS-13 in patients with lung cancer.

    Science.gov (United States)

    Liu, Xia; Chen, Xiaogang; Yang, Jiezuan; Guo, Renyong

    2017-09-01

    Coagulative and fibrinolytic disorders appear to be associated with the development of lung cancer. The aim of the present study was to determine plasma levels of von Willebrand factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif 13 (ADAMTS-13), and factor VIII (FVIII) activity, in association with O and non-O blood groups in patients with lung cancer. Plasma levels of VWF and ADAMTS-13, and FVIII activity were measured in 115 patients with lung cancer and 98 healthy subjects. Phenotyping of the ABO blood groups was also performed for the two groups. Significantly increased VWF levels and FVIII activity, as well as significantly decreased ADAMTS-13 levels, were observed in patients with distant metastasis as compared with those without distant metastasis and the healthy controls. Plasma VWF levels and FVIII activity were significantly increased in subjects with non-O type blood compared with those with type O blood in the two groups. However, a significant decrease in ADAMTS-13 levels was observed only in the control group among those with non-O type blood, compared with those with type O blood. The results of the present study indicate that increased VWF and decreased ADAMTS-13 levels facilitate the invasiveness and metastasis of lung cancer. Non-O blood groups constitute a risk factor for increased VWF and FVIII in plasma. Continued monitoring of VWF and ADAMTS-13 levels, and of FVIII activity in patients with lung cancer with distinct blood groups may help to minimize the incidence of thrombotic events and improve assessment of disease progression.

  12. Platelet-type von Willebrand Disease: Diagnostic Challenges. Flaws and Pitfalls Experienced in the THROMKID Quality Project.

    Science.gov (United States)

    Maurer, M; Mesters, R; Schneppenheim, R; Knoefler, R; Streif, W

    2015-05-01

    Primary haemostasis defects comprise von Willebrand disease (VWD) and platelet disorders (PD). Although presenting with mild to moderate bleeding tendency in most cases, severe bleeding and blood loss may occur unexpectedly in trauma and surgery. Diagnosis of VWD and PD often remains difficult owing to the wide spectrum of clinical and laboratory manifestations. Platelet-type von Willebrand disease (PT-VWD) is frequently misdiagnosed as type 2B VWD. Discrimination between type 2B VWD and PT-VWD is crucial as treatment differs. A literature review revealed difficulties in diagnostic work-up and choice of optimal treatment of PT-VWD. Guidelines favour the therapeutic use of platelet concentrates. A telephone survey of diagnostic practice with regard to type 2B VWD/PT-VWD was conducted. The prevalence and incidence of type 2B and PT-VWD remained unclear, but PT-VWD may be underestimated. An international study estimated that PT-VWD constitutes up to 15% of the total number of patients diagnosed with type 2B VWD. Our survey confirmed difficulties with diagnosis and showed that some centres did not exclude PT-VWD in type 2B patients. Some authors emphasize that genetic testing is the gold standard for diagnosis, but functional testing allows immediate diagnosis. Due to the important therapeutic implications we suggest that type 2B VWD be confirmed by genetic testing and that in case of a negative result PT-VWD should be excluded. PT-VWD should be excluded in all suspected cases of type 2B. PT-VWD should be treated with platelet concentrates. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Increased active von Willebrand factor during disease development in the aging diabetic patient population.

    Science.gov (United States)

    Chen, Shuang Feng; Xia, Zuo Li; Han, Ji Ju; Wang, Yi Ting; Wang, Ji Yue; Pan, Shao Dong; Wu, Ya Ping; Zhang, Bin; Li, Guang Yao; Du, Jing Wei; Gao, Hen Qiang; de Groot, Philip G; de Laat, Bas; Hollestelle, Martine J

    2013-02-01

    Type 2 diabetes is known to cause endothelial activation resulting in the secretion of von Willebrand factor (VWF). We have shown that levels of VWF in a glycoprotein Ib-binding conformation are increased in specific clinical settings. The aim of the current study is to investigate whether active VWF levels increase during aging and the development of diabetes within the population of patients suffering from type 2 diabetes. Patients and controls were divided into two groups based on age: older and younger than 60 years of age. VWF antigen, VWF propeptide, VWF activation factor and total active VWF were measured. Patients older than 60 years of age had increased levels of total active VWF, VWF activation factor and VWF propeptide compared to younger patients and controls. All measured VWF parameters were associated with age in diabetic patients. Total active VWF and VWF propeptide correlated with the period of being diagnosed with diabetes. Regression analyses showed that especially the VWF activation factor was strongly associated with diabetes in patients older than 60 years of age. In conclusion, we found that the conformation of VWF could be involved in the disease process of diabetes and that the VWF in a glycoprotein Ib-binding conformation could play a role as risk marker during the development of diabetes in combination with an increase in age. Our study shows that the active quality of VWF was more important than the quantity.

  14. Regulation of plasma von Willebrand factor [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Karl C Desch

    2018-01-01

    Full Text Available Von Willebrand factor (VWF is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.

  15. Characterization of an entomopathogenic fungi target integument protein, Bombyx mori single domain von Willebrand factor type C, in the silkworm, Bombyx mori.

    Science.gov (United States)

    Han, F; Lu, A; Yuan, Y; Huang, W; Beerntsen, B T; Huang, J; Ling, E

    2017-06-01

    The insect cuticle works as the first line of defence to protect insects from pathogenic infections and water evaporation. However, the old cuticle must be shed in order to enter the next developmental stage. During each ecdysis, moulting fluids are produced and secreted into the area among the old and new cuticles. In a previous study, the protein Bombyx mori single domain von Willebrand factor type C (BmSVWC; BGIBMGA011399) was identified in the moulting fluids of Bo. mori and demonstrated to regulate ecdysis. In this study we show that in Bo. mori larvae, BmSVWC primarily locates to the integument (epidermal cells and cuticle), wing discs and head. During the moulting stage, BmSVWC is released into the moulting fluids, and is then produced again by epidermal cells after ecdysis. Fungal infection was shown to decrease the amount of BmSVWC in the cuticle, which indicates that BmSVWC is a target protein of entomopathogenic fungi. Thus, BmSVWC is mainly involved in maintaining the integrity of the integument structure, which serves to protect insects from physical damage and pathogenic infection. © 2017 The Royal Entomological Society.

  16. Detection of von Willebrand factor and tissue factor in platelets-fibrin rich coronary thrombi in acute myocardial infarction.

    Science.gov (United States)

    Yamashita, Atsushi; Sumi, Takahiro; Goto, Shinya; Hoshiba, Yasunari; Nishihira, Kensaku; Kawamoto, Riichirou; Hatakeyama, Kinta; Date, Haruhiko; Imamura, Takuroh; Ogawa, Hisao; Asada, Yujiro

    2006-01-01

    The rapid closure of coronary arteries due to occlusive thrombi is the major cause of acute myocardial infarction. However, the mechanisms of coronary thrombus formation have not been elucidated. We immunohistochemically assessed the localizations and their changes over time of glycoprotein IIb/IIIa, fibrin, von Willebrand factor (vWF), and tissue factor (TF), after the onset of chest pain (platelets, fibrin, vWF, and TF from the early phase of onset, and glycoprotein IIb/IIIa and fibrin were closely associated with vWF and TF, respectively. vWF and/or TF may contribute to occlusive thrombus formation and be novel therapeutic candidates for treating patients with coronary thrombosis.

  17. Von-Willebrand Disease Presenting as Intractable Epistaxis after Nasal Polypectomy

    Directory of Open Access Journals (Sweden)

    Jeong Jin Park

    2014-01-01

    Full Text Available Von-Willebrand disease (VWD is one of the platelet dysfunction disorders that results from a deficiency of Von-Willebrand factor, which is essential for hemostasis. VWD patients typically have normal laboratory results on screening for bleeding disorders. To suspect and diagnose VWD, a careful review of past medical history and laboratory tests is critical. A 59-year-old male patient presented with intractable nasal bleeding after nasal polypectomy. The bleeding was controlled by platelet transfusion, and he was later diagnosed with VWD.

  18. Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage

    Directory of Open Access Journals (Sweden)

    Arunima Ghosh

    2012-01-01

    Full Text Available von Willebrand disease (VWD is the most common inherited human bleeding disorder and is caused by quantitative or qualitative defects in von Willebrand factor (VWF. VWF is a secreted glycoprotein that circulates as large multimers. While reduced VWF is associated with bleeding, elevations in overall level or multimer size are implicated in thrombosis. The zebrafish is a powerful genetic model in which the hemostatic system is well conserved with mammals. The ability of this organism to generate thousands of offspring and its optical transparency make it unique and complementary to mammalian models of hemostasis. Previously, partial clones of zebrafish vwf have been identified, and some functional conservation has been demonstrated. In this paper we clone the complete zebrafish vwf cDNA and show that there is conservation of domain structure. Recombinant zebrafish Vwf forms large multimers and pseudo-Weibel-Palade bodies (WPBs in cell culture. Larval expression is in the pharyngeal arches, yolk sac, and intestinal epithelium. These results provide a foundation for continued study of zebrafish Vwf that may further our understanding of the mechanisms of VWD.

  19. Acquired von Willebrand syndrome: A rare disorder of heterogeneous etiology

    Directory of Open Access Journals (Sweden)

    P Kasatkar

    2013-01-01

    Full Text Available Context: Acquired von Willebrand syndrome (AVWS is a rare bleeding disorder that mimics the inherited form of von Willebrand disease (VWD in terms of laboratory findings and clinical presentation. Aims: To study the etiology of acquired VWD. Settings and Design: The patients referred from various hospitals in and out of Mumbai were included in the study. Materials and Methods: Six patients with AVWS diagnosed at this center over the last 10 years were analyzed against 171 patients with inherited VWD. The differential diagnosis of AVWS was made based on reduced levels of von Willebrand antigen and von Willebrand ristocetin cofactor, decrease in ristocetin induced platelet aggregation, absence of correction in mixing studies with no prior history of bleeding problems and a negative family history for bleeding disorders. Results: In three patients, the disease was associated with systematic lupus erythematosus, out of which one was also associated with Kikuchi lymphadenitis and second with autoimmune hemolytic anemia. Fourth case was associated with hypothyroidism and fifth was a case of dermatitis and vitiligo. The last patient was a case of hemophilia A with Burkitts lymphoma, who developed autoantibodies to von Willebrand factor. Except two patients, all other patients responded to immune suppressive therapy with corticosteroids, while the patient with hypothyroidism responded to oral thyroxine. Conclusion: AVWS is a rare condition and may often be missed or diagnosed as inherited disease associated with heterogeneous disease conditions.

  20. Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population.

    Science.gov (United States)

    Wang, Zongkui; Dou, Miaomiao; Du, Xi; Ma, Li; Sun, Pan; Cao, Haijun; Ye, Shengliang; Jiang, Peng; Liu, Fengjuan; Lin, Fangzhao; Zhang, Rong; Li, Changqing

    2017-01-01

    ABO blood group is a hereditary factor of plasma levels of coagulation factor VIII (FVIII) and von Willebrand factor (VWF). Age and gender have been shown to influence FVIII, VWF, fibrinogen (Fbg), and ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 motif, 13). We investigated the effects of ABO type, age, and gender on plasma levels of FVIII, Fbg, VWF, and ADAMTS13 in a Chinese population. A total of 290 healthy volunteers were eligible for this study. ABO blood group was determined by indirect technique. FVIII:C and Fbg were measured by clotting assays. VWF antigen (VWF:Ag), collagen-binding activity (VWF:CBA), and ADAMTS13 antigen were assessed by ELISA, whereas VWF ristocetin cofactor activity (VWF:Rcof) was performed by agglutination of platelets with ristocetin. Mean FVIII:C and VWF levels (VWF:Ag, VWF:CBA, and VWF:Rcof) were significantly higher in non-O than in O type subjects ( p  blood group, age, and gender showed different effects on plasma levels of FVIII:C, Fbg, VWF:Ag, VWF:CBA, VWF:Rcof, and ADAMTS13 antigen. These new data on a Chinese population are quite helpful to compare with other ethnic groups.

  1. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Directory of Open Access Journals (Sweden)

    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats with the asymptomatic infection of BN (Brown Norway. Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains, displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus named Hse6 towards the end of chromosome 4 (160.89-174Mb containing the Vwf (von Willebrand factor gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism. Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008 after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  2. Descripción de un inmunoensayo enzimático que reconoce anticuerpos anti-factor VIII/von Willebrand obtenidos a partir de hibridomas múridos Description of an enzime immunoassay that recognizes anti-factor VIII/von Willebrand antibodies obtained from murine hybridomas

    Directory of Open Access Journals (Sweden)

    Renée González Sampedro

    1999-04-01

    Full Text Available Se describe un inmunoensayo enzimático (ELISA que detecta anticuerpos anti-Factor-VIII/von Willebrand (FVIII/vW, con una relación de enlace > 5, que permite reconocer dichos anticuerpos tempranamente en los cultivos de hibridomas múridos. Para la adsorción de las placas del inmunoensayo se utilizaron preparados semipurificados de FVIII/vW obtenidos en Cuba. Se inmunizaron ratones Balb/c con la finalidad de generar los anticuerpos monoclonales detectados por este ELISA. Se obtuvo un clon con crecimiento estable y varios subclones positivos por el ELISA con actividad biológica específica de anticuerpos inhibidores de FVIIIAn enzime immunoassay (ELISA that detects anti-Factor VIII/von Willebrand (FVIII/vw antibodies with a binding relationship > 5 that allows the early recognition of such antibodies in the cultures of murine hybridomas is described. Semipurified preparations of FVIII/vw obtained in Cuba were used for the adsorption of the immunoassay plates. Balb/c mice were immunized in order to generate the monoclonal antibodies detected by this ELISA. A clone with stable growth and several positive subclones were obtained by ELISA with specific biological activity of FVIII-inhibiting antibodies

  3. A pilot study of homocyst(e)ine levels in essential hypertension: relationship to von Willebrand factor, an index of endothelial damage.

    Science.gov (United States)

    Lip, G Y; Edmunds, E; Martin, S C; Jones, A F; Blann, A D; Beevers, D G

    2001-07-01

    An interaction between homocyst(e)ine and the endothelium in hypertensive patients may promote thrombogenesis and atherogenesis, leading to adverse cardiovascular events. We hypothesized that homocyst(e)ine levels are abnormal in patients with essential hypertension, and that this may be related to an adverse effect on the vascular endothelium. Accordingly, we compared plasma levels of homocyst(e)ine and von Willebrand factor (marking endothelial damage) in 83 patients (43 men; mean age 54 +/- standard deviation 15.9 years) with essential hypertension (> 160/90 mm Hg), with levels in 25 healthy normotensive controls (13 men; mean age 56+/-11.8 years). Baseline levels of the markers and other clinical indices were then related to adverse cardiovascular events at follow-up. Plasma homocyst(e)ine (P = .0001) and von Willebrand factor (P = .031) levels were significantly higher in hypertensives compared to controls. After a mean follow-up of 76 patients for 45 months (range, 1 to 66 months), 17 subjects experienced an end point of either cardiovascular death (n = 10) or adverse cardiovascular event (n = 7). Comparing these 17 with the 59 free of an end point, the former were older (P = .0002) and had a longer duration of known hypertension (P = .018). There was a nonsignificant trend toward higher median plasma homocyst(e)ine levels in the patients sustaining a vascular end point (P = .07). In this pilot study, we suggest that essential hypertension may be associated with increased plasma homocyst(e)ine levels, but that this amino acid is unrelated to endothelial damage (von Willebrand factor), clinical indices, or prognosis.

  4. Decrease of hemostatic cardiovascular risk factors by aggressive vs. conventional atorvastatin treatment in patients with Type 2 diabetes mellitus.

    NARCIS (Netherlands)

    Ree, M.A. van de; Maat, M.P. de; Kluft, C.; Meinders, A.E.; Princen, H.M.; Huisman, M.V.

    2003-01-01

    BACKGROUND: Patients with Type 2 diabetes mellitus have increased levels of hemostatic risk variables for cardiovascular disease, such as fibrinogen, von Willebrand factor (VWF), factor (F)VIIa, d-dimer and plasminogen activator inhibitor-1 (PAI-1). OBJECTIVES: To evaluate the effect of aggressive

  5. Dogs with hearth diseases causing turbulent high-velocity blood flow have changes in patelet function and von Willebrand factor multimer distribution

    DEFF Research Database (Denmark)

    Tarnow, Inge; Kristensen, Annemarie Thuri; Olsen, Lisbeth Høier

    2005-01-01

    The purpose of this prospective study was to investigate platelet function using in vitro tests based on both high and low shear rates and von Willebrand factor (vWf) multimeric composition in dogs with cardiac disease and turbulent high-velocity blood flow. Client-owned asymptomatic, untreated d...

  6. Increased metastatic potential of tumor cells in von Willebrand factor-deficient mice.

    Science.gov (United States)

    Terraube, V; Pendu, R; Baruch, D; Gebbink, M F B G; Meyer, D; Lenting, P J; Denis, C V

    2006-03-01

    The key role played by von Willebrand factor (VWF) in platelet adhesion suggests a potential implication in various pathologies, where this process is involved. In cancer metastasis development, tumor cells interact with platelets and the vessel wall to extravasate from the circulation. As a potential mediator of platelet-tumor cell interactions, VWF could influence this early step of tumor spread and therefore play a role in cancer metastasis. To investigate whether VWF is involved in metastasis development. In a first step, we characterized the interaction between murine melanoma cells B16-BL6 and VWF in vitro. In a second step, an experimental metastasis model was used to compare the formation of pulmonary metastatic foci in C57BL/6 wild-type and VWF-null mice following the injection of B16-BL6 cells or Lewis lung carcinoma cells. In vitro adhesion assays revealed that VWF is able to promote a dose-dependent adhesion of B16-BL6 cells via its Arg-Gly-Asp (RGD) sequence. In the experimental metastasis model, we found a significant increase in the number of pulmonary metastatic foci in VWF-null mice compared with the wild-type mice, a phenotype that could be corrected by restoring VWF plasma levels. We also showed that increased survival of the tumor cells in the lungs during the first 24 h in the absence of VWF was the cause of this increased metastasis. These findings suggest that VWF plays a protective role against tumor cell dissemination in vivo. Underlying mechanisms remain to be investigated.

  7. Exercise-induced shear stress is associated with changes in plasma von Willebrand factor in older humans

    OpenAIRE

    Gonzales, Joaquin U.; Thistlethwaite, John R.; Thompson, Benjamin C.; Scheuermann, Barry W.

    2009-01-01

    Shear stress is the frictional force of blood against the endothelium, a stimulus for endothelial activation and the release of von Willebrand factor (vWF). This study tested the hypothesis that the increase in shear stress associated with exercise correlates with plasma vWF. Young (n = 14, 25.7 ± 5.4 y) and older (n = 13, 65.6 ± 10.7 y) individuals participated in 30 min of dynamic handgrip exercise at a moderate intensity. Brachial artery diameter and blood flow were measured using ultrasou...

  8. Clinical and laboratory diagnosis of von Willebrand disease: A synopsis of the 2008 NHLBI/NIH guidelines

    Science.gov (United States)

    Nichols, William L.; Rick, Margaret E.; Ortel, Thomas L.; Montgomery, Robert R.; Sadler, J. Evan; Yawn, Barbara P.; James, Andra H.; Hultin, Mae B.; Manco-Johnson, Marilyn J.; Weinstein, Mark

    2017-01-01

    Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd). PMID:19415721

  9. Von willebrand factor cleaving protease activity in the physiopathology of microangiopathic disorders Detección de la actividad de la proteasa que cliva al factor von Willebrand en la patofisiología de las microangiopatías

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    M. M. Amaral

    2003-04-01

    Full Text Available The von Willebrand factor cleaving protease (VWFCP modulates the von Willebrand factor (VWF multimeric size in normal plasma. VWFCP activity levels are decreased in different physiological and pathologic situations. Different techniques have been developed to unfold the purified VWF (perfusion at high shear rate, dialysis against urea in nitrocellulose filters, to detect the VWFCP activity on it (multimeric analysis of VWF, collagen binding to VWF assay and to use the patient plasma both as the source of the enzyme and substrate. In this paper we compared the above mentioned methods with new ones: normal plasma dialyzed on membranes instead of purified VWF, dialysis of the samples against urea in tubing instead of nitrocellulose filters, and sonicated plasma to remove the endogenous VWF. The perfusion assay and detection by multimeric analysis showed a limit of detection (25% of VWFCP activity. Dialysis against urea in both supports and detection by multimeric analysis, showed a better limit of detection (3%, but the recovery of the samples was not as efficient in nitrocellulose filters as it was in tubing. The detection by collagen binding to VWF has more advantages because it allows to analyze more samples than the multimeric analysis does in the same assay. The dialysis of plasma by membranes to obtain the source of exogenous VWF requires no complex equipment. The method, which uses patient plasma as the source of the enzyme and substrate, was inapplicable in our experience because the values could not be interpolated in the reference curve.La proteasa que cliva al factor von Willebrand (VWFCP controla el tamaño multimérico del factor von Willebrand (VWF en plasma normal. Sus niveles se encuentran disminuidos en diferentes situaciones fisiológicas y patológicas. Diferentes técnicas se desarrollaron para desplegar al VWF purificado (perfusión a alta fuerza de cizallamiento, diálisis contra urea en filtros de nitrocelulosa, para detectar

  10. Modeling Shear Induced Von Willebrand Factor Binding to Collagen

    Science.gov (United States)

    Dong, Chuqiao; Wei, Wei; Morabito, Michael; Webb, Edmund; Oztekin, Alparslan; Zhang, Xiaohui; Cheng, Xuanhong

    2017-11-01

    Von Willebrand factor (vWF) is a blood glycoprotein that binds with platelets and collagen on injured vessel surfaces to form clots. VWF bioactivity is shear flow induced: at low shear, binding between VWF and other biological entities is suppressed; for high shear rate conditions - as are found near arterial injury sites - VWF elongates, activating its binding with platelets and collagen. Based on parameters derived from single molecule force spectroscopy experiments, we developed a coarse-grain molecular model to simulate bond formation probability as a function of shear rate. By introducing a binding criterion that depends on the conformation of a sub-monomer molecular feature of our model, the model predicts shear-induced binding, even for conditions where binding is highly energetically favorable. We further investigate the influence of various model parameters on the ability to predict shear-induced binding (vWF length, collagen site density and distribution, binding energy landscape, and slip/catch bond length) and demonstrate parameter ranges where the model provides good agreement with existing experimental data. Our results may be important for understanding vWF activity and also for achieving targeted drug therapy via biomimetic synthetic molecules. National Science Foundation (NSF),Division of Mathematical Sciences (DMS).

  11. Association of von Willebrand factor blood levels with exercise hypertension.

    Science.gov (United States)

    Nikolic, Sonja B; Adams, Murray J; Otahal, Petr; Edwards, Lindsay M; Sharman, James E

    2015-05-01

    A hypertensive response to moderate intensity exercise (HRE) is associated with increased cardiovascular risk. The mechanisms of an HRE are unclear, although previous studies suggest this may be due to haemostatic and/or haemodynamic factors. We investigated the relationships between an HRE with haemostatic and hemodynamic indices. Sixty-four participants (57 ± 10 years, 71 % male) with indication for exercise stress testing underwent cardiovascular assessment at rest and during moderate intensity exercise, from which 20 participants developed an HRE (defined as moderate exercise systolic BP ≥ 170 mmHg/men and ≥ 160 mmHg/women). Rest, exercise and post-exercise blood samples were analysed for haemostatic markers, including von Willebrand factor (vWf), and haemodynamic measures of brachial and central blood pressure (BP), aortic stiffness and systemic vascular resistance index (SVRi). HRE participants had higher rest vWf compared with normotensive response to exercise (NRE) participants (1,927 mU/mL, 95 % CI 1,240-2,615, vs. 1,129 mU/mL, 95 % CI 871-1,386; p = 0.016). vWf levels significantly decreased from rest to post-exercise in HRE participants (p = 0.005), whereas vWf levels significantly increased from rest to exercise in NRE participants (p = 0.030). HRE participants also had increased triglycerides, rest BP, aortic stiffness and exercise SVRi (p HRE at moderate intensity.

  12. Percutaneous coronary intervention and the management of acute coronary syndromes in patients with von Willebrand disease.

    Science.gov (United States)

    Rathore, Sulaiman; Deleon, Dexter; Akram, Hafsa; Sane, David; Ball, Timothy

    2013-04-01

    Von Willebrand disease (vWD) results from quantitative or qualitative deficiency of von Willebrand factor (vWF). The occurrence of myocardial infarction is very rare in patients with vWD. A few case reports of acute coronary syndrome (ACS) in vWD patients are present in the literature, but no definite management recommendations are available for such patients. We report a case of successful percutaneous coronary intervention (PCI) with bare-metal stent (BMS) implantation in a 46-year-old woman with type 1 vWD and history of coronary artery disease (CAD). She received periprocedural dual-antiplatelet therapy for 2 weeks and then continued aspirin without any bleeding complications. The optimal management of patients with vWD and ACS is complex and presents a therapeutic challenge. We propose that dual-antiplatelet therapy can be used safely in most vWD patients presenting with ACS as most of them are type 1 vWD. PCI with BMS can be done safely. Long-term management of these patients requires a systemic approach including hematological consultation, ascertaining vWF levels, as well as patient education and close outpatient follow-up.

  13. Testosterone and acute stress are associated with fibrinogen and von Willebrand factor in African men: the SABPA study.

    Science.gov (United States)

    Malan, Nicolaas T; von Känel, Roland; Schutte, Alta E; Huisman, Hugo W; Schutte, Rudolph; Smith, Wayne; Mels, Carina M; Kruger, Ruan; Meiring, Muriel; van Rooyen, Johannes M; Malan, Leoné

    2013-10-12

    Low testosterone, acute and chronic stress and hypercoagulation are all associated with hypertension and hypertension-related diseases. The interaction between these factors and future risk for coronary artery disease in Africans has not been fully elucidated. In this study, associations of testosterone, acute cardiovascular and coagulation stress responses with fibrinogen and von Willebrand factor in African and Caucasian men in a South African cohort were investigated. Cardiovascular variables were studied by means of beat-to-beat and ambulatory blood pressure monitoring. Fasting serum-, salivary testosterone and citrate coagulation markers were obtained from venous blood samples. Acute mental stress responses were evoked with the Stroop test. The African group demonstrated a higher cardiovascular risk compared to Caucasian men with elevated blood pressure, low-grade inflammation, chronic hyperglycemia (HbA1c), lower testosterone levels, and elevated von Willebrand factor (VWF) and fibrinogen levels. Blunted testosterone acute mental stress responses were demonstrated in African males. In multiple regression analyses, higher circulating levels of fibrinogen and VWF in Africans were associated with a low T environment (R(2) 0.24-0.28; p≤0.01), but only circulating fibrinogen in Caucasians. Regarding endothelial function, a low testosterone environment and a profile of augmented α-adrenergic acute mental stress responses (diastolic BP, D-dimer and testosterone) were associated with circulating VWF levels in Africans (Adj R(2) 0.24; pstress, salivary testosterone, D-dimer and vascular responses existed in African males in their association with circulating VWF but no interdependence of the independent variables occurred with fibrinogen levels. © 2013.

  14. Thrombomodulin and von Willebrand factor as markers of radiation-induced endothelial injury

    International Nuclear Information System (INIS)

    Zhou Quansheng; Zhao Yimin; Li Peixia; Bai Xia; Ruan Changgeng

    1992-02-01

    Cultured confluent human umbilical vein endothelial cells were irradiated in vitro by 60 Co-gamma ray at doses from 0 to 50 Gy. After irradiation Thrombomodulin in the supernatants of endothelial cell culture medium, on the surface of the cells and within the cells was measured at different times over six days. At twenty-four hours after irradiation, an increase in the release of Thrombomodulin and von Willebrand factor from irradiated endothelial cells and an increase in the number of molecules and the activity of Thrombomodulin on the surface of the cells were observed, which were radiation-dose dependent. The capacity of the cells to produce and release Thrombomodulin was decreased from two to six days after exposure to 60 Co-gamma ray. Our data indicate that radiation can injure endothelial cells and that Thrombomodulin may be as a marker of radiation-induced endothelial cell injury. The relationship between dysfunction of irradiated endothelial cells and the pathological mechanisms of acute radiation sickness are discussed

  15. Towards personalised therapy for von Willebrand disease: a future role for recombinant products.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2016-05-01

    von Willebrand disease (VWD) is reportedly the most common bleeding disorder and is caused by deficiencies and/or defects in the adhesive plasma protein von Willebrand factor (VWF). Functionally, normal VWF prevents bleeding by promoting both primary and secondary haemostasis. In respect to primary haemostasis, VWF binds to both platelets and sub-endothelial matrix components, especially collagen, to anchor platelets to damaged vascular tissue and promote thrombus formation. VWF also stabilises and protects factor VIII in the circulation, delivering FVIII to the site of injury, which then facilitates secondary haemostasis and fibrin formation/thrombus stabilisation. As a result of this, patients with VWD suffer a bleeding diathesis reflective of a primary defect caused by defective/deficient VWF, which in some patients is compounded by a reduction in FVIII. Management of VWD, therefore, chiefly entails replacement of VWF, and sometimes also FVIII, to protect against bleeding. The current report principally focuses on the future potential for "personalised" management of VWD, given the emerging options in recombinant therapies. Recombinant VWF has been developed and is undergoing clinical trials, and this promising therapy may soon change the way in which VWD is managed. In particular, we can envisage a personalised treatment approach using recombinant VWF, with or without recombinant FVIII, depending on the type of VWD, the extent of deficiencies, and the period and duration of treatment.

  16. The impact of statin therapy on plasma levels of von Willebrand factor antigen. Systematic review and meta-analysis of randomised placebo-controlled trials

    NARCIS (Netherlands)

    Sahebkar, Amirhossein; Serban, Corina; Ursoniu, Sorin; Mikhailidis, Dimitri P.; Undas, Anetta; Lip, Gregory Y. H.; Bittner, Vera; Ray, Kausik; Watts, Gerald F.; Hovingh, G. Kees; Rysz, Jacek; Kastelein, John J. P.; Banach, Maciej

    2016-01-01

    Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are associated with high risk of coronary artery disease. The effect of statin therapy on vWF:Ag levels remains uncertain. Therefore the aim of this meta-analysis was to evaluate the effect of statin therapy on vWF:Ag Levels. A

  17. Functional characterisation of the type 1 von Willebrand disease candidate VWF gene variants: p.M771I, p.L881R and p.P1413L.

    Science.gov (United States)

    Berber, Ergul; Ozbil, Mehmet; Brown, Christine; Baslar, Zafer; Caglayan, S Hande; Lillicrap, David

    2017-10-01

    Abnormalities in the biosynthetic pathway or increased clearance of plasma von Willebrand factor (VWF) are likely to contribute to decreased plasma VWF levels in inherited type 1 von Willebrand disease (VWD). Recent studies demonstrated that 65% of type 1 VWD patients have candidate VWF mutations, the majority of which are missense variants. The purpose of this study was to explore the effects of three VWF missense mutations (p.M771I, p.L881R and p.P1413L) located in different functional domains of VWF, reported as candidate mutations in type 1 VWD patients in the course of the MCMDM-1VWD study. The focus of these studies was on the intracellular biosynthetic processing and localisation of VWF in a heterologous cell system. Molecular dynamic simulation for p.M771I and p.P1413L was also performed to analyse the conformational effects of the changes. As determined by immunofluorescence antibody staining and confocal microscopy of HEK293 cells, the intracellular localisation of recombinant VWF with the p.M771I variation was impaired. Transient transfection studies and phorbol myristate acetate stimulation in COS-7 cells revealed significant intracellular retention. In addition, major loss of VWF multimers was observed for only the p.M771I mutation. Molecular dynamic simulations on p.M771I mutant VWF revealed distinct structural rearrangements including a large deviation in the E' domain, and significant loss of β-sheet secondary structure. The pathogenic effects of candidate VWF gene mutations were explored in this study. In vitro expression studies in heterologous cell systems revealed impaired secretion of VWF and a dominant negative effect on the processing of the wild-type protein for only the p.M771I mutation and none of the mutations affected the regulated secretion.

  18. 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.

  19. Comparative study on collagen-binding enzyme-linked immunosorbent assay and ristocetin cofactor activity assays for detection of functional activity of von Willebrand factor.

    Science.gov (United States)

    Turecek, Peter L; Siekmann, Jürgen; Schwarz, Hans Peter

    2002-04-01

    For more than two decades, the ristocetin cofactor (RCo) assay, which measures the von Willebrand factor (vWF)-mediated agglutination of platelets in the presence of the antibiotic ristocetin, has been the most common method for measuring the functional activity of vWF. There is, however, general agreement among clinical analysts that this method has major practical disadvantages in performance and reproducibility. Today, collagen-binding assays (CBA) based on the enzyme-linked immunosorbent assay (ELISA) technique that measure the interaction of vWF and collagen are an alternative analytic procedure based on a more physiological function than that of the RCo procedure. We used both assay systems in a comparative study to assess the functional activity of vWF in plasma as well as in therapeutic preparations. We measured RCo activities of plasma from healthy donors and patients with different types of von Willebrand disease (vWD) and of vWF as a drug substance in factor (F) VIII/vWF concentrates using both the aggregometric and the macroscopic methods. In addition, we measured collagen-binding activity (vWF:CB) using a recently developed commercially available CBA system. To investigate the relation between the structure and the functional activity of vWF, we isolated vWF species with different numbers of multimers from FVIII/vWF concentrates by affinity chromatography on immobilized heparin. The vWF:RCo and vWF:CB of the different fractions were measured, and the multimeric structure of vWF was analyzed by sodium dodecyl sulfate (SDS) agarose gel electrophoresis. (vWF:CB and vWF:RCo are part of the nomenclature proposed by the International Society on Thrombosis and Hemostasis Scientific and Standardization Committee [ISTH SSC] subcommittee on von Willebrand factor, in Maastricht, Germany, June 16, 2000.) Measurement of functional vWF activity by CBA can be carried out with substantially higher interassay reproducibility than can measurement of RCo. Both assay

  20. Prophylaxis escalation in severe von Willebrand disease: A prospective study from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    T.C. Abshire (Thomas Calvin); J. Cox-Gill; C.L. Kempton; F.W.G. Leebeek (Frank); M. Carcao (M.); P. Kouides (P.); S. Donfield (S.); E. Berntorp

    2015-01-01

    textabstractBackground: Treatment of mucosal bleeding (epistaxis, gastrointestinal bleeding, and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may

  1. Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure.

    Science.gov (United States)

    Freestone, Bethan; Gustafsson, Finn; Chong, Aun Yeong; Corell, Pernille; Kistorp, Caroline; Hildebrandt, Per; Lip, Gregory Y H

    2008-05-01

    Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p NT-proBNP (p NT-proBNP levels (Spearman r = 0.139; p = 0.017). There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

  2. Technological advances in diagnostic testing for von Willebrand disease: new approaches and challenges.

    Science.gov (United States)

    Hayward, C P M; Moffat, K A; Graf, L

    2014-06-01

    Diagnostic tests for von Willebrand disease (VWD) are important for the assessment of VWD, which is a commonly encountered bleeding disorder worldwide. Technical innovations have been applied to improve the precision and lower limit of detection of von Willebrand factor (VWF) assays, including the ristocetin cofactor activity assay (VWF:RCo) that uses the antibiotic ristocetin to induce plasma VWF binding to glycoprotein (GP) IbIXV on target platelets. VWF-collagen-binding assays, depending on the type of collagen used, can improve the detection of forms of VWD with high molecular weight VWF multimer loss, although the best method is debatable. A number of innovations have been applied to VWF:RCo (which is commonly performed on an aggregometer), including replacing the target platelets with immobilized GPIbα, and quantification by an enzyme-linked immunosorbent assay (ELISA), immunoturbidimetric, or chemiluminescent end-point. Some common polymorphisms in the VWF gene that do not cause bleeding are associated with falsely low VWF activity by ristocetin-dependent methods. To overcome the need for ristocetin, some new VWF activity assays use gain-of-function GPIbα mutants that bind VWF without the need for ristocetin, with an improved precision and lower limit of detection than measuring VWF:RCo by aggregometry. ELISA of VWF binding to mutated GPIbα shows promise as a method to identify gain-of-function defects from type 2B VWD. The performance characteristics of many new VWF activity assays suggest that the detection of VWD, and monitoring of VWD therapy, by clinical laboratories could be improved through adopting newer generation VWF assays. © 2014 John Wiley & Sons Ltd.

  3. Hemophilia and von Willebrand's disease: 1. Diagnosis, comprehensive care and assessment. Association of Hemophilia Clinic Directors of Canada.

    Science.gov (United States)

    1995-07-01

    To present current strategies for the assessment and comprehensive care of patients with hemophilia and von Willebrand's disease. Hospital care, home care, single-provider care and multidisciplinary care. Morbidity and quality of life associated with bleeding and treatment. Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of own reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and to a predetermined outline. The availability of treatment products in Canada was also considered. Minimizing morbidity and maximizing functional status and quality of life were given a high value. The optimal use of treatment procedures and home care offers patients the advantages of minimized disability, improved survival and financial benefit. It is also cost effective. Potential harm, including the risk of hepatitis B, hepatitis C and HIV infection, has now been minimized through viral inactivation of plasma-derived coagulation-factor concentrates and through the use of recombinant clotting factor concentrates and other non-plasma-derived hemostatic agents. Patients with hemophilia and severe von Willebrand's disease should be followed in comprehensive care centres that offer expertise in the diagnosis, assessment and management of bleeding and complications and that can meet the educational and counselling needs of patients, family members and health care providers. Eligible patients should

  4. The structure of the TFIIH p34 subunit reveals a von Willebrand factor A like fold.

    Directory of Open Access Journals (Sweden)

    Dominik R Schmitt

    Full Text Available RNA polymerase II dependent transcription and nucleotide excision repair are mediated by a multifaceted interplay of subunits within the general transcription factor II H (TFIIH. A better understanding of the molecular structure of TFIIH is the key to unravel the mechanism of action of this versatile protein complex within these vital cellular processes. The importance of this complex becomes further evident in the context of severe diseases like xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy, that arise from single point mutations in TFIIH subunits. Here we describe the structure of the p34 subunit of the TFIIH complex from the eukaryotic thermophilic fungus Chaetomium thermophilum. The structure revealed that p34 contains a von Willebrand Factor A (vWA like domain, a fold which is generally known to be involved in protein-protein interactions. Within TFIIH p34 strongly interacts with p44, a positive regulator of the helicase XPD. Putative protein-protein interfaces are analyzed and possible binding sites for the p34-p44 interaction suggested.

  5. Taq I polymorphism in the 5' region of the von Willebrand Factor (vWF) gene

    Energy Technology Data Exchange (ETDEWEB)

    Lavergne, J M; Bahnak, B R; Assouline, Z; Pietu, G; Kerbiriou-Nabias, D; Meulien, P; Pavirani, A; Meyer, D

    1988-03-25

    pvWFIPC8 is a 2.28 Kb partial cDNA clone for human von Willebrand factor (vWF) isolated from a human lung cDNA library and inserted into the EcoRI site of pUC9. The sequence includes the last 1330 nucleotides that encode for vWF propeptide and 950 nucleotides that encode for mature vWF. Taq I (TCGA) identifies plural invariant bands and two variant bands with alleles at 2.3 (Al) and 1.0 (A2). The frequency was determined in 33 unrelated European and North American caucasians. The extreme 3' region of pvWFIPC8 corresponds to the 5' boundary of an area that could possibly hybridize with similar sequences on human chromosome 22. The 5' 1.74 Kb portion of pvWFIPC8 generated by Bam HI digestion that corresponds to sequences only on chromosome 12 also demonstrates the polymorphism. Co-dominant segregation was demonstrated in 6 families of 48 individuals.

  6. Bleeding spectrum in children with moderate or severe von Willebrand disease: Relevance of pediatric-specific bleeding

    NARCIS (Netherlands)

    Sanders, Yvonne V.; Fijnvandraat, Karin; Boender, Johan; Mauser-Bunschoten, Evelien P.; van der Bom, Johanna G.; de Meris, Joke; Smiers, Frans J.; Granzen, Bernd; Brons, Paul; Tamminga, Rienk Y. J.; Cnossen, Marjon H.; Leebeek, Frank W. G.

    2015-01-01

    The bleeding phenotype of children with von Willebrand disease (VWD) needs to be characterized in detail to facilitate diagnosis during childhood and aid in the planning and assessment of treatment strategies. The objective was to evaluate the occurrence, type, and severity of bleeding in a large

  7. Pattern of von Willebrand factor in hypertensive patients in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Ann Abiola Ogbenna

    2018-01-01

    Full Text Available Background and Objective: Hypertension alone accounts for 50% of death from stroke. Its ability to induce endothelial dysfunction leads to the release of von Willebrand factor (vWF, a prothrombotic glycoprotein. The increase secretion of vWF may account for increased risk of stroke in hypertensive disorders. This study aimed to determine the vWF:antigen (Ag levels among hypertensives and assess its relationship with blood pressure and occurrence of stroke in hypertensives. Subjects and Methods: The study included 66 hypertensives, 33 with stroke (HS and 33 without stroke (HWS, and 33 controls matched for age and sex. Structured questionnaires were used to obtain biodata and clinical information. Blood pressure was taken after 15 min rest. Four milliliters of blood was collected into 0.1 ml of 3.2% trisodium citrate for vWF:Ag assay and 4 ml into K-ethylenediaminetetraacetic acid anticoagulant bottles for blood grouping and erythrocyte sedimentation rate. Data were analyzed with SPSS version 21. Confidence interval was set at 95%. Results: Mean vWF:Ag levels were significantly higher in hypertensives compared with nonhypertensives (P = 0.005, but no statistically significant difference was observed between HS and HWS (P = 0.874. A positive correlation of vWF with systolic blood pressure was observed (r = 0.335, P = 0.001. Conclusion: Our study suggests that higher systolic blood pressure is associated with higher levels of endothelial activation and release of vWF.

  8. Coats' disease, Turner syndrome, and von Willebrand disease in a patient with Wildtype Norrie disease pseudoglioma.

    Science.gov (United States)

    Desai, Rajen U; Saffra, Norman A; Krishna, Rati P; Rosenberg, Steven E

    2011-01-01

    The authors describe a girl diagnosed as having Coats' disease, Turner syndrome (45X karyotype), and type 1 von Willebrand disease. She tested negative for the Norrie disease pseudoglioma (NDP) gene located on the X-chromosome, which has been suspected of contributing to Coats' disease. Copyright 2010, SLACK Incorporated.

  9. Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients.

    Science.gov (United States)

    Borràs, Nina; Batlle, Javier; Pérez-Rodríguez, Almudena; López-Fernández, María Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carme; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Víctor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Berrueco, Rubén; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María Del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Vidal, Francisco; Corrales, Irene

    2017-12-01

    Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF , including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF , 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. Copyright© 2017 Ferrata Storti Foundation.

  10. An immunoradiometric assay for procoagulant factor VIII antigen: results in haemophilia, von Willebrand's disease and fetal plasma and serum

    International Nuclear Information System (INIS)

    Peake, I.R.; Bloom, A.L.; Giddings, J.C.; Ludlam, C.A.

    1979-01-01

    An immunoradiometric assay (IRMA) has been developed based on the inhibitor which arose in a polytransfused severe haemophiliac. The two-site IRMA measured antigens closely associated with the procoagulant parts of the factor VIII complex, which are termed FVIIIC antigens or FVIIICAG. FVIIICAG was present in normal plasma and also, at a slightly lower concentration, in normal serum. In 37 patients with haemophilia A, 36 had FVIIICAG levels of less than 10% of the normal plasma pool. In patients with von Willebrand's disease the levels of FVIIIC and FVIIICAG were in good agreement, both before and after treatment with cryoprecipitate or DDAVP. FVIIICAG was relatively stable in plasma at 37 0 C and could also be detected in cord and fetal serum. The assay is of potential value for detecting reduced levels of factor VIII, for carrier detection and for the prenatal diagnosis of haemophilia. (author)

  11. Fluid-phase immunoradiometric assay for the detection of qualitative abnormalities of factor VIII/von Willebrand factor in variants of von Willebrand's disease

    International Nuclear Information System (INIS)

    Girma, J.P.; Ardaillou, N.; Meyer, D.; Lavergne, J.M.; Larrieu, M.J.

    1979-01-01

    Antigenic reactivity of F.VIII/WF in variants of von Willebrand's disease (vWd) was studied with both fluid-phase and solid-phase immunoradiometric assays. Two different (rabbit and goat) 125 I-labeled specific antibodies against purified F.VIII/WF were used in both their divalent (lgG) and their monovalent (Fab fragment) forms. Dose-response curves obtained by reacting a constant amount of antibody with serial dilutions of plasmas from normal or homozygous vWd demonstrated the specificity of the test. The accuracy was significantly higher with 125 I-Fab fragments of goat anti-F.VIII/WF antiserum than intact goat lgG or rabbit lgG or Fab fragments. The significant decrease of the slope of the dose-response curves obtained with plasma from variants of vWd has been interpreted as due to the presence of abnormal F.VIII/WF molecules with decreased antigenic reactivity. A similar anomaly was found in cryosupernatant prepared from normal plasma, paralleling similarities demonstrated between variants of vWd and cryosupernatant. Results of experiments performed by reacting constant plasma dilutions from control or variants of vWd and varying concentrations of anti-F.VIII/WF Fab fragments (rabbit or goat) confirmed the decreased antigenic reactivity of variant F.VIII/WF

  12. Relationship between ABO blood groups and von Willebrand factor, ADAMTS13 and factor VIII in patients undergoing hemodialysis.

    Science.gov (United States)

    Rios, Danyelle R A; Fernandes, Ana Paula; Figueiredo, Roberta C; Guimarães, Daniela A M; Ferreira, Cláudia N; Simões E Silva, Ana C; Carvalho, Maria G; Gomes, Karina B; Dusse, Luci Maria Sant' Ana

    2012-05-01

    Several studies have demonstrated that non-O blood groups subjects present an increased VTE risk as compared to those carrying O blood group. The aim of this study was to investigate the ABO blood groups influence on factor VIII (FVIII) activity, von Willebrand factor (VWF), and ADAMTS13 plasma levels in patients undergoing hemodialysis (HD). Patients undergoing HD (N=195) and 80 healthy subjects (control group) were eligible for this cross-sectional study. The ABO blood group phenotyping was performed by the reverse technique. FVIII activity was measured through coagulometric method, and VWF and ADAMTS13 antigens were assessed by ELISA. FVIII activity and VWF levels were significantly higher and ADAMTS13 levels was decreased in HD patients, as compared to healthy subjects (P blood groups showed a significant increase in FVIII activity (P = 0.001) and VWF levels (P blood group. However, no significant difference was observed in ADAMTS13 levels (P = 0.767). In the control group, increased in FVIII activity (P = 0.001) and VWF levels (P = 0.002) and decreased in ADAMTS13 levels (P = 0.005) were observed in subjects carrying non-O blood groups as compared to carriers of O blood group.Our data confirmed that ABO blood group is an important risk factor for increased procoagulant factors in plasma, as FVIII and VWF. Admitting the possible role of kidneys in ADAMTS13 synthesis or on its metabolism, HD patients were not able to increase ADAMTS13 levels in order to compensate the increase of VWF levels mediated by ABO blood groups. Considering that non-O blood groups constitute a risk factor for thrombosis, it is reasonable to admit that A, B and AB HD patients need a careful and continuous follow-up in order to minimize thrombotic events.

  13. Cesariana em paciente com doença de von Willebrand associada à infecção pelo HIV: relato de caso Cesárea en paciente con enfermedad de von Willebrand asociada a la infección por el HIV: relato de caso Anesthesia for cesarean section in patient with von Willebrand's disease and HIV infection: case report

    Directory of Open Access Journals (Sweden)

    Vanessa Rezende Balle

    2004-12-01

    Willebrand y HIV positiva sometida a cesárea. RELATO DEL CASO: Paciente de 24 años, portadora de anemia microcítica, enfermedad de von Willebrand y HIV, llegó a la emergencia obstétrica en inicio de trabajo de alumbramiento. No realizó prenatal. Fue indicada cesárea a fin de disminuir los riesgos de transmisión vertical en paciente con carga vírica de HIV desconocida. Presentaba hematomas por el cuerpo e historia de hematoma de pared abdominal en cesárea anterior. Los tests de coagulación estaban un poco alterados. Después de infusión de concentrado de factor VIII fue realizada anestesia general. Madre y recién nacido presentaron evolución satisfactoria. CONCLUSIONES: La evaluación de manifestaciones clínicas en pacientes con coagulopatia es fundamental en la decisión del tipo de anestesia que será indicada para cada paciente. La evaluación debe ser individualizada, considerando los riesgos y beneficios de la técnica escogida. En estas pacientes, se debe siempre restringir al máximo la indicación de interrupción de la gestación por vía alta, optándose siempre por los métodos menos invasivos. La terapia con concentrado de factor VIII es actualmente la mejor opción de tratamiento, corrigiendo la deficiencia específica y dismunuyendo los riesgos de transmisión vírica.BACKGROUND AND OBJECTIVES: Von Willebrand's disease is the most common hereditary coagulation disorder in young women. The incidence of HIV infection among women has been progressively increasing, and vertical transmission may account for 25% of cases. This report aimed at describing the case of an HIV-positive patient with von Willebrand's disease scheduled for cesarean section. CASE REPORT: Female HIV-positive patient, 24 years old, with microcytic anemia and von Willebrand's disease, admitted to the emergency room in early labor. She had no pre-natal care. Cesarean section was indicated to lower vertical transmission risks since HIV viral count was unknown. Patient had hematomas

  14. Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.

    Directory of Open Access Journals (Sweden)

    Danielle N Drury-Stewart

    Full Text Available The coagulation protein von Willebrand Factor (VWF is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood.To better understand the changes in VWF provoked by pregnancy, we studied VWF-associated parameters in samples collected over the course of healthy pregnancies.We measured VWF antigen (VWF:Ag, VWF propeptide (VWFpp, Factor VIII (FVIII, and ADAMTS13 activity in samples collected from 46 women during pregnancy and at non-pregnant baseline. We also characterized pregnant vs. non-pregnant VWF multimer structure in 21 pregnancies, and performed isoelectric focusing (IEF of VWF in two pregnancies which had samples from multiple trimesters.VWF:Ag and FVIII levels were significantly increased during pregnancy. ADAMTS13 activity was unchanged. VWFpp levels increased much later in pregnancy than VWF:Ag, resulting in a progressive decrease in VWFpp:Ag ratios. FVIII:VWF ratios also decreased in pregnancy. Most pregnancies exhibited a clear loss of larger VWF multimers and altered VWF triplet structure. Further evidence of acquired VWF qualitative changes in pregnancy was found in progressive, reversible shifts in VWF IEF patterns over gestation.These data support a new view of pregnancy in which VWF can acquire qualitative changes associated with advancing gestational age. Modeling supports a scenario in which both increased VWF production and doubling of the VWF half-life would account for the data observed. We propose that gestation induces a prolongation in VWF survival, which likely contributes to increased total VWF levels and altered VWF structure.

  15. Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells.

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    Maartje van den Biggelaar

    Full Text Available BACKGROUND: Point mutations resulting in reduced factor VIII (FVIII binding to von Willebrand factor (VWF are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule biogenesis are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We studied intracellular trafficking of FVIII variants implicated in mild/moderate hemophilia A together with VWF in HEK293 cells and primary endothelial cells. The role of VWF binding was addressed using FVIII variants displaying reduced VWF interaction. Binding studies using purified FVIII proteins revealed moderate (Arg2150His, Del2201, Pro2300Ser to severe (Tyr1680Phe, Ser2119Tyr VWF binding defects. Expression studies in HEK293 cells and primary endothelial cells revealed that all FVIII variants were present within VWF-containing organelles. Quantitative studies showed that the relative amount of FVIII storage was independent of various mutations. Substantial amounts of FVIII variants are co-stored in VWF-containing storage organelles, presumably by virtue of their ability to interact with VWF at low pH. CONCLUSIONS: Our data suggest that the potential of FVIII co-storage with VWF is not affected in mild/moderate hemophilia A caused by reduced FVIII/VWF interaction in the circulation. These data support the hypothesis that Weibel-Palade bodies comprise the desmopressin-releasable FVIII storage pool in vivo.

  16. Exercise-induced shear stress is associated with changes in plasma von Willebrand factor in older humans.

    Science.gov (United States)

    Gonzales, Joaquin U; Thistlethwaite, John R; Thompson, Benjamin C; Scheuermann, Barry W

    2009-07-01

    Shear stress is the frictional force of blood against the endothelium, a stimulus for endothelial activation and the release of von Willebrand factor (vWF). This study tested the hypothesis that the increase in shear stress associated with exercise correlates with plasma vWF. Young (n = 14, 25.7 +/- 5.4 years) and older (n = 13, 65.6 +/- 10.7 years) individuals participated in 30 min of dynamic handgrip exercise at a moderate intensity. Brachial artery diameter and blood flow were measured using ultrasound Doppler and blood samples were collected before, immediately after, and following 30 min of recovery from exercise with plasma levels of vWF. Plasma levels of vWF increased (P exercise. The change in plasma vWF was linearly correlated with the increase in shear stress during exercise in older individuals (post-exercise: r = 0.78, 30 min recovery: r = 0.77, P < 0.01), but no association was found in the young individuals. These changes in plasma levels of vWF in humans suggest that aging influences endothelial activation and hemostasis.

  17. Von Willebrand Factor as a Novel Player in Valvular Heart Disease: From Bench to Valve Replacement.

    Science.gov (United States)

    Gragnano, Felice; Crisci, Mario; Bigazzi, Maurizio Cappelli; Bianchi, Renatomaria; Sperlongano, Simona; Natale, Francesco; Fimiani, Fabio; Concilio, Claudia; Cesaro, Arturo; Pariggiano, Ivana; Diana, Vincenzo; Limongelli, Giuseppe; Cirillo, Plinio; Russo, Mariagiovanna; Golia, Enrica; Calabrò, Paolo

    2018-02-01

    von Willebrand Factor (vWF) is a well-known mediator of hemostasis and vascular inflammation. Its dynamic modulation in the bloodstream, according to hemodynamic conditions, makes it an appealing biomarker in patients with valvular heart disease (VHD). Recent studies highlight the close connection between vWF and VHD, with possible implications in the pathogenesis of VHD, promoting valve aging and calcification or favoring the development of infective endocarditis. Moreover, vWF has been recently proposed as a new diagnostic and prognostic tool in patients with valve stenosis or regurgitation, showing a strict correlation with severity of valve disease, outcome, and bleeding (Heyde syndrome). A novel role for vWF is also emerging in patients undergoing percutaneous or surgical valve repair/replacement to select and stratify patients, evaluate periprocedural bleeding risk, and detect procedural complications. We also report our single-center experience, suggesting, for the first time, possible clinical implications for vWF in percutaneous mitral valve repair (MitraClip). This review summarizes recent advances in the role of vWF in VHD with an updated overview going from bench to operating room.

  18. Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

    Directory of Open Access Journals (Sweden)

    de Backer Marijke WA

    2010-08-01

    Full Text Available Abstract Background Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion. Results We fused the signal peptide from the Von Willebrand Factor (VWF to a furin site followed by a processed form of the Agouti related protein (AgRP, AgRP83-132 or α-melanocyte stimulating hormone. In vitro, these minigenes were secreted and biologically active. Additionally, the proteins of the minigenes were not transported into projections of primary neurons, thereby ensuring local release. In vivo administration of VWF-AgRP83-132 , using an adeno-associated viral vector as a delivery vehicle, into the paraventricular hypothalamus increased body weight and food intake of these rats compared to rats which received a control vector. Conclusions This study demonstrated that removal of the N-terminal part of full length AgRP and addition of a VWF signal peptide is a successful strategy to deliver neuropeptide minigenes to the brain and establish local neuropeptide secretion.

  19. Frequency of von willebrand disease in patients of heavy menstrual bleeding

    International Nuclear Information System (INIS)

    Anjum, N.; Shaheen, Z.; Altaf, C.

    2016-01-01

    Objective: To determine the frequency of Von Willebrand disease (vWD) in patients of heavy menstrual bleeding (HMB). Study Design: Hospital based cross sectional study. Place and Duration of Study: Study was conducted at the Gynecology and Obstetrics department, Military Hospital, Rawalpindi in collaboration with Haematology Department of Armed Forces Institute of Pathology (AFIP) Rawalpindi, from Jul to Dec 2015. Material and Methods: Women presenting with HMB were enrolled in the study after informed consent. HMB was defined as cyclical bleeding at normal intervals but patient is using more than 5 pads per day or increase in duration 8/28 or more for at least last 06 months. Venous blood samples were taken and screened for the hemoglobin level (Hb), platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT) and Von Willebrand antigen (vWF:Ag) in addition to bleeding time (BT) at the Armed Forces Institute of Pathology (AFIP). The demographic details (age, age at menarche), clinical features (menstrual history, quantity of bleeding) and laboratory findings were recorded on the study proforma. Results: A total of 200 patients were enrolled in this study with mean age of 32.3 +- 8.5 years. Mean flow of menstrual blood was 9.8 +- 2.5 pads / day. Mean Hb percent was 8.1 +- 1.4 g/dl. Twenty nine (14.5 percent) patients were having low level of vWF:Ag. Conclusion: There is high frequency of von Willebrand disease among females presenting with heavy menstrual bleeding in our set up. Therefore all patients with heavy menstrual bleeding except those with obvious causes like multiple fibroid should be screened for von Willebrand disease. (author)

  20. Use of routine histopathology and factor VIII-related antigen/von Willebrand factor immunohistochemistry to differentiate primary hemangiosarcoma of bone from telangiectatic osteosarcoma in 54 dogs.

    Science.gov (United States)

    Giuffrida, M A; Bacon, N J; Kamstock, D A

    2017-12-01

    Hemangiosarcoma (HSA) of bone and telangiectatic osteosarcoma (tOSA) can appear similar histologically, but differ in histogenesis (malignant endothelial cells versus osteoblasts), and may warrant different treatments. Immunohistochemistry (IHC) for endothelial cell marker factor VIII-related antigen/von Willebrand factor (FVIII-RAg/vWF) is a well-documented ancillary test to confirm HSA diagnoses in soft tissues, but its use in osseous HSA is rarely described. Archived samples of 54 primary appendicular bone tumours previously diagnosed as HSA or tOSA were evaluated using combination routine histopathology (RHP) and IHC. Approximately 20% of tumours were reclassified on the basis of FVIII-RAg/vWF immunoreactivity, typically from an original diagnosis of tOSA to a reclassified diagnosis of HSA. No sample with tumour osteoid clearly identified on RHP was immunopositive for FVIII-RAg/vWF. RHP alone was specific but not sensitive for diagnosis of HSA, compared with combination RHP and IHC. Routine histopathological evaluation in combination with FVIII-RAg/vWF IHC can help differentiate canine primary appendicular HSA from tOSA. © 2016 John Wiley & Sons Ltd.

  1. Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise.

    Science.gov (United States)

    van Loon, Janine E; Sonneveld, Michelle A H; Praet, Stephan F E; de Maat, Moniek P M; Leebeek, Frank W G

    2014-01-01

    Physical stress triggers the endothelium to release von Willebrand Factor (VWF) from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise. 105 healthy individuals (18-35 years) were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag) levels, VWF collagen binding (VWF:CB) levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599), Syntaxin-2 (STX2, rs7978987) and VWF (promoter, rs7965413) were determined. The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (pexercise (median increase 43% and 12%, both pexercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001), which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase. VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter.

  2. Beneficial Effects of High-Density Lipoproteins on Acquired von Willebrand Syndrome in Aortic Valve Stenosis.

    Science.gov (United States)

    Gebhard, C; Maafi, F; Stähli, B E; Bonnefoy, A; Gebhard, C E; Nachar, W; de Oliveira Moraes, A Benjamim; Mecteau, M; Mihalache-Avram, T; Lavoie, V; Kernaleguen, A E; Shi, Y; Busseuil, D; Chabot-Blanchet, M; Perrault, L P; Rhainds, D; Rhéaume, E; Tardif, J C

    2018-02-01

     Infusions of apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins (HDL), result in aortic valve stenosis (AVS) regression in experimental models. Severe AVS can be complicated by acquired von Willebrand syndrome, a haemorrhagic disorder associated with loss of high-molecular-weight von Willebrand factor (vWF) multimers (HMWM), the latter being a consequence of increased shear stress and enhanced vWF-cleaving protease (ADAMTS-13) activity. Although antithrombotic actions of HDL have been described, its effects on ADAMTS-13 and vWF in AVS are unknown.  We assessed ADAMTS-13 activity in plasma derived from a rabbit model of AVS ( n  = 29) as well as in plasma collected from 64 patients with severe AVS (age 65.0 ± 10.4 years, 44 males) undergoing aortic valve replacement (AVR). In both human and rabbit AVS plasma, ADAMTS-13 activity was higher than that in controls ( p  AVS patients had less HMWM than controls (66.3 ± 27.2% vs. 97.2 ± 24.1%, p  AVS rabbits as compared with the placebo group (2.0 ± 0.5 RFU/sec vs. 3.8 ± 0.4 RFU/sec, p  AVS ( r  = -0.3, p  = 0.045).  Our data indicate that HDL levels are associated with reduced ADAMTS-13 activity and increased HMWM. HDL-based therapies may reduce the haematologic abnormalities of the acquired von Willebrand syndrome in AVS. Schattauer GmbH Stuttgart.

  3. The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size.

    Science.gov (United States)

    Zwicker, Jeffrey I; Peyvandi, Flora; Palla, Roberta; Lombardi, Rossana; Canciani, Maria Teresa; Cairo, Andrea; Ardissino, Diego; Bernardinelli, Luisa; Bauer, Kenneth A; Lawler, Jack; Mannucci, Pier

    2006-08-15

    The N700S polymorphism of thrombospondin-1 (TSP-1) has been identified as a potential genetic risk factor for myocardial infarction (MI). In a large case-control study of 1425 individuals who survived a myocardial infarction prior to age 45, the N700S polymorphism was a significant risk factor for myocardial infarction in both homozygous (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.3, P = .01) and heterozygous carriers of the S700 allele (OR 1.4, 95% CI 1.1-3.3, P = .01). TSP-1 has been shown to reduce von Willebrand factor (VWF) multimer size, and the domain responsible for VWF-reducing activity has been localized to the calcium-binding C-terminal sequence. As the N700S polymorphism was previously shown to alter the function of this domain, we investigated whether the altered VWF-reducing activity of TSP-1 underlies the observed prothrombotic phenotype. The TSP1 N700S polymorphism did not influence VWF multimer size in patients homozygous for either allele nor was there a significant reduction of VWF multimer size following incubation with recombinant N700S fragments or platelet-derived TSP-1.

  4. Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1.

    Science.gov (United States)

    Anthony, P P; Ramani, P

    1991-01-01

    A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver. QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does. Staining was uniformly strong and clear in all histological variants of these two tumours. QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver.

  5. Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise.

    Directory of Open Access Journals (Sweden)

    Janine E van Loon

    Full Text Available Physical stress triggers the endothelium to release von Willebrand Factor (VWF from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise.105 healthy individuals (18-35 years were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag levels, VWF collagen binding (VWF:CB levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599, Syntaxin-2 (STX2, rs7978987 and VWF (promoter, rs7965413 were determined.The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (p<0.0001. VWF:CB levels and ADAMTS13 activity both also increased after exhaustive exercise (median increase 43% and 12%, both p<0.0001. The strongest determinants of the VWF:Ag level increase are performance related (p<0.0001. We observed a gender difference in VWF:Ag response to exercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001, which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase.VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter.

  6. Analysis of expression of von Willebrand factor, endothelin-1, vascular endothelial growth factor in Budd-Chiari syndrome with membranous obstruction

    International Nuclear Information System (INIS)

    Han Xinqiang; Zu Maoheng

    2011-01-01

    Objective: To investigate whether the injured vascular endothelial plays an important role in the membranous formation of the inferior vena cava (IVC). Methods: There were 40 cases of membranous obstruction of inferior vena cava (MOVC) in the experimental group and 40 arrhythmic inpatients in the control group from affiliated hospital. There were 23 males and 17 females in experimental group while 21 males and 19 females in control group, and the age were (41.8±8.1) yrs and (43.2± 7.6) yrs respectively. All of them had no anti-coagulation (clotting) drug history and smoking history, no hypertension, no pulmonary artery hypertension, no coronary heart disease, no valvular disease, no myocardial disease, no blood disease, no diabetes, no connective tissue disease and malignancy, and liver and renal function must be normal. And then the serum concentrations of von Willebrand factor (vWF), endothelin-l (ET-1), vascular endothelial growth factor (VEGF) were defined by enzyme-linked immunosorbent assay (ELISA). The results were analyzed with independent sample t-test. Results: In MOVC patients, the serum concentrations of vWF, ET-1 and VEGF [(37.8±6.6) μg/L, (31.9± 6.0) ng/L, (20.84±5.78) μg/L] were higher than those in the control group [(3.3±1.3) μg/L, (5.3±1.8) ng/L, (4.2±1.2) μg/L. t=32.65, 26.70, 17.85, P<0.01, respectively]. Conclusions: The injury of vascular endothelium is related to the formation of membrane in the IVC. (authors)

  7. Unconjugated Bilirubin Inhibits Proteolytic Cleavage of von Willebrand Factor by ADAMTS13 Protease

    Science.gov (United States)

    Lu, Rui-Nan; Yang, Shangbin; Wu, Haifeng M.; Zheng, X. Long

    2015-01-01

    Summary Background Bilirubin is a yellow breakdown product of heme catabolism. Increased serum levels of unconjugated bilirubin are conditions commonly seen in premature neonates and adults with acute hemolysis including thrombotic microangiopathy. Previous studies have shown that unconjugated bilirubin lowers plasma ADAMTS13 activity, but the mechanism is not fully understood. Objectives The study is to determine whether unconjugated bilirubin directly inhibits the cleavage of von Willebrand factor (VWF) and its analogs by ADAMTS13. Methods Fluorogenic, SELDI-TOF mass spectrometric assay, and Western blotting analyses were employed to address this question. Results Unconjugated bilirubin inhibits the cleavage of F485-rVWF73-H, D633-rVWF73-H, and GST-rVWF71-11K by ADAMTS13 in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of ~13 μM, ~70 μM, and ~17 μM, respectively. Unconjugated bilirubin also dose-dependently inhibits the cleavage of multimeric VWF by ADAMTS13 under denaturing conditions. The inhibitory activity of bilirubin on the cleavage of D633-rVWF73-H and multimeric VWF, but not F485-rVWF73-H, was eliminated after incubation with bilirubin oxidase that converts bilirubin to biliverdin. Furthermore, plasma ADAMTS13 activity in patients with hyperbilirubinemia is lower prior to than after treatment with bilirubin oxidase. Conclusions unconjugated bilirubin directly inhibits ADAMTS13’s ability to cleave both peptidyl and native VWF substrates in addition to its interference with certain fluorogenic assays. Our findings may help proper interpretation of ADAMTS13 results under pathological conditions. Whether elevated serum unconjugated bilirubin has an adverse effect in vivo remains to be determined in our future study. PMID:25782102

  8. Molecular cloning of the human gene for von Willebrand factor and identification of the transcription initiation site

    International Nuclear Information System (INIS)

    Collins, C.J.; Underdahl, J.P.; Levene, R.B.; Ravera, C.P.; Morin, M.J.; Dombalagian, M.J.; Ricca, G.; Livingston, D.M.; Lynch, D.C.

    1987-01-01

    A series of overlapping cosmid genomic clones have been isolated that contain the entire coding unit of the human gene for van Willebrand factor (vWf), a major component of the hemostatic system. The cloned segments span ≅ 175 kilobases of human DNA sequence, and hybridization analysis suggest that the vWf coding unit is ≅150 kilobases in length. Within one of these clones, the vWF transcription initiation site has been mapped and a portion of the vWf promoter region has been sequenced, revealing a typical TATA box, a downstream CCAAT box, and a perfect downstream repeat of the 8 base pairs containing the transcription start site. Sequencing of a segment of another genomic clone has revealed the vWF translation termination codon. Where tested, comparative restriction analysis of cloned and chromosomal DNA segments strongly suggests that no major alterations occurred during cloning and that there is only one complete copy of the vWf gene in the human haploid genome. Similar analyses of DNA from vWf-producing endothelial cells and nonexpressing leukocytes suggest that vWf gene expression is not accompanied by gross genomic rearrangements. In addition, there is significant homology of C-terminal coding sequences among the vWf genes of several vertebrate species

  9. Von Willebrand's Disease in Two Families of Doberman Pinschers

    OpenAIRE

    Johnstone, I. B.; Crane, S.

    1981-01-01

    The history, clinical symptoms and laboratory results in two families of Doberman pinschers with von Willebrand's disease are described. The affected animals illustrate the rather nonspecific bleeding problems that may be encountered in mild and moderate forms of this disease. In both families a bleeding diathesis was suspected when one member of the family underwent surgery with serious postoperative bleeding complications. These cases illustrate the importance of a thorough presurgical hist...

  10. D-dimer, factor VIII and von Willebrand factor predict a non-dipping pattern of blood pressure in hypertensive patients.

    Science.gov (United States)

    Agorasti, Athanasia; Trivellas, Theodoros; Mourvati, Efthimia; Papadopoulos, Vasilios; Tsatalas, Konstantinos; Vargemezis, Vasilios; Passadakis, Ploumis

    2013-06-01

    The aim of this study is to assess whether the haemostatic markers D-dimer, factor VIII (FVIII) and von Willebrand factor (VWF) are predictive of non-dipping status in treated hypertensive patients; so, as easy available laboratory data can predict non-dipping pattern and help with the selection of the patients whom circadian blood pressure should be re-examined. Forty treated hypertensive patients with essential hypertension were included in the study. Twenty-four-hour ambulatory blood pressure monitoring was performed in all patients. Daytime and nocturnal average systolic, diastolic and mean blood pressures were calculated. Patients were characterised as "non-dippers" on the basis of a less than 10 % decline in nocturnal blood pressure (BP); either systolic or diastolic or mean (MAP). D-dimer as marker of fibrinolytic function, FVIII activity and VWF antigen as marker of endothelial dysfunction were measured on plasma. The predictive efficiency was analysed by receiver operating characteristic (ROC) curves. Youden index was used for the estimation of the cut-off points and the associated values for sensitivity and 1-specificity. Plasma levels of D-dimer, FVIII and VWF were significantly higher in non-dippers as compared with dippers, irrespective of the classification used (BP index); all P AUC(ROC) = 0.697, 0.715 and 0.774), FVIII (AUC(ROC) = 0.714, 0.692 and 0.755) and VWF (AUC(ROC) = 0.706, 0.740 and 0.708) in distinguishing non-dipping pattern (systolic, diastolic or mean) in the study population; all P 168 ng/ml (sensitivity/1-specificity for systolic BP non-dippers of 0.789/0.381, for diastolic BP non-dippers 0.923/0.444 and for MAP non-dippers 0.875/0.375). In conclusion, D-dimer has a good predictive value for non-dipping pattern and the decision for the 24-h ambulatory blood pressure re-monitoring among dippers could rely on its values.

  11. Space and Time Resolved Detection of Platelet Activation and von Willebrand Factor Conformational Changes in Deep Suspensions.

    Science.gov (United States)

    Biasetti, Jacopo; Sampath, Kaushik; Cortez, Angel; Azhir, Alaleh; Gilad, Assaf A; Kickler, Thomas S; Obser, Tobias; Ruggeri, Zaverio M; Katz, Joseph

    2017-01-01

    Tracking cells and proteins' phenotypic changes in deep suspensions is critical for the direct imaging of blood-related phenomena in in vitro replica of cardiovascular systems and blood-handling devices. This paper introduces fluorescence imaging techniques for space and time resolved detection of platelet activation, von Willebrand factor (VWF) conformational changes, and VWF-platelet interaction in deep suspensions. Labeled VWF, platelets, and VWF-platelet strands are suspended in deep cuvettes, illuminated, and imaged with a high-sensitivity EM-CCD camera, allowing detection using an exposure time of 1 ms. In-house postprocessing algorithms identify and track the moving signals. Recombinant VWF-eGFP (rVWF-eGFP) and VWF labeled with an FITC-conjugated polyclonal antibody are employed. Anti-P-Selectin FITC-conjugated antibodies and the calcium-sensitive probe Indo-1 are used to detect activated platelets. A positive correlation between the mean number of platelets detected per image and the percentage of activated platelets determined through flow cytometry is obtained, validating the technique. An increase in the number of rVWF-eGFP signals upon exposure to shear stress demonstrates the technique's ability to detect breakup of self-aggregates. VWF globular and unfolded conformations and self-aggregation are also observed. The ability to track the size and shape of VWF-platelet strands in space and time provides means to detect pro- and antithrombotic processes.

  12. Assembly and activation of alternative complement components on endothelial cell-anchored ultra-large von Willebrand factor links complement and hemostasis-thrombosis.

    Directory of Open Access Journals (Sweden)

    Nancy A Turner

    Full Text Available Vascular endothelial cells (ECs express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. The alternative complement pathway (AP is an important non-antibody-requiring host defense system. Thrombotic microangiopathies can be associated with defective regulation of the AP (atypical hemolytic-uremic syndrome or with inadequate cleavage by ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombotic thrombocytopenic purpura. Our goal was to determine if EC-anchored ULVWF strings caused the assembly and activation of AP components, thereby linking two essential defense mechanisms.We quantified gene expression of these complement components in cultured human umbilical vein endothelial cells (HUVECs by real-time PCR: C3 and C5; complement factor (CF B, CFD, CFP, CFH and CFI of the AP; and C4 of the classical and lectin (but not alternative complement pathways. We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of >150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition. We found that HUVEC-released C4 did not attach to ULVWF strings, ruling out activation of the classical and lectin pathways by the strings. In contrast, C3, FB, FD, FP and C5, FH and FI attached to ULVWF strings in quantitative patterns consistent with assembly of the AP components into active complexes. This was verified when non-functional FB blocked the formation of AP C3 convertase complexes (C3bBb on ULVWF strings.AP components are assembled and activated on EC-secreted/anchored ULVWF multimeric strings. Our findings provide one possible molecular mechanism for clinical

  13. Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Soares, R.P.S. [Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, SP (Brazil); Bydlowski, S.P.; Nascimento, N.M. [Laboratório de Investigação Médica-31, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Thomaz, A.M.; Bastos, E.N.M.; Lopes, A.A. [Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-04-05

    Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

  14. Thrombomodulin, von Willebrand factor and E-selectin as plasma markers of endothelial damage/dysfunction and activation in pregnancy induced hypertension.

    Science.gov (United States)

    Nadar, Sunil K; Al Yemeni, Eman; Blann, Andrew D; Lip, Gregory Y H

    2004-01-01

    Endothelial disturbance (whether activation, dysfunction or damage) is a likely pathogenic mechanism in pre-eclampsia and pregnancy-induced hypertension (PIH). We set out to determine which of three plasma markers of endothelial disturbance, indicating endothelial activation (E-selectin) or damage/dysfunction (von Willebrand factor (vWf), soluble thrombomodulin), would provide the best discriminator of PIH compared to normotensive pregnancy. Cross-sectional study of 36 consecutive women with PIH (age 31+/-6 years) and 36 consecutive women with normotensive pregnancies (age 29+/-5 years) of similar parity. Plasma levels of vWf, E-selectin and thrombomodulin were measured using ELISA. As expected, women with PIH had significantly higher levels of plasma vWf (by 19%, p=0.003), E-selectin (by 40%, p<0.001) and thrombomodulin (by 61%, p=0.01) than normotensive women. However, on stepwise multiple regression analysis, only thrombomodulin was an independent significant predictor of the presence of PIH (p=0.023). We conclude that although vWf, E-selectin and thrombomodulin are all raised in PIH, only thrombomodulin was independently associated with PIH. This molecule could potentially be useful in monitoring and in providing clues in aetiology and pathophysiology, and may have implications for the clinical complications associated with PIH.

  15. One-pot preparation of conducting composite containing abundant amino groups on electrode surface for electrochemical detection of von willebrand factor

    Science.gov (United States)

    Wang, Wen; Ma, Chao; Li, Yi; Liu, Baihui; Tan, Liang

    2018-03-01

    A one-pot protocol based on cyclic voltammetric scan was employed to prepare new conducting composite that was abundant in amino groups. The scanning electron microscope, atomic force microscope, X-ray photoelectron spectroscopy and infrared spectrum characterization demonstrate that poly(azure A), gold nanoparticles, chitosan and cysteine were immobilized simultaneously on glassy carbon electrode surface. Von Willebrand factor (vWF) antibody (Ab) was subsequently assembled by using glutaraldehyde to construct the Ab/composite-modified electrode. The capture of vWF could inhibit the charge transfer between the ferri-/ferrocyanide probe and the electrode and exert the negative effect on the electrochemical response of the dye polymer in the conducting composite due to the strong steric hindrance effect. The DPV peak current change before and after the immunoreaction was found to be proportional to the logarithm of the vWF concentration from 0.001 to 100 μg mL-1 with a detection limit of 0.4 ng mL-1. The proposed label-free electrochemical method was employed in the investigation on the release of vWF by oxidation-injured vascular endothelial cells. The experimental results exhibit that the vWF content in growth medium was increased when the oxidation injury of the cells was intensified in the presence of H2O2.

  16. A systematic review of the effects of hemophilia and von Willebrand disease on arterial trombosis

    NARCIS (Netherlands)

    Biere-Rafi, Sara; Zwiers, M.; Peters, Marjolein; Van Der Meer, Jan; Rosendaal, Frits R; Buller, Harry R; Kamphuisen, Pieter W

    Background: Patients with hemophilia and von Willebrand disease (VWD) may be protected against arterial thrombosis, through a hy-pocoagulable state or atherosclerosis. We performed a systematic review to assess the association between these clotting disorders, arterial thrombosis and the prevalence

  17. Analysis of von Willebrand factor A domain-related protein (WARP polymorphism in temperate and tropical Plasmodium vivax field isolates

    Directory of Open Access Journals (Sweden)

    Zakeri Sedigheh

    2009-06-01

    Full Text Available Abstract Background The identification of key molecules is crucial for designing transmission-blocking vaccines (TBVs, among those ookinete micronemal proteins are candidate as a general class of malaria transmission-blocking targets. Here, the sequence analysis of an extra-cellular malaria protein expressed in ookinetes, named von Willebrand factor A domain-related protein (WARP, is reported in 91 Plasmodium vivax isolates circulating in different regions of Iran. Methods Clinical isolates were collected from north temperate and southern tropical regions in Iran. Primers have been designed based on P. vivax sequence (ctg_6991 which amplified a fragment of about 1044 bp with no size variation. Direct sequencing of PCR products was used to determine polymorphism and further bioinformatics analysis in P. vivax sexual stage antigen, pvwarp. Results Amplified pvwarp gene showed 886 bp in size, with no intron. BLAST analysis showed a similarity of 98–100% to P. vivax Sal-I strain; however, Iranian isolates had 2 bp mismatches in 247 and 531 positions that were non-synonymous substitution [T (ACT to A (GCT and R (AGA to S (AGT] in comparison with the Sal-I sequence. Conclusion This study presents the first large-scale survey on pvwarp polymorphism in the world, which provides baseline data for developing WARP-based TBV against both temperate and tropical P. vivax isolates.

  18. Von Willebrand factor indicates bacterial translocation, inflammation, and procoagulant imbalance and predicts complications independently of portal hypertension severity.

    Science.gov (United States)

    Mandorfer, M; Schwabl, P; Paternostro, R; Pomej, K; Bauer, D; Thaler, J; Ay, C; Quehenberger, P; Fritzer-Szekeres, M; Peck-Radosavljevic, M; Trauner, M; Reiberger, T; Ferlitsch, A

    2018-04-01

    Elevated plasma von Willebrand factor antigen (vWF) has been shown to indicate the presence of clinically significant portal hypertension, and thus, predicts the development of clinical events in patients with cirrhosis. To investigate the impact of bacterial translocation and inflammation on vWF, as well as the association between vWF and procoagulant imbalance. Moreover, we assessed whether vWF predicts complications of cirrhosis, independent of the severity of portal hypertension. Our study population comprised 225 patients with hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg without active bacterial infections or hepatocellular carcinoma. vWF correlated with markers of bacterial translocation (lipopolysaccharide-binding protein [LBP; ρ = 0.201; P = 0.021]), inflammation (interleukin 6 [IL-6; ρ = 0.426; P protein [CRP; ρ = 0.249; P protein C ratio; ρ = 0.507; P model for transplant-free mortality. Finally, the independent prognostic value of vWF/CRP groups for mortality was confirmed by competing risk analysis. Our results demonstrate that vWF is not only a marker of portal hypertension but also independently linked to bacterial translocation, inflammation and procoagulant imbalance, which might explain its HVPG-independent association with most clinical events. Prognostic groups based on vWF/CRP efficiently discriminate between patients with a poor 5-year survival and patients with a favourable prognosis. © 2018 John Wiley & Sons Ltd.

  19. von Willebrand factor as a novel noninvasive predictor of portal hypertension and esophageal varices in hepatitis B patients with cirrhosis.

    Science.gov (United States)

    Wu, Hao; Yan, Shiping; Wang, Guangchuan; Cui, Shaobo; Zhang, Chunqing; Zhu, Qiang

    2015-01-01

    At present, there is no perfect noninvasive method to assess portal hypertension and esophageal varices. Early predicting esophageal varices can provide evidence for managing cirrhotic patients. We aimed to further investigate von Willebrand factor (vWF) as a noninvasive predictor of portal hypertension, especially of esophageal varices. A total of 60 hepatitis B patients with cirrhosis and 45 healthy subjects were enrolled in this study. Levels of six markers were examined. All patients underwent hepatic venous pressure gradient (HVPG) and esophagogastroduodenoscopy. We evaluated the performance of six factors for diagnosis of portal hypertension and esophageal varices. The vWF levels in liver tissues were observed by immunohistochemistry. Correlations between the level of vWF in liver tissues and HVPG and between levels of vWF in tissues and plasma were examined. Cutoff values of plasma vWF (1510.5 mU/mL and 1701 mU/mL) showed high positive predictive value (PPV, 90.2% and 87.5%) in predicting clinically significant portal hypertension and severe portal hypertension. Cutoff values of vWF (1414 mU/ml and 1990 mU/mL, PPV 90.3% and 86.3%, respectively) were provided to detect the presence and degree of esophageal varices. Linear correlations were observed between levels of vWF in liver tissues and HVPG (r(2) = 0.552, p portal hypertension and esophageal varices in hepatitis B patients with cirrhosis. Increased levels of vWF in liver tissues may induce the elevated plasma vWF levels, but molecular mechanism is needed for further study.

  20. Neutrophil Protease Cleavage of Von Willebrand Factor in Glomeruli – An Anti-thrombotic Mechanism in the Kidney

    Directory of Open Access Journals (Sweden)

    Ramesh Tati

    2017-02-01

    Full Text Available Adequate cleavage of von Willebrand factor (VWF prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM was studied as a reflection of processes occurring in the subendothelial glomerular space. VWF was incubated with human GBMs and VWF cleavage was assessed by multimer structure analysis, immunoblotting and mass spectrometry. VWF was cleaved into the smallest multimers by the GBM, which contained ADAMTS13 as well as neutrophil proteases, elastase, proteinase 3 (PR3, cathepsin-G and matrix-metalloproteinase 9. The most potent components of the GBM capable of VWF cleavage were in the serine protease or metalloprotease category, but not ADAMTS13. Neutralization of neutrophil serine proteases inhibited GBM-mediated VWF-cleaving activity, demonstrating a marked contribution of elastase and/or PR3. VWF-platelet strings formed on the surface of primary glomerular endothelial cells, in a perfusion system, were cleaved by both elastase and the GBM, a process blocked by elastase inhibitor. Ultramorphological studies of the human kidney demonstrated neutrophils releasing elastase into the GBM. Neutrophil proteases may contribute to VWF cleavage within the subendothelium, adjacent to the GBM, and thus regulate thrombus size. This anti-thrombotic mechanism would protect the normal kidney during inflammation and could also explain why most patients with ADAMTS13 deficiency do not develop severe kidney failure.

  1. Multiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis

    Directory of Open Access Journals (Sweden)

    Kanbe Katsuaki

    2008-06-01

    Full Text Available Abstract The von Willebrand Factor A (vWF A domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED, however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 mediates formation of a filamentous matrix network through metal-ion dependent adhesion sites in the domain. Here we show two new functions of the vWF A domain in cartilage-specific matrilins (1 and 3. First, vWF A domain regulates oligomerization of matrilins. Insertion of a vWF A domain into matrilin-3 converts the formation of a mixture of matrilin-3 tetramer, trimer, and dimer into a tetramer only, while deletion of a vWF A domain from matrilin-1 converts the formation of the native matrilin-1 trimer into a mixture of trimer and dimer. Second, the vWF A domain protects matrilin-1 from proteolysis. We identified a latent proteolytic site next to the vWF A2 domain in matrilin-1, which is sensitive to the inhibitors of matrix proteases. Deletion of the abutting vWF A domain results in degradation of matrilin-1, presumably by exposing the adjacent proteolytic site. In addition, we also confirmed the vWF A domain is vital for the secretion of matrilin-3. Secretion of the mutant matrilin-3 harbouring a point mutation within the vWF A domain, as occurred in MED patients, is markedly reduced and delayed, resulting from intracellular retention of the mutant matrilin-3. Taken together, our data suggest that different mutations/deletions of the vWF A domain in matrilins may lead to distinct pathological mechanisms due to the multiple functions of the vWF A domain.

  2. Identification and characterization of a novel P2Y 12 variant in a patient diagnosed with type 1 von Willebrand disease in the European MCMDM-1VWD study.

    Science.gov (United States)

    Daly, Martina E; Dawood, Ban B; Lester, William A; Peake, Ian R; Rodeghiero, Francesco; Goodeve, Anne C; Makris, Michael; Wilde, Jonathan T; Mumford, Andrew D; Watson, Stephen P; Mundell, Stuart J

    2009-04-23

    We investigated whether defects in the P2Y(12) ADP receptor gene (P2RY12) contribute to the bleeding tendency in 92 index cases enrolled in the European MCMDM-1VWD study. A heterozygous mutation, predicting a lysine to glutamate (K174E) substitution in P2Y(12), was identified in one case with mild type 1 von Willebrand disease (VWD) and a VWF defect. Platelets from the index case and relatives carrying the K174E defect changed shape in response to ADP, but showed reduced and reversible aggregation in response to 10 muM ADP, unlike the maximal, sustained aggregation observed in controls. The reduced response was associated with an approximate 50% reduction in binding of [(3)H]2MeS-ADP to P2Y(12), whereas binding to the P2Y(1) receptor was normal. A hemagglutinin-tagged K174E P2Y(12) variant showed surface expression in CHO cells, markedly reduced binding to [(3)H]2MeS-ADP, and minimal ADP-mediated inhibition of forskolin-induced adenylyl cyclase activity. Our results provide further evidence for locus heterogeneity in type 1 VWD.

  3. Protéolyse du facteur Willebrand et cardiopathies à forces de cisaillement élevées : nouvelles approches diagnostiques et thérapeutiques

    OpenAIRE

    Rauch , Antoine

    2014-01-01

    In the first part of the thesis, we describe a novel approach based on antibody-based therapy to prevent the acquired von Willebrand factor (VWF) degradation observed in continuous-flow mechanical circulatory assist device therapy. Via a murine monoclonal antibody directed against VWF D4 domain and thus interfering with VWF-ADAMTS13 binding, a partial inhibition of VWF degradation is observed in whole blood using an ex vivo circulatory assist device model. In the second part of the thesis, we...

  4. von Willebrand factor and its cleaving protease ADAMTS13 balance in coronary artery vessels: Lessons learned from thrombotic thrombocytopenic purpura. A narrative review.

    Science.gov (United States)

    Morici, Nuccia; Cantoni, Silvia; Panzeri, Francesco; Sacco, Alice; Rusconi, Chiara; Stucchi, Miriam; Oliva, Fabrizio; Cattaneo, Marco

    2017-07-01

    Deficiency of the von Willebrand factor-cleaving protease ADAMTS13 is central to the pathophysiology of thrombotic thrombocytopenic purpura (TTP), a microangiopathic syndrome that presents as an acute medical emergency. In this review we will explore the evidence of a two-way relationship between TTP and ACS. Moreover, we will review the evidence emerged from epidemiological studies of an inverse relationship between the plasma levels of ADAMTS13 and the risk of ACS. Pubmed, MEDLINE and EMBASE, CINHAL, COCHRANE and Google Scholar databases were searched from inception to January 2017. The search yielded 43 studies representing 23 unique patient cases, 5 case series, 5 cohort studies and 10 case-control studies. Most ACS cases developing in the setting of TTP resolved with standard treatment of the underlying microangiopathy, with only a few requiring coronary invasive management. Antiplatelet therapy was not usually prescribed and all of the currently used P2Y 12 were felt to be a potential trigger for a TTP-like syndrome, although our review revealed that the occurrence of TTP in patients treated with new P2Y 12 antagonists is rare. Most studies confirmed the inverse association among ADAMTS13 levels and ACS. The heart is a definite target organ in TTP. The clinical spectrum of its involvement is probably influenced by local factors that add on to the systemic deficiency characteristic of TTP. It follows that patients with TTP should be carefully monitored for ACS events, especially when multiple risk factors for coronary disease exist. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Elevated Factor VIII and von Willebrand Factor Levels Predict Unfavorable Outcome in Stroke Patients Treated with Intravenous Thrombolysis

    Directory of Open Access Journals (Sweden)

    Noémi Klára Tóth

    2018-01-01

    Full Text Available IntroductionPlasma factor VIII (FVIII and von Willebrand factor (VWF levels have been associated with the rate and severity of arterial thrombus formation and have been linked to outcomes following thrombolytic therapy in acute myocardial infarction patients. Here, we aimed to investigate FVIII and VWF levels during the course of thrombolysis in acute ischemic stroke (AIS patients and to find out whether they predict long-term outcomes.Materials and methodsStudy population included 131 consecutive AIS patients (median age: 69 years, 60.3% men who underwent i.v. thrombolysis with recombinant tissue plasminogen activator (rt-PA. Blood samples were taken on admission, 1 and 24 h after rt-PA administration to measure FVIII activity and VWF antigen levels. Neurological deficit of patients was determined according to the National Institutes of Health Stroke Scale (NIHSS. ASPECT scores were assessed using computer tomography images taken before and 24 h after thrombolysis. Intracranial hemorrhage was classified according to the European Cooperative Acute Stroke Study (ECASS II criteria. Long-term functional outcome was determined at 90 days after the event by the modified Rankin scale (mRS.ResultsVWF levels on admission were significantly elevated in case of more severe AIS [median and IQR values: NIHSS <6:189.6% (151.9–233.2%; NIHSS 6–16: 199.6% (176.4–250.8%; NIHSS >16: 247.8% (199.9–353.8%, p = 0.013]; similar, but non-significant trend was observed for FVIII levels. FVIII and VWF levels correlated well on admission (r = 0.748, p < 0.001 but no significant correlation was found immediately after thrombolysis (r = 0.093, p = 0.299, most probably due to plasmin-mediated FVIII degradation. VWF levels at all investigated occasions and FVIII activity before and 24 h after thrombolysis were associated with worse 24 h post-lysis ASPECT scores. In a binary backward logistic regression analysis including age, gender

  6. Joint assessment in von Willebrand disease : Validation of the Haemophilia Joint Health score and Haemophilia Activities List

    NARCIS (Netherlands)

    van Galen, Karin P. M.; Timmer, Merel A.; de Kleijn, Piet; Fischer, Kathelijn; Foppen, Wouter; Schutgens, Roger E. G.; Eikenboom, Jeroen; Meijer, Karina; Cnossen, Marjon H.; Fijnvandraat, Karin; van der Bom, Johanna G.; Laros-van Gorkom, Britta A. P.; Leebeek, Frank W. G.; Mauser-Bunschoten, Eveline P.

    Assessment of clinical outcome after joint bleeding is essential to identify joint damage and optimise treatment, to prevent disability. However, disease-specific tools to assess the musculoskeletal status in patients with von Willebrand disease (VWD) are lacking. We aimed to determine validity and

  7. Generation and validation of the Condensed MCMDM-1VWD Bleeding Questionnaire for von Willebrand disease.

    Science.gov (United States)

    Bowman, M; Mundell, G; Grabell, J; Hopman, W M; Rapson, D; Lillicrap, D; James, P

    2008-12-01

    Given the challenges involved in obtaining accurate bleeding histories, attempts at standardization have occurred and the value of quantifying hemorrhagic symptoms has been recognized. An extensive validated bleeding questionnaire (MCMDM-1VWD) was condensed by eliminating all details that did not directly affect the bleeding score (BS) and the correlation between the two versions was tested. Additionally, the diagnostic utility of the condensed version was prospectively tested. Data on 259 individuals who were administered the questionnaire are presented here; 217 being prospectively investigated for von Willebrand disease (VWD) (group 1) and 42 previously known to have type 1, 2 or 3 VWD (group 2). Of the 217 prospectively investigated, 35 had positive BS (> or =4) and 182 had negative scores. Seven individuals (all with positive BS) had laboratory results consistent with type 1 VWD. This results in a sensitivity of 100% and a specificity of 87%. The positive predictive value is 0.20 and the negative predictive value is 1. The correlation between the full MCMDM-1VWD and condensed versions is excellent (Spearman's 0.97, P type 2 > type 1 VWD (anova P < 0.001). There is a strong inverse relationship between VWF:Ag level and BS (Spearman's -0.411, P < 0.001). The Condensed MCMDM-1VWD Bleeding Questionnaire is an efficient, effective tool in the evaluation of patients for VWD.

  8. Cyclical thrombocytosis, acquired von Willebrand syndrome and aggressive non-melanoma skin cancers are common in patients with Philadelphia-negative myeloproliferative neoplasms treated with hydroxyurea.

    Science.gov (United States)

    Verner, Emma; Forsyth, Cecily; Grigg, Andrew

    2014-05-01

    Abstract Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea complications have been reported in Philadelphia-negative myeloproliferative neoplasms (MPNs), but their incidence and clinical consequences have not been defined in a large cohort of patients. We conducted a retrospective analysis of 188 consecutive patients with MPNs specifically addressing the incidence of these complications. Cyclical thrombocytosis was documented in 29 patients (15%), the majority of whom were receiving hydroxyurea. Acquired von Willebrand syndrome was identified in 17 of the 84 screened patients (20%), but was not associated with any major bleeding complications. Non-melanoma skin cancers were reported in 51 patients (27%). Hydroxyurea-related fever occurred in nine of 149 patients (6%) who received hydroxyurea. Seventy-three patients (39%) experienced a total of 98 major thrombotic events, with the majority of these occurring prior to or within 3 months of the diagnosis. Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea-related complications are not infrequent in MPNs and have important clinical consequences for management.

  9. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial

    Directory of Open Access Journals (Sweden)

    Jensen GS

    2016-10-01

    Full Text Available Gitte S Jensen,1 Miki Lenninger,1 Michael P Ero,2 Kathleen F Benson,1 1NIS Labs, Klamath Falls, OR, 2Machaon Diagnostics, Inc., Oakland, CA, USA Objective: The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations.Materials and methods: A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD, a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF, and platelet factor-4. Seventy-four people completed the study with good compliance.Results: Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (P<0.05, and reached a high level of significance for males consuming nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (P<0.006. A decrease in vWF was seen in the female population consuming nattokinase (P<0.1. In the subpopulation with low plasma renin activity levels at baseline (<0.29 ng/mL/h, an increase was seen for 66% of the people after 8-week consumption of nattokinase (P

  10. Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Lund, Søren S; Tarnow, Lise; Stehouwer, Coen D A

    2008-01-01

    -month washout between interventions. RESULTS: Levels of tumour necrosis factor-alpha, plasminogen activator inhibitor-1 antigen, tissue-type plasminogen activator antigen, von Willebrand factor, soluble intercellular adhesion molecule-1 and soluble E-selectin were significantly lower during metformin...... versus repaglinide treatments. In contrast, Amadori albumin and heart rate were higher during metformin versus repaglinide. Levels of interleukin-6, fibrinogen, soluble vascular cell adhesion molecule-1, asymmetric dimethylarginine and advanced glycation end products as well as glycaemic levels...

  11. Epidemiologic features of von Willebrand's disease in Doberman pinschers, Scottish terriers, and Shetland sheepdogs: 260 cases (1984-1988)

    Science.gov (United States)

    Brooks, M; Dodds, W J; Raymond, S L

    1992-04-15

    During a study period from 1985 through 1988, plasma von Willebrand's factor antigen (vWF:Ag) concentration was measured as a marker for prevalence of the von Willebrand's disease (vWD) trait in Doberman Pinschers (doberman, n = 5,554), Scottish Terriers (scottie, n = 1,363), and Shetland Sheepdogs (sheltie, n = 4,279). Significant increase in prevalence of the trait was seen in scotties and shelties during this period. In 1988, 73% of dobermans, 30% of scotties, and 28% of shelties tested had abnormal vWF:Ag concentration (less than 50% vWF:Ag). We found significant differences between breeds with respect to age and vWF:Ag concentration of clinically affected dogs at time of diagnosis. The affected dobermans were older (doberman mean age, 4.6 years; scottie mean age, 1.7 years; sheltie mean age, 1.9 years) and had higher concentration of plasma vWF:Ag (doberman mean vWF:Ag, 15%; scottie mean vWF:Ag, 0%; sheltie mean vWF:Ag, 8%). Bleeding in affected dogs of all 3 breeds was observed predominantly from mucosal surfaces and from cutaneous sites of surgery or trauma. The most common site of mucosal bleeding in scotties and shelties was oral or nasal cavity, and in dobermans was the urogenital tract. Differences in clinical manifestations of vWD in purebred dogs may reflect heterogeneous defects within the vWF gene, causing a variety of abnormalities in production, structure, and function of vWF protein. Analogous to vWD in human beings, acquired deficiencies of vWF may also contribute to the clinical variability of vWD in dogs.

  12. Elevated levels of von Willebrand factor and high mobility group box 1 (HMGB1) are associated with disease severity and clinical outcome of scrub typhus.

    Science.gov (United States)

    Chen, Hongliu; Ning, Zong; Qiu, Ying; Liao, Yuanli; Chang, Haihua; Ai, Yuanyuan; Wei, Yinghua; Deng, Yiming; Shen, Ying

    2017-08-01

    This study aimed to investigate whether von Willebrand factor (vWF) and high mobility group box 1 (HMGB1) are associated with the severity and clinical outcome of scrub typhus and to seek novel biomarkers for surveillance and prediction of the prognosis of this infection. Serum concentrations of vWF and HMGB1 were measured twice by ELISA for scrub typhus patients (n=103), once prior to doxycycline therapy and then on day 7 of doxycycline therapy; concentrations were measured once for healthy controls (n=32). Among the total 103 patients enrolled, 38 had disease complicated by multiple organ dysfunction syndrome (MODS). Serum concentrations of vWF and HMGB1 were significantly higher in all the patients than in the healthy controls, both prior to doxycycline treatment and on day 7 of doxycycline treatment (pscrub typhus (area under the curve (AUC)=0.864, p=0.001, and AUC=0.862, p=0.001, respectively). Elevated levels of vWF and HMGB1 are associated with the severity and clinical outcome of scrub typhus. These represent possible new biomarkers for use in the assessment and prognostic prediction of this infection. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bouwens, E.A.M.; Kootstra, N.A.; Hebbel, R.P.; Voorberg, J.; Mertens, K.

    2009-01-01

    Background Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this

  14. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, Maartje; Bouwens, Eveline A. M.; Kootstra, Neeltje A.; Hebbel, Robert P.; Voorberg, Jan; Mertens, Koen

    2009-01-01

    Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this study, we

  15. Effects of coagulation factors and inflammatory cytokines on ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research April 2016; 15 (4): 827-831. ISSN: 1596-5996 (print); ... fibrinogen (Fg) and von Willebrand factor (vWF) in plasma were analyzed by enzyme-linked ... determined by Western blot analysis. Inflammatory ... Currently, coronary heart disease (CHD) has become one .... membrane.

  16. Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States.

    Science.gov (United States)

    Flood, Veronica H; Christopherson, Pamela A; Gill, Joan Cox; Friedman, Kenneth D; Haberichter, Sandra L; Bellissimo, Daniel B; Udani, Rupa A; Dasgupta, Mahua; Hoffmann, Raymond G; Ragni, Margaret V; Shapiro, Amy D; Lusher, Jeanne M; Lentz, Steven R; Abshire, Thomas C; Leissinger, Cindy; Hoots, W Keith; Manco-Johnson, Marilyn J; Gruppo, Ralph A; Boggio, Lisa N; Montgomery, Kate T; Goodeve, Anne C; James, Paula D; Lillicrap, David; Peake, Ian R; Montgomery, Robert R

    2016-05-19

    von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. von Willebrand factor (VWF) laboratory testing and full-length VWF gene sequencing was performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the International Society on Thrombosis and Haemostasis bleeding assessment tool. At study entry, 64% of subjects had VWF antigen (VWF:Ag) or VWF ristocetin cofactor activity below the lower limit of normal, whereas 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag <30 IU/dL (82%), whereas subjects with type 1 VWD and VWF:Ag ≥30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls (14%). All subjects with severe type 1 VWD and VWF:Ag ≤5 IU/dL had an abnormal bleeding score (BS), but otherwise BS did not correlate with VWF:Ag. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal BS compared with subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population. © 2016 by The American Society of Hematology.

  17. Vascular endothelial cell function and cardiovascular risk factors in patients with chronic renal failure

    DEFF Research Database (Denmark)

    Haaber, A B; Eidemak, I; Jensen, T

    1995-01-01

    Cardiovascular risk factors and markers of endothelial cell function were studied in nondiabetic patients with mild to moderate chronic renal failure. The transcapillary escape rate of albumin and the plasma concentrations of von Willebrand factor, fibrinogen, and plasma lipids were measured in 29...

  18. Thalidomide for treatment of gastrointestinal bleedings due to angiodysplasia : a case report in acquired von Willebrand syndrome and review of the literature

    NARCIS (Netherlands)

    Engelen, E T; van Galen, K P M; Schutgens, R E G

    INTRODUCTION: Acquired von Willebrand syndrome is a rare bleeding disorder and treatment of the associated gastrointestinal (GI) bleeding due to angiodysplasia is challenging. AIM: The aim of this study was to present a new case on the successful use of thalidomide in a patient with acquired von

  19. Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort.

    Science.gov (United States)

    Kander, Elizabeth M; Raza, Sania; Zhou, Zheng; Gao, Juehua; Zakarija, Anaadriana; McMahon, Brandon J; Stein, Brady L

    2015-11-01

    The BCR-ABL1-negative myeloproliferative neoplasms (MPN) share an increased risk of thrombotic and hemorrhagic complications. Risk factors for hemorrhage are less well defined than those for thrombosis. Because patients with CALR mutations have higher platelet counts compared to JAK2 V617F-mutated patients, bleeding rates may be increased in this group. Our aim was to retrospectively evaluate whether acquired von Willebrand disease (AvWD), thrombocytosis, mutational status, or treatment history are associated with bleeding in a cohort of MPN patients. Using an electronic database, MPN patients seen between 2005 and 2013 were retrospectively identified using ICD-9 codes and billing records. A bleeding event was defined as one that was identified in the medical record and graded based on the Common Terminology Criteria for Adverse Event (CTCAE) version 4.0. Among 351 MPN patients, 15.6 % experienced 64 bleeding event types. There was no association of bleeding with mutational status, gender, MPN subtype, aspirin use, prior thrombosis, or platelet count at presentation. There was an association between bleeding and older age at diagnosis. aVWD was identified in six patients. In this single-center retrospective study, bleeding events were identified in 15 % of patients, and associated with older age at diagnosis. aVWD was rarely tested for in this cohort.

  20. Endothelial dysfunction, ambulatory pulse pressure and albuminuria are associated in Type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Knudsen, Søren Tang; Jeppesen, Peter; Frederiksen, Christian Alcaraz

    2007-01-01

    as three urinary albumin/creatinine ratios. Von Willebrand factor (vWF), fibrinogen, E-selectin and soluble intercellular adhesion molecule 1 (ICAM-1) were measured in plasma. RESULTS: Thirty-four patients had normoalbuminuria (group N) and 12 had micro- or macroalbuminuria (group A). PP levels increased...

  1. Factor VIII and von Willebrand factor co-delivery by endothelial cells

    NARCIS (Netherlands)

    Bouwens, E.A.M.|info:eu-repo/dai/nl/314061894

    2011-01-01

    A defect in coagulation factor VIII (FVIII) results in the inherited bleeding disorder hemophilia A. Current treatment of hemophilia A is hampered by the need of frequent administration of costly FVIII products. Therefore gene therapy is an attractive alternative for protein replacement to treat

  2. Haemodynamic responses and changes of haemostatic risk factors in cold-adapted humans.

    Science.gov (United States)

    De Lorenzo, F; Kadziola, Z; Mukherjee, M; Saba, N; Kakkar, V V

    1999-09-01

    Epidemiological studies have shown an increase in acute myocardial infarctions or deaths due to myocardial infarction in colder weather; the mechanisms most likely involve increased blood levels of haemostatic risk factors, and increases in arterial blood pressure and heart rate. We studied the relationship between cold adaptation, haemostatic risk factors and haemodynamic variables. Cold adaptation was obtained by a programme of immersion of the whole body up to the neck in a water-filled bath, the temperature of which was gradually decreased from 22 degrees C to 14 degrees C, time of exposure being increased from 5 to 20 min over a period of 90 days. We studied 428 patients (44% men) and measured blood levels of fibrinogen, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator antigen (t-PA), plasma viscosity, von Willebrand factor, D-dimer and platelet count, both at baseline and after 90 days of daily immersion. There were significant reductions in von Willebrand factor (-3%; p cold adaptation (-310; p = 0.004). Cold adaptation, compared with exposure to cold weather, induces different haemodynamic responses and changes of blood levels of haemostatic risk factors.

  3. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial.

    Science.gov (United States)

    Jensen, Gitte S; Lenninger, Miki; Ero, Michael P; Benson, Kathleen F

    2016-01-01

    The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations. A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD), a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg) who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF), and platelet factor-4. Seventy-four people completed the study with good compliance. Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg ( P nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg ( P nattokinase ( P nattokinase ( P nattokinase consumption in a North American population is associated with beneficial changes to BP in a hypertensive population, indicating sex-specific mechanisms of action of nattokinase's effect on vWF and hypertension.

  4. Successful Ultrasound-Guided Femoral Nerve Blockade and Catheterization in a Patient with Von Willebrand Disease

    Directory of Open Access Journals (Sweden)

    Youmna E. DiStefano

    2015-01-01

    Full Text Available Peripheral nerve blockade (PNB is superior to neuraxial anesthesia and/or opioid therapy for perioperative analgesia in total knee replacement (TKR. Evidence on the safety of PNB in patients with coagulopathy is lacking. We describe the first documented account of continuous femoral PNB for perioperative analgesia in a patient with Von Willebrand Disease (vWD. Given her history of opioid tolerance and after an informative discussion, a continuous femoral PNB was planned for in this 34-year-old female undergoing TKR. A Humate-P intravenous infusion was started and the patient was positioned supinely. Using sterile technique with ultrasound guidance, a Contiplex 18 Gauge Tuohy needle was advanced in plane through the fascia iliaca towards the femoral nerve. A nerve catheter was threaded through the needle and secured without complications. Postoperatively, a levobupivacaine femoral catheter infusion was maintained, and twice daily Humate-P intravenous infusions were administered for 48 hours; enoxaparin thromboprophylaxis was initiated thereafter. The patient was discharged uneventfully on postoperative day 4. Given documentation of delayed, unheralded bleeding from PNB in coagulopathic patients, we recommend individualized PNB in vWD patients. Multidisciplinary team involvement is required to guide factor supplementation and thromboprophylaxis, as is close follow-up to elicit signs of bleeding throughout the delayed postoperative period.

  5. Cloning of the cDNA for murine von Willebrand factor and identification of orthologous genes reveals the extent of conservation among diverse species.

    Science.gov (United States)

    Chitta, Mohan S; Duhé, Roy J; Kermode, John C

    2007-05-01

    Interaction of von Willebrand factor (VWF) with circulating platelets promotes hemostasis when a blood vessel is injured. The A1 domain of VWF is responsible for the initial interaction with platelets and is well conserved among species. Knowledge of the cDNA and genomic DNA sequences for human VWF allowed us to predict the cDNA sequence for murine VWF in silico and amplify its entire coding region by RT-PCR. The murine VWF cDNA has an open reading frame of 8,442 bp, encoding a protein of 2,813 amino acid residues with 83% identity to human pre-pro-VWF. The same strategy was used to predict in silico the cDNA sequence for the ortholog of VWF in a further six species. Many of these predictions diverged substantially from the putative Reference Sequences derived by ab initio methods. Our predicted sequences indicated that the VWF gene has a conserved structure of 52 exons in all seven mammalian species examined, as well as in the chicken. There is a minor structural variation in the pufferfish Takifugu rubripes insofar as the VWF gene in this species has 53 exons. Comparison of the translated amino acid sequences also revealed a high degree of conservation. In particular, the cysteine residues are conserved precisely throughout both the pro-peptide and the mature VWF sequence in all species, with a minor exception in the pufferfish VWF ortholog where two adjacent cysteine residues are omitted. The marked conservation of cysteine residues emphasizes the importance of the intricate pattern of disulfide bonds in governing the structure of pro-VWF and regulating the function of the mature VWF protein. It should also be emphasized that many of the conserved features of the VWF gene and protein were obscured when the comparison among species was based on the putative Reference Sequences instead of our predicted cDNA sequences.

  6. The important role of von Willebrand factor in platelet-derived FVIII gene therapy for murine hemophilia A in the presence of inhibitory antibodies.

    Science.gov (United States)

    Shi, Q; Schroeder, J A; Kuether, E L; Montgomery, R R

    2015-07-01

    Our previous studies have demonstrated that targeting FVIII expression to platelets results in FVIII storage together with von Willebrand factor (VWF) in platelet α-granules and that platelet-derived FVIII (2bF8) corrects the murine hemophilia A phenotype even in the presence of high-titer anti-FVIII inhibitory antibodies (inhibitors). To explore how VWF has an impact on platelet gene therapy for hemophilia A with inhibitors. 2bF8 transgenic mice in the FVIII(-/-) background (2bF8(tg+/-) F8(-/-) ) with varying VWF phenotypes were used in this study. Animals were analyzed by VWF ELISA, FVIII activity assay, Bethesda assay and tail clip survival test. Only 18% of 2bF8(tg+/-) F8(-/-) VWF(-/-) animals, in which VWF was deficient, survived the tail clip challenge with inhibitor titers of 3-8000 BU mL(-1) . In contrast, 82% of 2bF8(tg+/-) F8(-/-) VWF(+/+) mice, which had normal VWF levels, survived tail clipping with inhibitor titers of 10-50,000 BU mL(-1) . All 2bF8(tg+/-) F8(-/-) VWF(-/-) mice without inhibitors survived tail clipping and no VWF(-/-) F8(-/-) mice survived this challenge. Because VWF is synthesized by endothelial cells and megakaryocytes and is distributed in both plasma and platelets in peripheral blood, we further investigated the effect of each compartment of VWF on platelet-FVIII gene therapy for hemophilia A with inhibitors. In the presence of inhibitors, 42% of animals survived tail clipping in the group with plasma-VWF and 50% survived in the platelet-VWF group. VWF is essential for platelet gene therapy for hemophilia A with inhibitors. Both platelet-VWF and plasma-VWF are required for optimal platelet-derived FVIII gene therapy for hemophilia A in the presence of inhibitors. © 2015 International Society on Thrombosis and Haemostasis.

  7. von Willebrand Factor Test

    Science.gov (United States)

    ... with infections, inflammation, trauma, and with physical and emotional stressors. They are also increased with pregnancy and with the use of estrogen medications such as oral contraceptives. Is there anything else I should know? A ...

  8. Expression of connective tissue growth factor (CTGF/CCN2) in breast cancer cells is associated with increased migration and angiogenesis.

    Science.gov (United States)

    Chien, Wenwen; O'Kelly, James; Lu, Daning; Leiter, Amanda; Sohn, Julia; Yin, Dong; Karlan, Beth; Vadgama, Jay; Lyons, Karen M; Koeffler, H Phillip

    2011-06-01

    Connective tissue growth factor (CTGF/CCN2) belongs to the CCN family of matricellular proteins, comprising Cyr61, CTGF, NovH and WISP1-3. The CCN proteins contain an N-terminal signal peptide followed by four conserved domains sharing sequence similarities with the insulin-like growth factor binding proteins, von Willebrand factor type C repeat, thrombospondin type 1 repeat, and a C-terminal growth factor cysteine knot domain. To investigate the role of CCN2 in breast cancer, we transfected MCF-7 cells with full-length CCN2, and with four mutant constructs in which one of the domains had been deleted. MCF-7 cells stably expressing full-length CCN2 demonstrated reduced cell proliferation, increased migration in Boyden chamber assays and promoted angiogenesis in chorioallantoic membrane assays compared to control cells. Deletion of the C-terminal cysteine knot domain, but not of any other domain-deleted mutants, abolished activities mediated by full-length CCN2. We have dissected the role of CCN2 in breast tumorigenesis on a structural basis.

  9. The Carmat Bioprosthetic Total Artificial Heart Is Associated With Early Hemostatic Recovery and no Acquired von Willebrand Syndrome in Calves.

    Science.gov (United States)

    Smadja, David M; Susen, Sophie; Rauch, Antoine; Cholley, Bernard; Latrémouille, Christian; Duveau, Daniel; Zilberstein, Luca; Méléard, Denis; Boughenou, Marie-Fazia; Belle, Eric Van; Gaussem, Pascale; Capel, Antoine; Jansen, Piet; Carpentier, Alain

    2017-10-01

    To determine hemostasis perturbations, including von Willebrand factor (VWF) multimers, after implantation of a new bioprosthetic and pulsatile total artificial heart (TAH). Preclinical study SETTING: Single-center biosurgical research laboratory. Female Charolais calves, 2-to-6 months old, weighing 102-to-122 kg. Surgical implantation of TAH through a mid-sternotomy approach. Four of 12 calves had a support duration of several days (4, 4, 8, and 10 days), allowing for the exploration of early steps of hemostasis parameters, including prothrombin time; coagulation factor levels (II, V, VII+X, and fibrinogen); and platelet count. Multimeric analysis of VWF was performed to detect a potential loss of high-molecular weight (HMW) multimers, as previously described for continuous flow rotary blood pumps. Despite the absence of anticoagulant treatment administered in the postoperative phase, no signs of coagulation activation were detected. Indeed, after an immediate postsurgery decrease of prothrombin time, platelet count, and coagulation factor levels, most parameters returned to baseline values. HMW multimers of VWF remained stable either after initiation or during days of support. Coagulation parameters and platelet count recovery in the postoperative phase of the Carmat TAH (Camat SA, Velizy Villacoublay Cedex, France) implantation in calves, in the absence of anticoagulant treatment and associated with the absence of decrease in HMW multimers of VWF, is in line with early hemocompatibility that is currently being validated in human clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

    Science.gov (United States)

    McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J

    2015-01-15

    Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. NCBI nr-aa BLAST: CBRC-TTRU-01-0026 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TTRU-01-0026 ref|YP_001642747.1| ATPase [Bacillus weihenstephanensis KBAB4] gb...|ABY46772.1| AAA ATPase containing von Willebrand factor type A (vWA)-like domain [Bacillus weihenstephanensis KBAB4] YP_001642747.1 5e-80 50% ...

  12. Decreased plasma ADAMTS-13 activity as a predictor of postoperative bleeding in cyanotic congenital heart disease

    Directory of Open Access Journals (Sweden)

    Rosangela P.S. Soares

    2013-04-01

    Full Text Available OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity. The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years. The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001. An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081, was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029 and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004. Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group, preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79, 1.096 (95% CI 1.016 to 1.183, and 37.43 (95% CI 1.79 to 782.73. CONCLUSION: Low plasma ADAMTS-13

  13. Renal arteriovenous fistula: A rare complication of electro-hydraulic ...

    African Journals Online (AJOL)

    A 62-year-old man with type 1 Von Willebrand's disease was electively admitted to a Northern Ireland district general hospital for endoscopic management of a 1 cm right lower pole calculus. After pre-operative administration of appropriate haematological factors, flexible ureteroscopic electro-hydraulic lithotripsy (EHL).

  14. Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low vitamin D serum concentration.

    Science.gov (United States)

    Busch, Albert; Hoffjan, Sabine; Bergmann, Frauke; Hartung, Birgit; Jung, Helena; Hanel, Daniela; Tzschach, Andeas; Kadar, Janos; von Kodolitsch, Yskert; Germer, Christoph-Thomas; Trobisch, Heiner; Strasser, Erwin; Wildenauer, René

    2016-08-03

    The vascular type represents a very rare, yet the clinically most fatal entity of Ehlers-Danlos syndrome (EDS). Patients are often admitted due to arterial bleedings and the friable tissue and the altered coagulation contribute to the challenge in treatment strategies. Until now there is little information about clotting characteristics that might influence hemostasis decisively and eventually worsen emergency situations. 22 vascular type EDS patients were studied for hemoglobin, platelet volume and count, Quick and activated partial thromboplastin time, fibrinogen, factor XIII, von Willebrand disease, vitamin D and platelet aggregation by modern standard laboratory methods. Results show a high prevalence of over 50 % for platelet aggregation disorders in vascular type EDS patients, especially for collagen and epinephrine induced tests, whereas the plasmatic cascade did not show any alterations. Additionally, more than half of the tested subjects showed low vitamin D serum levels, which might additionally affect vascular wall integrity. The presented data underline the importance of detailed laboratory screening methods in vascular type EDS patients in order to allow for targeted application of platelet-interacting substances that might be of decisive benefit in the emergency setting.

  15. A case of refractory thrombotic thrombocytopenic purpura treated ...

    African Journals Online (AJOL)

    Background. Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threaten- ing disorder that occurs due to deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member. 13), which is a von Willebrand factor (VWF) cleaving protein.[1]. The absent or severely reduced activity ...

  16. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

    LENUS (Irish Health Repository)

    Larkin, Deirdre

    2009-03-01

    Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF) and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20) and cerebral (n = 13) P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag) level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB) was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU\\/ml versus 1.9 IU\\/ml; p<0.005). This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005). Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1). These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

  17. Classification of Unknown Thermocouple Types Using Similarity Factor Measurement

    Directory of Open Access Journals (Sweden)

    Seshu K. DAMARLA

    2011-01-01

    Full Text Available In contrast to classification using PCA method, a new methodology is proposed for type identification of unknown thermocouple. The new methodology is based on calculating the degree of similarity between two multivariate datasets using two types of similarity factors. One similarity factor is based on principle component analysis and the angles between the principle component subspaces while the other is based on the Mahalanobis distance between the datasets. Datasets containing thermo-emfs against given temperature ranges are formed for each type of thermocouple (e.g. J, K, S, T, R, E, B and N type by experimentation are considered as reference datasets. Datasets corresponding to unknown type are captured. Similarity factor between the datasets one of which being the unknown type and the other being each known type are compared. When maximum similarity factor occurs, then the class of unknown type is allocated to that of known type.

  18. The metal-ion-dependent adhesion site in the Von Willebrand factor-A domain of α2δ subunits is key to trafficking voltage-gated Ca2+ channels

    Science.gov (United States)

    Cantí, C.; Nieto-Rostro, M.; Foucault, I.; Heblich, F.; Wratten, J.; Richards, M. W.; Hendrich, J.; Douglas, L.; Page, K. M.; Davies, A.; Dolphin, A. C.

    2005-01-01

    All auxiliary α2δ subunits of voltage-gated Ca2+ (CaV) channels contain an extracellular Von Willebrand factor-A (VWA) domain that, in α2δ-1 and -2, has a perfect metal-ion-dependent adhesion site (MIDAS). Modeling of the α2δ-2 VWA domain shows it to be highly likely to bind a divalent cation. Mutating the three key MIDAS residues responsible for divalent cation binding resulted in a MIDAS mutant α2δ-2 subunit that was still processed and trafficked normally when it was expressed alone. However, unlike WT α2δ-2, the MIDAS mutant α2δ-2 subunit did not enhance and, in some cases, further diminished CaV1.2, -2.1, and -2.2 currents coexpressed with β1b by using either Ba2+ or Na+ as a permeant ion. Furthermore, expression of the MIDAS mutant α2δ-2 reduced surface expression and strongly increased the perinuclear retention of CaVα1 subunits at the earliest time at which expression was observed in both Cos-7 and NG108–15 cells. Despite the presence of endogenous α2δ subunits, heterologous expression of α2δ-2 in differentiated NG108–15 cells further enhanced the endogenous high-threshold Ca2+ currents, whereas this enhancement was prevented by the MIDAS mutations. Our results indicate that α2δ subunits normally interact with the CaVα1 subunit early in their maturation, before the appearance of functional plasma membrane channels, and an intact MIDAS motif in the α2δ subunit is required to promote trafficking of the α1 subunit to the plasma membrane by an integrin-like switch. This finding provides evidence for a primary role of a VWA domain in intracellular trafficking of a multimeric complex, in contrast to the more usual roles in binding extracellular ligands in other exofacial VWA domains. PMID:16061813

  19. Are there differences in acute phase inflammation markers regarding the type of heart failure?

    Directory of Open Access Journals (Sweden)

    Jaime Agüero-Ramón-Llin

    2011-09-01

    Full Text Available This study aimed to determine if there are differences in inflammatory markers in the acute phase between systolic heart failure and heart failure with preserved systolic function. One hundred and thirty-one patients with acute heart failure were recruited consecutively. At admission, plasma fibrinogen, Creactive protein, sialic acid, von Willebrand factor, vascular endothelial growth factor, interleukin-6 and NTproBNP were all evaluated. If the ejection fraction was 45% or over patients were included in the HF-PSF group; the remaining patients were included in the SHF group. The HF-PSF patients were older (72±10 vs 63±12 years, P<0.001, presented a higher rate of atrial fibrillation (56.1 vs 21.3%, P<0.001, and had a lower rate of hemoglobin (12.2±2 vs 13.3±2.1 g/dL, P<0.01. No significant differences were observed in the inflammation markers analyzed among SHF and HFPSF groups. In the acute phase of heart failure there is a marked elevation of inflammatory markers but there are no differences in the inflammatory markers analyzed between the two different types of heart failure

  20. 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.

  1. A case of von Willebrand disease discovered during treatment of a sacral pressure ulcer.

    Science.gov (United States)

    Murakami, Masahiro; Fukaya, Sumiko; Furuya, Masaichi; Hyakusoku, Hiko

    2010-12-01

    A sacral pressure ulcer developed in a patient hospitalized for cerebral infarction. Each time necrotic tissue was debrided from the ulcer, pressure hemostasis was necessary to stop the bleeding. As treatment continued, the pressure required to stop the bleeding caused the ulcer to worsen, leading to a downward spiral in the patient's condition. While trying to determine the cause of this problem, we discovered that the patient had von Willebrand disease. Medication controlled the bleeding, and the pressure ulcer began to heal at the same time. It was clear to us that conservative treatment would lead to a complete cure but that the healing process would take a long time and require continued administration of an expensive drug. We decided, therefore, to close the wound with a fasciocutaneous flap so that the patient could be quickly transferred to a rehabilitation hospital. About 1 month after surgery, epithelialization was complete, we were able to discontinue medication, and the patient was discharged. This experience demonstrates the importance of determining the cause of any deviation from the normal course of healing in pressure ulcers. It also indicates that the use of fasciocutaneous flaps, which involve little intraoperative bleeding in short surgeries, is appropriate in cases like this one.

  2. Loading factor and inclination parameter of diagonal type MHD generators

    International Nuclear Information System (INIS)

    Ishikawa, Motoo

    1979-01-01

    Regarding diagonal type MHD generators is studied the relation between the loading factor and inclination parameter which is required for attaining the maximum power density with a given electrical efficiency on the assumption of infinitely segmented electrodes. The average current density on electrodes is calculated against the Hall parameter, loading factor, and inclination parameter. The diagonal type generator is compared with Faraday type generator regarding the average current density. Decreasing the loading factor from inlet to outlet is appropriate to small size generators but increasing to large size generators. The inclination parameter had better decrease in both generators, being smaller for small generators than for large ones. The average current density on electrodes of diagonal type generators varies less with the loading factor than the Faraday type. In large size generators its value can become smaller compared with that of the Faraday type. (author)

  3. Acquired von Willebrand Syndrome Associated to Secondary IgM MGUS Emerging after Autologous Stem Cell Transplantation for AL Amyloidosis.

    Science.gov (United States)

    Qamar, Hina; Lee, Adrienne; Valentine, Karen; Skeith, Leslie; Jimenez-Zepeda, Victor H

    2017-01-01

    Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT). Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

  4. Acquired von Willebrand Syndrome associated to secondary IgM MGUS emerging after Autologous Stem Cell Transplantation for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Victor H Jimenez-Zepeda

    2017-05-01

    Full Text Available Acquired von Willebrand syndrome (AVWS is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT. Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

  5. Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure.

    Science.gov (United States)

    Meitinger, T; Meindl, A; Bork, P; Rost, B; Sander, C; Haasemann, M; Murken, J

    1993-12-01

    The X-lined gene for Norrie disease, which is characterized by blindness, deafness and mental retardation has been cloned recently. This gene has been thought to code for a putative extracellular factor; its predicted amino acid sequence is homologous to the C-terminal domain of diverse extracellular proteins. Sequence pattern searches and three-dimensional modelling now suggest that the Norrie disease protein (NDP) has a tertiary structure similar to that of transforming growth factor beta (TGF beta). Our model identifies NDP as a member of an emerging family of growth factors containing a cystine knot motif, with direct implications for the physiological role of NDP. The model also sheds light on sequence related domains such as the C-terminal domain of mucins and of von Willebrand factor.

  6. Immunoexpression of vascular endothelial growth factor in periapical granulomas, radicular cysts, and residual radicular cysts.

    Science.gov (United States)

    Nonaka, Cassiano Francisco Weege; Maia, Alexandre Pinto; Nascimento, George João Ferreira do; de Almeida Freitas, Roseana; Batista de Souza, Lélia; Galvão, Hébel Cavalcanti

    2008-12-01

    Our aim was to assess and compare the immunoexpression of vascular endothelial growth factor (VEGF) in periapical granulomas (PGs), radicular cysts (RCs), and residual radicular cysts (RRCs), relating it to the angiogenic index and the intensity of the inflammatory infiltrate. Twenty PGs, 20 RCs, and 10 RRCs were evaluated by immunohistochemistry using anti-VEGF antibody. Angiogenic index was determined by microvessel count (MVC) using anti-von Willebrand factor antibody. The PGs and RCs showed higher expression of VEGF than the RRCs. Lesions presenting few inflammatory infiltrate revealed the lowest immunoexpression of VEGF (P .05). VEGF is present in periapical inflammatory lesions but at a lower level in RRCs. The expression of this proangiogenic factor is closely related to the intensity of the inflammatory infiltrate in these lesions.

  7. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

    Science.gov (United States)

    Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

    2015-01-01

    Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID

  8. Type D Personality : a five-factor model perspective

    NARCIS (Netherlands)

    de Fruyt, F.; Denollet, J.K.L.

    2002-01-01

    This study investigated the position of Type D (high Negative Affectivity and high Social Inhibition) within the Five-Factor Model (FFM) of personality. A sample of 155 healthy subjects were administered the Type D Scale and the NEO-FFI, assessing the FFM traits. Subjects also filled out the General

  9. Life-threatening subdural hematoma after aortic valve replacement in a patient with Heyde syndrome: a case report.

    Science.gov (United States)

    Uchida, Tetsuro; Hamasaki, Azumi; Ohba, Eiichi; Yamashita, Atsushi; Hayashi, Jun; Sadahiro, Mitsuaki

    2017-08-08

    Heyde syndrome is known as a triad of calcific aortic stenosis, anemia due to gastrointestinal bleeding from angiodysplasia, and acquired type 2A von Willebrand disease. This acquired hemorrhagic disorder is characterized by the loss of the large von Willebrand factor multimers due to the shear stress across the diseased aortic valve. The most frequently observed type of bleeding in these patients is mucosal or skin bleeding, such as epistaxis, followed by gastrointestinal bleeding. On the other hand, intracranial hemorrhage complicating Heyde syndrome is extremely rare. A 77-year-old woman presented to our hospital with severe aortic stenosis and severe anemia due to gastrointestinal bleeding and was diagnosed with Heyde syndrome. Although aortic valve replacement was performed without recurrent gastrointestinal bleeding, postoperative life-threatening acute subdural hematoma occurred with a marked midline shift. Despite prompt surgical evacuation of the hematoma, she did not recover consciousness and she died 1 month after the operation. Postoperative subdural hematoma is rare, but it should be kept in mind as a devastating hemorrhagic complication, especially in patients with Heyde syndrome.

  10. A Viral Nanoparticle with Dual Function as an Anthrax Antitoxin and Vaccine

    Science.gov (United States)

    Manayani, Darly J; Thomas, Diane; Dryden, Kelly A; Reddy, Vijay; Siladi, Marc E; Marlett, John M; Rainey, G. Jonah A; Pique, Michael E; Scobie, Heather M; Yeager, Mark; Young, John A. T; Manchester, Marianne; Schneemann, Anette

    2007-01-01

    The recent use of Bacillus anthracis as a bioweapon has stimulated the search for novel antitoxins and vaccines that act rapidly and with minimal adverse effects. B. anthracis produces an AB-type toxin composed of the receptor-binding moiety protective antigen (PA) and the enzymatic moieties edema factor and lethal factor. PA is a key target for both antitoxin and vaccine development. We used the icosahedral insect virus Flock House virus as a platform to display 180 copies of the high affinity, PA-binding von Willebrand A domain of the ANTXR2 cellular receptor. The chimeric virus-like particles (VLPs) correctly displayed the receptor von Willebrand A domain on their surface and inhibited lethal toxin action in in vitro and in vivo models of anthrax intoxication. Moreover, VLPs complexed with PA elicited a potent toxin-neutralizing antibody response that protected rats from anthrax lethal toxin challenge after a single immunization without adjuvant. This recombinant VLP platform represents a novel and highly effective, dually-acting reagent for treatment and protection against anthrax. PMID:17922572

  11. Expression of Selected Markers in Immunohistochemical Diagnosis of Canine and Human Testicular Tumours

    Directory of Open Access Journals (Sweden)

    Ciaputa Rafał

    2015-04-01

    Full Text Available Immunohistochemical profiles of the most common canine testicular tumours, including the Leydig cell tumours, seminomas, and Sertoli cell tumours were analysed, and the results were compared with those obtained in the corresponding types of human testicular neoplasms. The expressions of vimentin, von Willebrand factor (FVIII, chromogranin A, synaptophysin, and MCM3 were quantified. In the case of Sertoli cell tumours, only canine ones were analysed, since this type of tumour is very rarely diagnosed in men. The expression of the analysed proteins in the testicular tumours was similar. The von Willebrand factor exhibited the strongest expression in Leydig cell tumours in dogs and men, while vimentin was expressed more strongly in dogs (96.7% had an intensity at +++ than in men (62.5% had +++ in the Leydigioma. The immunoexpression of MCM3 in seminomas was high in both men and dogs – 90% +++ and 100% +++ respectively. The lack of chromogranin A and synaptophysin was observed in almost 100% of seminomas in men and dogs. This differed from the results obtained for Leydigioma, where chromogranin A was expressed in 70% of dogs at +++ and in 100% of men at ++++. The results may indicate that the antibodies were selected correctly. Their analysis and interpretation provides valuable information concerning the nature of the studied tumours.

  12. Hepatocellular hypoxia-induced vascular endothelial growth factor expression and angiogenesis in experimental biliary cirrhosis.

    Science.gov (United States)

    Rosmorduc, O; Wendum, D; Corpechot, C; Galy, B; Sebbagh, N; Raleigh, J; Housset, C; Poupon, R

    1999-10-01

    We tested the potential role of vascular endothelial growth factor (VEGF) and of fibroblast growth factor-2 (FGF-2) in the angiogenesis associated with experimental liver fibrogenesis induced by common bile duct ligation in Sprague-Dawley rats. In normal rats, VEGF and FGF-2 immunoreactivities were restricted to less than 3% of hepatocytes. One week after bile duct ligation, hypoxia was demonstrated by the immunodetection of pimonidazole adducts unevenly distributed throughout the lobule. After 2 weeks, hypoxia and VEGF expression were detected in >95% of hepatocytes and coexisted with an increase in periportal vascular endothelial cell proliferation, as ascertained by Ki67 immunolabeling. Subsequently, at 3 weeks the density of von Willebrand-labeled vascular section in fibrotic areas significantly increased. Semiquantitative reverse transcription polymerase chain reaction showed that VEGF(120) and VEGF(164) transcripts, that correspond to secreted isoforms, increased within 2 weeks, while VEGF(188) transcripts remained unchanged. FGF-2 mainly consisting of a 22-kd isoform, according to Western blot, was identified by immunohistochemistry in 49% and 100% of hepatocytes at 3 and 7 weeks, respectively. Our data provide evidence that in biliary-type liver fibrogenesis, angiogenesis is stimulated primarily by VEGF in response to hepatocellular hypoxia while FGF-2 likely contributes to the maintenance of angiogenesis at later stages.

  13. Precipitating and relieving factors of migraine versus tension type headache

    Directory of Open Access Journals (Sweden)

    Haque Badrul

    2012-08-01

    Full Text Available Abstract Background To determine the differences of precipitating and relieving factors between migraine and tension type headache. Methods This is a cross sectional study. We retrospectively reviewed the records of 250 migraine patients and 250 patients diagnosed as tension type headache from the specialized headache clinic in Dept. of Neurology, Dhaka Medical College Hospital. Data were collected through a predesigned questionnaire containing information on age, sex, social status and a predetermined list of precipitating and relieving factors. Results In this study, the female patients predominated (67%. Most of the patients were within 21–30 years age group (58.6%. About 58% of them belonged to middle class families. The common precipitating factors like stress, anxiety, activity, journey, reading, cold and warm were well distributed among both the migraine and tension type headache (TTH patients. But significant difference was demonstrated for fatigue (p  Conclusion The most frequent precipitating factors for headache appear to be identical for both migraine and TTH patients. Even though some factors like fatigue, sleep deprivation, sunlight and food significantly precipitate migraine and drug, massage are effective maneuver for relieving pain among migrianeurs.

  14. Bleeding score in Type 1 von Willebrand disease patients using the ISTH-BAT questionnaire.

    Science.gov (United States)

    Pathare, A; Al Omrani, S; Al Hajri, F; Al Obaidani, N; Al Balushi, B; Al Falahi, K

    2018-04-01

    Bleeding assessment tools have evolved in the last decade to standardize the assessment of the severity of bleeding symptom in a consistent way. In 2010, the International Society on Thrombosis and Hemostasis-Bleeding Assessment Tool (ISTH-BAT) was developed and validated. Our aim was to administer ISTH-BAT questionnaire to the Omani patients with type 1 VWD and obtain the bleeding score (BS). We also studied the severity of their bleeding symptoms and correlated it with the BS as well as with the laboratory parameters. Forty-eight type I VWD index cases and 52 normal subjects were interviewed and the ISTH-BAT questionnaire administered. The BS was calculated based on a history of bleeding symptoms from 12 different sites according to the standard ISTH-BAT questionnaire. Laboratory parameters were obtained from patient's medical records. The mean age of this cohort was 27 years (range, 6-49) with 60% being females. The median time to administer this questionnaire was 10 minutes with an interquartile range (IQR) from 8 to 17 minutes. Overall, the median BS was 7 (IQR; 2,11) although individual scores ranged between 0 and 36. The BS was negatively correlated with VWF: Ag, VWF: RCo, and VWF: CB and the Spearman's correlation coefficient "rho" was, respectively, -0.15, -0.08, and -0.22. The ISTH-BAT BS is designed to reflect the severity of bleeding. Our results demonstrate the inherent variability of this bleeding pattern. We also found that the ISTH-BAT BS significantly correlated with VWF: Ag and VWF: CB. © 2017 John Wiley & Sons Ltd.

  15. Job Strain as a Risk Factor for Type 2 Diabetes

    DEFF Research Database (Denmark)

    Nyberg, Solja T; Fransson, Eleonor I; Heikkilä, Katriina

    2014-01-01

    with baseline questionnaires. Incident type 2 diabetes at follow-up was ascertained using national health registers, clinical screening, and self-reports. We analyzed data for each study using Cox regression and pooled the study-specific estimates in fixed-effect meta-analyses. RESULTS: There were 3,703 cases......OBJECTIVE: The status of psychosocial stress at work as a risk factor for type 2 diabetes is unclear because existing evidence is based on small studies and is subject to confounding by lifestyle factors, such as obesity and physical inactivity. This collaborative study examined whether stress...... at work, defined as "job strain," is associated with incident type 2 diabetes independent of lifestyle factors. RESEARCH DESIGN AND METHODS: We extracted individual-level data for 124,808 diabetes-free adults from 13 European cohort studies participating in the IPD-Work Consortium. We measured job strain...

  16. Synergistic shortening of the bleeding time by desmopressin and ethamsylate in patients with various constitutional bleeding disorders.

    Science.gov (United States)

    Kobrinsky, N L; Israels, E D; Bickis, M G

    1991-01-01

    Desmopressin and ethamsylate were evaluated for possible synergistic effects on the bleeding time. The drugs were administered individually and together to 12 patients with markedly prolonged bleeding times known to be relatively or absolutely unresponsive to desmopressin alone. The bleeding disorders studied included Glanzmann's thrombasthenia (one), other disorders of platelet function (four), pseudo-von Willebrand disease (one), and von Willebrand disease type I (three), type II (two), and type III (one). Desmopressin alone shortened the bleeding time from 23.9 +/- 1.5 to 19.5 +/- 2.3 min (p = 0.03). Ethamsylate alone was without effect. Desmopressin and ethamsylate together shortened the bleeding time to 11.2 +/- 1.4 min (p less than 0.01 compared to baseline, p = 0.02 compared to desmopressin alone). The combination was ineffective in three patients, with Glanzmann's thrombasthenia (one), and von Willebrand disease type I (one) and type III (one). Toxic effects of the drugs were not observed. Five patients received desmopressin and ethamsylate prior to dental work with mandibular block (one), heart surgery requiring cardiopulmonary bypass (two), and adenotonsillectomy surgery (two). Normal hemostasis was achieved in each case. A synergistic shortening of the bleeding time was observed with the combination of desmopressin and ethamsylate in a wide range of bleeding disorders.

  17. Clinical risk factors, DNA variants, and the development of type 2 diabetes

    DEFF Research Database (Denmark)

    Lyssenko, Valeriya; Jonsson, Anna Elisabet; Almgren, Peter

    2008-01-01

    Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts.......Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts....

  18. Idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in a 17-year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Patschan Daniel

    2011-12-01

    Full Text Available Abstract Introduction Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is a life-threatening condition with various etiopathogeneses. Without therapy approximately 90% of all patients die from the disease. Case presentation We report the case of a 17-year-old Caucasian woman with widespread hematomas and headache. Due to hemolytic anemia, thrombocytopenia, and schistocytosis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected and plasma exchange therapy was initiated immediately. Since her thrombocyte level did not increase during the first week of therapy, plasma treatment had to be intensified to a twice-daily schedule. Further diagnostics showed markedly reduced activities of both ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 - also known as von Willebrand factor-cleaving protease and factor H. Test results for antibodies against both proteins were positive. While plasma exchange therapy was continued, rituximab was given once weekly for four consecutive weeks. After the last dose, thrombocytes and activities of ADAMTS-13 and factor H increased into the normal range. Our patient improved and was discharged from the hospital. Conclusions Since no clinical symptoms/laboratory findings indicated a malignant or specific autoimmune-mediated disorder, the diagnosis made was thrombotic thrombocytopenic purpura-hemolytic uremic syndrome due to idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency.

  19. Risk Factors for Type 2 Diabetes in Bangladesh: A Systematic Review

    Directory of Open Access Journals (Sweden)

    T Sal-sabil

    2016-01-01

    Full Text Available Diabetes is one of the most significant public health challenge in developing countries. The risk factors for diabetes are poorly understood among the Bangladeshi population. This study aimed to explore the potential risk factors for type 2 diabetes in Bangladesh. A systematic review was performed. Studies describing the risk factors for type 2 diabetes in Bangladesh published between 1994 to 2014 were included and summarized. Of the 35 studies identified, we included 14 studies that met the inclusion criteria. The prevalence of diabetes was higher among females compared to males. Fourteen common risk factors for diabetes in Bangladesh were identified, namely increased age, obesity, waist- hip ratio, social class, hypertension, family history, sedentary life style among others. The p otential risk factors differed by urban-rural areas and by gender. Several risk factors contribute to the increasing prevalence of type 2 diabetes. Our reviews suggest "metabolically-disadvantageous" body composition of more abdominal and visceral fat in Bangladeshi adults might cause higher diabetes risk at a lower BMI compared to Western population. Preventive strategies targeting to control risk factors for diabetes is a priority public health issue and should be considered for early intervention by clinicians and policy makers.

  20. Risk Factors for Type 1 Diabetes Mellitus among Children and Adolescents in Basrah

    Directory of Open Access Journals (Sweden)

    Athar Abdul Samad Majeed

    2011-05-01

    Full Text Available Objectives: Environmental factors play an important role in the pathogenesis of type 1 diabetes mellitus, many of these factors have been uncovered despite much research. A case-control study was carried out to determine the potential maternal, neonatal and early childhood risk factors for type 1 diabetes mellitus in children and adolescents in Basrah.Methods: A total of 96 diabetic patients who have been admitted to the pediatric wards at 3 main hospitals in Basrah, and those who have visited primary health care centers over the period from the 4th of November 2006 to the end of May 2007 were recruited. In addition, 299 non-diabetic children were included, their age ranged from 18 months to 17 years.Results: Family history of type 1 diabetes mellitus and thyroid diseases in first and second degree relatives was found to be an independent risk factor for type 1 diabetes mellitus, (p<0.001. Regarding maternal habits and illnesses during pregnancy, the study has revealed that tea drinking during pregnancy is a risk factor for type 1 diabetes mellitus in their offspring, (p<0.05. In addition, maternal pre-eclampsia and infections were found to be significant risk factor for type 1 diabetes mellitus, (p<0.001. Neonatal infections, eczema and rhinitis during infancy were also significantly associated with development of type 1 diabetes mellitus. Moreover, the results revealed that duration of <6 months breast feeding is an important trigger of type 1 diabetes mellitus.Conclusion: Exposure to environmental risk factors during pregnancy (tea drinking, pre-eclampsia, and infectious diseases, neonatal period (respiratory distress, jaundice and infections and early infancy are thought to play an important role in triggering the immune process leading to B-cell destruction and the development of type 1 diabetes mellitus.

  1. Factors controlling phase formation of novel Sr-based Y-type ...

    Indian Academy of Sciences (India)

    2017-01-04

    Jan 4, 2017 ... Pramana – J. Phys. (2017) 88: 27 c ... geneity, particle shape and size, because such factors affect the ... Among the various types of hexagonal ferrites, Y-type ... C by a magnetic stirrer until the water slowly evaporated and.

  2. Genetics Home Reference: von Willebrand disease

    Science.gov (United States)

    ... mildest and most common of the three types, accounting for 75 percent of affected individuals. Type 3 ... diseases that affect bone marrow or immune cell function. This rare form of the condition is characterized ...

  3. Erythrocytes and von Willebrand factor in venous thrombosis

    NARCIS (Netherlands)

    Smeets, M.W.J.

    2018-01-01

    Venous thromboembolism represents the third leading vascular disease after myocardial infarction and stroke. Erythrocytes, the most abundant cells in venous thrombi, were thought to be innocent bystanders that become tangled up in the fibrin mesh of venous thrombi. However, this thesis describes

  4. Risk factors for type 2 diabetes mellitus in adolescents secondary ...

    African Journals Online (AJOL)

    Background: The prevalence of Type 2 diabetes mellitus (T2 DM) in children and ... had none of the risk factors while 272(30.9%) had at least one risk factor. Using the American Diabetes Association criteria for identification of those at risk for ...

  5. [Choice of type of delivery: factors reported by puerperal woman].

    Science.gov (United States)

    Nascimento, Raquel Ramos Pinto do; Arantes, Sandra Lucia; Souza, Eunice Delgado Cameron de; Contrera, Luciana; Sales, Ana Paula Assis

    2015-01-01

    To know the factors listed by puerperal woman that influenced the choice in type of delivery. Qualitative research, developed with 25 puerperal women in a University Hospital of Mato Grosso do Sul, between September and November 2014. A semi-structured interview was used for data collection and the Collective Subject Discourse was used to organize and tabulate the data collected. The Collective Subject Discourses resulted in the following categories: Desire for the type of delivery; Respect for the chosen type of delivery and Factors that influenced the choice. Most of the women interviewed (76%) expressed a preference for normal birth due to rapid recovery, less pain and suffering. The influence of family members, previous experience with childbirth, professional-customer interaction and internet information influenced the type of delivery chosen, which reinforces the importance of health education since the pre-natal stage, highlighting the need to equip women to perform a conscious choice.

  6. Form factor of some types of toroidal solenoids

    International Nuclear Information System (INIS)

    Koryavko, V.I.; Litvinenko, Yu.A.

    1979-01-01

    Obtained were the type of dependence between consumed power and formed field for toroidal helical-wound solenoids and the expression for the form factor analogous to the Fabry coefficient for cylindrical solenoids. Determined were optimum dimensions of the helical winding of ''forceless'' toroidal solenoids satisfying the condition of the formation of maximum field at minimum consumed power. Investigations also covered some types of conventional toroidal solenoids. Presented in the paper diagrams permitted to chose dimensions of the considered toroidal solenoids according to their consumed power and winding material volume

  7. Factors associated with hypoglycemia episodes in hospitalized type ...

    African Journals Online (AJOL)

    Purpose: To determine the factors associated with severity of hypoglycemia in hospitalized type 2 diabetes mellitus patients in a tertiary health facility in Malaysia. Methods: This retrospective study involved 207 hospitalised T2DM patients with hypoglycaemia episodes from January 2008 to December 2012 and was ...

  8. Types of abuse and risk factors associated with elder abuse.

    Science.gov (United States)

    Simone, Lacher; Wettstein, Albert; Senn, Oliver; Rosemann, Thomas; Hasler, Susann

    2016-01-01

    Detecting elder abuse is challenging because it is a taboo, and many cases remain unreported. This study aimed to identify types of elder abuse and to investigate its associated risk factors. Retrospective analyses of 903 dossiers created at an Independent Complaints Authority for Old Age in the Canton of Zurich, Switzerland, from January 1, 2008 to October 31, 2012. Characteristics of victims and perpetrators, types of abuse, and associated risk factors related to the victim or the perpetrator were assessed. Bi- and multivariate analysis were used to identify abuse and neglect determinants. A total of 150 cases reflected at least one form of elder abuse or neglect; 104 cases were categorised as abuse with at least one type of abuse (overall 135 mentions), 46 cases were categorised as neglect (active or passive). Psychological abuse was the most reported form (47%), followed by financial (35%), physical (30%) and anticonstitutional abuse (18%). In 81% of the 150 cases at least two risk factors existed. In 13% no associated risk factor could be identified. Compared with neglect, elders with abuse were less likely to be a nursing home resident than living at home (odds ratio [OR] 0.02, 95% confidence interval [CI] 0.00-0.19). In addition, they were more likely to be cohabiting with their perpetrators (OR 18.01, 95% CI 4.43-73.19). For the majority of the reported elder abuse cases at least two associated risk factors could be identified. Knowledge about these red flags and a multifaceted strategy are needed to identify and prevent elder abuse.

  9. Cyclosporin A Impairs the Secretion and Activity of ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeat)*

    Science.gov (United States)

    Hershko, Klilah; Simhadri, Vijaya L.; Blaisdell, Adam; Hunt, Ryan C.; Newell, Jordan; Tseng, Sandra C.; Hershko, Alon Y.; Choi, Jae Won; Sauna, Zuben E.; Wu, Andrew; Bram, Richard J.; Komar, Anton A.; Kimchi-Sarfaty, Chava

    2012-01-01

    The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients. PMID:23144461

  10. Cyclosporin A impairs the secretion and activity of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat).

    Science.gov (United States)

    Hershko, Klilah; Simhadri, Vijaya L; Blaisdell, Adam; Hunt, Ryan C; Newell, Jordan; Tseng, Sandra C; Hershko, Alon Y; Choi, Jae Won; Sauna, Zuben E; Wu, Andrew; Bram, Richard J; Komar, Anton A; Kimchi-Sarfaty, Chava

    2012-12-28

    The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients.

  11. Acquired Von Willebrand’s Syndrome in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Sara Taveras Alam

    2014-01-01

    Full Text Available Acquired von Willebrand syndrome (AVWS is an uncommon, underdiagnosed, and heterogeneous disease which is increasingly recognized as a cause of bleeding diatheses. Systemic lupus erythematosus (SLE is an infrequent cause of AVWS. Herein, we report a case of AVWS diagnosed during the initial presentation of SLE in a previously healthy young man with no family history of bleeding diathesis who presented with worsening epistaxis, gastrointestinal bleeding, and anasarca. He was found to have severe anemia and prolonged activated partial thromboplastin time (aPTT with severely decreased levels of von Willebrand factor (VWF measurements in addition to markedly decreased factor VIII levels. Further evaluation revealed nephrotic syndrome and interstitial lung disease due to SLE. He initially received combination therapy with intravenous immunoglobulin (IVIG and von Willebrand factor/factor VIII concentrates without significant improvement. Treatment with steroids, cyclophosphamide, and rituximab was followed by clinical improvement evidenced by cessation of bleeding. The short follow-up did not allow us to definitely prove the therapeutic effect of immunosuppressive treatment on AVWS in SLE patients. This case adds to the literature supporting the relationship between AVWS and SLE and highlights the importance of combination therapy in the treatment of severe AVWS as well as the role of IVIG, cyclophosphamide, and rituximab in AVWS associated with SLE.

  12. Frequency and risk factors of severe hypoglycaemia in insulin-treated Type 2 diabetes

    DEFF Research Database (Denmark)

    Akram, K; Pedersen-Bjergaard, U; Carstensen, B

    2006-01-01

    AIMS: The reported risk of severe hypoglycaemia in insulin-treated Type 2 diabetes is highly variable and few studies have evaluated the influence of risk factors. We assessed the incidence and the influence of potential risk factors for severe hypoglycaemia in a questionnaire survey in subjects...... with insulin-treated Type 2 diabetes receiving currently recommended multifactorial intervention. METHODS: Consecutive patients with insulin-treated Type 2 diabetes (n = 401) completed a questionnaire about occurrence of hypoglycaemia in the past, hypoglycaemia awareness and socio-demographic factors. A zero...... treatment and treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor antagonists (ARBs) were associated with reduced risk. C-peptide concentration and HbA1c were not associated with the risk of severe hypoglycaemia. CONCLUSIONS: In this cohort of insulin-treated Type 2...

  13. Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR)

    DEFF Research Database (Denmark)

    Christensen, Anders; Kiss, Katalin; Lelkaitis, Giedrius

    2017-01-01

    Background: Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhib...... with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer....

  14. Vasa vasorum in the tunica media and tunica adventitia of the porcine aorta

    Czech Academy of Sciences Publication Activity Database

    Tonar, Z.; Tomášek, P.; Loskot, P.; Janáček, Jiří; Králíčková, M.; Witter, K.

    2016-01-01

    Roč. 205, č. 2016 (2016), s. 22-36 ISSN 0940-9602 Institutional support: RVO:67985823 Keywords : artery * microvessels * pig * stereology * vascular wall * von Willebrand factor Subject RIV: EA - Cell Biology Impact factor: 1.864, year: 2016

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... interferes with the body’s ability to make hemoglobin. Family history and genetics Von Willebrand disease is an ... deficiency anemia. Return to Risk Factors to review family history, lifestyle, unhealthy environments, or other factors that ...

  16. Early Life Factors and Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Xinli Jiang

    2013-01-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a multifactorial disease, and its aetiology involves a complex interplay between genetic, epigenetic, and environmental factors. In recent years, evidences from both human and animal experiments have correlated early life factors with programming diabetes risk in adult life. Fetal and neonatal period is crucial for organ development. Many maternal factors during pregnancy may increase the risk of diabetes of offsprings in later life, which include malnutrition, healthy (hyperglycemia and obesity, behavior (smoking, drinking, and junk food diet, hormone administration, and even stress. In neonates, catch-up growth, lactation, glucocorticoids administration, and stress have all been found to increase the risk of insulin resistance or T2DM. Unfavorable environments (socioeconomic situation and famine or obesity also has long-term negative effects on children by causing increased susceptibility to T2DM in adults. We also address the potential mechanisms that may underlie the developmental programming of T2DM. Therefore, it might be possible to prevent or delay the risk for T2DM by improving pre- and/or postnatal factors.

  17. Precipitating and relieving factors of migraine versus tension type headache

    OpenAIRE

    Haque, Badrul; Rahman, Kazi Mohibur; Hoque, Azharul; Hasan, ATM Hasibul; Chowdhury, Rajib Nayan; Khan, Sharif Uddin; Alam, Mondal Badrul; Habib, Mansur; Mohammad, Quazi Deen

    2012-01-01

    Abstract Background To determine the differences of precipitating and relieving factors between migraine and tension type headache. Methods This is a cross sectional study. We retrospectively reviewed the records of 250 migraine patients and 250 patients diagnosed as tension type headache from the specialized headache clinic in Dept. of Neurology, Dhaka Medical College Hospital. Data were collected through a predesigned questionnaire containing information on age, sex, social status and a pre...

  18. Innovation types at smes and external influencing factors

    Directory of Open Access Journals (Sweden)

    Monika Walicka

    2014-12-01

    Full Text Available Stimulating innovation is one of the pressing policy challenges facing many countries in the world today. The paper analyses the external factors that Polish entrepreneurs find most detrimental to their innovative activity. A sample of 199 small and medium size enterprises (SMEs in Poland were subjected to a survey. The data collected revealed the innovation types of SMEs in Poland and external financial factors influencing innovation the most. The results show external factors such as legal regulations, access to external financing, bureaucracy of institutions, financial government support, the tax system, time necessary to comply with regulations, and crisis and instability are very important for SMEs. According to the results, process and marketing innovations are applied more frequently than product and organisational innovations. Finally, the results indicate that entrepreneurs indicate that lack of government support and weakness of tax incentives is an important barrier to the innovation process.

  19. Differential regulation of type I interferon and epidermal growth factor pathways by a human Respirovirus virulence factor.

    Directory of Open Access Journals (Sweden)

    Grégory Caignard

    2009-09-01

    Full Text Available A number of paramyxoviruses are responsible for acute respiratory infections in children, elderly and immuno-compromised individuals, resulting in airway inflammation and exacerbation of chronic diseases like asthma. To understand the molecular pathogenesis of these infections, we searched for cellular targets of the virulence protein C of human parainfluenza virus type 3 (hPIV3-C. We found that hPIV3-C interacts directly through its C-terminal domain with STAT1 and GRB2, whereas C proteins from measles or Nipah viruses failed to do so. Binding to STAT1 explains the previously reported capacity of hPIV3-C to block type I interferon signaling, but the interaction with GRB2 was unexpected. This adaptor protein bridges Epidermal Growth Factor (EGF receptor to MAPK/ERK pathway, a signaling cascade recently found to be involved in airway inflammatory response. We report that either hPIV3 infection or transient expression of hPIV3-C both increase cellular response to EGF, as assessed by Elk1 transactivation and phosphorylation levels of ERK1/2, 40S ribosomal subunit protein S6 and translation initiation factor 4E (eIF4E. Furthermore, inhibition of MAPK/ERK pathway with U0126 prevented viral protein expression in infected cells. Altogether, our data provide molecular basis to explain the role of hPIV3-C as a virulence factor and determinant of pathogenesis and demonstrate that Paramyxoviridae have evolved a single virulence factor to block type I interferon signaling and to boost simultaneous cellular response to growth factors.

  20. [Risk factors for schizophrenia patients with type 2 diabetes: a metaanalysis].

    Science.gov (United States)

    Zhou, Min; Xiao, Chuan; Yang, Min; Yuan, Ping; Liu, Yuanyuan

    2015-03-01

    To investigate risk factors for schizophrenia patients with complication of type 2 diabetes mellitus and to provide scientific evidence for prevention and management of this disease. Relevant studies on schizophrenia with type 2 diabetes mellitus in China were searched through PubMed, Medline, CBM, CNKI and VIP from 1997 to 2014. Meta-analysis was performed using RevMan 5.2 soft ware. A total of 26 studies involving 6 373 participants (including 957 cases and 5 416 controls) were included. The results of Meta-analysis showed that the risk factors for schizophrenic patients with complication of type 2 diabetes mellitus were: gender (female) (OR=1.28, 95%CI: 1.09-1.50), age (≥ 40 year) (OR=6.02, 95%CI: 4.48-8.09), overweight (OR=2.32, 95%CI: 1.52-2.88), family history of diabetes (OR=6.12, 95%CI: 3.16-11.86), duration of schizophrenia (>10 years) (OR=3.60, 95%CI: 2.39-5.41), triglycerides (MD=0.38, 95%CI: 0.05-0.71). Male, old age, overweight, family history of diabetes, longer duration and high level of triglycerides are risk factors for schizophrenic patients with complication of diabetes mellitus.

  1. Canine classical seminoma: a specific malignant type with human classifications is highly correlated with tumor angiogenesis

    International Nuclear Information System (INIS)

    Kim, Jong-Hyuk; Yu, Chi-Ho; Yhee, Ji-Young; Im, Keum-Soon; Kim, Na-Hyun; Sur, Jung-Hyang

    2010-01-01

    Human seminoma is classified as classical seminoma (SE) and spermatocytic seminoma (SS). Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD) being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels. Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns) were classified as SE or SS by immunohistochemistry (IHC) using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF) and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS) program was used for various statistical analyses. The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8%) and PLAP-/PAS- SSs were 15/23 (61.2%). All SE cases (8/8, 100%) were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%), 9 diffuse (9/15, 60%), and 4 intratubular/diffuse (4/15, 26.7%) types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion. In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels were a correlated vascular parameter. Although

  2. Canine classical seminoma: a specific malignant type with human classifications is highly correlated with tumor angiogenesis

    Directory of Open Access Journals (Sweden)

    Kim Jong-Hyuk

    2010-05-01

    Full Text Available Abstract Background Human seminoma is classified as classical seminoma (SE and spermatocytic seminoma (SS. Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels. Methods Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns were classified as SE or SS by immunohistochemistry (IHC using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS program was used for various statistical analyses. Results The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8% and PLAP-/PAS- SSs were 15/23 (61.2%. All SE cases (8/8, 100% were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%, 9 diffuse (9/15, 60%, and 4 intratubular/diffuse (4/15, 26.7% types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion. Conclusion In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels

  3. Medication Adherence and its Related Factors in Patients with Type II Diabetes

    Directory of Open Access Journals (Sweden)

    Behzad Gholamaliei

    2016-03-01

    Full Text Available Background and Objectives: Low levels of medication adherence in patients with type 2 diabetes is one of the greatest challenges in the treatment and control of diabetes. This study was designed to determine medication adherence and its related factors in patients with type II diabetes. Materials and Methods: In this cross-sectional study, a total of 300patients with type 2diabetes records in the health centers of Tuyserkan city were randomly selected in 2015. Data collection instrument was a self-made questionnaire, which consisted of factors related to the medication adherence. Questionnaires were completed after confirmation of validity and reliability, by interviews. To analyze the data, descriptive and inferential statistics (T-test, AnOVA, Simple and multiple linear regression were applied, using SPSS software, version 19. Results: Overall, %26.3 of patients were male and %73.7 were female. Also, %65 of patients were illiterate, %24 had some degree of symptoms, and %59.4 had poor medication adherence. There was a significant relationship between age, education, patient care and treatment expenditure, health care team and health system, therapy-related factors and condition-related factors, beliefs about illness, efficacy, and concerns about drugs and medication adherence (P < 0.05. Conclusions: This study showed that medication adherence in patients with diabetes was not suitable and individual, economical and social factors were influential.Therefore, the role of these factors must be considered when designing intervention programs.

  4. Pleiotropic effects of type 2 diabetes management strategies on renal risk factors.

    Science.gov (United States)

    Muskiet, Marcel H A; Tonneijck, Lennart; Smits, Mark M; Kramer, Mark H H; Heerspink, Hiddo J Lambers; van Raalte, Daniël H

    2015-05-01

    In parallel with the type 2 diabetes pandemic, diabetic kidney disease has become the leading cause of end-stage renal disease worldwide, and is associated with high cardiovascular morbidity and mortality. As established in landmark randomised trials and recommended in clinical guidelines, prevention and treatment of diabetic kidney disease focuses on control of the two main renal risk factors, hyperglycaemia and systemic hypertension. Treatment of systemic hypertension with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers is advocated because these drugs seem to exert specific renoprotective effects beyond blood pressure lowering. Emerging evidence shows that obesity, glomerular hyperfiltration, albuminuria, and dyslipidaemia might also adversely affect the kidney in diabetes. Control of these risk factors could have additional benefits on renal outcome in patients with type 2 diabetes. However, despite multifactorial treatment approaches, residual risk for the development and progression of diabetic kidney disease in patients with type 2 diabetes remains, and novel strategies or therapies to treat the disease are urgently needed. Several drugs used in the treatment of type 2 diabetes are associated with pleiotropic effects that could favourably or unfavourably change patients' renal risk profile. We review the risk factors and treatment of diabetic kidney disease, and describe the pleiotropic effects of widely used drugs in type 2 diabetes management on renal outcomes, with special emphasis on antihyperglycaemic drugs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Factors influencing the usage of different types of malaria prevention ...

    African Journals Online (AJOL)

    Objective: To examine factors which influence the use of different types of malaria prevention ... risk areas, religion, education and income influenced ITN usage, whereas only age, malaria .... the uptake of IPTp given that the person would not.

  6. Molecular characterization of exon 28 of von Willebrand's factor ...

    African Journals Online (AJOL)

    2016-05-12

    May 12, 2016 ... were mostly among individuals with Arab ancestry.[3] In. Zimbabwe ... bleeding symptoms are epistaxis, menorrhagia (in women), easy bruising, oral cavity ... North American, British, and Japanese populations. rs1800383 ...

  7. Nuclear factor erythroid 2-related factor 2 deletion impairs glucose tolerance and exacerbates hyperglycemia in type 1 diabetic mice.

    Science.gov (United States)

    Aleksunes, Lauren M; Reisman, Scott A; Yeager, Ronnie L; Goedken, Michael J; Klaassen, Curtis D

    2010-04-01

    The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) induces a battery of cytoprotective genes after oxidative stress. Nrf2 aids in liver regeneration by altering insulin signaling; however, whether Nrf2 participates in hepatic glucose homeostasis is unknown. Compared with wild-type mice, mice lacking Nrf2 (Nrf2-null) have lower basal serum insulin and prolonged hyperglycemia in response to an intraperitoneal glucose challenge. In the present study, blood glucose, serum insulin, urine flow rate, and hepatic expression of glucose-related genes were quantified in male diabetic wild-type and Nrf2-null mice. Type 1 diabetes was induced with a single intraperitoneal dose (200 mg/kg) of streptozotocin (STZ). Histopathology and serum insulin levels confirmed depleted pancreatic beta-cells in STZ-treated mice of both genotypes. Five days after STZ, Nrf2-null mice had higher blood glucose levels than wild-type mice. Nine days after STZ, polyuria occurred in both genotypes with more urine output from Nrf2-null mice (11-fold) than wild-type mice (7-fold). Moreover, STZ-treated Nrf2-null mice had higher levels of serum beta-hydroxybutyrate, triglycerides, and fatty acids 10 days after STZ compared with wild-type mice. STZ reduced hepatic glycogen in both genotypes, with less observed in Nrf2-null mice. Increased urine output and blood glucose in STZ-treated Nrf2-null mice corresponded with enhanced gluconeogenesis (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase)- and reduced glycolysis (pyruvate kinase)-related mRNA expression in their livers. Furthermore, the Nrf2 activator oltipraz lowered blood glucose in wild-type but not Nrf2-null mice administered STZ. Collectively, these data indicate that the absence of Nrf2 worsens hyperglycemia in type I diabetic mice and Nrf2 may represent a therapeutic target for reducing circulating glucose levels.

  8. Prevalence and risk factors of type II endoleaks after endovascular aneurysm repair: A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qiang Guo

    Full Text Available This systematic review and meta-analysis aims to determine the current evidence on risk factors for type II endoleaks after endovascular aneurysm repair (EVAR.A systematic literature search was carried out for studies that evaluated the association of demographic, co-morbidity, and other patient-determined factors with the onset of type II endoleaks. Pooled prevalence of type II endoleaks after EVAR was updated.Among the 504 studies screened, 45 studies with a total of 36,588 participants were included in this review. The pooled prevalence of type II endoleaks after EVAR was 22% [95% confidence interval (CI, 19%-25%]. The main factors consistently associated with type II endoleaks included age [pooled odds ratio (OR, 0.37; 95% CI, 0.31-0.43; P<0.001], smoking (pooled OR, 0.71; 95% CI, 0.55-0.92; P<0.001, patent inferior mesenteric artery (pooled OR, 1.98; 95% CI, 1.06-3.71; P = 0.012, maximum aneurysm diameter (pooled OR, 0.23; 95% CI, 0.17-0.30; P<0.001, and number of patent lumbar arteries (pooled OR, 3.07; 95% CI, 2.81-3.33; P<0.001. Sex, diabetes, hypertension, anticoagulants, antiplatelet, hyperlipidemia, chronic renal insufficiency, types of graft material, and chronic obstructive pulmonary diseases (COPD did not show any association with the onset of type II endoleaks.Clinicians can use the identified risk factors to detect and manage patients at risk of developing type II endoleaks after EVAR. However, further studies are needed to analyze a number of potential risk factors.

  9. Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes

    Science.gov (United States)

    Zheng, Rendong; Cao, Lin; Cao, Wen; Chu, Xiaoqiu; Hu, Yongxin; Zhang, Huifeng; Xu, Juan; Sun, Hongping; Bao, Weiping; Liu, Kemian; Liu, Chao

    2016-01-01

    Background. Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. Methods. A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. Results. Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes. PMID:27006953

  10. Disease: H00225 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ID:18574040 ... AUTHORS ... Sadler JE ... TITLE ... Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopen...MID:17124092 ... AUTHORS ... Sadler JE ... TITLE ... Thrombotic thrombocytopenic purpura: a moving target. ... JOURN

  11. Psychosocial factors affecting various types of intimate partner violence against women.

    Science.gov (United States)

    Güleç Öyekçin, Demet; Yetim, Dilek; Şahin, Erkan Melih

    2012-01-01

    Intimate partner violence against women is a growing global public health problem that is related to various psychosocial, cultural, mental, and economic factors. In this study, psychosocial factors affecting various types of intimate partner violence against women were investigated based upon affected individuals' statements. Demographic data, exposure to various types of partner violence, individual habits, partner habits, family functioning, and social support were inquired about during face to face interviews with 306 women chosen by stratified sampling to represent adult women living in Edirne, Turkey. Among the participants, 54.5% were exposed to psychological violence, 30.4% were exposed to physical violence, 19.3% were exposed to economic violence, and 6.3% were exposed to sexual violence. Partner's age and the duration of marriage had a protective effect on intimate partner violence while worsening of marital relations, marriage by family decision, marriage against family consent, and the presence of a violent history against women in a partner's family had incremental effects on intimate partner violence. The duration of marriage, the worsening of marital relations and a history of violent exposure during childhood increased physical violence. Additionally, a decreasing family income, increasing economic violence, worsening of marital relations, and a decreasing social support network increased sexual violence against women. Recognizing and defining the effecting factors of intimate partner violence will aid in the understanding of the sources that generate and feed the violent behavior. Risk factors of different types of intimate partner violence vary. Our results indicate that any kind of violent behavior increases intimate partner violence against women.

  12. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes

    DEFF Research Database (Denmark)

    Krabbe, K. S.; Nielsen, A. R.; Krogh-Madsen, R.

    2006-01-01

    Aims/hypothesis  Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of Alzheimer's disease and depression. These disorders are associated with type 2 diabetes, and animal models suggest that BDNF plays a role in insulin resistance. We therefore...... explored whether BDNF plays a role in human glucose metabolism. Subjects and methods  We included (Study 1) 233 humans divided into four groups depending on presence or absence of type 2 diabetes and presence or absence of obesity; and (Study 2) seven healthy volunteers who underwent both a hyperglycaemic...... and a hyperinsulinaemic-euglycaemic clamp. Results  Plasma levels of BDNF in Study 1 were decreased in humans with type 2 diabetes independently of obesity. Plasma BDNF was inversely associated with fasting plasma glucose, but not with insulin. No association was found between the BDNF G196A (Val66Met) polymorphism...

  13. Case report

    African Journals Online (AJOL)

    abp

    2017-06-29

    Jun 29, 2017 ... described by the Finish physician Erik von Willebrand in 1926. VWD ... on day 4 and showed normal factor IX level but factor VIII level was low at 16.6%. ... and hemophilia A or between VWD 2B and a platelet disorder.

  14. Glucose variability for cardiovascular risk factors in type 2 diabetes: a meta-analysis

    OpenAIRE

    Liang, Shuang; Yin, Hang; Wei, Chunxiang; Xie, Linjun; He, Hua; Liu, Xiaoquan

    2017-01-01

    Aims It is consensus that glucose variability (GV) plays an important role in maccomplications of type 2 diabetes, but whether GV has a causal role is not yet clear for cardiovascular disease (CVD). This study sought to explore the effect on GV for CVD risk factors with type 2 diabetes. Methods The systematic literature search was performed to identify all GV and CVD risk factors, including total cholesterol (TC), LDL cholesterol (LDL-C), triglyceride (TG), HDL cholesterol (HDL-C), Body Mass ...

  15. HEMOSTATIC SYSTEM CONDITION AND HEART REMODELING IN PATIENTS WITH Q-WAVE MYOCARDIAL INFARCTION WITH ACUTE ANEURYSMS AND LEFT VENTRICLE THROMBUS

    Directory of Open Access Journals (Sweden)

    V. D. Syvolap

    2014-02-01

    elements of the blood coagulation system, responsible for the formation of parietal blood clots on the background of low levels of protein C, which leads to an imbalance of coagulation-anticoagulation-fibrinolysis towards coagulation and suppression of fibrinolysis, associated with thrombosis. Vascular adhesion molecule sVCAM-1 can be regarded not only as an indicator reflecting the state of the blood coagulation system, but also as a marker of immunoinflammatory reactions and endothelial dysfunction, as an increase in their expression due to the increased systemic secretion of proinflammatory cytokines. Activation of immunoinflammatory reactions confirmed by the increase in serum levels of immune system mediators such as fibrinogen and prothrombin. Higher levels of von Willebrand factor is a marker of immune inflammation on a background of endothelial dysfunction. Synergies increase of fibrinogen and von Willebrand factor indicates a high propensity to parietal thrombus formation. Conclusion. It was found that in patients with Q-wave myocardial infarction, complicated by formation of acute aneurysm and parietal thrombus of LV, postinfarction heart remodeling processes are characterized by dilation of the left heart chambers and eccentric left ventricular hypertrophy, a violation of local contractility by dyskinetic type, parietal thrombus formation, the development of diastolic dysfunction of type II and closely associated with high procoagulant and aggregation serum potential with decreased activity of natural anticoagulants on the background of immunoinflammatory reactions and activation of endothelial dysfunction.

  16. Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release

    Directory of Open Access Journals (Sweden)

    Marco Goeijenbier

    2015-03-01

    Full Text Available Puumala virus (PUUV infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVECs and subsequently specifically to PUUV virus particles. Infection of HUVECs with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1 compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased tissue factor expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.

  17. Detection and significance of serum insulin-like growth factor-1 in patients with type 2 diabetes, osteoporosis and type 2 diabetic osteoporosis

    Institute of Scientific and Technical Information of China (English)

    Yan-Rong Kang; Pei-Li Gu

    2016-01-01

    Objective:To investigate the content of insulin-like growth factor-1 (IGF-1) in serum and the relationship with type 2 diabetes, osteoporosis and type 2 diabetic osteoporosis.Methods:A total of 86 cases of patients with type 2 diabetes, 82 cases of patients with osteoporosis, 79 cases of patients with type 2 diabetic osteoporosis and 86 cases of healthy person were selected, the levels of IGF-1, diabetes related factors (fasting plasma c-peptide, FIN, HbA1c, GLU) and osteoporosis related factors (BMP, osteocalcin,β-CTx, P1NP, lumbar vertebra BMD) were detected, the relationship between the above indicators were compared with those of the disease.Results: In each group, content change of IGF-1 was not statistically significant; content changes of IGF-1, BMP and osteocalcin were control group>type 2 diabetes group>osteoporosis group>type 2 diabetic osteoporosis group. Diabetic osteoporosis enhanced the decrease of IGF-1 content. The contents ofβ-CTx and P1NP in osteoporosis group and diabetic osteoporosis group were similar, which were significantly lower than that in control group and type 2 diabetes group. The level of lumbar vertebra BMD in osteoporosis group and diabetic osteoporosis group were the lowest. Fasting plasma c-peptide in diabetes group and diabetic osteoporosis group were significantly lower than that in control group and osteoporosis group, and the content of fasting plasma c-peptide in diabetic osteoporosis group was the lowest. The contents of FIN, HbA1c and GLU in type 2 diabetes group and type 2 diabetic osteoporosis group were significantly higher than that in control group and osteoporosis group.Conclusion:IGF-1 was related with type 2 diabetes, osteoporosis and type 2 diabetic osteoporosis, and could offer help for predicting type 2 diabetes and osteoporosis in the future.

  18. Industrial production of clotting factors: Challenges of expression, and choice of host cells.

    Science.gov (United States)

    Kumar, Sampath R

    2015-07-01

    The development of recombinant forms of blood coagulation factors as safer alternatives to plasma derived factors marked a major advance in the treatment of common coagulation disorders. These are complex proteins, mostly enzymes or co-enzymes, involving multiple post-translational modifications, and therefore are difficult to express. This article reviews the nature of the expression challenges for the industrial production of these factors, vis-à-vis the translational and post-translational bottlenecks, as well as the choice of host cell lines for high-fidelity production. For achieving high productivities of vitamin K dependent proteins, which include factors II (prothrombin), VII, IX and X, and protein C, host cell limitation of γ-glutamyl carboxylation is a major bottleneck. Despite progress in addressing this, involvement of yet unidentified protein(s) impedes a complete cell engineering solution. Human factor VIII expresses at very low levels due to limitations at several steps in the protein secretion pathway. Protein and cell engineering, vector improvement and alternate host cells promise improvement in the productivity. Production of Von Willebrand factor is constrained by its large size, complex structure, and the need for extensive glycosylation and disulfide-bonded oligomerization. All the licensed therapeutic factors are produced in CHO, BHK or HEK293 cells. While HEK293 is a recent adoption, BHK cells appear to be disfavored. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Factorization method for difference equations of hypergeometric type on nonuniform lattices

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez-Nodarse, R. [Departamento de Analisis Matematico, Universidad de Sevilla, Sevilla (Spain); Instituto Carlos I de Fisica Teorica y Computacional, Universidad de Granada, Granada (Spain); Costas-Santos, R.S. [Departamento de Analisis Matematico, Universidad de Sevilla, Sevilla (Spain)

    2001-07-13

    We study the factorization of the hypergeometric-type difference equation of Nikiforov and Uvarov on nonuniform lattices. An explicit form of the raising and lowering operators is derived and some relevant examples are given. (author)

  20. Investigating Factors Associated with Depression of Type 2 Diabetic Retinopathy Patients in China.

    Directory of Open Access Journals (Sweden)

    Xujuan Xu

    Full Text Available To assess the depression status of type 2 diabetic retinopathy patients in Nantong China and to identify factors associated with depression.Two hundred and ninety-four patients with type 2 diabetic retinopathy were recruited from the Affiliated Hospital of Nantong University. The severity of DR was measured in the worse eye. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D; the quality of life was measured with the Medical Outcomes Study Short Form 36 (SF-36. The logistic regression analyses were used to identify the independent factors of depression.The mean age of the study subjects was 57.77 years (SD: 9.64. Approximately 35.7% of subjects reported depressive symptoms (n = 105.Multiple logistic regression analyses showed that female gender (p = 0.014, low monthly income (p = 0.01, poor vision in the better eye (P = 0.002, laser treatment history (p = 0.01 were significant risk factors for depression. The quality of life of individuals with CES-D score<16 was significantly better compared with individuals with CES-D score≥16.The reported depressive symptoms among type 2 diabetic retinopathy population is higher in Nantong China. Gender, salary, vision acuity and treatment history were important risk factors linked to this disorder in the Chinese type 2 diabetic retinopathy population from Nantong. More attention by medical care personnel needs to be paid to the psychological health of this population.

  1. Protective Effects of Female Reproductive Factors on Lauren Intestinal-Type Gastric Adenocarcinoma.

    Science.gov (United States)

    Kim, Su Mi; Min, Byung Hoon; Lee, Jeeyun; An, Ji Yeong; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Jae J; Kang, Won Ki; Kim, Sung; Choi, Min Gew

    2018-01-01

    Gastric cancer shows a male predominance that might be explained by protective effects from estrogens in females. Two Lauren classification histological subtypes, intestinal and diffuse, have distinct carcinogeneses. The purpose of this study was to estimate the effects of sex hormone on female gastric cancer according to Lauren classification. We reviewed medical records for and administered questionnaires, surveying reproductive and hormonal factors, to 758 patients who underwent gastrectomy for gastric cancer at Samsung Medical Center from May 2012 to November 2014. Clinicopathological characteristics were compared between females and males. The incidence of intestinal-type gastric cancer was compared between females subgroups, consist of premenopausal women and three groups of postmenopausal women (five-year intervals after menopause), and males. The association between reproductive factors and intestinal-type gastric cancer was analyzed by multivariate models for the female group. In total, 227 females (29.9%) and 531 males (70.9%) were included in the analysis. Undifferentiated adenocarcinoma and diffuse-type histology were more frequent in female patients than male patients. While 221 (41.6%) male patients had intestinal-type gastric cancer, no premenopausal female patient had this type of gastric cancer. The incidence of intestinal-type gastric cancer increased with time after menopause, and was similar to males after 10 years from menopause. Parity was associated with an increased risk of intestinal-type gastric cancer in menopausal women. These findings support that female sex hormones might be protective against intestinal-type gastric cancer. © Copyright: Yonsei University College of Medicine 2018

  2. Tae-Eum Type as an Independent Risk Factor for Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Seung Ku Lee

    2013-01-01

    Full Text Available Obstructive sleep apnea (OSA is prevalent and associated with several kinds of chronic diseases. There has been evidence that a specific type of Sasang constitution is a risk factor for metabolic and cardiovascular diseases that can be found in patients with OSA, but there are no studies that address the association between the Sasang constitution type (SCT and OSA. The purpose of this study was to investigate the association between the SCT and OSA. A total of 652 participants were included. All participants were examined for demographic information, medical history, and completed an interviewer-administered questionnaire on life style and sleep-related variables. Biochemical analyses were performed to determine the glucose and lipid profiles. An objective recording of OSA was done with an unattended home PSG using an Embla portable device. The apnea-hypopnea index (AHI and oxygen desaturation index (ODI were significantly higher in the Tae-eum (TE type as compared to the So-eum (SE and the So-yang (SY types. Even after adjusting for confounding variables, the TE type still had a 2.34-fold (95% CI, 1.11–4.94; P=0.0262 increased risk for OSA. This population-based cohort study found that the TE constitutional type is an independent risk factor for the development of OSA.

  3. Mediating factors of coping process in parents of children with type 1 diabetes.

    Science.gov (United States)

    Oskouie, Fatemeh; Mehrdad, Neda; Ebrahimi, Hossein

    2013-05-14

    Type 1 diabetes is a lifelong condition for children and their parents, the management for which imposes a vast responsibility. This study explores the mediating factors that affect Iranian parents' coping processes with their children's type 1 diabetes. Research was conducted using the grounded theory method. Participants were selected purposefully, and we continued with theoretical sampling. Constant comparative analysis was used to analyze the data. The mediating factors of the parental coping process with their child's diabetes consist of the child's cooperation, crises and experiences, economic challenges, and parental participation in care. Findings highlight the necessity of well-informed nurses with insightful understanding of the mediating factors in parental coping with juvenile diabetes in order to meet the particular needs of this group.

  4. Alcohol and type 2 diabetes: The role of socioeconomic, lifestyle and psychosocial factors.

    Science.gov (United States)

    Agardh, Emilie E; Lundin, Andreas; Lager, Anton; Allebeck, Peter; Koupil, Ilona; Andreasson, Sven; Östenson, Claes-Göran; Danielsson, Anna-Karin

    2018-05-01

    We investigate (a) alcohol consumption in association with type 2 diabetes, taking heavy episodic drinking (HED), socioeconomic, health and lifestyle, and psychosocial factors into account, and (b) whether a seemingly protective effect of moderate alcohol consumption on type 2 diabetes persists when stratified by occupational position. This population-based longitudinal cohort study comprises 16,223 Swedes aged 18-84 years who answered questionnaires about lifestyle, including alcohol consumption in 2002, and who were followed-up for self-reported or register-based diabetes in 2003-2011. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated in a multivariable-adjusted logistic regression model for all participants and stratified by high and low occupational position. We adjusted for HED, socioeconomic (occupational position, cohabiting status and unemployment), health and lifestyle (body mass index (BMI), blood pressure, smoking, physical inactivity, poor general health, anxiety/depression and psychosocial (low job control and poor social support) characteristics one by one, and the sets of these factors. Moderate consumption was inversely associated with type 2 diabetes after controlling for health and lifestyle (OR=0.47; 95% CI: 0.29-0.79) and psychosocial factors (OR=0.40; 95% CI: 0.22-0.79) when compared to non-drinkers. When adjusting for socioeconomic factors, there was still an inverse but non-significant association (OR=0.59; 95% CI: 0.35-1.00). In those with high occupational position, there was no significant association between moderate consumption and type 2 diabetes after adjusting for socioeconomic (OR=0.67; 95% CI: 0.3-1.52), health and lifestyle (OR=0.70; 95% CI: 0.32-1.5), and psychosocial factors (OR=0.75; 95% CI: 0.23-2.46). On the contrary, in those with low occupational position, ORs decreased from 0.55 (95% CI: 0.28-1.1) to 0.35 (95% CI: 0.15-0.82) when adjusting for psychosocial factors, a decrease that was solely due to low

  5. Childhood subdural hemorrhage, macrocephaly, and coagulopathy associated with Prader-Willi syndrome: case report and review of the literature.

    Science.gov (United States)

    Carr, Robert B; Khanna, Paritosh C; Saneto, Russell P

    2012-07-01

    A 16-month-old girl with a history of Prader-Willi syndrome and progressive macrocephaly manifested large, bilateral, subdural hemorrhages of differing ages on magnetic resonance imaging. Subsequent evaluation revealed a deficiency of von Willebrand factor, but after repeated evaluations, no conclusive evidence of nonaccidental trauma became apparent. Subdural hemorrhages of varying ages are frequently associated with nonaccidental trauma during early childhood. However, several uncommon conditions may present as subdural hemorrhages and thus mimic nonaccidental trauma. Our patient demonstrates a combination of Prader-Willi syndrome, von Willebrand factor deficiency, and enlargement of the extra-axial spaces. All of these in isolation were associated with subdural hemorrhages. We review the scant literature on subdural hemorrhages in Prader-Willi syndrome and other conditions that mimic nonaccidental trauma. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. KLT-type relations for QCD and bicolor amplitudes from color-factor symmetry

    Science.gov (United States)

    Brown, Robert W.; Naculich, Stephen G.

    2018-03-01

    Color-factor symmetry is used to derive a KLT-type relation for tree-level QCD amplitudes containing gluons and an arbitrary number of massive or massless quark-antiquark pairs, generalizing the expression for Yang-Mills amplitudes originally postulated by Bern, De Freitas, and Wong. An explicit expression is given for all amplitudes with two or fewer quark-antiquark pairs in terms of the (modified) momentum kernel. We also introduce the bicolor scalar theory, the "zeroth copy" of QCD, containing massless biadjoint scalars and massive bifundamental scalars, generalizing the biadjoint scalar theory of Cachazo, He, and Yuan. We derive KLT-type relations for tree-level amplitudes of biadjoint and bicolor theories using the color-factor symmetry possessed by these theories.

  7. Peroxiredoxin isoforms are associated with cardiovascular risk factors in type 2 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    El Eter, E. [Physiology Department, Faculty of Medicine, King Saud University, Riyadh (Saudi Arabia); Cardiovascular Research Group, Faculty of Medicine, King Saud University, Riyadh (Saudi Arabia); Physiology Department, Faculty of Medicine, Alexandria University, Alexandria (Egypt); Al-Masri, A.A. [Physiology Department, Faculty of Medicine, King Saud University, Riyadh (Saudi Arabia); Cardiovascular Research Group, Faculty of Medicine, King Saud University, Riyadh (Saudi Arabia)

    2015-03-03

    The production of oxygen free radicals in type 2 diabetes mellitus contributes to the development of complications, especially the cardiovascular-related ones. Peroxiredoxins (PRDXs) are antioxidant enzymes that combat oxidative stress. The aim of this study was to investigate the associations between the levels of PRDX isoforms (1, 2, 4, and 6) and cardiovascular risk factors in type 2 diabetes mellitus. Fifty-three patients with type 2 diabetes mellitus (28F/25M) and 25 healthy control subjects (7F/18M) were enrolled. We measured the plasma levels of each PRDX isoform and analyzed their correlations with cardiovascular risk factors. The plasma PRDX1, -2, -4, and -6 levels were higher in the diabetic patients than in the healthy control subjects. PRDX2 and -6 levels were negatively correlated with diastolic blood pressure, fasting blood sugar, and hemoglobin A1c. In contrast, PRDX1 levels were positively correlated with low-density lipoprotein and C-reactive protein levels. PRDX4 levels were negatively correlated with triglycerides. In conclusion, PRDX1, -2, -4, and -6 showed differential correlations with a variety of traditional cardiovascular risk factors. These results should encourage further research into the crosstalk between PRDX isoforms and cardiovascular risk factors.

  8. Peroxiredoxin isoforms are associated with cardiovascular risk factors in type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    El Eter, E.; Al-Masri, A.A.

    2015-01-01

    The production of oxygen free radicals in type 2 diabetes mellitus contributes to the development of complications, especially the cardiovascular-related ones. Peroxiredoxins (PRDXs) are antioxidant enzymes that combat oxidative stress. The aim of this study was to investigate the associations between the levels of PRDX isoforms (1, 2, 4, and 6) and cardiovascular risk factors in type 2 diabetes mellitus. Fifty-three patients with type 2 diabetes mellitus (28F/25M) and 25 healthy control subjects (7F/18M) were enrolled. We measured the plasma levels of each PRDX isoform and analyzed their correlations with cardiovascular risk factors. The plasma PRDX1, -2, -4, and -6 levels were higher in the diabetic patients than in the healthy control subjects. PRDX2 and -6 levels were negatively correlated with diastolic blood pressure, fasting blood sugar, and hemoglobin A1c. In contrast, PRDX1 levels were positively correlated with low-density lipoprotein and C-reactive protein levels. PRDX4 levels were negatively correlated with triglycerides. In conclusion, PRDX1, -2, -4, and -6 showed differential correlations with a variety of traditional cardiovascular risk factors. These results should encourage further research into the crosstalk between PRDX isoforms and cardiovascular risk factors

  9. Effects of Endovascular Interventions on vWF and Fb Levels in Type 2 Diabetic Patients with Peripheral Artery Disease.

    Science.gov (United States)

    Yao, Hua-Qiang; Wang, Fu-Jun; Kang, Zhen

    2016-05-01

    von Willebrand Factor (vWF) and fibrinogen (Fb) are associated with hypercoagulability and thrombosis, which are the pathology and symptom of arterial disease. This research aims to study the effects of endovascular interventions on blood vWF and Fb levels in patients with diabetic peripheral artery disease (PAD). Totally, 66 type 2 diabetic patients with PAD (intervention group) and 26 type 2 diabetic patients without PAD (control group) were enrolled. These patients are matched at gender, age, and diabetes duration. For PAD patients, percutaneous interventions (balloon dilation or stent implantation) were performed, and blood samples were collected before, during, and after interventions. Then, enzyme-linked immunosorbent assay and prothrombin time-derived method were used to detect the levels of vWF and Fb, respectively. For intervention group, vWF and Fb levels in distal ischemic regions (vWF: 231.3%, Fb: 4.97 g/L) were significantly higher than that in nonischemic regions (vWF: 147.6%, Fb: 3.91 g/L, P value Fb levels were significantly increased (vWF: 299.2%, Fb: 5.69 g/L, P value Fb levels reached a peak (vWF: 199.3%, Fb: 4.96 g/L) and then decreased gradually to lower than the preinterventional levels (vWF: 148.3%, Fb: 3.88 g/L, P value Fb in the first week postintervention, leading to endothelial dysfunction and blood hypercoagulability. It suggested endothelial function protection and anticoagulant therapies should be applied to diabetic PAD patients after interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Elevated urinary albumin excretion is associated with impaired arterial dilatory capacity in clinically healthy subjects

    DEFF Research Database (Denmark)

    Clausen, P; Jensen, J S; Jensen, G

    2001-01-01

    (endothelium-dependent, flow-associated dilation) and to nitroglycerin (endothelium-independent, nitroglycerin-induced dilation). Plasma concentrations of the endothelial markers nitrate/nitrite, thrombomodulin, and von Willebrand factor antigen were also measured. Both flow-associated and nitroglycerin...

  11. Hypothermia and Platelet Dysfunction

    National Research Council Canada - National Science Library

    Michelson, A

    1994-01-01

    ... (the GPIIb-IIIa complex). Circulating platelets are normally in a resting state and, despite the presence of platelet surface GPIb-IX and GPIIb-IIIa complexes, they bind neither plasma von Willebrand factor nor plasma fibrinogen...

  12. Impairment-Factor-Based Audiovisual Quality Model for IPTV: Influence of Video Resolution, Degradation Type, and Content Type

    Directory of Open Access Journals (Sweden)

    Garcia MN

    2011-01-01

    Full Text Available This paper presents an audiovisual quality model for IPTV services. The model estimates the audiovisual quality of standard and high definition video as perceived by the user. The model is developed for applications such as network planning and packet-layer quality monitoring. It mainly covers audio and video compression artifacts and impairments due to packet loss. The quality tests conducted for model development demonstrate a mutual influence of the perceived audio and video quality, and the predominance of the video quality for the overall audiovisual quality. The balance between audio quality and video quality, however, depends on the content, the video format, and the audio degradation type. The proposed model is based on impairment factors which quantify the quality-impact of the different degradations. The impairment factors are computed from parameters extracted from the bitstream or packet headers. For high definition video, the model predictions show a correlation with unknown subjective ratings of 95%. For comparison, we have developed a more classical audiovisual quality model which is based on the audio and video qualities and their interaction. Both quality- and impairment-factor-based models are further refined by taking the content-type into account. At last, the different model variants are compared with modeling approaches described in the literature.

  13. Meat Consumption as a Risk Factor for Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Neal Barnard

    2014-02-01

    Full Text Available Disease risk factors identified in epidemiological studies serve as important public health tools, helping clinicians identify individuals who may benefit from more aggressive screening or risk-modification procedures, allowing policymakers to prioritize intervention programs, and encouraging at-risk individuals to modify behavior and improve their health. These factors have been based primarily on evidence from cross-sectional and prospective studies, as most do not lend themselves to randomized trials. While some risk factors are not modifiable, eating habits are subject to change through both individual action and broader policy initiatives. Meat consumption has been frequently investigated as a variable associated with diabetes risk, but it has not yet been described as a diabetes risk factor. In this article, we evaluate the evidence supporting the use of meat consumption as a clinically useful risk factor for type 2 diabetes, based on studies evaluating the risks associated with meat consumption as a categorical dietary characteristic (i.e., meat consumption versus no meat consumption, as a scalar variable (i.e., gradations of meat consumption, or as part of a broader dietary pattern.

  14. An assay for serum vitamin-B12 and for intrinsic factor antibody type I by means of hog intrinsic factor

    International Nuclear Information System (INIS)

    Hudak, J.; Berger, Z.; Varga, L.

    1980-01-01

    A new radioassay method was elaborated for the determination of the plasma level of vitamin B 12 and of the intrinsic factor antibody type I. The assay applies vitamin-B 12 labelled with 58 Co, but replaces human intrinsic factor by hog intrinsic factor. 124 cases were investigated by both the original and this modified method, and the results were in very good agreement. (L.E.)

  15. Elevated vascular endothelial growth factor in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Hovind, P; Tarnow, L; Oestergaard, P B

    2000-01-01

    patients with and without proliferative retinopathy were detected. CONCLUSIONS: Our data suggest that VEGF is elevated early in the course of diabetic nephropathy in men with type 1 diabetes mellitus. Baseline albuminuria, arterial blood pressure and male gender was predictors of diabetic nephropathy......BACKGROUND: Growth factors have been suggested to play a role in the development and progression of diabetic nephropathy. Vascular endothelial growth factor (VEGF) is a potent cytokine family that induces angiogenesis and markedly increases endothelial permeability. The aim of the present study...... was to investigate plasma levels of VEGF in a large cohort of type 1 diabetic patients with diabetic nephropathy and in long-standing type 1 diabetic patients with persistent normoalbuminuria, and to evaluate VEGF as a predictor of nephropathy progression. METHODS: We measured VEGF with an enzyme...

  16. Levels of serum vascular endothelial growth factor in type 2 diabetics with retinopathy

    International Nuclear Information System (INIS)

    Parveen, N.; Rahman, S.; Khan, Q.

    2012-01-01

    Background: Ischemic retina in diabetic patients releases a number of chemical substances including vascular endothelial growth factor which leads to retinal vascular proliferation and blindness following rupture and bleeding of vessels. Strategies to control this action can considerably halt this process. Objectives: To determine the relationship of various stages of diabetic retinopathy with the levels vascular endothelial growth factor in the serum of type 2 diabetic patients. Study type, settings and duration: This cross sectional analytical study was done over one year (2010-2011) in three major public sector hospitals of Peshawar. Patients and Methods: Adult patients of either gender having type 2 diabetes mellitus with proliferative or non proliferative retinopathy and those without retinopathy were selected for the study. Retinopathy was diagnosed on fundoscopy. Non-diabetic patients without retinopathy were selected as controls. Serum levels of vascular endothelial growth factor were done in patients and controls using ELISA. Results: Serum vascular endothelial growth factor levels were significantly higher in all cases having retinopathy as compared to controls. These levels progressively increased with the grades of retinopathy. Levels were higher in females. Conclusions: Levels of vascular endothelial growth factor are raised in diabetic retinopathy and rising levels can alert the clinician in worsening of retinopathy so that preventive and therapeutic measures can be taken promptly. Policy message: Further larger scale studies are recommended on national level to pave way for the establishment of appropriate management paradigms for diabetic retinopathy through anti-VEGF treatment. (author)

  17. PTSD's factor structure and measurement invariance across subgroups with differing count of trauma types.

    Science.gov (United States)

    Contractor, Ateka A; Caldas, Stephanie V; Dolan, Megan; Lagdon, Susan; Armour, Chérie

    2018-06-01

    To investigate the effect of the count of traumatizing event (TE) types on post-trauma mental health, several studies have compared posttraumatic stress disorder (PTSD) severity between individuals experiencing one versus multiple TE types. However, the validity of these studies depends on the establishment of measurement invariance of the construct(s) of interest. The current study examined the stability of the most optimal PTSD Model symptom cluster constructs (assessed by the PTSD Checklist for DSM-5 [PCL-5]) across subgroups experiencing one versus multiple TE types. The sample included university students (n = 556) endorsing at least one TE (Stressful Life Events Screening Questionnaire). Using data from the entire sample, results suggest that the PCL-5-assessed Hybrid Model provided a significantly better fit compared to other models. Results also indicated invariance of factor loadings (metric), and intercepts (scalar) for the PCL-5-assessed Hybrid Model factors across subgroups endorsing one (n = 191) versus multiple TE types (n = 365). Our findings thus support the stability, applicability, and meaningful comparison of the PCL-assessed Hybrid Model factor structure (including subscale severity scores) across subgroups experiencing one versus multiple TE types. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Influence of Lexical Factors on Word-Finding Accuracy, Error Patterns, and Substitution Types

    Science.gov (United States)

    Newman, Rochelle S.; German, Diane J.; Jagielko, Jennifer R.

    2018-01-01

    This retrospective, exploratory investigation examined the types of target words that 66 children with/without word-finding difficulties (WFD) had difficulty naming, and the types of errors they made. Words were studied with reference to lexical factors (LFs) that might influence naming performance: word frequency, familiarity, length, phonotactic…

  19. Hypothermia and Platelet Dysfunction

    National Research Council Canada - National Science Library

    Michelson, Alan

    1993-01-01

    ... (the OPlib-Illa complex).3 Circulating platelets are normally in a resting state and, despite the presence of platelet surface GPTh-IX and OPlib-Illa complexes, they bind neither plasma von Willebrand factor nor plasma fibrinogen...

  20. Depression and Associated Factors in Patients with Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Hashim, N A; Ariaratnam, S; Salleh, M R; Said, M A; Sulaiman, A H

    2016-06-01

    To determine the prevalence of major depressive disorder and its association with socio-demographic and clinical factors in patients with type 2 diabetes mellitus. This was a cross-sectional study of patients with type 2 diabetes mellitus who attended the hospital-based primary care clinics at the University Malaya Medical Centre, Kuala Lumpur, Malaysia. The patients were interviewed using the Mini-International Neuropsychiatric Interview to diagnose depression based on the DSM-IV criteria. The socio-demographic and clinical data were obtained by interviewing the patients and subsequently verified against their respective case notes. A total of 204 patients were recruited. The prevalence of major depressive disorder was 15.7%. Major depressive disorder was significantly associated with younger age of patients (mean ± standard deviation, 57.8 ± 15.1 years, p = 0.04), younger age at diagnosis of diabetes mellitus (46.2 ± 13.0 years, p = 0.01), having secondary education (p = 0.02), and having a history of depression (p = 0.002). Multivariate analysis showed that current age (p = 0.04), duration of diabetes mellitus (p = 0.04), age at diagnosis of diabetes mellitus (p = 0.01), and secondary education (p = 0.01) were significant factors. The prevalence of major depressive disorder was high among patients with type 2 diabetes mellitus. Screening of patients with type 2 diabetes mellitus for depression should be performed periodically or routinely, especially in the primary care setting.

  1. Orientation factor and number of fibers at failure plane in ring-type steel fiber reinforced concrete

    International Nuclear Information System (INIS)

    Lee, C.; Kim, H.

    2010-01-01

    Considering the probabilistic distributions of fibers in ring-type steel fiber reinforced concrete, the orientation factor and the number of ring-type steel fibers crossing the failure plane were theoretically derived as a function of fiber geometry, specimen dimensions, and fiber volume fraction. A total number of 24 specimens were tested incorporating different fiber types, specimen geometry, and fiber volume fractions of 0.2% and 0.4%: 5 beams and 5 panels containing straight steel fibers; and 6 beams and 8 panels containing ring-type steel fibers. Measurements were made to assess the number of fibers at fractured surfaces of steel fiber reinforced concrete. The developed theoretical expressions reasonably predicted the orientation factor and the number of ring-type steel fibers at failure plane: the average and the standard deviation for the ratios of the test to theory were 1.03 and 0.26, respectively. Theoretical investigations and comparisons were made for the values of orientation factor and the number of fibers at failure plane for straight steel fibers and ring-type steel fibers.

  2. Development of a current-type PWM converter with high power factor. 1

    International Nuclear Information System (INIS)

    Miura, Yushi; Matsukawa, Makoto; Miyachi, Kengo; Kimura, Toyoaki

    1998-01-01

    A power supply system for superconducting poloidal field coils of a next generation tokamak-type fusion device can be operated on the relatively low voltage for the duration of discharge except the plasma initiation. In the case of the conventional phase-controlled thyristor converters are adopted in such a system, the input power factor would be low in average, and a reactive power fluctuation caused by the change of DC output voltage may produce serious effects on the commercial transmission line. From the above viewpoint, a current-type PWM (Pulse Width Modulation) converter, which can work with the power factor of unity for the input power, is regarded as one of the promising candidates of the converters for the power supplies of next generation fusion devices. Hence, a 100kW-class current-type PWM converter has been developed by using IGBT (Insulated Gate Bipolar Transistor) as switching devices. In this development, the basic performance has been preliminary investigated whether this converter is applicable to the power supply for the next generation fusion device. In addition, two different PWM control methods were examined whether these methods can realize a unit power factor and suppress the transient oscillation of converter input current at the same time in case that the reference of DC output current is changed rapidly. (author)

  3. Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura

    African Journals Online (AJOL)

    Abe Olugbenga

    historical pentad of clinical features once thought to be needed to make the diagnosis include fever .... bond in the central A2 subunit of Von Willebrand Factor .... there were some catheter related and plasma ... and venous thrombosis (9).

  4. Factors associated with therapy noncompliance in type-2 diabetes patients

    Directory of Open Access Journals (Sweden)

    Hernández-Ronquillo Lizbeth

    2003-01-01

    Full Text Available OBJECTIVE: To identify the frequency and factors associated with therapy noncompliance in type-2 diabetes mellitus patients. MATERIAL AND METHODS: A cross-sectional study was carried out in 79 patients with type-2 diabetes mellitus seen in major hospitals of Mexico City. Patients were visited at home, from March 1998 to August 1999, to measure compliance with prescribed therapy. Complying patients were defined as those taking at least 80% of their pills or 80% of their corresponding insulin dose. The degree of compliance with therapy components (diet, amount of exercise, and keeping appointments was measured. RESULTS: The average age of study subjects was 59 years (SD 11 years; 73% (n=58 were female subjects. The overall frequency of noncompliance was 39%. Noncompliance rates were: 62% for dietary recommendations, 85% for exercise, 17% for intake of oral hypoglycemic medication, 13% for insulin application, and 3% for appointment keeping. Hypertension plus obesity was the only factor significantly associated with noncompliance (OR 4.58, CI 95% 1.0, 22.4, p=0.02. CONCLUSIONS: The frequency of therapy noncompliance was very high, especially for diet and exercise.

  5. Risk Factors for and Management of MPN-Associated Bleeding and Thrombosis.

    Science.gov (United States)

    Martin, Karlyn

    2017-10-01

    The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are characterized by both thrombotic and bleeding complications. The purpose of this review is to describe the risk factors associated with bleeding and thrombosis in MPN, as well as to review prevention strategies and management of these complications. Well-described risk factors for thrombotic complications include older age and history of prior thrombosis, along with traditional cardiovascular and venous thromboembolic risk factors. More recently, JAK2 V617F mutation has been found to carry an increased risk of thrombotic complications, whereas CALR has a lower risk than JAK2 mutation. Factors associated with an increased risk of bleeding in MPN include a prior history of bleeding, acquired von Willebrand syndrome, and primary myelofibrosis. Recent findings suggest that thrombocytosis carries a higher risk of bleeding than thrombosis in MPN, and aspirin may exacerbate this risk of bleeding, particularly in CALR-mutated ET. Much of the management of MPN focuses on predicting risk of bleeding and thrombosis and initiating prophylaxis to prevent complications in those at high risk of thrombosis. Emerging evidence suggests that sub-populations may have bleeding risk that outweighs thrombotic risk, particularly in setting of antiplatelet therapy. Future work is needed to better characterize this balance. At present, a thorough assessment of the risks of bleeding and thrombosis should be undertaken for each patient, and herein, we review risk factors for and management of these complications.

  6. Environmental/lifestyle factors in the pathogenesis and prevention of type 2 diabetes.

    Science.gov (United States)

    Kolb, Hubert; Martin, Stephan

    2017-07-19

    Environmental and lifestyle changes, in addition to the ageing of populations, are generally believed to account for the rapid global increase in type 2 diabetes prevalence and incidence in recent decades. In this review, we present a comprehensive overview of factors contributing to diabetes risk, including aspects of diet quality and quantity, little physical activity, increased monitor viewing time or sitting in general, exposure to noise or fine dust, short or disturbed sleep, smoking, stress and depression, and a low socioeconomic status. In general, these factors promote an increase in body mass index. Since loss of β-cell function is the ultimate cause of developing overt type 2 diabetes, environmental and lifestyle changes must have resulted in a higher risk of β-cell damage in those at genetic risk. Multiple mechanistic pathways may come into play. Strategies of diabetes prevention should aim at promoting a 'diabetes-protective lifestyle' whilst simultaneously enhancing the resistance of the human organism to pro-diabetic environmental and lifestyle factors. More research on diabetes-protective mechanisms seems warranted.

  7. Effects of liraglutide on cardiovascular risk factors in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Dejgaard, Thomas F; Johansen, Nanna B; Frandsen, Christian S

    2016-01-01

    We investigated the short-term effect of adding liraglutide 1.8 mg once daily to insulin treatment on cardiovascular risk factors in patients with type 1 diabetes. In total, 100 overweight (BMI ≥25 kg/m(2) ) adult patients (age ≥18 years) with type 1 diabetes and HbA1c ≥ 8% (64 mmol/mol) were....... In conclusion, in patients with long-standing type 1 diabetes, liraglutide as add-on to insulin increased heart rate and did not improve other cardiovascular risk factors after 24 weeks of treatment....... randomized to liraglutide 1.8 mg or placebo added to insulin treatment in a 24-week double-blinded, placebo-controlled trial. At baseline and after 24 weeks of treatment, 24-hour blood pressure and heart rate, pulse pressure, pulse wave velocity and carotid intima-media thickness were evaluated. Compared...

  8. What is the relationship between mental workload factors and cognitive load types?

    Science.gov (United States)

    Galy, Edith; Cariou, Magali; Mélan, Claudine

    2012-03-01

    The present study tested the hypothesis of an additive interaction between intrinsic, extraneous and germane cognitive load, by manipulating factors of mental workload assumed to have a specific effect on either type of cognitive load. The study of cognitive load factors and their interaction is essential if we are to improve workers' wellbeing and safety at work. High cognitive load requires the individual to allocate extra resources to entering information. It is thought that this demand for extra resources may reduce processing efficiency and performance. The present study tested the effects of three factors thought to act on either cognitive load type, i.e. task difficulty, time pressure and alertness in a working memory task. Results revealed additive effects of task difficulty and time pressure, and a modulation by alertness on behavioral, subjective and psychophysiological workload measures. Mental overload can be the result of a combination of task-related components, but its occurrence may also depend on subject-related characteristics, including alertness. Solutions designed to reduce incidents and accidents at work should consider work organization in addition to task constraints in so far that both these factors may interfere with mental workload. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Treatment of reperfusion injury with recombinant ADAMTS13 in a porcine model of acute myocardial infarction

    NARCIS (Netherlands)

    Eerenberg, E.S.; Teunissen, P.F.A.; Van Den Born, B.J.; Meijers, J.C.; Hollander, M.; Aly, M.; Niessen, H.W.M.; Kamphuisen, P.W.; Levi, M.; Van Royen, N.

    Background: No reflow and decreased microvascular perfusion after percutaneous coronary intervention increase morbidity and mortality in ST-elevation myocardial infarction (STEMI) patients. No reflow may be mediated by platelet vessel wall interaction that is governed by von Willebrand factor.

  10. Is exposure to chronic stressors a risk factor for Type 2 diabetes?

    OpenAIRE

    Kelly, Shona; Ismail, Mubarak

    2014-01-01

    Background - Current policy around Type 2 diabetes (T2D) interventions to reduce rates largely invokes a bio-behavioural model. This approach is also reflected in the research literature where most research that attempts to predict the development of diabetes is restricted to conventional clinical risk factors. However, a few researchers are now suggesting that psychosocial factors (PSF), acting via the physiologic stress response (PSR) systems, increases the risk of developing diabetes. Card...

  11. Cell-type specificity of ChIP-predicted transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Håndstad Tony

    2012-08-01

    Full Text Available Abstract Background Context-dependent transcription factor (TF binding is one reason for differences in gene expression patterns between different cellular states. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq identifies genome-wide TF binding sites for one particular context—the cells used in the experiment. But can such ChIP-seq data predict TF binding in other cellular contexts and is it possible to distinguish context-dependent from ubiquitous TF binding? Results We compared ChIP-seq data on TF binding for multiple TFs in two different cell types and found that on average only a third of ChIP-seq peak regions are common to both cell types. Expectedly, common peaks occur more frequently in certain genomic contexts, such as CpG-rich promoters, whereas chromatin differences characterize cell-type specific TF binding. We also find, however, that genotype differences between the cell types can explain differences in binding. Moreover, ChIP-seq signal intensity and peak clustering are the strongest predictors of common peaks. Compared with strong peaks located in regions containing peaks for multiple transcription factors, weak and isolated peaks are less common between the cell types and are less associated with data that indicate regulatory activity. Conclusions Together, the results suggest that experimental noise is prevalent among weak peaks, whereas strong and clustered peaks represent high-confidence binding events that often occur in other cellular contexts. Nevertheless, 30-40% of the strongest and most clustered peaks show context-dependent regulation. We show that by combining signal intensity with additional data—ranging from context independent information such as binding site conservation and position weight matrix scores to context dependent chromatin structure—we can predict whether a ChIP-seq peak is likely to be present in other cellular contexts.

  12. Angiogenic Type I Collagen Extracellular Matrix Integrated with Recombinant Bacteriophages Displaying Vascular Endothelial Growth Factors.

    Science.gov (United States)

    Yoon, Junghyo; Korkmaz Zirpel, Nuriye; Park, Hyun-Ji; Han, Sewoon; Hwang, Kyung Hoon; Shin, Jisoo; Cho, Seung-Woo; Nam, Chang-Hoon; Chung, Seok

    2016-01-21

    Here, a growth-factor-integrated natural extracellular matrix of type I collagen is presented that induces angiogenesis. The developed matrix adapts type I collagen nanofibers integrated with synthetic colloidal particles of recombinant bacteriophages that display vascular endothelial growth factor (VEGF). The integration is achieved during or after gelation of the type I collagen and the matrix enables spatial delivery of VEGF into a desired region. Endothelial cells that contact the VEGF are found to invade into the matrix to form tube-like structures both in vitro and in vivo, proving the angiogenic potential of the matrix. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Three months of strictly controlled daily endurance exercise reduces thrombin generation and fibrinolytic risk markers in younger moderately overweight men

    DEFF Research Database (Denmark)

    Gram, Anne Sofie; Bladbjerg, Else-Marie; Skov, Jane

    2015-01-01

    -PA), plasminogen activator inhibitor type 1 (PAI-1), and von Willebrand factor (vWF). RESULTS: We observed significant within-group decreases in ETP (MOD 7 %; HIGH 6 %) and in t-PA (MOD 22 %; HIGH 21 %) and PAI-1 (MOD 16 %; HIGH 32 %) in both training groups, and no changes in the CON group. At 3 months, between......-group differences were observed for ETP (p = 0.016) and t-PA (p = 0.012) due to significantly lower values in MOD and HIGH compared with CON. Borderline significant between-group differences were observed for PAI-1 (p = 0.082). A significant increase was observed in vWF in HIGH, but with no between...

  14. Biomarkers of endothelial dysfunction are elevated and related to prognosis in chronic heart failure patients with diabetes but not in those without diabetes

    DEFF Research Database (Denmark)

    Kistorp, C.; Chong, A.Y.; Gustafsson, F.

    2008-01-01

    Biomarkers of endothelial dysfunction, such as soluble E-selectin, and von Willebrand factor (vWf) are elevated in patients with chronic heart failure (CHF). The impact of diabetes mellitus (DM) on these biomarkers, and their relation to prognosis remains unknown....

  15. Platelet-vessel wall interaction in health and disease

    NARCIS (Netherlands)

    Löwenberg, E. C.; Meijers, J. C. M.; Levi, M. [=Marcel M.

    2010-01-01

    Upon vessel wall injury platelets rapidly adhere to the exposed subendothelial matrix which is mediated by several cellular receptors present on platelets or endothelial cells and various adhesive proteins such as von Willebrand factor, collagen and fibrinogen. Subsequent platelet activation results

  16. Importance of genetic factors in the occurrence of epilepsy syndrome type: a twin study

    DEFF Research Database (Denmark)

    Corey, Linda A; Pellock, John M; Kjeldsen, Marianne J

    2011-01-01

    not appear to play an important role in determining risk for frontal, occipital or temporal lobe epilepsy. These results suggest that, while genetic factors contribute to risk for major syndrome types, determined when possible, their contribution to risk for localization-related syndrome sub......Although there is strong evidence that genetic factors contribute to risk for epilepsy, their role in the determination of syndrome type is less clear. This study was undertaken to address this question. Information related to epilepsy was obtained from twins included in 455 monozygotic and 868...... dizygotic pairs ascertained from population-based twin registries in Denmark, Norway and the United States. Syndrome type was determined based on medical record information and detailed clinical interviews and classified using the International Classification Systems for the Epilepsies and Epileptic...

  17. Risk factors for diabetic retinopathy in Kuwaiti type 2 diabetic patients

    International Nuclear Information System (INIS)

    Al-Adsani, Afaf M.S.

    2007-01-01

    To determine the risk factors associated with diabetic retinopathy in Kuwaiti subjects with type 2 diabetes. Kuwaiti subjects with type 2 diabetes (n=165) attending the Diabetic Clinic at Al-sabah Hospital, Kuwait between October 2000 and March 2005 were screened for diabetic retinopathy. Any diabetic retinopathy was found in 40% while 20.6% had sight threatening retinopathy. Mild NPDR was present in 21.2%, moderate to severe non-proliferative diabetic retinopathy (NPDR) in 7.9%, and proliferative diabetic retinopathy in 3.0%. Maculopathy was present in 10.3% and 7.9 % pf patients were photocoagulated. Compared to those without retinopathy, diabetic patients with any retinopathy were significantly older (51.7+-10.3 versus 47.2+-9.5 years; p<0.005), had longer duration of diabetes (13.1+-6.3 versus 4.7 +-5.4 years; p<0.0001), higher systolic blood pressure (142.9+-23.0 versus 130.3+-20.2; p<0.0001) and poor glycemic control (Hemoglobin A1c=10.1+-2.4 versus 8.9+-2.3; p<0.005). The prevalence of hypertension and nephropathy was significantly higher in patients with any retinopathy than those without retinopathy (70.8% versus 49.5%; p<0.01 and 64.4% versus 30.8%; p<0.0001) respectively. Longer duration of diabetes and presence of nephropathy was the most significant independent factors associated with any retinopathy and sight-threatening retinopathy. Treatment with sulphonylurea or insulin, and poor glycemic control were other significant independent factors associated with any retinopathy. Longer duration of diabetes, presence of nephropathy, glycemic control and mode of treatment were the most significant independent factors of diabetic retinopathy. However, population-based study is warranted to identify the risk factors, as well as the prevalence of diabetic retinopathy. (author)

  18. Association of parental history of type 2 diabetes with age, lifestyle, anthropometric factors, and clinical severity at type 2 diabetes diagnosis

    DEFF Research Database (Denmark)

    Svensson, Elisabeth; Berencsi, Klara; Sander, Simone

    2016-01-01

    in Type 2 Diabetes cohort. We examined the prevalence ratios (PR) of demographic, lifestyle, anthropometric, and clinical factors according to parental history, using Poisson regression adjusting for age and gender. RESULTS: Of 2825 T2D patients, 34% (n = 964) had a parental history of T2D. Parental......BACKGROUND: We investigated whether parental history of type 2 diabetes mellitus (T2D) is associated with age, lifestyle, anthropometric factors, and clinical severity at the time of T2D diagnosis. METHODS: We conducted a cross-sectional study based on the Danish Centre for Strategic Research...... history was associated with younger age at diagnosis [adjusted (a)PR 1.66, 95% confidence interval: 1.19, 2.31) for age

  19. Risk Factors for Thyroid Dysfunction among Type 2 Diabetic Patients in a Highly Diabetes Mellitus Prevalent Society

    Directory of Open Access Journals (Sweden)

    Metab Al-Geffari

    2013-01-01

    Full Text Available Diabetes and thyroid dysfunction found to exist simultaneously. In this regard, the present study looked into the prevalence of different forms of thyroid dysfunction and their risk factors among Type 2 diabetic Saudi patients. Methodology. A cross-sectional retrospective randomized hospital-based study of 411 Type 2 diabetic Saudi patients of >25 years of age was conducted to test the prevalence of different types of thyroid dysfunction and their risk factors. Results. The prevalence of different types of thyroid dysfunction is 28.5%, of which 25.3% had hypothyroidism, where 15.3%, 9.5%, and 0.5% are clinical, subclinical, and overt hypothyroidism, respectively. The prevalence of hyperthyroidism is 3.2%, of which subclinical cases accounted for 2.7% and overt hyperthyroidism accounted for 0.5%. Risk factors for thyroid dysfunction among Saudi Type 2 diabetic patients are family history of thyroid disease, female gender, and duration of diabetes of >10 years, while the risk was not significant in patients with history of goiter and patients aged >60 years. Smoking and parity show a nonsignificant reduced risk. Conclusion. Thyroid dysfunction is highly prevalent among Saudi Type 2 diabetic patients, and the most significant risk factors are family history of thyroid disease, female gender, and >10 years duration of diabetes.

  20. Factors related to high and low levels of drug adherence according to patients with type 2 diabetes

    NARCIS (Netherlands)

    Borgsteede, S.D.; Westerman, M.J.; Kok, I.L.; Meeuse, J.C.; de Vries, T.P.G.M.; Hugtenburg, J.G.

    2011-01-01

    Objective Adherence to medication in patients with type 2 diabetes varies widely, yet the factors that influence adherence according to patients are not fully known. The aim of this study is to explore both factors related to high and lower levels of adherence that patients with type 2 diabetes

  1. Case report

    African Journals Online (AJOL)

    ebutamanya

    4 déc. 2015 ... 1Service d'Anesthésie–Réanimation, Hôpital Maternité Souissi, Centre Hospitalier ... parturiente présentant une maladie de Von Willebrand de type 1 ... se lie également et stabilise le facteur de coagulation sanguine VIII.

  2. Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes?

    DEFF Research Database (Denmark)

    Cameron, F.J.; Skinner, T.C.; Beaufort, C.E. de

    2008-01-01

    -parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P gender or insulin treatment regimen......Aims To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. Methods Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate...... a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P 2; d.f. = 3; P diabetes care (r = 0.11; P

  3. A comparison study on detection of key geochemical variables and factors through three different types of factor analysis

    Science.gov (United States)

    Hoseinzade, Zohre; Mokhtari, Ahmad Reza

    2017-10-01

    Large numbers of variables have been measured to explain different phenomena. Factor analysis has widely been used in order to reduce the dimension of datasets. Additionally, the technique has been employed to highlight underlying factors hidden in a complex system. As geochemical studies benefit from multivariate assays, application of this method is widespread in geochemistry. However, the conventional protocols in implementing factor analysis have some drawbacks in spite of their advantages. In the present study, a geochemical dataset including 804 soil samples collected from a mining area in central Iran in order to search for MVT type Pb-Zn deposits was considered to outline geochemical analysis through various fractal methods. Routine factor analysis, sequential factor analysis, and staged factor analysis were applied to the dataset after opening the data with (additive logratio) alr-transformation to extract mineralization factor in the dataset. A comparison between these methods indicated that sequential factor analysis has more clearly revealed MVT paragenesis elements in surface samples with nearly 50% variation in F1. In addition, staged factor analysis has given acceptable results while it is easy to practice. It could detect mineralization related elements while larger factor loadings are given to these elements resulting in better pronunciation of mineralization.

  4. Effect of a group-based rehabilitation programme on glycaemic control and cardiovascular risk factors in type 2 diabetes patients: The Copenhagen Type 2 Diabetes Rehabilitation Project

    DEFF Research Database (Denmark)

    Vadstrup, Eva Soelberg; Frølich, Anne; Perrild, Hans Jørgen Duckert

    2011-01-01

    To compare the effectiveness of a group-based rehabilitation programme with an individual counselling programme at improving glycaemic control and cardiovascular risk factors among patients with type 2 diabetes.......To compare the effectiveness of a group-based rehabilitation programme with an individual counselling programme at improving glycaemic control and cardiovascular risk factors among patients with type 2 diabetes....

  5. Risk factors affecting fatal bus accident severity: Their impact on different types of bus drivers.

    Science.gov (United States)

    Feng, Shumin; Li, Zhenning; Ci, Yusheng; Zhang, Guohui

    2016-01-01

    While the bus is generally considered to be a relatively safe means of transportation, the property losses and casualties caused by bus accidents, especially fatal ones, are far from negligible. The reasons for a driver to incur fatalities are different in each case, and it is essential to discover the underlying risk factors of bus fatality severity for different types of drivers in order to improve bus safety. The current study investigates the underlying risk factors of fatal bus accident severity to different types of drivers in the U.S. by estimating an ordered logistic model. Data for the analysis are retrieved from the Buses Involved in Fatal Accidents (BIFA) database from the USA for the years 2006-2010. Accidents are divided into three levels by counting their equivalent fatalities, and the drivers are classified into three clusters by the K-means cluster analysis. The analysis shows that some risk factors have the same impact on different types of drivers, they are: (a) season; (b) day of week; (c) time period; (d) number of vehicles involved; (e) land use; (f) manner of collision; (g) speed limit; (h) snow or ice surface condition; (i) school bus; (j) bus type and seating capacity; (k) driver's age; (l) driver's gender; (m) risky behaviors; and (n) restraint system. Results also show that some risk factors only have impact on the "young and elder drivers with history of traffic violations", they are: (a) section type; (b) number of lanes per direction; (c) roadway profile; (d) wet road surface; and (e) cyclist-bus accident. Notably, history of traffic violations has different impact on different types of bus drivers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Cardiovascular risk factors and incident albuminuria in screen-detected type 2 diabetes

    NARCIS (Netherlands)

    Webb, D. R.; Zaccardi, F.; Davies, M. J.; Griffin, S. J.; Wareham, N. J.; Simmons, R. K.; Rutten, G. E.; Sandbaek, A.; Lauritzen, T.; Borch-Johnsen, K.; Khunti, K.

    2017-01-01

    Background: It is unclear whether cardiovascular risk factor modification influences the development of renal disease in people with type 2 diabetes identified through screening. We determined predictors of albuminuria 5 years after a diagnosis of screen-detected diabetes within the ADDITION-Europe

  7. Strengths, Risk Factors, and Resilient Outcomes in Adolescents With Type 1 Diabetes

    DEFF Research Database (Denmark)

    Hilliard, Marisa E; Hagger, Virginia; Hendrieckx, Christel

    2017-01-01

    OBJECTIVE: Despite the challenges of living with type 1 diabetes, many adolescents achieve "resilient outcomes": high engagement in self-management behaviors such as self-monitoring of blood glucose (SMBG), good quality of life (QOL), and within-target glycemic outcomes (HbA1c). Adaptive diabetes...... factors. RESEARCH DESIGN AND METHODS: A total of 471 Australian adolescents with type 1 diabetes (mean age 15.7 ± 1.9 years; diabetes duration 6.9 ± 4.2 years; 62% female; 53% using insulin pumps) completed a national cross-sectional survey about their diabetes-related strengths, risk factors (depressive....../anxiety symptoms, family conflict), and resilient outcomes (SMBG frequency, general QOL, HbA1c). RESULTS: Greater diabetes strengths were significantly related to resilient outcomes: more frequent SMBG (r = 0.39), lower HbA1c (r = -0.31), and higher general QOL (r = 0.50), as well as to lower risks: fewer...

  8. Obesity and vehicle type as risk factors for injury caused by motor vehicle collision.

    Science.gov (United States)

    Donnelly, John P; Griffin, Russell Lee; Sathiakumar, Nalini; McGwin, Gerald

    2014-04-01

    This study sought to describe variations in the risk of motor vehicle collision (MVC) injury and death by occupant body mass index (BMI) class and vehicle type. We hypothesized that the relationship between BMI and the risk of MVC injury or mortality would be modified by vehicle type. This is a retrospective cohort study of occupants involved in MVCs using data from the Crash Injury Research and Engineering Network and the National Automotive Sampling System Crashworthiness Data System. Occupants were grouped based on vehicle body style (passenger car, sport utility vehicle, or light truck) and vehicle size (compact or normal, corresponding to below- or above-average curb weight). The relationship between occupant BMI class (underweight, normal weight, overweight, or obese) and risk of injury or mortality was examined for each vehicle type. Odds ratios (ORs) adjusted for various occupant and collision characteristics were estimated. Of an estimated 44 million occupants of MVCs sampled from 2000 to 2009, 37.1% sustained an injury. We limited our analysis to injuries achieving an Abbreviated Injury Scale (AIS) score of 2 or more severe, totaling 17 million injuries. Occupants differed substantially in terms of demographic and collision characteristics. After adjustment for confounding factors, we found that obesity was a risk factor for mortality caused by MVC (OR, 1.6; 95% confidence interval [CI], 1.2-2.0). When stratified by vehicle type, we found that obesity was a risk factor for mortality in larger vehicles, including any-sized light trucks (OR, 2.1; 95% CI, 1.3-3.5), normal-sized passenger cars (OR, 1.6; 95% CI, 1.1-2.3), and normal-sized sports utility vehicles or vans (OR, 2.0; 95% CI, 1.0-3.8). Being overweight was a risk factor in any-sized light trucks (OR, 1.5; 95% CI, 1.1-2.1). We identified a significant interaction between occupant BMI class and vehicle type in terms of MVC-related mortality risk. Both factors should be taken into account when

  9. Dental caries-associated risk factors and type 1 diabetes mellitus.

    Science.gov (United States)

    Sampaio, Norma; Mello, Sandra; Alves, Cresio

    2011-01-01

    Type 1 diabetes mellitus (T1DM) is associated with various oral complications. However there is no consensus regarding the association of T1DM and caries. Critical revision of dental caries-associated risk factors and type 1 diabetes mellitus. Search of the MEDLINE and LILACS databases from 2000 to 2010, using, in different combination, the key words "dental caries", "diabetes mellitus" and "type 1 diabetes mellitus". The association between T1DM and dental caries remains controversial. Although some studies demonstrate a higher prevalence of caries due to the increased concentration of salivary glucose, acidity of the oral cavity, salivary viscosity, reduced salivary flow rate, and salivary gland dysfunction; other studies report a reduction of caries levels, probably caused by decreased ucrose ingestion. Although patients with uncontrolled T1DM and poor oral hygiene may present increased prevalence of dental caries, the literature does not describe a consistent relationship between T1DM and dental caries. Further investigations are warranted. If a true association is substantiated, intervention studies to prevent or reduce the occurrence of caries in this population should follow.

  10. Psychosocial factors associated with migraine and tension-type headache in medical students

    DEFF Research Database (Denmark)

    Lebedeva, Elena R; Kobzeva, Natalia R; Gilev, Denis V

    2017-01-01

    BACKGROUND: In our previous study of workers, blood donors and medical students, students stood out with a higher 1-year prevalence of migraine (28%) and tension-type headache (TTH) (74%). General factors associated with headache were common for all groups except low physical activity. The hypoth...

  11. Pigment epithelium derived factor inhibits the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yanmei Sun

    Full Text Available Angiogenesis is a prerequisite for the formation and development of endometriosis. Pigment epithelium derived factor (PEDF is a natural inhibitor of angiogenesis. We previously demonstrated a reduction of PEDF in the peritoneal fluid, serum and endometriotic lesions from women with endometriosis compared with women without endometriosis. Here, we aim to investigate the inhibitory effect of PEDF on human endometriotic cells in vivo and in vitro. We found that PEDF markedly inhibited the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro by up-regulating PEDF expression and down-regulating vascular endothelial growth factor (VEGF expression. Moreover, apoptotic index was significantly increased in endometriotic lesions in vivo and endometriotic stromal cells in vitro when treated with PEDF. In mice treated with PEDF, decreased microvessel density labeled by Von Willebrand factor but not by α-Smooth Muscle Actin was observed in endometriotic lesions. And it showed no increase in PEDF expression of the ovary and uterus tissues. These findings suggest that PEDF gene therapy may be a new treatment for endometriosis.

  12. Population-Level Prediction of Type 2 Diabetes From Claims Data and Analysis of Risk Factors.

    Science.gov (United States)

    Razavian, Narges; Blecker, Saul; Schmidt, Ann Marie; Smith-McLallen, Aaron; Nigam, Somesh; Sontag, David

    2015-12-01

    We present a new approach to population health, in which data-driven predictive models are learned for outcomes such as type 2 diabetes. Our approach enables risk assessment from readily available electronic claims data on large populations, without additional screening cost. Proposed model uncovers early and late-stage risk factors. Using administrative claims, pharmacy records, healthcare utilization, and laboratory results of 4.1 million individuals between 2005 and 2009, an initial set of 42,000 variables were derived that together describe the full health status and history of every individual. Machine learning was then used to methodically enhance predictive variable set and fit models predicting onset of type 2 diabetes in 2009-2011, 2010-2012, and 2011-2013. We compared the enhanced model with a parsimonious model consisting of known diabetes risk factors in a real-world environment, where missing values are common and prevalent. Furthermore, we analyzed novel and known risk factors emerging from the model at different age groups at different stages before the onset. Parsimonious model using 21 classic diabetes risk factors resulted in area under ROC curve (AUC) of 0.75 for diabetes prediction within a 2-year window following the baseline. The enhanced model increased the AUC to 0.80, with about 900 variables selected as predictive (p differences between AUCs). Similar improvements were observed for models predicting diabetes onset 1-3 years and 2-4 years after baseline. The enhanced model improved positive predictive value by at least 50% and identified novel surrogate risk factors for type 2 diabetes, such as chronic liver disease (odds ratio [OR] 3.71), high alanine aminotransferase (OR 2.26), esophageal reflux (OR 1.85), and history of acute bronchitis (OR 1.45). Liver risk factors emerge later in the process of diabetes development compared with obesity-related factors such as hypertension and high hemoglobin A1c. In conclusion, population-level risk

  13. Mexican American Parents' Perceptions of Childhood Risk Factors for Type 2 Diabetes

    Science.gov (United States)

    Head, Barbara J.; Barr, Kathleen L.; Baker, Sharon K.

    2011-01-01

    A study was conducted to identify the norms, values, and perceptions of urban immigrant Mexican American (MA) parents of school children relative to physical activity, healthy eating, and child risk factors for type 2 diabetes. Investigators facilitated five focus groups in an urban elementary school setting and analyzed data using qualitative…

  14. Reduced endothelial activation after exercise is associated with improved HbA1c in patients with type 2 diabetes and coronary artery disease.

    Science.gov (United States)

    Byrkjeland, Rune; Njerve, Ida U; Arnesen, Harald; Seljeflot, Ingebjørg; Solheim, Svein

    2017-03-01

    We have previously reported insignificant changes in HbA 1c after exercise in patients with both type 2 diabetes and coronary artery disease. In this study, we investigated the effect of exercise on endothelial function and possible associations between changes in endothelial function and HbA 1c . Patients with type 2 diabetes and coronary artery disease ( n = 137) were randomised to 12 months exercise or standard follow-up. Endothelial function was assessed by circulating biomarkers (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, von Willebrand factor, tissue plasminogen activator antigen, asymmetric dimethylarginine and L-arginine/asymmetric dimethylarginine ratio). Differences between the randomised groups were analysed by analysis of covariance and correlations by Spearman's rho or Pearson's correlation. No effect of exercise on endothelial function was demonstrated. The changes in HbA 1c in the exercise group correlated with changes in E-selectin ( r = 0.56, p < 0.001), intercellular adhesion molecule-1 ( r = 0.27, p = 0.052), vascular cell adhesion molecule-1 ( r = 0.32, p = 0.022) and tissue plasminogen activator antigen ( r = 0.35, p =  0.011). HbA 1c decreased significantly more in patients with versus without a concomitant reduction in E-selectin ( p =  0.002), intercellular adhesion molecule-1 ( p =  0.011), vascular cell adhesion molecule-1 ( p =  0.028) and tissue plasminogen activator antigen ( p =  0.009). Exercise did not affect biomarkers of endothelial function in patients with both type 2 diabetes and coronary artery disease. However, changes in biomarkers of endothelial activation correlated with changes in HbA 1c , and reduced endothelial activation was associated with improved HbA 1c after exercise.

  15. A radioisotope dilution assay for unlabelled vitamin B12-intrinsic factor complex employing the binding intrinsic factor antibody: probable evidence for two types of binding antibody

    International Nuclear Information System (INIS)

    Jacob, E.; O'Brien, H.A.W.; Mollin, D.L.

    1977-01-01

    A new radioisotope dilution assay for vitamin B 12 -intrinsic factor complex is described. The method is based on the use of the binding type intrinsic antibody (the binding reagent), which when combined with the intrinsic factor-vitamin B 12 complex (labelled ligand), is quantitatively adsorbed onto zirconium phosphate gel pH 6.25. The new assay has been shown to provide a measure of intrinsic factor comparable with other intrinsic factor assays, but it has the important advantage of being able to measure the unlabelled vitamin B 12 -intrinsic factor complex (unlabelled ligand), and will, therefore, be valuable in the study of physiological events in the gastrointestinal tract. During the study, it was found that there is some evidence for at least two types of binding intrinsic factor antibody: One which combines preferentially with the intrinsic factor-vitamin B 12 complex and one which combines equally well with this complex or with free intrinsic factor. (author)

  16. Mother, Infant, and Household Factors Associated with the Type of Food Infants Receive in Developing Countries

    Directory of Open Access Journals (Sweden)

    Benjamin eYarnoff

    2014-02-01

    Full Text Available Objectives: We explore the complex factors associated with infant feeding by analyzing what mother, infant, and household factors are associated with the types of food given to infants. We seek to quantify associations in order to inform public health policy about the importance of target populations for infant feeding programs. Methods: We used data from the Demographic Health Survey in 20 developing countries for multiple years to examine mother, infant, and household factors associated with six types of food given to infants (exclusive breastfeeding, non-exclusive breastfeeding, infant formula, milk liquids, non-milk liquids, and solid foods. We performed a seemingly unrelated regressions analysis with community-year fixed effects to account for correlation between food types and control for confounding factors associated with community resources, culture, time period, and geography in the pooled analysis.Results: We found that several mother, infant, and household characteristics were associated with each of the feeding types. Most notably, mother’s education, working status, and weight are significantly associated with the type of food given to infants. We provide quantified estimates of the association of each of these variables with six types of food given to infants. Conclusions: By identifying maternal characteristics associated with infant feeding and quantifying those associations, we help public health policymakers generate priorities for targeting infant feeding programs to specific populations that are at greatest risk. Higher educated, working mothers are best to target with exclusive breastfeeding programs for young infants. Mothers with lower education are best to target with complementary feeding programs in infants older than 1 year. Finally, while maternal weight is associated with higher levels of exclusive breastfeeding the association is too weak to merit targeting of breastfeeding programs to low-weight mothers.

  17. Van Willebrand's disease in the Western Cape

    African Journals Online (AJOL)

    agglutinate normal platelets but does not have an effect on platelets from patients with VWD. The ristocetin co-factor. (RiCo~ assay measures the ability of plasma to agglutinate fixed platelets and is therefore regarded as an indirect measure of VWF activity. Qualitative analysis of VWF antigen. 0JWF-Ag) is required for ...

  18. Effect of exercise on platelet activation during aspirin or clopidogrel intake in healthy men

    DEFF Research Database (Denmark)

    Hjorth Madsen, Esben; Christiansen, Morten Krogh; Schmidt, Erik Berg

    2009-01-01

    aggregometry. A significant increase in plasma von Willebrand Factor was also found in response to exercise. In conclusion, platelet activation occurs during exercise in healthy individuals. This activation is not prevented by use of aspirin or clopidogrel, and may partly be explained by an increase in plasma...

  19. Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Hougaard, S; Nørgaard, P; Abrahamsen, N

    1999-01-01

    Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung...

  20. Medical and Psychological Risk Factors for Incident Hypertension in Type 1 Diabetic African-Americans

    Directory of Open Access Journals (Sweden)

    Monique S. Roy

    2011-01-01

    Conclusions. The development of hypertension in African-Americans living with type 1 diabetes appears to be multifactorial and includes both medical (overt proteinuria as well as psychological (high hostility risk factors.

  1. Risk factors for necrobiosis lipoidica in Type 1 diabetes mellitus.

    Science.gov (United States)

    Hammer, E; Lilienthal, E; Hofer, S E; Schulz, S; Bollow, E; Holl, R W

    2017-01-01

    To compare the clinical and metabolic characteristics of patients with Type 1 diabetes and necrobiosis lipoidica with those of patients with Type 1 diabetes who do not have necrobiosis lipoidica. A multicentre analysis was performed. Clinical and laboratory data were obtained from 64 133 patients (aged 0-25 years) with Type 1 diabetes with and without necrobiosis lipoidica who were registered in the German/Austrian Diabetes Prospective Documentation Initiative registry. Data were analysed using multivariable regression modelling. Age, diabetes duration, treatment year and sex were considered as confounding factors. Results adjusted for demographic variables are presented. In patients with necrobiosis lipoidica, metabolic control was worse (HbA 1c 72 vs. 67 mmol/mol, 8.7% vs. 8.3%; P = 0.0065) and the duration of diabetes was longer [6.24 (3.28-9.97) vs. 5.11 (2.08-8.83) years; P = 0.014; not adjusted]. Patients with necrobiosis lipoidica required higher insulin doses than those without (1.02 vs. 0.92 U/kg/day; P 1). There was no significant difference in the frequency of microvascular complications (microalbuminuria and retinopathy) between the groups. Furthermore, 24.8% and 17.5% of patients with Type 1 diabetes with and without necrobiosis lipoidica, respectively, had elevated thyroid antibodies (P = 0.051). Necrobiosis lipoidica was correlated with coeliac disease in patients with Type 1 diabetes (3.4% vs. 1.0%; P = 0.0035). Our data indicate a strong correlation between hyperglycaemia and the development of necrobiosis lipoidica. We postulate that the underlying pathogenic processes differ from those leading to microalbuminuria and retinopathy, and additional immunological mechanisms may play a role. © 2016 Diabetes UK.

  2. Using Factor Mixture Models to Evaluate the Type A/B Classification of Alcohol Use Disorders in a Heterogeneous Treatment Sample

    Science.gov (United States)

    Hildebrandt, Tom; Epstein, Elizabeth E.; Sysko, Robyn; Bux, Donald A.

    2017-01-01

    Background The type A/B classification model for alcohol use disorders (AUDs) has received considerable empirical support. However, few studies examine the underlying latent structure of this subtyping model, which has been challenged as a dichotomization of a single drinking severity dimension. Type B, relative to type A, alcoholics represent those with early age of onset, greater familial risk, and worse outcomes from alcohol use. Method We examined the latent structure of the type A/B model using categorical, dimensional, and factor mixture models in a mixed gender community treatment-seeking sample of adults with an AUD. Results Factor analytic models identified 2-factors (drinking severity/externalizing psychopathology and internalizing psychopathology) underlying the type A/B indicators. A factor mixture model with 2-dimensions and 3-classes emerged as the best overall fitting model. The classes reflected a type A class and two type B classes (B1 and B2) that differed on the respective level of drinking severity/externalizing pathology and internalizing pathology. Type B1 had a greater prevalence of women and more internalizing pathology and B2 had a greater prevalence of men and more drinking severity/externalizing pathology. The 2-factor, 3-class model also exhibited predictive validity by explaining significant variance in 12-month drinking and drug use outcomes. Conclusions The model identified in the current study may provide a basis for examining different sources of heterogeneity in the course and outcome of AUDs. PMID:28247423

  3. Correlation between expressions of hypoxia -inducible factor (HIF-1α, blood vessels density, cell proliferation, and apoptosis intensity in canine fibromas and fibrosarcomas

    Directory of Open Access Journals (Sweden)

    Madej Janusz A.

    2014-03-01

    Full Text Available The study aimed to demonstrate the expression of hypoxia-inducible factor (HIF-1α in soft tissue mesenchymal tumours (fibroma and fibrosarcoma in dogs. An attempt was made to correlate the obtained results with density of blood vessels (expression of von Willebrand Factor, vWF, expression of Ki-67 proliferation antigen, and with intensity of apoptosis in studied tumours. The study was performed on paraffin sections of 15 fibromas and 40 fibrosarcomas sampled from 55 female dogs aged 6 to 16 years. Immunohistochemical staining against HIF-1α, vWF, and Ki-67 was performed. Apoptosis was detected with the use of TUNEL reaction. A significantly higher HIF-1α expression was noted in fibrosarcomas in comparison to fibromas (P < 0.0001. HIF-1α expression in fibromas manifested strong positive correlation with tumour vascularity (r = 0.67, P = 0.007. Moreover, HIF-1α expression in fibrosarcomas manifested a moderate positive correlation with tumour malignancy grade (r = 0.44, P = 0.004, tumour vascularity (r = 0.52, P < 0.001, Ki-67 antigen expression (r = 0.42; P = 0.007, and TUNELpositive cells (r = 0.37, P = 0.017. Expression of HIF-1α was detected in 86.7% of fibroma type tumours and in 100% of fibrosarcomas. In all studied tumours expression of HIF-1α manifested positive correlation with the density of blood vessels, and in fibrosarcomas it correlated also with malignancy grade, intensity of Ki-67 expression, and with intensity of apoptosis in tumour cells.

  4. Distribution patterns of infection with multiple types of human papillomaviruses and their association with risk factors.

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    Sara Soto-De Leon

    Full Text Available BACKGROUND: Infection with multiple types of human papillomavirus (HPV is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. PRINCIPAL FINDINGS: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%, while this risk decreased in women who had given birth more than 4 times (-31.1%, or were of mestizo (-24.6% or black (-40.9% ethnicity. CONCLUSIONS: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.

  5. Menstrual and reproductive factors and type 2 diabetes risk: the Japan Public Health Center-based Prospective Study.

    Science.gov (United States)

    Nanri, Akiko; Mizoue, Tetsuya; Noda, Mitsuhiko; Goto, Atsushi; Sawada, Norie; Tsugane, Shoichiro

    2018-04-18

    Menstrual and reproductive factors, including age at menarche, parity, and breastfeeding, have been linked to type 2 diabetes risk. We prospectively investigated the association between these factors and type 2 diabetes risk in a large Japanese cohort. Participants were 37,511 women aged 45-75 years who participated in the baseline (1990-1993), second (1995-1998), and third surveys (2000-2003) of the Japan Public Health Center-based Prospective Study and who had no history of diabetes at the second survey. Menstrual and reproductive history was ascertained using questionnaires at the baseline and second surveys. Odds ratios of self-reported, physician-diagnosed type 2 diabetes over the 5-year period from the second survey were estimated using logistic regression. At the third survey, 513 new cases of type 2 diabetes were self-reported. The odds ratios of type 2 diabetes tended to increase with the number of parity, after adjustment for covariates other than body mass index (P for trend = 0.029). The multivariable-adjusted odds ratios (95% confidence interval) of type 2 diabetes for women with ≥3 births was 1.56 (0.96-2.53) compared to those who were nulliparous. The association between parity and type 2 diabetes risk was attenuated after additional adjustment for body mass index (P for trend = 0.12). No factors other than parity were significantly associated with type 2 diabetes risk. Higher parity may be associated with increased risk of type 2 diabetes among Japanese women, partly through increasing body weight. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Albuminuria and associated risk factors in type II diabetics

    International Nuclear Information System (INIS)

    Hashim, R.; Ahmed, T.A.; Mushtaq, S.; Zafar, L.; Attique, M.; Khalil-ur-Rehman

    2004-01-01

    Objective: To determine the frequency of microalbuminuria (MA) and its associated medical risk factors in type II diabetic patients. Materials and Methods: Study population included 150 type II diabetic patients (70 women, 80 men) attending outpatient department of the hospital. Patients having clinical albuminuria and with other causes of proteinuria were excluded. Results: Women and men were of comparable ages. Women (26.4 kg/m/sup 2/) had higher body mass index (BMI) than men 24.3 kg/m/sup 2/). The frequency of MA was 46.7%, higher in males (50.6%) than females (41.5%). Fasting plasma glucose HbA/sub 1c/ levels were significantly higher in patients with MA compared to those with normo albuminuria (p < 0.001). The microalbuminuria patients had significantly decreased HDL-c levels compared to normoalbuminuric subjects (p< 0.001). However, no relation of MA with age, gender, known duration of diabetes, BMI, history of smoking, hypertension and serum: total cholesterol, LDL-c, triglyceride, urea and creatinine was found. Conclusion: There is a strong association of poor glycaemic control and decreased HDL-c levels with the presence of micro albuminuria. (author)

  7. Factors Related to the Glycemic Control in Lithuanian Adolescents with Type 1 Diabetes Mellitus

    OpenAIRE

    Kassem, Salem

    2017-01-01

    1) Adolescent female patients with type 1 diabetes mellitus have better glycemic control and higher levels of diabetes distress than male patients. 2) Parents of adolescents using insulin pumps experience higher diabetes distress than parents of adolescents using multiple daily injections. 3) No differences in diabetes-related factors, emotional state, diabetes-related distress (in adolescent patients and in their primary care-givers) and social factors in groups of adolescent patients ...

  8. Complement activation, endothelial dysfunction, insulin resistance and chronic heart failure

    DEFF Research Database (Denmark)

    Bjerre, M.; Kistorp, C.; Hansen, T.K.

    2010-01-01

    CRP), endothelial activation (soluble E-selectin, sEsel)), endothelial damage/dysfunction (von Willebrand factor, vWf) and insulin resistance (IR) and prognosis in CHF remains unknown. Design. We investigated the association(s) between plasma sMAC, hsCRP, sEsel, vWf and IR (assessed by homeostatic model assessment...

  9. Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Isbister

    Full Text Available Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming.In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT, activated partial thromboplastin time (aPTT, coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13, associated with low fibrinogen [median,3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02 and aPTT (r = 0.19, p = 0.03 were correlated (non-parametric Spearman analysis.Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.

  10. Biomarkers of coagulation, fibrinolysis, endothelial function, and inflammation in arterialized venous blood

    DEFF Research Database (Denmark)

    Gram, Anne Sofie; Skov, Jane; Ploug, Thorkil

    2014-01-01

    Effects of venous blood arterialization on cardiovascular risk markers are still unknown. We evaluated biomarkers of inflammation, coagulation, fibrinolysis, and endothelial function in arterialized compared with regular venous blood. Cubital venipunctures were obtained from 10 healthy volunteers....... Arterialization was generated by 10 min heating of the contralateral hand. Concentrations of albumin, C-reactive protein (CRP), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and von Willebrand factor (vWF) were measured by validated assays. Concentrations of albumin......, CRP, and vWF were significantly lower in arterialized than in venous blood (albumin: 43.8 g/l and 44.8 g/l, P = 0.02). Differences in CRP and vWF became insignificant after adjusting for albumin. The endogenous thrombin potential (ETP) was significantly higher in arterialized than in venous blood...

  11. Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Minara Shamkhalovna Shamkhalova

    2010-09-01

    Full Text Available Aim. To identify profibrogenic mediators, markers of endothelial dysfunction and hemostasis in patients with diabetes mellitus (DM and chronickidney disease (CKD. Materials and methods. The study included 120 patients with DM and 20 age-matched normotensive subjects without DM showing the glomerularfiltration rate (GFR > 60 ml/min/1.73 m3. Four groups of patients were distinguished: 1 - DM2 patients without renal pathology (n=33, 2 - DM2 patients with diabetic nephropathy (n=24, 3 - DM2 patients with ischemic nephropathy (IN (n=33 verified by contrast visualization techniques(multispiral CM of abdominal aorta and renal arteries, abdominal angiography of renal arteries or MR angiography of renal arteries and abdominal aorta, 4 - DM1 patients with DN (n=30. Clinical examination included assessment of complaints, analysis of medical history of the main diseaseand concomitant disorders, determination of the main clinical and biochemical characteristics of blood and urine, measurement of НbА1с and 24-hralbuminuria (AU by standard methods, estimation of GFR by the MDRD formula, ECG, echocardiography, 24-hr AP monitoring, counseling bycardiologist and ophthalmologist (fundal examination by ophthalmoscopy. Standard kits were used to detect profibrogenic mediators and markersof endothelial dysfunction including transforming growth factor-beta (TGF-b, angiotensin II (AT II, monocyte chemoattractant protein (MCP-1,regulated on activation normal T cell expressed and secreted (RANTES, adhesion factors (intracellular adhesion molecule (ICAM-1, vascular celladhesion molecule (VCAM-1 vascular endothelial growth factor (VEGF, interleukin-6 (IL-6, asymmetric dimethylargnine (ADMA, homocysteine(HCYST, metalloproteinases (MMP, von Willebrand factor (vWF, plasminogen activator inhibitor (PAI-I. Results. DM patients with CKD had elevated blood profibrogenic cytokine (MCP-1, TGF-1b, IL-6 and extracellular matrix degradation factor(MMP-9 levels compared with

  12. Age and homocystein were risk factor for peripheral arterial disease in elderly with type 2 diabetes mellitus.

    Science.gov (United States)

    Kuswardhani, R A Tuty; Suastika, Ketut

    2010-04-01

    to find out the magnitude of risk of some traditional and non-traditional risk factors for PAD event in the elderly with Type 2 diabetes mellitus (T2DM) patients. a case-control study involved 40 subjects of each arms (case and control group) at Geriatric Outpatient Clinic Sanglah Hospital, Denpasar, Bali, Indonesia was conducted. the study showed that compared to patients without PAD, patients with PAD had higher age (70.7 vs. 65.0 years; phomocystein levels (13.4 vs. 11.5 mmol/L, p=0.023); while other variables revealed no any significantly difference between two groups. Although no any significant difference, subjects with PAD tend to do exercise less prevalent, consumed anti-hyperlipidemic and anti-thrombotic more frequent compared to subjects without PAD. High age (70-80 years) has risk 7.4 time than those lower age (60-69 years), and high homocystein level (> or =11 mmol/L) has risk 2.5 time than those with lower level to develop PAD. By multivariate analysis (logistic regression), only age has a role in PAD event, while homocystein tend to be risk factor for PAD event. some traditional risk factors and non-traditional risk factors unproved as risk factors for PAD event in the elderly with type 2 diabetes. Older age and homocystein level were risk factors for PAD event in the elderly with type 2 diabetes subjects.

  13. NETosis before and after Hyperglycemic Control in Type 2 Diabetes Mellitus Patients.

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    Agostina Carestia

    Full Text Available Diabetes is characterized by chronic inflammation, endothelial dysfunction, increased risk of infections and early cardiovascular disease. By releasing neutrophil extracellular traps (NETs, neutrophils kill bacteria and exert pro-inflammatory and pro-thrombotic activities. Increased NETosis has been found in cross-sectional studies including treated type 2 diabetes mellitus (T2DM patients. In this study, we determined whether the ability of neutrophils to form NETs differs in diabetic patients pre- and post-hyperglycemic control versus healthy donors (HD, and the relationship between NETosis with pro-thrombotic, pro-inflammatory biomarkers and thrombotic clinical events.Diabetic patients recently diagnosed and after 6 and 12 months of treatment (N = 25 and HD (N = 25 were included. NET formation was studied by microscopy and fluorometry. Nucleosomes, HNE-DNA complexes, von Willebrand factor (vWF, IL6 and TNFα plasma levels were measured by ELISA and P-selectin on the platelet surface was assessed by cytometry.Basal levels of NETs in recently diagnosed T2DM patients were higher compared to HD. While TNFα stimulation of control neutrophils resulted in DNA release, patient neutrophils were not responsive. Although glycemia decreased after 6 months of metformin treatment, basal and TNFα and PMA-stimulated NETs reached normal values after 12 months. Compared to controls, nucleosomes, HNE-DNA complexes, IL-6 and TNFα levels were increased in recently diagnosed patients and decreased after 12 months of treatment. P-selectin and vWF levels were similar in both populations.Our data suggest that NETs could represent a biomarker for T2DM. Increased NETosis in T2DM patients does not appear to be the consequence of impaired glycemic control but rather due to pro-inflammatory cytokines and is not related to thrombotic events.

  14. A Lagrange multiplier-type test for idiosyncratic unit roots in the exact factor model under misspecification

    NARCIS (Netherlands)

    Zhou, X.; Solberger, M.

    2013-01-01

    We consider an exact factor model and derive a Lagrange multiplier-type test for unit roots in the idiosyncratic components. The asymptotic distribution of the statistic is derived under the misspecification that the differenced factors are white noise. We prove that the asymptotic distribution is

  15. The mucosal factors retinoic acid and TGF-B induce phenotypically and functionally distinct dendritic cell types

    NARCIS (Netherlands)

    Hartog, den C.G.; Altena, van S.E.C.; Savelkoul, H.F.J.; Neerven, van R.J.J.

    2013-01-01

    Non-inflammatory dendritic cell (DC) subsets play an essential role in preventing massive inflammation in mucosal tissues. We investigated whether mucosa-related factors, namely retinoic acid (RA) and transforming growth factor-ß (TGF-ß1), can induce such DC types. DCs were differentiated from

  16. Longer breastfeeding is an independent protective factor against development of type 1 diabetes mellitus in childhood.

    Science.gov (United States)

    Sadauskaite-Kuehne, Vaiva; Ludvigsson, Johnny; Padaiga, Zilvinas; Jasinskiene, Edita; Samuelsson, Ulf

    2004-01-01

    Early weaning diet, early introduction of breast milk substitution and cow's milk have been shown to increase the risk of type 1 diabetes later in life. It is also shown that older maternal age, maternal education, preeclampsia, prematurity, neonatal illness and neonatal icterus caused by blood group incompatibility, infections and stress might be risk factors for type 1 diabetes. We aimed to determine whether early nutrition is an independent risk factor for diabetes despite other life events. Data from 517 children (268 boys and 249 girls) in south-east of Sweden and 286 children (133 boys and 153 girls) in Lithuania in the age group of 0 to 15 years with newly diagnosed type 1 diabetes mellitus were included into analysis. Three age- and sex-matched healthy controls were randomly selected. Response rate in control families in Sweden was 72.9% and in Lithuania 94.8%. Information was collected via questionnaires. Exclusive breastfeeding longer than five months (odds ratio 0.54, 95% confidence interval 0.36-0.81) and total breastfeeding longer than 7 (0.56, 0.38-0.84) or 9 months (0.61, 0.38-0.84), breastfeeding substitution that started later than the third month (0.57, 0.33-0.98) among Swedish children 5 to 9 years old and later than the seventh month (0.24, 0.07-0.84) among all Swedish children is protective against diabetes when adjusted for all other above-listed risk factors. In Lithuania, exclusive breastfeeding longer than two months in the age group of 5 to 9 years is protective (0.58, 0.34-0.99) when adjusted for other factors. Longer exclusive and total breastfeeding appears as an independent protective factor against type 1 diabetes. Copyright 2004 John Wiley & Sons, Ltd.

  17. Factorization of the hypergeometric-type difference equation on non-uniform lattices: dynamical algebra

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez-Nodarse, R [Departamento de Analisis Matematico, Universidad de Sevilla, Apdo. 1160, E-41080 Sevilla (Spain); Atakishiyev, N M [Instituto de Matematicas, UNAM, Apartado Postal 273-3, CP 62210 Cuernavaca, Morelos, Mexico (Germany); Costas-Santos, R S [Departamento de Matematicas, EPS, Universidad Carlos III de Madrid, Ave. Universidad 30, E-28911, Leganes, Madrid (Spain)

    2005-01-07

    We argue that one can factorize the difference equation of hypergeometric type on non-uniform lattices in the general case. It is shown that in the most cases of q-linear spectrum of the eigenvalues, this directly leads to the dynamical symmetry algebra su{sub q}(1, 1), whose generators are explicitly constructed in terms of the difference operators, obtained in the process of factorization. Thus all models with the q-linear spectrum (some of them, but not all, previously considered in a number of publications) can be treated in a unified form.

  18. Hypoxia-induced mitogenic factor enhances angiogenesis by promoting proliferation and migration of endothelial cells

    International Nuclear Information System (INIS)

    Tong Qiangsong; Zheng Liduan; Li Bo; Wang Danming; Huang Chuanshu; Matuschak, George M.; Li Dechun

    2006-01-01

    Our previous studies have indicated that hypoxia-induced mitogenic factor (HIMF) has angiogenic properties in an in vivo matrigel plug model and HIMF upregulates expression of vascular endothelial growth factor (VEGF) in mouse lungs and cultured lung epithelial cells. However, whether HIMF exerts angiogenic effects through modulating endothelial cell function remains unknown. In this study, mouse aortic rings cultured with recombinant HIMF protein resulted in enhanced vascular sprouting and increased endothelial cell spreading as confirmed by Dil-Ac-LDL uptake, von Willebrand factor and CD31 staining. In cultured mouse endothelial cell line SVEC 4-10, HIMF dose-dependently enhanced cell proliferation, in vitro migration and tubulogenesis, which was not attenuated by SU1498, a VEGFR2/Flk-1 receptor tyrosine kinase inhibitor. Moreover, HIMF stimulation resulted in phosphorylation of Akt, p38 and ERK1/2 kinases in SVEC 4-10 cells. Treatment of mouse aortic rings and SVEC 4-10 cells with LY294002, but not SB203580, PD098059 or U0126, abolished HIMF-induced vascular sprouting and angiogenic responses. In addition, transfection of a dominant-negative mutant of phosphatidylinositol 3-kinase (PI-3K), Δp85, blocked HIMF-induced phosphorylation of Akt, endothelial activation and tubulogenesis. These results indicate that HIMF enhances angiogenesis by promoting proliferation and migration of endothelial cells via activation of the PI-3K/Akt pathways

  19. Risk factors associated with diabetic retinopathy among type 2 diabetes patients at teaching hospital in Malaysia.

    Science.gov (United States)

    Abougalambou, Salwa Selim Ibrahim; Abougalambou, Ayman S

    2015-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in the United States and it is the leading cause of new cases of blindness in adults aged 20-74. It is estimated that about 20% of patients with type 2 DM have evidence of diabetic retinopathy at diagnosis with diabetes. To evaluate the prevalence of DR and to determine risk factors related to diabetic retinopathy among type 2 diabetes patients attending endocrinology clinics at Hospital Universiti Sains Malaysia (HUSM). The study design was observational prospective longitudinal follow-up study, the study was conducted with sample of 1077 type 2 diabetes mellitus outpatient recruited via attended the diabetes clinics at HUSM. Diagnosis of retinopathy is based on finding the diagnostic signs of retinopathy on eye exams by fundoscopy. Logistic regression analysis was used to assess the independent variables that affect the development of retinopathy. The prevalence of retinopathy was 39.3%. It has been noticed from this study findings, that the progression of retinopathy is been influenced by five independent risk factors such as duration of diabetes, presence neuropathy, total cholesterol at second and third visit and createnine clearance. DR is highly prevalent among type 2 DM. The progression of retinopathy is been influenced by five independent risk factors such as duration of diabetes, presence neuropathy, total cholesterol at second and third visit and createnine clearance. DR is a serious diabetic complication and public health strategies are required in order to reduce its risk factors and decrease its prevalence. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  20. Depression as a risk factor for the onser of type 2 diabetes mellitus. A meta-analysis.

    NARCIS (Netherlands)

    Knol, M.J.; Twisk, J.W.; Beekman, A.T.F.; Heine, R.J.; Snoek, F.J.; Pouwer, F.

    2006-01-01

    Aims/hypothesis: Evidence strongly suggests that depression and type 2 diabetes are associated, but the direction of the association is still unclear. Depression may occur as a consequence of having diabetes, but may also be a risk factor for the onset of type 2 diabetes. This study examined the

  1. Non-adherence to life-style modification and its factors among type 2 diabetic patients

    OpenAIRE

    Shirin Jahan Mumu; Farzana Saleh; Ferdous Ara; Fadia Afnan; Liaquat Ali

    2014-01-01

    Non-adherence to preventive and therapeutic life-style recommendations among patients with diabetes is special challenge in the management of these patients. This study aimed to measure the proportion of non-adherence to life-style modification and factors associated with these among a group of Bangladeshi type 2 diabetic patients. Under an analytical cross-sectional design 374 type 2 diabetic patients (age >20 years), diagnosed for at least 1 year, were selected from different health care ce...

  2. Risk factors of diabetic retinopathy in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    CAI Xiao-ling; WANG Fang; JI Li-nong

    2006-01-01

    Background Advances in treatment have greatly reduced the risk of blindness from this disease, but because diabetes is so common, diabetic retinopathy remains an important problem. The purpose of this study is to investigate the risk factors of diabetic retinopathy (DR) in Chinese type 2 diabetic patients.Methods Totally 746 type 2 diabetic patients were selected for biochemical and clinical characteristics test and examined by the retina-camera for diabetic retinopathy and the average age was 55.9 years old.Results A total of 526 patients was classified as non-DR, 159 patients as non-proliferative-DR and 61 patients as proliferative-DR. Duration of diabetes [(66.09±72.51) months vs (143.71 ±93.27) months vs (174.30±81.91)months, P=0.00], systolic blood pressure [(131.95±47.20) mmHg vs (138.71 ±21.36) mmHg vs (147.58±24.10)mmHg, P=0.01], urine albumin [(32.79± 122.29) mg/L vs (190.96±455.65) mg/L vs (362.00±552.51) mg/L,P=0.00], glycated hemoglobin (HbA1c) [(8.68 ± 2.26)% vs (9.42±1.84)% vs (9.42±1.96)%, P=0.04],C-reactive protein (CRP) [(3.19±7.37) mg/L vs (6.36± 23.59) mg/L vs (3.02±4.34) mg/L, P=0.03],high-density lipoprotein cholesterol (HDL-C) [(1.23±0.37) mmol/L vs (1.33±0.35) mmol/L vs (1.24±0.33)mmol/L, P=0.01], uric acid (UA) [(288.51 ±90.85) mmol/L vs (300.29±101.98) mmol/L vs (337.57±115.09)mmol/L, P=0.00], creatinine (CREA) [(84.22±16.31) μmol/L vs (89.35±27.45) μmol/L vs (103.28±48.64)μmol/L, P=0.00], blood urine nitrogen (BUN) [(5.62± 1.62) mmol/L vs (6.55±2.74) mmol/L vs (8.11±3.60)mmol/L, P=0.00] were statistically different among the three groups. Logistic regression analysis showed that diabetic duration and urine albumin were two independent risk factors of DR (the OR values were 1.010 and 1.003 respectively).Conclusions Diabetic duration and urine albumin are two independent risk factors of diabetic retinopathy in elderly type 2 diabetic patients.

  3. J-GLOBAL MeSH Dictionary: von Willebrand病 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term von Willebrand病 名詞 一般 * * * * von Willebrand...病 ... MeSH D014842 200906053707829497 C LS51 UNKNOWN_2 von Willebrand

  4. Safety, tolerability, pharmacokinetics and pharmacodynamics of anti-VWF nanobody® ALX-0681 after single and multiple subcutaneous administrations to healthy volunteers

    NARCIS (Netherlands)

    Abd-Elaziz, Khalid; Kamphuisen, Pieter W; Lyssens, Christophe; Reuvers, Mariska; Den Daas, Izaak; Van Bockstaele, Femke; Vercruysse, Kristof; Ulrichts, Hans; Baumeister, Judith; Crabbe, Patricia; Compernolle, Veerle; Holz, Josefin-Beate

    2009-01-01

    ALX-0681 is a humanized bivalent Nanobody®, that binds to the A1 domain of von Willebrand factor (vWF) and hence blocks its interaction with platelet receptor GPIb-IX-V. Given its mode of action, ALX-0681 could provide an alternative treatment option for thrombotic thrombocytopenic purpura (TTP), a

  5. Suicide, Schizophrenia, and Schizoid-Type Psychosis: Role of Life Events and Childhood Factors

    Science.gov (United States)

    Tousignant, Michel; Pouliot, Louise; Routhier, Danielle; Vrakas, Georgia; McGirr, Alexander; Turecki, Gustavo

    2011-01-01

    The first objective was to identify the provoking events of suicide in patients with schizophrenia or schizoid-type disorder, and to assess the humiliation component of these events. The second objective was to verify if quality of care during childhood is a vulnerability factor for suicide in patients with schizophrenia or schizoid-type…

  6. Association of market, organizational and financial factors with the number, and types of capital expenditures.

    Science.gov (United States)

    McCue, Michael J

    2011-01-01

    Prior literature provides only a descriptive view of the types and numbers of capital expenditures made by hospitals. This study conducted an empirical analysis to assess simultaneously what market, organizational, and financial factors relate to the number of capital projects as well as the specific types: medical equipment, expansion, and maintenance projects. Sampling California hospital capital expenditure data from 2002 to 2007, this study aggregated the number of capital projects by each type of capital investment decision: medical equipment, expansion, and maintenance/renovation per hospital. Using ordinary least squares regression, this study evaluated the association of these factors with these types of capital investment projects. This study found that hospitals capturing a greater share of the market, maintaining high levels of liquidity, and operating with more than 350 beds invested in a greater number of capital projects per hospital as well as medical equipment and expansionary projects per hospital. Within the state of California, the demand for health care services within a hospital market as well as cash and investment reserves were key drivers in the hospital CEOs and boards' decision to increase their capital purchases. The types of purchases included capital outlays related to medical equipment, such as CT scanners, MRIs, and surgical systems, and revenue-generating expansionary projects, such as new bed towers, hospitals wings, operating and emergency rooms, and replacement hospitals from 2002 to 2007.

  7. Correlation of hs-CRP with environmental risk factors of nephropathy in type 2 diabetes

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    Jay Prakash Sah

    2015-06-01

    Full Text Available The objective of the present study was to investigate the association of hs-CRP levels with environmental risk factors of diabetic nephropathy like smoking, drinking alcohol, diet, age of diabetic patient, duration of diabetes, medication of diabetes, and blood pressure medication. A hospital-based quantitative study was conducted at the Department of Clinical Biochemistry of Manipal Teaching Hospital (MTH Pokhara, Nepal, with 89 patients suffering from type 2 diabetes. Blood samples (n=89 from the patients were collected and the serums were separated. On the other hand, data on environmental risk factors of nephropathy were collected by using standard questionnaire. In this study, serum hs-CRP level was not found to be correlated with smoking (p=0.111, alcohol consumption (p=0.722, diet (p=0.496, duration of diabetes (p=0.519, age of diabetic patient (p=0.369, medication of diabetes (p=0.734, and blood pressure medication (p=0.625. Hence, our study concludes that serum hs-CRP value in type 2 diabetic patients is insignificantly correlated with the risk factors especially smoking, drinking alcohol, diet, duration of diabetes, age of diabetic patient, medication of diabetes, and medication of blood pressure.

  8. Effects of Probiotic Yogurt Consumption on Cardiovascular Disease Risk Factors in Subjects with Type 2 Diabetes

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    F mohammadi

    2015-02-01

    Conclusion: Consumption of probiotic yogurt improved lipid profile and some inflammatory biomarkers in patients with type 2 diabetes. Also, probiotic yogurt caused significant decrease in HbA1c. It is suggested that probiotic yogurt may be used as an adjunct therapy to reduce the cardiovascular disease risk factors in type 2 diabetes mellitus patients

  9. Risk factors and complications in type 2 diabetes outpatients

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    Ellen Fernandes Flávio Silva

    Full Text Available Summary Objective: Our study investigated type 2 diabetes mellitus (T2DM outpatients attending a university hospital in Montes Claros, MG, to estimate the prevalence of risk factors and their association with diabetes complications. Method: This was a quantitative, documental, retrospective and analytical study. Medical records of 95 outpatients with T2DM treated in this hospital from 2011 to 2015 were analyzed. Data were collected according to a structured questionnaire surveying sociodemographic, anthropometric and biochemical data and clinical and lifestyle aspects. Regression analysis was used to evaluate the association between risk factor variables and complications. Results: With a mean age of 54 years, the study population showed irregular blood glucose control, despite the use of hypoglycemic medication, and did not have a healthy lifestyle. The main complication reported was high blood pressure (HBP, occurring in 70.9% of patients. The prevalence of complications was positively associated with patients receiving insulin treatment (p=0.042 and multidisciplinary monitoring (p=0.050. Conclusion: The associations identified reflect the condition of patients that were already treating diabetes and its complications, especially HBP. The characteristics of the study population indicate the need to improve clinical follow-up and increase motivation for healthy behaviors.

  10. Regional factors rather than forest type drive the community structure of soil living oribatid mites (Acari, Oribatida).

    Science.gov (United States)

    Erdmann, Georgia; Scheu, Stefan; Maraun, Mark

    2012-06-01

    Most European forests are managed by humans. However, the manner and intensity of management vary. While the effect of forest management on above-ground communities has been investigated in detail, effects on the below-ground fauna remain poorly understood. Oribatid mites are abundant microarthropods in forest soil and important decomposers in terrestrial ecosystems. Here, we investigated the effect of four forest types (i.e., managed coniferous forests; 30 and 70 years old managed beech forests; natural beech forests) on the density, diversity and community structure of oribatid mites (Acari). The study was replicated at three regions in Germany: the Swabian Alb, the Hainich and the Schorfheide. To relate changes in oribatid mite community structure to environmental factors, litter mass, pH, C and N content of litter, fine roots and C content of soil were measured. Density of oribatid mites was highest in the coniferous forests and decreased in the order 30 years old, 70 years old, and natural beech forests. Mass of the litter layer and density of oribatid mites were strongly correlated indicating that the litter layer is an important factor regulating oribatid mite densities. Diversity of oribatid mites was little affected by forest type indicating that they harbor similar numbers of niches. Species composition differed between the forest types, suggesting different types of niches. The community structure of oribatid mites differed more strongly between the three regions than between the forest types indicating that regional factors are more important than effects associated with forest type.

  11. Factors that could explain the increasing prevalence of type 2 diabetes among adults in a Canadian province: a critical review and analysis

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    Véronique Thibault

    2016-11-01

    Full Text Available Abstract Background The prevalence of diabetes has increased since the last decade in New Brunswick. Identifying factors contributing to the increase in diabetes prevalence will help inform an action plan to manage the condition. The objective was to describe factors that could explain the increasing prevalence of type 2 diabetes in New Brunswick since 2001. Methods A critical literature review was conducted to identify factors potentially responsible for an increase in prevalence of diabetes. Data from various sources were obtained to draw a repeated cross-sectional (2001–2014 description of these factors concurrently with changes in the prevalence of type 2 diabetes in New Brunswick. Linear regressions, Poisson regressions and Cochran Armitage analysis were used to describe relationships between these factors and time. Results Factors identified in the review were summarized in five categories: individual-level risk factors, environmental risk factors, evolution of the disease, detection effect and global changes. The prevalence of type 2 diabetes has increased by 120% between 2001 and 2014. The prevalence of obesity, hypertension, prediabetes, alcohol consumption, immigration and urbanization increased during the study period and the consumption of fruits and vegetables decreased which could represent potential factors of the increasing prevalence of type 2 diabetes. Physical activity, smoking, socioeconomic status and education did not present trends that could explain the increasing prevalence of type 2 diabetes. During the study period, the mortality rate and the conversion rate from prediabetes to diabetes decreased and the incidence rate increased. Suggestion of a detection effect was also present as the number of people tested increased while the HbA1c and the age at detection decreased. Period and birth cohort effect were also noted through a rise in the prevalence of type 2 diabetes across all age groups, but greater increases were

  12. Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1

    NARCIS (Netherlands)

    Visser, G.; Rake, J.P.; Labrune, P.; Leonard, J.V.; Moses, S.; Ullrich, K.; Wendel, U.; Groenier, K.H.; Smit, G.P.

    2002-01-01

    Patients with glycogen storage disease type 1b (GSD-1b) have neutropenia and neutrophil dysfunction that predispose to frequent infections and inflammatory bowel disease (IBD), for which granulocyte colony-stimulating factor (GCSF) is given. To investigate the use and the value of GCSF treatment in

  13. Study on molecule marker of pro-thromb state with diabetic retinopathy%糖尿病视网膜病变血栓前状态分子标志物的研究

    Institute of Scientific and Technical Information of China (English)

    周有利; 张健; 李明

    2009-01-01

    Objective To study the relationship between molecule marker of pro-thromb state and diabetic retinopathy by detecting the levels of thrombomodulin, yon Willebrand disease factor,plasminogen activator inhibitor-1 in blood plasma. Methods Sixty-three patients with type 2 diabetic mellitus were divided into two groups, 35 patients not complicated with diabetic retinopathy group and 28 patients with diabetic retinopathy. And the other 30 health people were as normal controls. The levels of thrombomodulin, yon Willebrand disease factor and plasminogen activator inhibitor-1 in plasma were detected and compared among the three groups. Results The levels of thrombomodulin, yon Willebrand disease factor and plasminogen activator inhibitor-1 of patients with type 2 diabetic mellitus were distinctly higher than those in control group(P<0.01) and in diabetic retinopathy group (P < 0.01). Conclusion The blood vessel endothelium damage, anticoagulation attenuating, degression of platelet adhering, aggregation and delicate dissolving activation may be a pathogenesis of diabetic retinopathy.%目的:观察糖尿病视网膜病变患者血浆中血栓调节蛋白、血管性血友病因子、纤溶酶原激活剂抑制物-1水平的变化,探讨血栓前状态分子标志物与糖尿病视网膜病变的关系.方法:将63例2型糖尿病患者分为:无糖尿病视网膜病变组35例,糖尿病视网膜病变组28例,同期健康体检者30例为对照组.测定各组血浆血栓调节蛋白、血管性血友病因子、纤溶酶原激活剂抑制物-1的水平,并对上述指标进行比较.结果:2型糖尿病患者血浆血栓调节蛋白、血管性血友病因子、纤溶酶原激活剂抑制物-1水平均明显高于对照组(P<0.01);糖尿病视网膜病变组也明显高于无糖尿病视网膜病变组(P<0.01).结论:糖尿病患者存在血管内皮损伤,抗凝作用减弱,血小板黏附与聚集,纤溶活性下降,可能是糖尿病视网膜病变的发病机制之一.

  14. Perinatal factors and type 1 diabetes-associated dysbiosis in Mexican infants.

    Science.gov (United States)

    Mejía-León, María Esther; Calderón de la Barca, Ana María

    Type 1 diabetes (T1D) is currently an autoimmune disease occurring more frequently and early in life. T1D development requires genetic predisposition and environmental factors, which influence the gut microbiota in early infancy and could increase the risk for T1D-associated autoimmunity. In Mexico there are no published microbiota studies in children <6 years old with T1D. We report two contrasting Mexican T1D cases of children <6 years of age and a third case of a healthy child prior to autoimmunity and T1D onset. Perinatal factors, feeding regimes in the first year of life and gut microbiota composition are discussed and related to the T1D onset. The three cases show a particular microbiota profile with decreased bacterial diversity as compared with healthy children, which could be related to environmental factors prior to the development of T1D and disease control. T1D infant cases presented a decreased bacterial diversity, which appeared before autoimmunity and T1D onset. Glycemic control could tend to correct the gut dysbiosis in T1D children. Prospective studies are needed to follow-up healthy children at high genetic risk to assess factors related to the microbiota structure. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  15. Modeling Occurrence of Urban Mosquitos Based on Land Use Types and Meteorological Factors in Korea

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    Yong-Su Kwon

    2015-10-01

    Full Text Available Mosquitoes are a public health concern because they are vectors of pathogen, which cause human-related diseases. It is well known that the occurrence of mosquitoes is highly influenced by meteorological conditions (e.g., temperature and precipitation and land use, but there are insufficient studies quantifying their impacts. Therefore, three analytical methods were applied to determine the relationships between urban mosquito occurrence, land use type, and meteorological factors: cluster analysis based on land use types; principal component analysis (PCA based on mosquito occurrence; and three prediction models, support vector machine (SVM, classification and regression tree (CART, and random forest (RF. We used mosquito data collected at 12 sites from 2011 to 2012. Mosquito abundance was highest from August to September in both years. The monitoring sites were differentiated into three clusters based on differences in land use type such as culture and sport areas, inland water, artificial grasslands, and traffic areas. These clusters were well reflected in PCA ordinations, indicating that mosquito occurrence was highly influenced by land use types. Lastly, the RF represented the highest predictive power for mosquito occurrence and temperature-related factors were the most influential. Our study will contribute to effective control and management of mosquito occurrences.

  16. Factors associated with poor Hemoglobin A1c control in Patients with Type 2 Diabetes.

    Science.gov (United States)

    Alqudah, Salam; Jarab, Anan S; Alefishat, Eman A; Mayyas, Fadia; Khdour, Maher; Pinto, Sharrel

    2018-05-10

    Background The limited implementation of clinical pharmacy service programs and the lack of studies identifying barriers to achieve blood glucose control have all attributed to the increased proportion of type 2 diabetes patients who have poor glycemic control in Jordan. Objective To explore factors associated with higher HbA1c in patients with type 2 diabetes in Jordan. Method Variables including socio-demographics, disease and treatment factors were collected from171 patients with type2 diabetes at an outpatient diabetes clinic in Amman. Validated questionnaires were used to assess medication adherence, self-care activities, diabetes knowledge and health-related quality of life in addition to data collected from medical records. After the single-predictor analysis, stepwise linear regression was performed to develop a model with variables that best predicted hemoglobin A1c. Results Medication adherence was inversely associated with HbA1c values (β = -0.275; t = 2.666; P diabetes duration (β = 0.092; t = 1.339; P diabetes and those with multiple comorbid diseases should be strongly considered in future diabetes management programs implemented to improve glycemic control in patients with type 2 diabetes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Bleeding from gastrointestinal angioectasias is not related to bleeding disorders - a case control study

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    Lärfars Gerd

    2010-09-01

    Full Text Available Abstract Background Angioectasias in the gastrointestinal tract can be found in up to 3% of the population. They are typically asymptomatic but may sometimes result in severe bleeding. The reasons for why some patients bleed from their angioectasias are not fully understood but it has been reported that it may be explained by an acquired von Willebrand syndrome (AVWS. This condition has similar laboratory findings to congenital von Willebrand disease with selective loss of large von Willebrand multimers. The aim of this study was to find out if AVWS or any other bleeding disorder was more common in patients with bleeding from angioectasias than in a control group. Methods We compared bleeding tests and coagulation parameters, including von Willebrand multimers, from a group of 23 patients with anemia caused by bleeding from angioectasias, with the results from a control group lacking angioectasias. Results No significant differences between the two groups were found in coagulation parameters, bleeding time or von Willebrand multimer levels. Conclusion These results do not support a need for routine bleeding tests in cases of bleeding from angioectasias and do not show an overall increased risk of AVWS among these patients.

  18. Comparison of Diabetes Type II Patients Life Style Effective Factors With That of Healthy People.

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    D Mostafaei

    2008-07-01

    Full Text Available Introduction:Diabetes is a significant and expensive health problem which had influenced all the ages in almost all the countries. Increasing prevalence of this disease has been caused by continued changes in lifestyle such as unsuitable nutrition, lack of physical activities and fatness which is often related to modern city life, mechanization and industrialization. It is an expensive disease, both for patients and the health and hygienic care systems. This research tried to examine the relationship between lifestyle risk factors and type II diabetes. Methods: This research was a case-control type by random sampling and studying140 diabetes type II patients as case group and 140 healthy people accompanying some other patients as the control group at Tonekabon Shahid Rajaei hospital. People were of both sexes, between 30 and 64 years of age and Tonekabon residents. The questionnaire used included demographic, nutritional, physical activities, stress tolerance and smoking status information. The SPSS 11.5 and excel software were used for statistic calculation and for analysis of data, T and Chi-Square tests were applied. Results: By analyzing the data collected, there was a meaningful statistical relationship between physical activities, stress residence, nutrition, smoking and the diabetes type II disease (P-value0.05. Conclusion: Results imply that some risk factors important in diabetes type II include unsuitable nutrition such as having too much of sweets and sugar,lack of fruits, vegetables, fish, proteins and also lack of physical activities, stress tolerance and control.

  19. Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

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    Michael Seiler

    2018-04-01

    Full Text Available Summary: Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA, and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like, or hotspot mutation profile (oncogene-like. Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis. : Seiler et al. report that 119 splicing factor genes carry putative driver mutations over 33 tumor types in TCGA. The most common mutations appear to be mutually exclusive and are associated with lineage-independent altered splicing. Samples with these mutations show deregulation of cell-autonomous pathways and immune infiltration. Keywords: splicing, SF3B1, U2AF1, SRSF2, RBM10, FUBP1, cancer, mutation

  20. [Hemostasiological, lipidemic, and hemodynamic indicators associated with the risk of cardiovascular death in high- and very high-risk patients according to the SCORE scale].

    Science.gov (United States)

    Kachkovskiĭ, M A; Simerzin, V V; Rybanenko, O A; Kirichenko, N A

    2014-01-01

    To identify lipidemic, hemostasiological, and hemodynamic indicators associated with the risk of cardiovascular death in high- and very high-risk patients. One hundred and forty-eight patients whose mean age was 50.8 +/- 4.4 years were examined. All the patients were divided into high (1 group) and very high (2 group) cardiovascular death risk groups according to the SCORE scale. Lipid metabolism, hemostatic system parameters (fibrinogen, time of ADP-induced platelet aggregation initiation, D-dimer), endothelial dysfunction markers (von Willebrand factor), and echocardiographic findings were studied. Multivariate regression analysis showed that the odds ratio for a cardiovascular death risk was 1.8 (95% confidence interval (CI), 1.1 to 4.2; p = 0.04) in patients with a D-dimer level of greater than 1 mg/ml, 0.77 (95% CI, 0.6 to 0.97; p = 0.03) in those with an ADP-induced platelet aggregation initiation time of 13.5 sec, 1.04 (95% CI, 1.01 to 1.07; p = 0.02) in those with an end-diastolic volume of more than 123 ml, 1.1 (95% CI, 1.04 to 1.2; p = 0.003) in those with an end-diastolic dimension of more than 51 mm, 1.5 (95% CI, 1.1 to 2.0; p = 0.009) in those with a ventricular septal thickness of more than 11.5 mm, and 2.1 (95% CI, 1.03 to 3.2; p = 0.0032) in those with avon Willebrand factor level of more than 140%. The high levels of von Willebrand factor, D-dimer, ADP-induced platelet aggregation, triglycerides, end-diastolic volume, end-diastolic dimension, and ventricular septal thickness are independent predictors of cardiovascular death in very high-risk patients. These indicators bear out a close relationship between lipid metabolic and hemostatic disturbances and between endothelial dysfunction and intracardiac hemodynamic worsening in these patients.

  1. Risk factors for development of impaired renal function in Type 2 diabetes mellitus patients in primary care.

    NARCIS (Netherlands)

    Naushahi, M.J.; Grauw, W.J.C. de; Avery, A.J.; Gerwen, W.H.E.M. van; Lisdonk, E.H. van de; Weel, C. van

    2004-01-01

    AIMS: To evaluate risk factors for the development of an impaired renal function, defined as a glomerular filtration rate (GFR) by Cockcroft-Gault formula < 50.5 ml/min, in primary care patients with Type 2 diabetes mellitus. METHODS: A case-control study of Type 2 diabetes mellitus patients with

  2. [Correspondence analysis of association between types of unintentional injuries and influential factors among rural rear pupils].

    Science.gov (United States)

    Dou, Dongmei; Wang, Peixi

    2015-07-01

    To explore the association between types of unintentional injuries and influential factors among rural rear pupils. The multistage stratified sampling method was used to select the study participant and thus 594 rural pupils were sampled, 292 rear pupils were confirmed and measured with unintentional injuries and influential factors of rural rear pupils scale. Binary logistic regression analysis indicate that the risk facts related to unintentional injury were left-behind status (OR = 2.68, 95% CI 1.06-6.79), gender (OR = 5.12, 95% C2.68-9.79) and surrounding environment (OR = 3.44, 95% CI 1.37-8.70). Correspondence analysis showed living with father, middle personality and low age were related possibly with traffic accident injury. Living with grandparents, extrovert personality and elder pupils were related possibly with unintentional falls injury. Living with mother, introvert personality and middle-age pupils were related possibly with animmal injury. The personality, ages and guardian types of rural rear pupils are correlated with types of unintentional injuries.

  3. Cuidados nos pacientes com hemofilia e doença de von Willebrand na cirurgia eletiva otorrinolaringológica

    Directory of Open Access Journals (Sweden)

    Marques Marise P. C.

    2003-01-01

    Full Text Available FORMA DE ESTUDO Clínico prospectivo. MATERIAL E MÉTODO: Foi realizado um estudo prospectivo de 10 anos de 20 pacientes com hemofilias ou doença de von Willebrand (DvW com indicação de cirurgia otorrinolaringológica. Os pacientes foram submetidos a um total de 25 cirurgias otorrinolaringológicas eletivas. A idade média foi de 23,75 anos (2 a 62 anos. O grupo de estudo consistiu em 14 hemofílicos, 11 com hemofilia A grave (1 do sexo feminino, uma portadora com 30% de atividade de fator VIII (FVIII, um hemofílico B leve e uma com deficiência grave de fator X; 6 com DvW, 4 tinham o tipo 1 (3 mulheres, um o tipo 2A e um o tipo 3. Treze hemofílicos tinham síndrome de imunodeficiência adquirida. A duração média do procedimento foi de 1 hora e 37 minutos (15 minutos a 12 horas. O defeito da coagulação foi corrigido com desmopressina (DDAVP, com concentrado de FVIII de pureza intermediária 8Y, com criopreciptado ou com complexo protrombínico não ativado (PPSB, de acordo com os níveis plasmáticos do fator e da severidade da cirurgia. O ácido épsilon aminocapróico também foi usado em associação. Em 1 hemofílico A grave houve sangramento pós-operatório que se resolveu com a elevação do nível mínimo de FVIII para 80% e em 1 paciente com DvW do Tipo 3 houve sangramento pós-operatório pela dificuldade de identificação do melhor concentrado a ser reposto. Após o uso do concentrado de pureza intermediária 8Y, houve controle do sangramento. RESULTADO: Todos os outros pacientes apresentaram a hemostasia considerada normal ou excelente. CONCLUSÃO: Concluiu-se que pacientes com hemofilias ou DvW não apresentam um risco cirúrgico aumentado se for realizada uma terapia adequada.

  4. Risk factors for Type 2 Diabetes Mellitus in college students: association with sociodemographic variables

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    Adman Câmara Soares Lima

    2014-06-01

    Full Text Available OBJECTIVE: identify the modifiable risk factors for type 2 diabetes mellitus in college students and associate these factors with their sociodemographic variables.METHOD: cross-sectional study, involving 702 college students from Fortaleza-CE, Brazil. Sociodemographic, anthropometric, physical exercise data and blood pressure and fasting plasma glucose levels were collected.RESULTS: the most prevalent risk factor was sedentariness, followed by overweight, central obesity, high fasting plasma glucose and arterial hypertension. A statistically significant association was found between overweight and sex (p=0.000, age (p=0.004 and marital status (p=0.012, as well as between central obesity and age (p=0.018 and marital status (p=0.007 and between high fasting plasma glucose and sex (p=0.033.CONCLUSION: distinct risk factors were present in the study population, particularly sedentariness and overweight.

  5. Investigation on risk factors of dry eye in type 2 diabetes patients

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    Hu-Xing Shen

    2018-01-01

    Full Text Available AIM: To estimate the correlation between diabetic duration, blood glucose levels, plasma C-peptide and dry eye, and the risk factors for dry eye in patients with type 2 diabetes mellitus(T2DMMETHODS: The clinical data of 51 patients(102 eyeswith type 2 diabetes diagnosed by the Department of Endocrinology, Jiangsu Provincial Hospital of Traditional Chinese Medicine was collected, in that 44 cases(88 eyesof patients diagnosed with dry eye. Those patients were detected for the levels of glycosylated hemoglobin A1c(HbA1c, fasting blood-glucose(FBG, postprandial 2h blood-glucose(2h PBG, fasting plasma C-peptide and insulin, 1h C-peptide and insulin. Corneal fluorescein staining(FL, tear break-up time(BUTand Schirmer Ⅰ test(SⅠtwere collected from all subjects. Compared biochemistry index and ocular surface index. The multiple Logistic regression was used to analyze the risk factors for dry eye in patients with T2DM. RESULTS: There was no significant differences between the patients with different diabetic duration, on BUT, SⅠt, winking frequency, vision, FL and the scores of dry eye symptoms(P>0.05. HbA1c was significantly correlated with FL(P0.05. There were significant differences in FL among patients with HbA1c in 8.1% to 11.8%(P0.01. FBG was significantly correlated with FL and winking frequency(P0.05. The 2h PBG was significantly correlated with tear secretion and vision(P0.05. Plasma C-peptide was significantly correlated with BUT(PP0.05. FBG and plasma C-peptide in T2DM patients were risk factors for occurrence of dry eye(P0.05. CONCLUSION: Poor function of insulin secretion and poor control of blood glucose in T2DM patients are risk factors for dry eye. Both of them can decline tear film stability. High blood glucose levels easily lead to decrease of tear secretion, vision and corneal epithelial defect.

  6. Frequency and risk factors of severe hypoglycemia in insulin-treated type 2 diabetes

    DEFF Research Database (Denmark)

    Akram, Kamran; Pedersen-Bjergaard, Ulrik; Borch-Johnsen, Knut

    2006-01-01

    Intensive treatment regimens including early initiation of insulin treatment are important to prevent late complications in type 2 diabetes. The assumed risk of severe hypoglycemia (SH) is a major barrier to initiation of insulin treatment. To assess the relevance of this risk we evaluated...... the frequency of SH as reported in the literature. Using Medline and Embase search we identified 11 studies (5 retrospective and 6 prospective) including at least 50 patients with insulin-treated type 2 diabetes followed for at least 6 months in which frequency of SH was reported. The incidence of SH....... Only few studies looked into the impact of risk factors on the rate of SH. Impaired hypoglycemia awareness, high age, long duration of diabetes and insulin therapy increased the risk, while no association was found with HbA1c and insulin dose. The present knowledge of SH in insulin-treated type 2...

  7. Ranking of integration factors within supply chains of forward and backward types - recommendations from researches

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    Bernd Hentschel

    2015-06-01

    Full Text Available Background: Integration trends are one of main determinants of the development of modern logistics. After the period of interest focused mainly on supply chains realizing one-way flows only, at present there is a time for supply chains characterized by two-way flows, realizing at the same time both forward and backward flows. The possibility of various configurations of such chains requires identification of integration factors and determination of their influence on the results of the whole supply chain. Experiences of the science as well as the practice of supply chains show the urgent need of learning of reasons of the integration within supply chains of the two-way type.  Material and methods: The researches on modeling and simulation of integration processes within supply chains of forward and backward type were carried out in the environment of iGrafx Process 2013 for Six Sigma. The empirical material obtained in these researches was put to the statistical analysis by the used of Minitab 17. The identification of the significance of differences was made with the help of analysis of variance ANOVA. Additionally the analysis of differences in form of absolute averages was made.  The following measures are main ones for the evaluation of the integration of a supply chain of forward and backward types: cashflow, profitability, service level.  Results: 8 192 simulation experiments were made for 6 integration factors: accessibility of recycled materials, production planning, stock management, integration of transport, unification of packing materials and optimization of the material flow. Based on the analysis of the significance and values of differences, the results of the influence of each integration factor on global results of supply chains of forward and backward type were obtained. They were used to prepare the ranking of integration factors. The main factors, forming the integration shape of two-way supply chains were: stock

  8. The Main Suppressing Factors of Dry Forage Intake in Large-type Goats

    Directory of Open Access Journals (Sweden)

    Tran Van Thang

    2012-03-01

    Full Text Available In large-type goats that were fed on dry forage twice daily, dry forage intake was markedly suppressed after 40 min of feeding had elapsed. The objective of this study was to determine whether or not marked decreases in dry forage intake after 40 min of feeding are mainly caused by the two factors, that is, ruminal distension and increased plasma osmolality induced thirst produced by dry forage feeding. Six large-type male esophageal- and ruminal-fistulated goats (crossbred Japanese Saanen/Nubian, aged 2 to 6 years, weighing 85.1±4.89 kg were used in two experiments. The animals were fed ad libitum a diet of roughly crushed alfalfa hay cubes for 2 h from 10:00 to 12:00 am during two experiments. Water was withheld during feeding in both experiments but was available for a period of 30 min after completion of the 2 h feeding period. In experiment 1, saliva lost via the esophageal fistula was replenished by an intraruminal infusion of artificial parotid saliva (RIAPS in sham feeding conditions (SFC control, and the treatment was maintained under normal feeding conditions (NFC. In experiment 2, a RIAPS and non-insertion of a balloon (RIAPS-NB control was conducted in the same manner as the SFC control of experiment 1. The intraruminal infusion of hypertonic solution and insertion of a balloon (RIHS-IB treatment was carried out simultaneously to reproduce the effects of changing salt content and ruminal distension due to feed entering the rumen. The results of experiment 1 showed that due to the effects of multiple dry forage suppressing factors when feed boluses entered the rumen, eating rates in the NFC treatment decreased (p<0.05 after 40 min of feeding and cumulative dry forage intake for the 2 h feeding period reduced to 43.8% of the SFC control (p<0.01. The results of experiment 2 indicated that due to the two suppressing factors of ruminal distension and increased plasma osmolality induced thirst, eating rates in the RIHS-IB treatment were

  9. Induction of specific neuron types by overexpression of single transcription factors.

    Science.gov (United States)

    Teratani-Ota, Yusuke; Yamamizu, Kohei; Piao, Yulan; Sharova, Lioudmila; Amano, Misa; Yu, Hong; Schlessinger, David; Ko, Minoru S H; Sharov, Alexei A

    2016-10-01

    Specific neuronal types derived from embryonic stem cells (ESCs) can facilitate mechanistic studies and potentially aid in regenerative medicine. Existing induction methods, however, mostly rely on the effects of the combined action of multiple added growth factors, which generally tend to result in mixed populations of neurons. Here, we report that overexpression of specific transcription factors (TFs) in ESCs can rather guide the differentiation of ESCs towards specific neuron lineages. Analysis of data on gene expression changes 2 d after induction of each of 185 TFs implicated candidate TFs for further ESC differentiation studies. Induction of 23 TFs (out of 49 TFs tested) for 6 d facilitated neural differentiation of ESCs as inferred from increased proportion of cells with neural progenitor marker PSA-NCAM. We identified early activation of the Notch signaling pathway as a common feature of most potent inducers of neural differentiation. The majority of neuron-like cells generated by induction of Ascl1, Smad7, Nr2f1, Dlx2, Dlx4, Nr2f2, Barhl2, and Lhx1 were GABA-positive and expressed other markers of GABAergic neurons. In the same way, we identified Lmx1a and Nr4a2 as inducers for neurons bearing dopaminergic markers and Isl1, Fezf2, and St18 for cholinergic motor neurons. A time-course experiment with induction of Ascl1 showed early upregulation of most neural-specific messenger RNA (mRNA) and microRNAs (miRNAs). Sets of Ascl1-induced mRNAs and miRNAs were enriched in Ascl1 targets. In further studies, enrichment of cells obtained with the induction of Ascl1, Smad7, and Nr2f1 using microbeads resulted in essentially pure population of neuron-like cells with expression profiles similar to neural tissues and expressed markers of GABAergic neurons. In summary, this study indicates that induction of transcription factors is a promising approach to generate cultures that show the transcription profiles characteristic of specific neural cell types.

  10. Factors Associated with Long-Term Control of Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Badedi, Mohammed; Solan, Yahiya; Darraj, Hussain; Sabai, Abdullah; Mahfouz, Mohamed; Alamodi, Saleh; Alsabaani, Abdullah

    2016-01-01

    Aims. This study assessed factors associated with glycemic control among Saudi patients with Type 2 diabetes mellitus (T2DM). Methods. We conducted an analytical cross-sectional study, which included a random sample of 288 patients with T2DM proportional to the diabetes population of each primary health care center in Jazan city, Kingdom of Saudi Arabia. Results. More than two-thirds (74%) of patients had poor glycemic control. Lack of education, polypharmacy, and duration of diabetes ≥ 7 years were significantly associated with higher glycated hemoglobin (HbA1c). Moreover, patients who were smoker or divorced were significantly more likely to have higher HbA1c. The patients who did not comply with diet or take their medications as prescribed had poor glycemic control. The study found lower HbA1c levels among patients who received family support or had close relationship with their physicians. Similarly, knowledgeable patients towards diabetes or those with greater confidence in ability to manage self-care behaviors had a lower HbA1c. In contrast, risk factors such as depression or stress were significantly correlated with poorer glycemic control. Conclusion. The majority of T2DM patients had poor glycemic control. The study identified several factors associated with glycemic control. Effective and tailored interventions are needed to mitigate exposure to these risk factors. This would improve glycemic control and reduce the risks inherent to diabetes complications.

  11. Factors Associated with Long-Term Control of Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Mohammed Badedi

    2016-01-01

    Full Text Available Aims. This study assessed factors associated with glycemic control among Saudi patients with Type 2 diabetes mellitus (T2DM. Methods. We conducted an analytical cross-sectional study, which included a random sample of 288 patients with T2DM proportional to the diabetes population of each primary health care center in Jazan city, Kingdom of Saudi Arabia. Results. More than two-thirds (74% of patients had poor glycemic control. Lack of education, polypharmacy, and duration of diabetes ≥ 7 years were significantly associated with higher glycated hemoglobin (HbA1c. Moreover, patients who were smoker or divorced were significantly more likely to have higher HbA1c. The patients who did not comply with diet or take their medications as prescribed had poor glycemic control. The study found lower HbA1c levels among patients who received family support or had close relationship with their physicians. Similarly, knowledgeable patients towards diabetes or those with greater confidence in ability to manage self-care behaviors had a lower HbA1c. In contrast, risk factors such as depression or stress were significantly correlated with poorer glycemic control. Conclusion. The majority of T2DM patients had poor glycemic control. The study identified several factors associated with glycemic control. Effective and tailored interventions are needed to mitigate exposure to these risk factors. This would improve glycemic control and reduce the risks inherent to diabetes complications.

  12. Potential risk factors for dental caries in Type 2 diabetic patients.

    Science.gov (United States)

    Almusawi, M A; Gosadi, I; Abidia, R; Almasawi, M; Khan, H A

    2018-05-11

    Diabetic patients are known to be at higher risk for dental caries. However, the role of potential risk factors such as blood glucose, salivary glucose and glycaemic control in the occurrence of dental caries in type 2 diabetes (T2D) is not clearly understood so far, and therefore, it was evaluated in this study. This cross-sectional study was conducted on 100 T2D patients from Saudi Arabia. The caries risk assessment was evaluated using the guidelines of Caries Management by Risk Assessment (CAMBRA). Cariogenic bacteria load in saliva was determined by a chair-side test kit. The levels of fasting blood glucose (FBG), salivary glucose and HbA1c were analysed. Majority of the patients had dental caries (84%), exposed root surfaces (92%) and heavy plaque (73%), whereas 66% of patients suffered from xerostomia. The frequency of patients with high counts of Streptococcus mutans and Lactobacilli (LB) were 78% and 42%, respectively. There were significant associations between dental caries risk and FBG, HbA1c and salivary glucose. After categorizing the patients into 3 categories of glycaemic control, we observed a significant association between glycaemic control and dental caries risk. Type 2 diabetes patients are at high risk for dental caries, which is directly associated with FBG, HbA1c and salivary glucose. This is the first study measuring dental caries and its risk factors in T2D patients from Saudi Arabia. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity

    Directory of Open Access Journals (Sweden)

    Di eFeng

    2013-09-01

    Full Text Available Patients with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS display increased levels of type I IFN-induced genes. Plasmacytoid dendritic cells (PDCs are natural interferon producing cells and considered to be a primary source of IFN-α in these two diseases. Differential expression patterns of type I IFN inducible transcripts can be found in different immune cell subsets and in patients with both active and inactive autoimmune disease. A type I IFN gene signature generally consists of three groups of IFN-induced genes - those regulated in response to virus-induced type I IFN, those regulated by the IFN-induced mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK pathway, and those by the IFN-induced phosphoinositide-3 kinase (PI-3K pathway. These three groups of type I IFN-regulated genes control important cellular processes such as apoptosis, survival, adhesion, and chemotaxis, that when dysregulated, contribute to autoimmunity. With the recent generation of large datasets in the public domain from next-generation sequencing and DNA microarray experiments, one can perform detailed analyses of cell type-specific gene signatures as well as identify distinct transcription factors that differentially regulate these gene signatures. We have performed bioinformatics analysis of data in the public domain and experimental data from our lab to gain insight into the regulation of type I IFN gene expression. We have found that the genetic landscape of the IFNA and IFNB genes are occupied by transcription factors, such as insulators CTCF and cohesin, that negatively regulate transcription, as well as IRF5 and IRF7, that positively and distinctly regulate IFNA subtypes. A detailed understanding of the factors controlling type I IFN gene transcription will significantly aid in the identification and development of new therapeutic strategies targeting the IFN pathway in autoimmune disease.

  14. Diet, Cardiometabolic Factors and Type-2 Diabetes Mellitus: The Role of Genetics.

    Science.gov (United States)

    Marcadenti, Aline

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is a highly prevalent condition and is associated with a number of metabolic risk factors such as excess of weight, impaired lipid profile and higher levels of blood pressure. As other complex diseases, it is strongly related to an environmental component such as sedentarism and unhealthy diet, and also to a genetic component. A cluster of variants (polymorphisms) in a large number of genes seem to interact with nutrients/dietary factors in modulating cardiometabolic parameters in healthy individuals. The role of total calories intake and also different kind of carbohydrates and dietary fats in worsening the excess of weight and/or metabolic profile in patients with diabetes is well known, but the extent to which genetic factors can modify these associations is not yet fully understood. Therefore, the aim of this mini-review is to discuss the interaction of genetics and diet in the T2DM setting, since both are strongly involved in the genesis and development of the disease.

  15. The primary haemostasis is more preserved in thrombocytopenic patients with liver cirrhosis than cancer

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Alnor, Anne B; Nybo, Mads

    2018-01-01

    aggregation using impedance aggregometry (Multiplate Analyzer), von Willebrand factor antigen (VWF:Ag), VWF:ristocetin-cofactor activity (VWF:RCo), activated partial thromboplastin time (aPTT), coagulation factor VIII, fibrinogen, and thrombin generation in adult hospitalized patients with platelet count less...... in patients with cirrhosis than cancer, 416 AU × min (IQR 257-676) versus 145 AU × min (IQR 50-326) for collagen-induced platelet aggregation, P time (aPTT), coagulation factor VIII, or thrombin generation between the patient groups...

  16. Analysis of Human Error Types and Performance Shaping Factors in the Next Generation Main Control Room

    International Nuclear Information System (INIS)

    Sin, Y. C.; Jung, Y. S.; Kim, K. H.; Kim, J. H.

    2008-04-01

    Main control room of nuclear power plants has been computerized and digitalized in new and modernized plants, as information and digital technologies make great progresses and become mature. Survey on human factors engineering issues in advanced MCRs: Model-based approach, Literature survey-based approach. Analysis of human error types and performance shaping factors is analysis of three human errors. The results of project can be used for task analysis, evaluation of human error probabilities, and analysis of performance shaping factors in the HRA analysis

  17. ROLE OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF IN THE DIAGNOSIS OF COGNTIVE DYSFUNCTION IN PATIENTS WITH TYPE 2 DIABETES

    Directory of Open Access Journals (Sweden)

    Irina Vladimirovna Gatskikh

    2016-02-01

    Full Text Available One of the heavy progressive vascular complications of type 2 diabetes is a central nervous system, manifesting cognitive dysfunction due to metabolic changes. Goal. Defining the role of brain-derived neurotrophic factor (BDNF in the diagnosis of cognitive dysfunction in patients with type 2 diabetes. Materials and methods. The study involved 83 patients with type 2 diabetes at the age of 40 - 70 years. Complex examination included clinical and laboratory examination, neuropsychological testing. To screen for cognitive impairment used the Montreal Cognitive Assessment Scale (MOS test. To identify early markers of cognitive impairment was determined the level of brain-derived neurotrophic factor (BDNF. Results. The study found a negative correlation between the level of BDNF and the HbA1c (r = - 0,494, p = 0.01, fasting glucose (r = - 0,499, p = 0.01, and a positive relationship between the level of BDNF and cognitive function in patients with type 2 diabetes. Conclusion. In patients with type 2 diabetes revealed cognitive dysfunction in the form of reduced memory, attention, optical-dimensional activity that correlated with chronic hyperglycemia. The role of brain-derived neurotrophic factor (BDNF in the complex diagnosis of cognitive dysfunction in patients with type 2 diabetes. With an increase in HbA1c in patients with type 2 diabetes reduces the level of BDNF in the blood plasma, and a decline in cognitive function. Recommended use of BDNF as an additional marker of cognitive dysfunction in patients with type 2 diabetes.

  18. Influence of Article Type on the Impact Factor of Dermatology Journals.

    Science.gov (United States)

    Rodríguez-Lago, L; Molina-Leyva, A; Pereiro-Ferreirós, M; García-Doval, I

    2018-06-01

    For scientific journals, achieving a high impact factor (IF) has become a goal in its own right. Our aim was to describe the influence of article type on the IF of dermatology journals. We used the Scopus database to calculate an IF for Actas Dermo-Sifiliográficas and the major dermatology journals, excluding articles without abstracts, letters to the editor, and conference proceedings. Included articles were classified into 4 categories: case reports, original articles, narrative reviews, and other. We also calculated the mean IF for each article type. We then compared our results with IFs published by the Institute for Scientific Information. The proportion of each type of article differed between journals. Original articles carried the greatest weight in the major journals (BJD, 76.8%; Contact, 81.1%; JAAD, 63.4%; JAMA Dermatol, 63.7%.) but not in Actas Dermo-Sifiliográficas, where only 31.7% were original research articles. A higher IF was associated with the publication of reviews and original articles; a lower IF was associated with the publication of case reports and other article types. Publishing case reports, which have lower citation rates, leads to a lower IF. Publishing reviews and original articles will lead to a higher IF. Journals that seek a higher IF should probably publish more reviews and original articles and fewer case reports. Editorial boards should seek a balance between the interests of their clinician readers and the journal's need for a higher IF. Copyright © 2018 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Psychosocial factors associated with migraine and tension-type headache in medical students.

    Science.gov (United States)

    Lebedeva, Elena R; Kobzeva, Natalia R; Gilev, Denis V; Kislyak, Nadezhda V; Olesen, Jes

    2017-11-01

    Background In our previous study of workers, blood donors and medical students, students stood out with a higher 1-year prevalence of migraine (28%) and tension-type headache (TTH) (74%). General factors associated with headache were common for all groups except low physical activity. The hypothesis of this study was therefore that a number of psychosocial factors relating to the personal sphere would better explain the high prevalence of migraine and TTH in students. Methods The study population consisted of 1042 students (719 females, 323 males, mean age 20.6, range 17-40). Headache diagnoses and associated factors were identified by direct professional semi-structured interview. We also interviewed about the following psychosocial factors: dissatisfaction with study, dissatisfaction with family life, dissatisfaction for personal reasons, bad financial situation, overwork, stress, not enough sleep, insomnia, depressed mood, anxiety, irritability, tendency towards conflicts and not being married. We report psychosocial factors associated with headache according to diagnosis and sex using univariate and multivariate logistic regression analyses. Results Several factors were significantly associated with migraine and TTH in the univariate analysis. In the multivariate analysis, two psychosocial factors were statistically significantly associated with migraine in all students: irritability (OR 2.2, 95% CI 1.4-3.6) and overwork (OR 2.2, 95% CI 1.4-3.5). Insomnia (2.7, 95% CI 1.1-6.9) and depressed mood (OR 2.1, 95% CI 1.1-4.2) were associated with migraine only in females. Two psychosocial factors were associated with TTH: dissatisfaction with study in males (OR 2.0, 95% CI 1.0-3.8) and depressed mood in females (OR 1.8, 95% CI 1.0-3.5). Conclusion Psychosocial factors from the personal sphere showed significant association with migraine and TTH in students. Such factors should therefore be major targets for preventive efforts to reduce the prevalence of primary

  20. Expression and Regulation of Corticotropin-Releasing Factor Receptor Type 2 beta in Developing and Mature Mouse Skeletal Muscle

    NARCIS (Netherlands)

    Kuperman, Yael; Issler, Orna; Vaughan, Joan; Bilezikjian, Louise; Vale, Wylie; Chen, Alon

    Corticotropin-releasing factor receptor type 2 (CRFR2) is highly expressed in skeletal muscle (SM) tissue where it is suggested to inhibit interactions between insulin signaling pathway components affecting whole-body glucose homeostasis. However, little is known about factors regulating SM CRFR2

  1. Incidence of diabetic macular edema and associated risk factors in a cohort of patients with type 1 diabetes in Denmark

    DEFF Research Database (Denmark)

    Rasmussen, Malin Lundberg

    Incidence of diabetic macular edema and associated risk factors in a cohort of patients with type 1 diabetes in Denmark. Rasmussen M.L.1, Pedersen R.B. 1, Sjølie A.K. 1, Grauslund J1 1University of Southern Denmark, Department of ophthalmology, Odense University Hospital, Denmark Purpose: To eval......Incidence of diabetic macular edema and associated risk factors in a cohort of patients with type 1 diabetes in Denmark. Rasmussen M.L.1, Pedersen R.B. 1, Sjølie A.K. 1, Grauslund J1 1University of Southern Denmark, Department of ophthalmology, Odense University Hospital, Denmark Purpose......: To evaluate the 16-year incidence of diabetic macular edema (DME) in a cohort of type 1 diabetic patients and to investigate possible risk factors of developing DME. Methods: This was a prospective cohort study of Danish type 1 diabetic patients. A total of 131 patients were examined at baseline in 1995...

  2. Frequency and risk factors associated with hypomagnesaemia in hypokalemic type-2 diabetic patients

    International Nuclear Information System (INIS)

    Shardha, A.K.; Vaswani, A.S.; Fraz, A.; Alam, M.T.; Kumar, P.

    2014-01-01

    Objective: To determine the frequency and factors associated with hypomagnesaemia in hypokalemic type-2 diabetic patients presenting at Civil Hospital, Karachi. Study Design: A cross-sectional study. Place and Duration of Study: Department of Medicine and Diabetic Clinic of Civil Hospital and Dow Medical College, Karachi, from November 2010 to May 2011. Methodology: A total of 358 adult type-2 diabetics with hypokalemia were selected for this study. With aseptic measures, venous blood was collected for serum magnesium, potassium, HDLc, LDLc Triglyceride (TGs) and glycosylated hemoglobin (HbA1c) from each subject after an overnight fasting and was analyzed on Roche Hitachi 820 Photo Spectrometry. The data was analyzed on SPSS version 17 to determine the factors associated with hypomagnesaemia like duration of diabetes, Body Mass Index (BMI), diabetic nephropathy, HDLc, LDLc Triglyceride (TGs) and glycosylated hemoglobin (HbA1c) level. Results: Mean age of study population was 55.62 +- 9.9 years. Most of them (n=228, 63.7%) were males. Out of the 358 subjects, 198 (55.3%) had hypomagnesaemia. There was significant association between hypomagnesaemia with duration of diabetes, Body Mass Index (BMI), diabetic nephropathy, HDLc, LDLc Triglyceride (TGs) and glycosylated hemoglobin (HbA1c) level. Conclusion: Hypomagnesaemia is very common in type-2 diabetic hypokalemic patients. Therefore, it should be routinely sought by the clinicians. Early recognition and subsequent treatment of hypomagnesaemia may help in better glycemic control, may delay the chronic complications and decrease the mortality in diabetic hypokalemic patients. (author)

  3. Localization and functional roles of corticotropin-releasing factor receptor type 2 in the cerebellum

    NARCIS (Netherlands)

    Gounko, Natalia V.; Gramsbergen, Albert; van der Want, Johannes J. L.

    The corticotropin-releasing factor (CRF) type 2 receptor has three splice variants alpha, beta, and gamma. In the rodent brain only CRF-R2 alpha is present. In the cerebellum, CRF-R2 alpha has two different isoforms: a full-length form (fl) and truncated (tr). Both forms CRF-R2 have a unique

  4. Risk Factors Accompanied with Nephropathy in Patients with Type II Diabetes; Test of the Biopsychosocial Model

    Directory of Open Access Journals (Sweden)

    I. Rahimian Boogar

    2012-07-01

    Full Text Available Introduction & Objective: The study of biopsychosocial factors influencing nephropathy as a most serious complication of type II diabetes is important. This study aimed to investigate risk factors accompanied with nephropathy in patients with type II diabetes based on the biopsychosocial model. Materials & Methods: In a cross-sectional descriptive study, 295 patients with type II diabetes were selected by convenience sampling in Tehran Shariati hospital outpatient clinics. The data were collected by demographical information questionnaire along with disease characteristics and depression anxiety stress scales (dass, quality of life scale (who- qol- bref, diabetes self-management scale (dsms, and diabetes knowledge scale (dks, then analyzed by chi-square, independent t-test and logistic regression with pasw software. Results: Hypertension (OR=3.841 & P0.05.Conclusion: It is important to pay attention to hypertension, glycated hemoglobin, body mass index, diabetes self-management, depression, quality of life, and diabetes knowledge for therapeutic intervention programming and diabetes complications control protocols for diabetic patients.(Sci J Hamadan Univ Med Sci 2012;19(2:44-53

  5. [Prevalence and risk factors of extra-coronary artery disease in patients with diabetes which confirmed atherosclerosis of coronary arteries].

    Science.gov (United States)

    Gracheva, S A; Biragova, M S; Glazunova, A M; Klefortova, I I; Melkozerov, K V; Shamkhalova, M Sh; Dzhavelidze, M I; Soldatova, T V; Il'in, A V; Deev, A D; Shestakova, M V; Tugeeva, E F; Buziashvili, Iu I

    2014-01-01

    To assess prevalence and risk factors of extra-coronary artery disease (peripheral artery (PA) disease (D) of lower extremities (LE), brachiocephalic arterial (BCA) stenosis (S), renal arterial (RA) S in type 1 and 2 (T1 and T2) diabetes (D) patients (P) with confirmed atherosclerosis of coronary arteries (CA). 100 P (48 with T2D, 18 with T1D, 34 without diabetes - PWD), with hemodynamically significant atherosclerosis of CA confirmed by coronary angiography. All patients underwent duplex ultrasonography of PA LE, BCA, RA. Other studies included assessment of clinical characteristics and measurement of the following parameters: profibrogenic cytokines (transforming growth factor [TGF] beta1, matrix metalloproteinase 9 [MMP9], monocyte chemotactic protein-1 [MCP-1], regulated on activation normal T-cell expressed and secreted [RANTES), markers of endothelial dysfunction (von Willebrand factor [VWF], homocystein [HCYST], plasminogen activator inhibitor-1 [PAI-1], vascular cell adhesion molecule [VCAM], soluble intercellular adhesion molecules-1 [sICAM], vascular endothelial growth factor [VEGF], asymmetric dimethylarginine [ADMAD, N-terminal fragment of pro-brain natriuretic peptide (NT-pro BNP), fibroblast growth factor 23 (FGF-23), and fibrinogen. Portions of P with multivessel CA disease were similar in all three groups (T1D - 88.9, T2D - 85.5, WD - 82.3%). Coexistence of atherosclerosis in 2 or more vascular beds was identified in 85.3% of T2D and in 50% of WD P (p = 0.005). In T1D group 61.1 and 11.1% of P had atherosclerosis in 2 and 3 vascular beds, respectively. Levels of profibrogenic cytokines and factors of endothelial activation (RANTES, MMP-9, PAI-I, VCAM, sICAM, ADMA) were significantly higher in P with diabetes vs P WD. P with diabetes and multifocal atherosclerosis demonstrated significant increases of CRP, fibrinogen, NT-proBNP, VWF, PAI-1, ADMA, sICAM, and decrease of GFR compared with P with atherosclerosis in 1 vascular bed. Logistic regression

  6. Emission factors from biomass burning in three types of appliances: fireplace, woodstove and pellet stove

    Science.gov (United States)

    Duarte, Márcio; Vicente, Estela; Calvo, Ana; Nunes, Teresa; Tarelho, Luis; Alves, Célia

    2014-05-01

    In the last years, the importance of biomass fuels has increased mainly for two reasons. One of them is the effort to control the emissions of greenhouse gases, and on the other hand, the increasing costs associated with fossil fuels. Besides that, biomass burning is now recognised as one of the major sources contributing to high concentrations of particulate matter, especially during winter time. Southern European countries have a lack of information regarding emission profiles from biomass burning. Because of that, in most source apportionment studies, the information used comes from northern and alpine countries, whose combustion appliances, fuels and habits are different from those in Mediterranean countries. Due to this lack of information, series of tests using different types of equipment, as well as fuels, were carried out in order to obtain emission profiles and emission factors that correspond to the reality in southern European countries. Tests involved three types of biomass appliances used in Portugal, a fireplace, a woodstove and a modern pellet stove. Emission factors (mg.kg-1 fuel, dry basis) for CO, THC and PM10 were obtained. CO emission factors ranged from 38, for pine on the woodstove, to 84 for eucalyptus in the fireplace. THC emissions were between 4 and 24, for pine in the woodstove and eucalyptus in the fireplace, respectively. PM10 emission factors were in the range from 3.99, for pine in the woodstove, to 17.3 for eucalyptus in the fireplace. On average, the emission factors obtained for the fireplace are 1.5 (CO) to 4 (THC) times higher than those of the woodstove. The fireplace has emission factors for CO, THC and PM10 10, 35 and 32 times, respectively, higher than the pellet stove.

  7. Prognostic Classification Factors Associated With Development of Multiple Autoantibodies, Dysglycemia, and Type 1 Diabetes?A Recursive Partitioning Analysis

    OpenAIRE

    Xu, Ping; Krischer, Jeffrey P.

    2016-01-01

    OBJECTIVE To define prognostic classification factors associated with the progression from single to multiple autoantibodies, multiple autoantibodies to dysglycemia, and dysglycemia to type 1 diabetes onset in relatives of individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS Three distinct cohorts of subjects from the Type 1 Diabetes TrialNet Pathway to Prevention Study were investigated separately. A recursive partitioning analysis (RPA) was used to determine the risk classes. Clini...

  8. Beyond genetics. Influence of dietary factors and gut microbiota on type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Dennis Sandris; Krych, Lukasz; Buschard, Karsten

    2014-01-01

    Type 1 diabetes (T1D) is an autoimmune disease ultimately leading to destruction of insulin secreting β-cells in the pancreas. Genetic susceptibility plays an important role in T1D etiology, but even mono-zygotic twins only have a concordance rate of around 50%, underlining that other factors than...... purely genetic are involved in disease development. Here we review the influence of dietary and environmental factors on T1D development in humans as well as animal models. Even though data are still inconclusive, there are strong indications that gut microbiota dysbiosis plays an important role in T1D...... development and evidence from animal models suggests that gut microbiota manipulation might prove valuable in future prevention of T1D in genetically susceptible individuals....

  9. Mutation analysis and clinical implications of von Willebrand factor-cleaving protease deficiency.

    NARCIS (Netherlands)

    Assink, K.F.H.; Schiphorst, R.H.M.; Allford, S.; Karpman, D.; Etzioni, A.; Brichard, B.; Kar, N.C.A.J. van de; Monnens, L.A.H.; Heuvel, L.P.W.J. van den

    2003-01-01

    BACKGROUND: The pentad of thrombocytopenia, hemolytic anemia, mild renal dysfunction, neurologic signs, and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults as an acquired form but a congenital form in children has also been

  10. Nitric oxide level and von Willebrand factor (vWF) secretion are not ...

    African Journals Online (AJOL)

    Jane

    2011-08-15

    Aug 15, 2011 ... potassium channels; RBECs, rat brain capillary endothelial cells. and transport of ... addition, adenine nucleotides modulate the release of endothelial-derive ..... A cellular model of endothelial cell ischemia. J Surg Res. 44(5): ...

  11. Trends for type 2 diabetes and other cardiovascular risk factors in Mexico from 1993-2006.

    Science.gov (United States)

    Villalpando, Salvador; Shamah-Levy, Teresa; Rojas, Rosalba; Aguilar-Salinas, Carlos A

    2010-01-01

    To describe the trends in the prevalence of type 2 diabetes (T2D), and other cardiovascular risk factors in three national health surveys (1993, 2000 and 2006). The databases of three surveys: ENEC 1993, ENSA 2000 and ENSANUT 2006 were gathered. Calculations of published data were reprocessed to do appropriate adjustments to assure comparability among surveys. From 1993 to 2006 the prevalence of type 2 diabetes (6.7-14.4%), metabolic syndrome (26.6-36.8%), hypertension (23.8-30.7%), hypercholesterolemia (27-43.6%), and high LDL-cholesterol (31.6-46%) increased rapidly. The prevalence of low HDL cholesterol was very high (60.5-63%) in all surveys and remained remarkably unchanged among surveys. This increasing trends for the prevalence of T2D and cardiovascular risk factors predicts larger increments in the near future for T2D and cardiovascular morbidity and mortality. Intensification of the preventive and remedy strategies is mandatory in order curve the foreseen dramatic increment in the disease burden.

  12. Assessment of job stress factors and organizational personality types for procedure-based jobs in nuclear power plants

    International Nuclear Information System (INIS)

    Kim, Dae-Ho; Lee, Yong-Hee; Lee, Jung-Woon

    2008-01-01

    The purpose of this study is to assess the organizational types and the job stress factors that affect procedure-based job performances in nuclear power plants. We derived 24 organizational factors affecting job stress level in nuclear power plants from the job stress analysis models developed by NIOSH, JDI, and IOR. Considering the safety characteristics in the operating tasks of nuclear power plants, we identified the job contents and characteristics through the analyses of job assignments that appeared in the organizational chart and the results of an activity-based costing. By using questionnaire surveys and structured interviews with the plant personnel and expert panels, we assessed 70 jobs among the 777 jobs managed officially in accordance with the procedures. They consist of the representative jobs of each department and are directly related to safety. We utilized the organizational personality type indicators to characterize the personality types of each organization in nuclear power plants. (author)

  13. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type

    DEFF Research Database (Denmark)

    Sode, Birgitte F; Allin, Kristine H; Dahl, Morten

    2013-01-01

    ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated...

  14. Preferences for learning different types of genome sequencing results among young breast cancer patients: Role of psychological and clinical factors.

    Science.gov (United States)

    Kaphingst, Kimberly A; Ivanovich, Jennifer; Lyons, Sarah; Biesecker, Barbara; Dresser, Rebecca; Elrick, Ashley; Matsen, Cindy; Goodman, Melody

    2018-01-29

    The growing importance of genome sequencing means that patients will increasingly face decisions regarding what results they would like to learn. The present study examined psychological and clinical factors that might affect these preferences. 1,080 women diagnosed with breast cancer at age 40 or younger completed an online survey. We assessed their interest in learning various types of genome sequencing results: risk of preventable disease or unpreventable disease, cancer treatment response, uncertain meaning, risk to relatives' health, and ancestry/physical traits. Multivariable logistic regression was used to examine whether being "very" interested in each result type was associated with clinical factors: BRCA1/2 mutation status, prior genetic testing, family history of breast cancer, and psychological factors: cancer recurrence worry, genetic risk worry, future orientation, health information orientation, and genome sequencing knowledge. The proportion of respondents who were very interested in learning each type of result ranged from 16% to 77%. In all multivariable models, those who were very interested in learning a result type had significantly higher knowledge about sequencing benefits, greater genetic risks worry, and stronger health information orientation compared to those with less interest (p-values psychological factors. Shared decision-making approaches that increase knowledge about genome sequencing and incorporate patient preferences for health information and learning about genetic risks may help support patients' informed choices about learning different types of sequencing results. © Society of Behavioral Medicine 2018.

  15. Assessment of endothelial function during oral contraception in women with insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, K R; Skouby, S O; Sidelmann, Johannes Jakobsen

    1994-01-01

    The effects of contraceptive steroids on the expression of endothelial homeostasis were examined by direct and indirect measures in women with insulin-dependent diabetes mellitus (IDDM) in a prospective nonrandomized controlled study. Study subjects were 13 women with uncomplicated IDDM treated...... with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene for 12 consecutive cycles and 13 women of comparable diabetic status as control. During the study period, none of the participants developed increased renal albumin excretion, which was used as a direct measure......-PA) and plasminogen activator inhibitor (type 1 [PAI-1]), whereas the activities of t-PA and PAI-1 were unchanged. Plasma levels of plasminogen and histidine-rich glycoprotein (HRG) increased and decreased, respectively, whereas an increase in von Willebrand factor was observed in the treatment group. No significant...

  16. High – Sensitivity C - reactive protein is associated with Traditional Cardiovascular Risk Factors in Indians with Type 2 Diabetes Mellitus

    OpenAIRE

    Asegaonkar, Shilpa B; Bavikar, Jayashree Suhas; Marathe, Amruta; Tekade, Mangesh; Asegaonkar, Balaji N.; Jayashree, Bardapurkar

    2013-01-01

    Background: India is experiencing twin epidemic of type 2 diabetes mellitus and cardiovascular diseases imposing huge toll on healthcare system. In type 2 diabetes 65-80% deaths occur due to cardiovascular disease whose etiology cannot be explained by chronic hyperglycemia, dyslipedemia and traditional cardiac risk factors. To improve risk stratification serum high-sensitivity C- reactive protein estimation is an adjunct to other risk factors. Study design: O.P.D. based Cross sectional study....

  17. Post-Renal Transplant Diabetes Mellitus in Korean Subjects: Superimposition of Transplant-Related Immunosuppressant Factors on Genetic and Type 2 Diabetic Risk Factors

    Directory of Open Access Journals (Sweden)

    Hyun Chul Lee

    2012-06-01

    Full Text Available Postrenal transplantation diabetes mellitus (PTDM, or new-onset diabetes after organ transplantation, is an important chronic transplant-associated complication. Similar to type 2 diabetes, decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind the development of PTDM. However, β-cell dysfunction rather than insulin resistance seems to be a greater contributing factor in the development of PTDM. Increased age, family history of diabetes, ethnicity, genetic variation, obesity, and hepatitis C are partially accountable for an increased underlying risk of PTDM in renal allograft recipients. In addition, the use of and kinds of immunosuppressive agents are key transplant-associated risk factors. Recently, a number of genetic variants or polymorphisms susceptible to immunosuppressants have been reported to be associated with calcineurin inhibition-induced β-cell dysfunction. The identification of high risk factors of PTDM would help prevent PTDM and improve long-term patient outcomes by allowing for personalized immunosuppressant regimens and by managing cardiovascular risk factors.

  18. Association of hypoxia inducible factor-1 alpha gene polymorphism with both type 1 and type 2 diabetes in a Caucasian (Hungarian sample

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    Panczel Pal

    2009-08-01

    Full Text Available Abstract Background Hypoxia inducible factor-1 alpha (HIF-1α is a transcription factor that plays an important role in neo-vascularisation, embryonic pancreas beta-cell mass development, and beta cell protection. Recently a non synonymous single nucleotide polymorphism (g.C45035T SNP, rs11549465 of HIF-1α gene, resulting in the p.P582S amino acid change has been shown to be associated with type 2 diabetes (T2DM in a Japanese population. Our aim was to replicate these findings on a Caucasian (Hungarian population, as well as to study whether this genetic effect is restricted to T2DM or can be expanded to diabetes in general. Methods A large Caucasian sample (N = 890 was recruited including 370 T2DM, 166 T1DM and 354 healthy subjects. Genotyping was validated by two independent methods: a restriction fragment analysis (RFLP and a real time PCR using TaqMan probes. An overestimation of heterozygotes by RFLP was observed as a consequence of a nearby SNP (rs34005929. Therefore genotyping results of the justified TaqMan system were accepted. The measured genotype distribution corresponded to Hardy-Weinberg equilibrium (P = 0.740 Results As the TT genotype was extremely rare in the population (0.6% in clinical sample and 2.5% in controls, the genotypes were grouped as T absent (CC and T present (CT and TT. Genotype-wise analysis showed a significant increase of T present group in controls (24.0% as compared to patients (16.8%, P = 0.008. This genetic effect was demonstrated in the separated samples of type 1 (15.1%, P = 0.020, and also in type 2 (17.6%, P = 0.032 diabetes. Allele-wise analysis gave identical results showing a higher frequency of the T allele in the control sample (13.3% than in the clinical sample (8.7%, P = 0.002 with similar results in type 1 (7.8%, P = 0.010 and type 2 (9.1%, P = 0.011 diabetes. The odds ratio for diabetes (either type 1 or 2 was 1.56 in the presence of the C allele. Conclusion We confirmed the protective effect

  19. Beam propagation factor and Kurtosis parameter of different types of flattened Gaussian beams

    International Nuclear Information System (INIS)

    Saghafi, S.; Forbes, G.W.; Sheppard, C.J.R.

    1999-01-01

    Full text: The beam propagation factor, M 2 and the Kurtosis parameter, K, are considered for three different models of flattened Gaussian beams. Plots of M 2 versus K reveal similarities between these flattened beams. In fact, for this type of beam, it is possible to predict K from the value of M 2 We also determine the values of the parameters that characterize those different types of flattened Gaussian beam modes for any given value of M 2 . Finally, once K and M 2 have been measured for any flattened beam, these equations can be used to determine the closeness of this real beam to members of the three well-known classes of flattened beams. This can facilitate the analyses of the beam and its propagation. Copyright (1999) Australian Optical Society

  20. Neuropsychological functioning in older people with type 2 diabetes: the effect of controlling for confounding factors.

    Science.gov (United States)

    Asimakopoulou, K G; Hampson, S E; Morrish, N J

    2002-04-01

    Neuropsychological functioning was examined in a group of 33 older (mean age 62.40 +/- 9.62 years) people with Type 2 diabetes (Group 1) and 33 non-diabetic participants matched with Group 1 on age, sex, premorbid intelligence and presence of hypertension and cardio/cerebrovascular conditions (Group 2). Data statistically corrected for confounding factors obtained from the diabetic group were compared with the matched control group. The results suggested small cognitive deficits in diabetic people's verbal memory and mental flexibility (Logical Memory A and SS7). No differences were seen between the two samples in simple and complex visuomotor attention, sustained complex visual attention, attention efficiency, mental double tracking, implicit memory, and self-reported memory problems. These findings indicate minimal cognitive impairment in relatively uncomplicated Type 2 diabetes and demonstrate the importance of control and matching for confounding factors.

  1. Adding Salt to Meals as a Risk Factor of Type 2 Diabetes Mellitus: A Case–Control Study

    Directory of Open Access Journals (Sweden)

    Lina Radzeviciene

    2017-01-01

    Full Text Available Objective: Type 2 diabetes mellitus (T2DM is thought to arise from the complex interplay between genetic and environmental factors. It is important to identify modifiable risk factors that may help to reduce the risk of diabetes. Data on salt intake and the risk of type 2 diabetes are limited. The aim of this study was to assess the relationship between adding salt to prepared meals and the risk of type 2 diabetes. Methods: In a case–control study, we included 234 cases, all of whom were patients aged 35–86 years with a newly confirmed diagnosis of T2DM, and 468 controls that were free of the disease. Cases and controls (ratio 1:2 were matched by gender and age (±5 years. A questionnaire was used to collect information on possible risk factors for diabetes. Adding salt to prepared meals was assessed according to: Never, when there was not enough, or almost every time without tasting. The odds ratios (OR, and 95% confidence intervals (CI for type 2 diabetes was calculated using a conditional logistic regression. Results: The cases had a higher body mass index and a significantly lower education level compared to the controls. Variables such as waist circumference, body mass index, eating speed, smoking, family history of diabetes, arterial hypertension, plasma triglycerides, educational level, occupational status, morning exercise, marital status, daily urine sodium excretion, and daily energy intake were retained in the models as confounders. After adjusting for possible confounders, an approximately two-fold increased risk of type 2 diabetes was determined in subjects who add salt to prepared meals when “it is not enough” or “almost every time without tasting” (1.82; 95% CI 1.19–2.78; p = 0.006 compared with never adding salt. Conclusion: Presented data suggest the possible relationship between additional adding of salt to prepared meals and an increased risk of type 2 diabetes.

  2. The Prevalence of High-Risk HPV Types and Factors Determining Infection in Female Colombian Adolescents.

    Directory of Open Access Journals (Sweden)

    Luisa Del Río-Ospina

    Full Text Available This study reports six HR-HPV types' infection prevalence discriminated by species and multiple infection in unvaccinated Colombian female adolescents, as well as some factors modulating the risk of infection. HPV DNA for six high-risk viral types was identified in cervical samples taken from 2,134 12-19 year-old females using conventional generic and type-specific PCR. Binomial logistical regression analysis was used for modelling HR-HPV infection and multiple infection risk. The interaction between variables in a stepwise model was also included in such analysis. Viral DNA was detected in 48.97% of the females; 28.52% of them had multiple infections, HPV-16 being the most frequently occurring type (37.44%. Cytological abnormality prevalence was 15.61%. Being over 16 years-old (1.66: 1.01-2.71 95%CI, white ethnicity (4.40: 1.16-16.73 95%CI, having had 3 or more sexual partners (1.77: 1.11-2.81 95%CI and prior sexually-transmitted infections (STI (1.65: 1.17-2.32 95%CI were associated with a greater risk of HPV infection. Having given birth was related to a higher risk of infection by A7 species and antecedent of abortion to less risk of coinfection. Where the females in this study came from also influenced the risk of infection by A7 species as female adolescents from the Andean region had a lower risk of infection (0.42: 0.18-0.99 95%CI. The presence of factors related to risky sexual behaviour in the study population indicated that public health services should pay special attention to female adolescents to modify the risk of infection by high-risk HPV types and decrease their impact on this age group.

  3. The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors: a systematic review and meta-analysis.

    Science.gov (United States)

    Stuijver, Danka J F; van Zaane, Bregje; Romualdi, Erica; Brandjes, Dees P M; Gerdes, Victor E A; Squizzato, Alessandro

    2012-12-01

    Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibrinolytic system in vivo . Data sources included MEDLINE (2006-2012), EMBASE (2006-2012), and reference lists. The sources were combined with our previous search containing studies from 1980-2006. Eligible studies were all observational or experimental studies. Two investigators independently extracted data and rated study quality. Weighted mean proportion and 95% confidence intervals were calculated and pooled using a fixed and a random-effects model. A total of 29 articles consisting of 51 studies were included, as in several articles more than one study was described. We included four intervention (before and after treatment in hyperthyroid patients), five cross-sectional (hyperthyroid subjects and euthyroid controls), and four experimental (before and after use of thyroid hormone in euthyroid subjects) medium/high quality studies for meta-analysis. We found that thyrotoxicosis shifts the haemostatic balance towards a hypercoagulable and hypofibrinolytic state with a rise in factors VIII and IX, fibrinogen, von Willebrand factor, and plasminogen activator inhibitor-1. This was observed in endogenous and exogenous thyrotoxicosis, and in subclinical as well as overt hyperthyroidism. We conclude that both subclinical and overt hyperthyroidism induce a prothrombotic state, which is therefore likely to be a risk factor for venous thrombosis.

  4. Is hypertension a major independent risk factor for retinopathy in type 1 diabetes?

    DEFF Research Database (Denmark)

    Nørgaard, K; Feldt-Rasmussen, B; Deckert, T

    1991-01-01

    Hypertension is an established risk factor for retinopathy. Whether it is an independent risk factor or acts only by association with nephropathy is not known. Therefore, we studied 273 Type 1 diabetic patients. They were divided into four groups. Group 1 (n = 55) were normotensive...... and normoalbuminuric, group 2 (n = 51) had hypertension but were normoalbuminuric, group 3 (n = 33) had nephropathy but were normotensive, and group 4 (n = 134) had nephropathy and hypertension. Hypertensive patients with normoalbuminuria (blood pressure 146 +/- 19 (+/-SD)/87 +/- 12 mmHg) had the same prevalence...... of retinopathy as normoalbuminuric normotensive patients (123 +/- 12/75 +/- 5 mmHg). Hypertensive nephropathic patients (blood pressure 147 +/- 18/87 +/- 8 mmHg) had more retinopathy than hypertensive normoalbuminuric patients despite similar blood pressure (normal retina/advanced retinopathy: 3%/73% vs 46...

  5. Risk factors for type 2 diabetes mellitus among patients attending a rural Kenyan hospital

    Directory of Open Access Journals (Sweden)

    Masemiano P. Chege

    2010-05-01

    Objectives: To describe the risk factors for type 2 diabetes mellitus among patients attending the outpatient clinics in a rural mission hospital in Kenya. Method: Forty-five diabetics and forty-five non-diabetics, resident in this rural hospital’s catchment area for at least 10 years, were randomly selected from patients attending outpatient clinics. Diabetics in a stable condition (not requiring hospitalisation, whose fasting blood sugars were below 6.1 mmol/L, were matched for age and gender with the non-diabetics who came to the hospital for outpatient services. A pilot-tested questionnaire on demography, current and past dietary habits, social habits, and family history was used to collect data. Waist circumference, height and weight were measured and BMI calculated. Data was analysed using SPSS for Windows. The Kruskal–Wallis test was used to compare the medians for the continuous variables, while the chi-squared test was used for the categorical variables. The z-test was used to calculate the relative risk. Results: Ninety participants (26 males, 64 females. The mean age was 61.8 for diabetics and 61.4 for non-diabetics. Childhood starvation (relative risk 2.08, p = 0.0090 and use of cassava for sustenance during childhood starvation (relative risk 3.12, p = 0.0090 were identified as risk factors. Diabetes in close relatives, another risk factor for this population (relative risk 2.2, p = 0.0131. Abdominal obesity was a risk factor for this population (in females relative risk 2.0, p = 0.0010. Conclusion: The risk factors for type 2 diabetes mellitus described in this rural population include advancing age, diabetes in a first-degree relative and abdominal obesity. This is similar to what has been cited in other studies. At variance, we found that more than 50% of the diabetics reported having suffered malnutrition/starvation in childhood, with more than half of them reporting their dependence on cassava as the only food source during starvation.

  6. Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Qing-Lin Lou

    2012-12-01

    Full Text Available BackgroundTo determine the frequency of chronic kidney disease (CKD and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009.MethodsPatients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g.ResultsWe recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9±12.0 years. The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval being 1.93 (1.28 to 2.93, 1.70 (1.09 to 2.64, and 1.03 (1.00 to 1.06, respectively.ConclusionIn conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.

  7. Intra-plaque production of platelet-activating factor correlates with neoangiogenesis in human carotid atherosclerotic lesions.

    Science.gov (United States)

    Lupia, Enrico; Pucci, Angela; Peasso, Paolo; Merlo, Maurizio; Baron, Paolo; Zanini, Cristina; Del Sorbo, Lorenzo; Rizea-Savu, Simona; Silvestro, Luigi; Forni, Marco; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

    2003-09-01

    Platelet-activating factor (PAF) is a phospholipid mediator synthesized by activated inflammatory and endothelial cells. Recently PAF has been shown to contribute to neoangiogenesis in several experimental models. Here we evaluated the presence of PAF and its potential role in neovascularization within human atherosclerotic plaques. The amount of PAF extracted from 18 carotid plaques (266.65+/-40.07 pg/100 mg dry tissue; mean +/- SE) was significantly higher than that extracted from 18 normal arterial specimens (6 from carotid artery and 12 from aorta) (4.72+/-2.31 pg/100 mg dry tissue; mean +/- SE). The levels of PAF significantly correlated with the infiltration of CD68-positive monocytes and the extent of neovascularization, detected as von Willebrand Factor-positive cells. The amount of PAF also correlated with the area occupied by TNF-alpha-expressing cells. The absence of enhanced level of PAF in the circulation of atherosclerotic patients suggests a local production of this mediator within the plaque. The lipid extracts of atherosclerotic plaques containing high levels of PAF-bioactivity, but not those of control arteries, were angiogenic in a murine Matrigel model. WEB 2170, a specific PAF receptor antagonist, significantly prevented angiogenesis induced by the lipid extracts of atherosclerotic plaques. Our results indicate a local production of PAF within the atherosclerotic plaques and suggest that it may contribute to intra-plaque neoangiogenesis.

  8. Identifying non-pharmacological risk factors for falling in older adults with type 2 diabetes mellitus: a systematic review.

    Science.gov (United States)

    Gravesande, Janelle; Richardson, Julie

    2017-07-01

    To identify the non-pharmacological risk factors for falling in older adults with type 2 diabetes mellitus (DM2). A systematic review of randomized controlled trials, prospective cohort studies, cross-sectional studies and before/after studies was conducted. Eligible studies identified non-pharmacological risk factors for falling in older adults with DM2. Medline, Embase, Pubmed and CINAHL were searched for relevant studies published through December 2015. Reference lists were also searched for relevant studies. Search terms were DM2, risk factors, falls and falling, older adults, aging, non-insulin dependent diabetes mellitus, accidental falls and trip. Publication language was restricted to English. Thirteen studies met the inclusion criteria: four cross-sectional, six prospective cohorts, two randomized controlled trials and one before/after study. These studies included a total of 13,104 participants, ≥50 years. The most common risk factors for falling were impaired balance, reduced walking velocity, peripheral neuropathy and comorbid conditions. However, lower extremity pain, being overweight and comorbid conditions had the greatest impact on fall risk. Interventions to reduce falling in older adults with type 2 diabetes mellitus should focus on reducing lower extremity pain, reducing body weight and managing comorbid conditions. Implications for Rehabilitation    Diabetes mellitus:   • Older adults with type 2 diabetes mellitus (DM2) have a higher risk for falling than older adults without.   • Older adults with DM2 are more likely to suffer serious injuries when they fall.   • Comprehensive risk factor identification is necessary for rehabilitation professionals to accurately determine whether their clients are at risk for falling.   • Rehabilitation professionals also need to tailor interventions based on the client's risk factors in order to effectively reduce falls and fall-related injuries.

  9. Factors of Formation of Various Types of Left Ventricular Diastolic Filling in Adolescents with Myocardium Pathology

    Directory of Open Access Journals (Sweden)

    L.F. Bogmat

    2016-08-01

    Full Text Available Objective: to study the main components of the formation of impaired left ventricular diastolic filling in adolescents with myocardial pathology. Materials and methods. The study involved 110 adolescents with myocardial pathology aged 13–18 years, of which 40 — with heart rhythm disorder, 40 — with dysplastic cardiomyopathy, 30 — with primary hypertension. Morphological and functional parameters of the heart were studied using ultrasound according to standard procedure. Left ventricular diastolic function has been studied in the pulsed wave Doppler mode with transmitral flow mapping from the apical access of four-chambered heart. For an adequate assessment of left ventricular diastolic function and detection of its earliest disorders, adolescents underwent tests with isometric exercise. Based on these results, adolescents were divided in terms of the E/A ratio. In order to identify common latent factors that explain the correlation between indicators, we have used the factor analysis, namely, the principal component analysis. All statistical procedures were performed using application packages Statgraphics Centurion. Results. On the initial stages of formation of diastolic dysfunction of the left ventricular myocardium in adolescents, a significant role is played by a number of factors, which can be conditionally defined as the geometric, functional and neurohumoral factors consistently included in the pathological process. Thus, during the formation of left ventricular diastolic dysfunction type 1, the number one is neurohumoral factor, namely, the activation of the sympathoadrenal system, then peripheral vascular tone is being involved in the pathological process, and, consequently, a geometric factor — changing the sizes of the left atrium. In the formation of left ventricular diastolic dysfunction type 2, the process consistently involves the renin-angiotensin system, namely, renin, a functional factor is presented by the indices

  10. The moderating effects of sample type as evidence of the effects of faking on personality scale correlations and factor structure

    Directory of Open Access Journals (Sweden)

    KEVIN M. BRADLEY

    2006-09-01

    Full Text Available Motivational differences as a function of sample type (applicants versus incumbents have frequently been suspected of causing meaningful differences in the psychometric properties of personality inventories due to the effects of faking. In this quantitative review, correlations among the Big Five personality constructs were estimated and sample type was examined as a potential moderator of the personality construct inter-correlations. The resulting subgroup meta-analytic correlation matrices were factor-analyzed, and the second order factor solutions for job incumbents and job applicants were compared. Results of the meta-analyses indicate frequent, but small moderating effects. The second order factor analyses indicated that the observed moderation had little effect on the congruence of factor loadings. Together, the results are consistent with the position that faking is of little practical consequence in selection settings.

  11. Cardiovascular risk factors and diseases precede oral hypoglycaemic therapy in patients with type 2 diabetes mellitus

    NARCIS (Netherlands)

    Erkens, JA; Herings, RMC; Stolk, RP; Spoelstra, JA; Grobbee, DE; Leufkens, HGM

    Although patients with type 2 diabetes mellitus and cardiovascular disease share common risk factors, the link between these diseases remains largely unexplained. In this case-control study, the earlier use of cardiovascular drugs (before the diagnosis of diabetes) was investigated among cases with

  12. Type 2 diabetes mellitus as a risk factor for the onset of depression

    DEFF Research Database (Denmark)

    Nouwen, Arie; Winkley, Kirsty; Twisk, Jos W R

    2010-01-01

    AIMS/HYPOTHESIS: An earlier meta-analysis showed that diabetes is a risk factor for the development and/or recurrence of depression. Yet whether this risk is different for studies using questionnaires than for those relying on diagnostic criteria for depression has not been examined. This study...... examined the association of diabetes and the onset of depression by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic. METHODS: EMBASE, MEDLINE and PsycInfo were searched for articles published up to September 2009. All studies that examined the relationship...... between type 2 diabetes and the onset of depression were included. Pooled relative risks were calculated using fixed and random effects models. RESULTS: Eleven studies met our inclusion criteria for this meta-analysis. Based on the pooled data, including 48,808 cases of type 2 diabetes without depression...

  13. Life Style Related Risk Factors of Type 2 Diabetes Mellitus and Its Increased Prevalence in Saudi Arabia: A Brief Review

    OpenAIRE

    Mohammad Fareed; Nasir Salam; Abdullah T Khoja; Mahmoud Abdulrahman Mahmoud; Maqusood Ahamed

    2017-01-01

    Aims: Role of life style related risk factors is very important in the pathogenesis and progression of Type 2 Diabetes Mellitus. The aim of this article is to review the disease burden of Type 2 diabetes mellitus (T2DM) among the population of Saudi Arabia due to unhealthy life style. Methods: In this review, the information was collected from published literatures related to risk factors like unhealthy dietary pattern and sedentary life style leading to T2DM. Additionally, some e...

  14. Risk factors for type 2 diabetes and cardiovascular disease in Mexican adult from different socio-economic levels. Highlights and achievements

    Energy Technology Data Exchange (ETDEWEB)

    Valencia Juillerat, M E [Centro de Investigacion en Alimentacion y Desarrollo (CIAD), Sonara (Mexico)

    2002-07-01

    Obesity, type 2 diabetes and cardiovascular disease (CVD) are a major concern in many parts of the world. In northern Mexico, these problems have been reported to be higher than in the rest of the country. To assess the different risk factors based on body status (body composition, body size, fat distribution) and lifestyle factors (diet and physical activity) for the development of type 2 diabetes and CVD in men and women from different socioeconomic levels in north-west Mexico.

  15. Risk factors for type 2 diabetes and cardiovascular disease in Mexican adult from different socio-economic levels. Highlights and achievements

    International Nuclear Information System (INIS)

    Valencia Juillerat, M.E.

    2002-01-01

    Obesity, type 2 diabetes and cardiovascular disease (CVD) are a major concern in many parts of the world. In northern Mexico, these problems have been reported to be higher than in the rest of the country. To assess the different risk factors based on body status (body composition, body size, fat distribution) and lifestyle factors (diet and physical activity) for the development of type 2 diabetes and CVD in men and women from different socioeconomic levels in north-west Mexico

  16. Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy

    DEFF Research Database (Denmark)

    Nguyen, T.Q.; Tarnow, L.; Jorsal, A.

    2008-01-01

    OBJECTIVE: We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF) in a prospective study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 198 type 1 diabetic patients with established diabetic nephropathy and 188 type 1 diabetic...

  17. Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy

    DEFF Research Database (Denmark)

    Nguyen, Tri Q; Tarnow, Lise; Jorsal, Anders

    2008-01-01

    OBJECTIVE: We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF) in a prospective study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 198 type 1 diabetic patients with established diabetic nephropathy and 188 type 1 diabetic pat...

  18. Contribution of modifiable risk factors for hypertension and type-2 diabetes in Peruvian resource-limited settings.

    Science.gov (United States)

    Bernabé-Ortiz, Antonio; Carrillo-Larco, Rodrigo M; Gilman, Robert H; Checkley, William; Smeeth, Liam; Miranda, J Jaime

    2016-01-01

    It is important to understand the local burden of non-communicable diseases including within-country heterogeneity. The aim of this study was to characterise hypertension and type-2 diabetes profiles across different Peruvian geographical settings emphasising the assessment of modifiable risk factors. Analysis of the CRONICAS Cohort Study baseline assessment was conducted. Cardiometabolic outcomes were blood pressure categories (hypertension, prehypertension, normal) and glucose metabolism disorder status (diabetes, prediabetes, normal). Exposures were study setting and six modifiable factors (smoking, alcohol drinking, leisure time and transport-related physical activity levels, TV watching, fruit/vegetables intake and obesity). Poisson regression models were used to report prevalence ratios (PR). Population attributable risks (PAR) were also estimated. Data from 3238 participants, 48.3% male, mean age 45.3 years, were analysed. Age-standardised (WHO population) prevalence of prehypertension and hypertension was 24% and 16%, whereas for prediabetes and type-2 diabetes it was 18% and 6%, respectively. Outcomes varied according to study setting (pdiabetes. PAR showed that obesity was an important determinant for hypertension (15.7%) and type-2 diabetes (23.9%). There is an evident heterogeneity in the prevalence of and risk factors for hypertension and diabetes within Peru. Prehypertension and prediabetes are highly prevalent across settings. Our results emphasise the need of understanding the epidemiology of cardiometabolic conditions to appropriately implement interventions to tackle the burden of non-communicable diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. The polymorphic integumentary mucin B.1 from Xenopus laevis contains the short consensus repeat.

    Science.gov (United States)

    Probst, J C; Hauser, F; Joba, W; Hoffmann, W

    1992-03-25

    The frog integumentary mucin B.1 (FIM-B.1), discovered by molecular cloning, contains a cysteine-rich C-terminal domain which is homologous with von Willebrand factor. With the help of the polymerase chain reaction, we now characterize a contiguous region 5' to the von Willebrand factor domain containing the short consensus repeat typical of many proteins from the complement system. Multiple transcripts have been cloned, which originate from a single animal and differ by a variable number of tandem repeats (rep-33 sequences). These different transcripts probably originate solely from two genes and are generated presumably by alternative splicing of an huge array of functional cassettes. This model is supported by analysis of genomic FIM-B.1 sequences from Xenopus laevis. Here, rep-33 sequences are arranged in an interrupted array of individual units. Additionally, results of Southern analysis revealed genetic polymorphism between different animals which is predicted to be within the tandem repeats. A first investigation of the predicted mucins with the help of a specific antibody against a synthetic peptide determined the molecular mass of FIM-B.1 to greater than 200 kDa. Here again, genetic polymorphism between different animals is detected.

  20. CLINICAL AND MORPHOLOGICAL RESEARCH INTO THE ROLE OF THE TRANSCRIPTION FACTOR NEUROD1 IN VARIOUS TYPES OF PITUITARY ADENOMAS

    Directory of Open Access Journals (Sweden)

    O. M. Raspopova

    2017-01-01

    Full Text Available The role of transcription factors in the pathogenesis of pituitary adenomas is extremely controversial.The aim of the study was to investigate the role of the transcription factor Neuro D1 in various types of pituitary adenomas.Materials and methods. A comparative clinico-morphological study was carried out with immunohistochemical analysis and confocal microscopy of the expression of the transcription factor NeuroD1, six adenohypophysis hormones and Ki-67 in 40 pituitary adenomas and 9 normal pituitary glands.Results. NeuroD1 was expressed in all cases and types of adenomas. The expression level of the transcription factor in adenomas was significantly different from that in the normal pituitary gland (p = 0.006. The average number of cells with expression of NeuroD1 in all tumors was higher than in the normal pituitary gland.Conclusion. NeuroD1 plays one of the key roles in the pathogenesis of pituitary adenomas, regardless of their hormonal status.

  1. Explaining the adjustment of adolescents with type 1 diabetes: Role of diabetes-specific and psychosocial factors

    NARCIS (Netherlands)

    Malik, J.A.; Koot, H.M.

    2009-01-01

    OBJECTIVE - The aim of this study was to explain adjustment (diabetes-related quality of life, general well-being, and psychopathology) in adolescents with type 1 diabetes by testing the direct, mediating, and moderating effects of diabetes-specific and psychosocial factors, using an adapted version

  2. Identification of rep-associated factors in herpes simplex virus type 1-induced adeno-associated virus type 2 replication compartments.

    Science.gov (United States)

    Nicolas, Armel; Alazard-Dany, Nathalie; Biollay, Coline; Arata, Loredana; Jolinon, Nelly; Kuhn, Lauriane; Ferro, Myriam; Weller, Sandra K; Epstein, Alberto L; Salvetti, Anna; Greco, Anna

    2010-09-01

    Adeno-associated virus (AAV) is a human parvovirus that replicates only in cells coinfected with a helper virus, such as adenovirus or herpes simplex virus type 1 (HSV-1). We previously showed that nine HSV-1 factors are able to support AAV rep gene expression and genome replication. To elucidate the strategy of AAV replication in the presence of HSV-1, we undertook a proteomic analysis of cellular and HSV-1 factors associated with Rep proteins and thus potentially recruited within AAV replication compartments (AAV RCs). This study resulted in the identification of approximately 60 cellular proteins, among which factors involved in DNA and RNA metabolism represented the largest functional categories. Validation analyses indicated that the cellular DNA replication enzymes RPA, RFC, and PCNA were recruited within HSV-1-induced AAV RCs. Polymerase delta was not identified but subsequently was shown to colocalize with Rep within AAV RCs even in the presence of the HSV-1 polymerase complex. In addition, we found that AAV replication is associated with the recruitment of components of the Mre11/Rad50/Nbs1 complex, Ku70 and -86, and the mismatch repair proteins MSH2, -3, and -6. Finally, several HSV-1 factors were also found to be associated with Rep, including UL12. We demonstrated for the first time that this protein plays a role during AAV replication by enhancing the resolution of AAV replicative forms and AAV particle production. Altogether, these analyses provide the basis to understand how AAV adapts its replication strategy to the nuclear environment induced by the helper virus.

  3. Are vaccine strain, type or administration protocol risk factors for canine parvovirus vaccine failure?

    Science.gov (United States)

    Altman, K D; Kelman, M; Ward, M P

    2017-10-01

    Canine parvovirus (CPV) is a highly contagious and worldwide cause of serious and often fatal disease in dogs, despite the widespread availability of vaccines. Which vaccine-related factors are associated with vaccination failure is largely unknown, and there are no reports from Australia. In this study - the first national population-level CPV study of its kind ever conducted - we analysed data on 594 cases of apparent CPV vaccination failure reported from an Australian national surveillance system to determine whether vaccine strain, type or administration protocol are risk factors for vaccination failures. The strain of CPV used in vaccine manufacture was not significantly associated with vaccination failure in clinical practice. The vaccine type (killed versus attenuated vaccine) for puppies diagnosed with CPV was associated with a lower mean age at time of vaccination (P=0.0495). The age at administration of the last CPV vaccination a puppy received prior to presenting with disease was a significant (P=0.0334) risk factor for vaccination failure, irrespective of whether the vaccine was marketed for a 10-week or 12-week or greater vaccination finish protocol. There was also a strong negative correlation between age at last vaccination prior to disease and vaccination failure (Pparvovirus vaccines, especially in outbreak situations. The large number of cases identified in this study confirms that CPV vaccination failure is occurring in Australia. Veterinarians should consider CPV as a differential diagnosis in cases with appropriate clinical presentation, regardless of the reported vaccination status of the dog. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Prolonged activated prothromboplastin time and breed specific variation in haemostatic analytes in healthy adult Bernese Mountain dogs

    DEFF Research Database (Denmark)

    Nielsen, Lise; Wiinberg, Bo; Kjelgaard-Hansen, Mads

    2011-01-01

    Coagulation tests are often performed in dogs suspected of haemostatic dysfunction and are interpreted according to validated laboratory reference intervals (RIs). Breed specific RIs for haematological and biochemical analytes have previously been identified in Bernese Mountain dogs, but it remains...... to be determined if breed specific RIs are necessary for haemostasis tests. Activated prothromboplastin time (aPTT), prothrombin time (PT), selected coagulation factors, D-dimers, fibrinogen, von Willebrand factor and thromboelastography (TEG) were analyzed in healthy Bernese Mountain dogs using the CLSI model...

  5. Cardiovascular Risk Factors and Distributions of the Ankle-Brachial Index among Type 2 Diabetes Mellitus Patients

    Directory of Open Access Journals (Sweden)

    Badaruddoza Doza

    2012-01-01

    Full Text Available Background. The aim of present study is to observe the association between the levels of ankle-brachial index (ABI and cardiovascular risk factors among people with type 2 diabetes mellitus in north India. A cross-sectional study was carried out at a centre for heart and diabetic clinic in the state of Punjab on 1121 subjects (671 males and 450 females with type 2 diabetes mellitus. History of symptoms related to cardiovascular diseases was noted, and blood pressure and anthropometric measurements were recorded. Ankle-brachial index (ABI was measured using ultrasonic Doppler flow detector. Subjects with ABI ≤0.9 and ≥1.30 were classified as having low and high ABI, respectively. Females had a higher BMI and brachial-ankle pulse wave velocity (<0.001. Whereas, males had higher diastolic blood pressure and duration of type 2 diabetes mellitus. The differences of systolic blood pressure and ankle-brachial index were not found significant between the sexes. The prevalence of low ABI (<0.9 was 4.47% in men and 4.67% in women and high ABI (≥1.30 was prevalent in 14% of men and 10.45% of women. Age, BMI, baPWV, and blood pressures were significantly associated with ABI value in both sexes. The results suggested that the ABI might be used as a strong indicator for cardiovascular risk factors in type 2 diabetic subjects.

  6. Risk factors for incident peripheral arterial disease in type 2 diabetes: results from the Bypass Angioplasty Revascularization Investigation in type 2 Diabetes (BARI 2D) Trial.

    Science.gov (United States)

    Althouse, Andrew D; Abbott, J Dawn; Forker, Alan D; Bertolet, Marnie; Barinas-Mitchell, Emma; Thurston, Rebecca C; Mulukutla, Suresh; Aboyans, Victor; Brooks, Maria Mori

    2014-01-01

    The aim of this article was to define risk factors for incidence of peripheral arterial disease (PAD) in a large cohort of patients with type 2 diabetes mellitus (T2DM), overall and within the context of differing glycemic control strategies. The Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) randomized controlled trial assigned participants to insulin-sensitizing (IS) therapy versus insulin-providing (IP) therapy. A total of 1,479 participants with normal ankle-brachial index (ABI) at study entry were eligible for analysis. PAD outcomes included new ABI ≤0.9 with decrease at least 0.1 from baseline, lower extremity revascularization, or lower extremity amputation. Baseline risk factors within the overall cohort and time-varying risk factors within each assigned glycemic control arm were assessed using Cox proportional hazards models. During an average 4.6 years of follow-up, 303 participants (20.5%) experienced an incident case of PAD. Age, sex, race, and baseline smoking status were all significantly associated with incident PAD in the BARI 2D cohort. Additional baseline risk factors included pulse pressure, HbA1c, and albumin-to-creatinine ratio (P < 0.05 for each). In stratified analyses of time-varying covariates, changes in BMI, LDL, HDL, systolic blood pressure, and pulse pressure were most predictive among IS patients, while change in HbA1c was most predictive among IP patients. Among patients with T2DM, traditional cardiovascular risk factors were the main predictors of incident PAD cases. Stratified analyses showed different risk factors were predictive for patients treated with IS medications versus those treated with IP medications.

  7. Genetic polymorphisms of hemostatic factors and thrombotic risk in non BCR-ABL myeloproliferative neoplasms: A pilot study

    Directory of Open Access Journals (Sweden)

    Dambrauskienė R

    2017-06-01

    Full Text Available The most important complications of Philadelphianegagive (non BCR-ABL myeloproliferative neoplasms (MPNs are vascular events. Our aim was to evaluate the effects of single nucleotide polymorphisms (SNPs, platelet glycoproteins (GPs (Ia/IIa, Ibα, IIb/IIIa and VI, von Willebrand factor (vWF, coagulation factor VII (FVII, β-fibrinogen, and the risk of thrombosis in patients with non BCR-ABL MPNs at the Lithuanian University of Health Sciences. Kaunas, Lithuania. Genotyping was done for 108 patients. The TT genotype of the GP Ia/IIa c.807C>T polymorphism was more frequently found in the group of MPN patients with arterial thrombosis compared to MPN patients who were thrombosis-free [26.5 vs. 11.5%, p = 0.049; odds ratio (OR 2.68; 95% confidence interval (95% CI 1.01-7.38]. The CT genotype of the β-fibrinogen c.-148C>T polymorphism occurred more frequently in MPN patients with arterial, and total thrombosis compared to the wild or homozygous genotype (57.7 vs. 40.0 vs. 12.5%; p = 0.027, (64.7 vs. 44.4 vs. 25%; p = 0.032, respectively. The carrier state for the c.-323P10 variant of FVII SNP (summation of P10/10 and P0/10 was more frequent in MPN patients with thrombosis compared to the wild-type genotype carriers (71.4 vs. 43.4%; p = 0.049; OR 3.26; 95% CI 1.01-11.31. The coexistence of heterozygous β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP, increased the risk of arterial thrombosis (21.1 vs. 3.7%, p = 0.008; OR 6.93; 95% CI 1.38-34.80. The TT genotype of GP Ia/IIa c.807C>T, the CT genotype of β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP could be associated with risk of thrombosis in MPN patients.

  8. [Variation characteristics and influencing factors of actual evapotranspiration under various vegetation types: A case study in the Huaihe River Basin, China.

    Science.gov (United States)

    Wu, Rong Jun; Xing, Xiao Yong

    2016-06-01

    The actual evapotranspiration was modelled utilizing the boreal ecosystem productivity simulator (BEPS) in Huaihe River Basin from 2001 to 2012. In the meantime, the quantitative analyses of the spatial-temporal variations of actual evapotranspiration characteristics and its influencing factors under different vegetation types were conducted. The results showed that annual evapotranspiration gradually decreased from southeast to northwest, tended to increase annually, and the monthly change for the average annual evapotranspiration was double-peak curve. The differences of evapotranspiration among vegetation types showed that the farmland was the largest contributor for the evapotranspiration of Huaihe Basin. The annual actual evapotranspiration of the mixed forest per unit area was the largest, and that of the bare ground per unit area was the smallest. The changed average annual evapotranspiration per unit area for various vegetation types indicated an increased tendency other than the bare ground, with a most significant increase trend for the evergreen broadleaf forest. The thermodynamic factors (such as average temperature) were the dominant factors affecting the actual evapotranspiration in the Huaihe Basin, followed by radiation and moisture factors.

  9. Regional metallogenic essential factor of granite-type uranium deposits in Guangdong province

    International Nuclear Information System (INIS)

    Pan Yongzheng

    1987-12-01

    The uranium origin, activation region, red basin, and fault depressed zone constitute the regional metallogenic essential factor of the four united like one granite-type uranium deposits in the post-Caledonian rise area in China. In the development of sub-geosyncline in the Caledonian, the clastic formation with widely deposited carbon, silicon, mud rich bearing organic matter, which drow a great amount of uranium formed the uranium-bearing system in the Sinian-Cambrian period. The magmagranite activation in a large scale in the Indosinian-Yenshanian period caused the continental crust to be suffered strong reformation and the uranium-bearing basement system to be eroded and remelted, and formed the rich uranium granite body. The multiple structure-magmatic movement further made the uranium in the rock body suffered the endogenic, structure, supergene active reformation, and produced mobile uranium concentrated area. Under the dry and hot paleoclimate condition in the Cretaceous-Tertiary period, strong weathering and hot water leaching forced uranium to be concentrated into the 'rock origin activation' type uranium deposits in the fault depressed zone

  10. Design-dependent gauge factors of highly doped n-type 4H-SiC piezoresistors

    International Nuclear Information System (INIS)

    Akiyama, T; Briand, D; De Rooij, N F

    2012-01-01

    This paper presents the experimentally obtained gauge factor (GF) of 4H-SiC piezoresistors, fabricated out of the n-type epitaxial layer and characterized on millimeter-size SiC cantilever beams at room temperature. It was found that the GF is dependent on the piezoresistor's length and width. Piezoresistors narrower than approximately 30 µm showed a width-dependent GF. The highest GF of 20.8 was obtained with a single element piezoresistor in transverse orientation. In longitudinal orientation, the highest GF was −10, which was obtained with a clustered piezoresistor with plural identical elements. Essential factors to consider for the design of optimum 4H-SiC piezoresistors for a Wheatstone bridge configuration are presented. (paper)

  11. Purification and characterization of factor VIII 1,689-Cys: a nonfunctional cofactor occurring in a patient with severe hemophilia A.

    Science.gov (United States)

    O'Brien, D P; Tuddenham, E G

    1989-06-01

    We have purified the factor VIII from a CRM+ Hemophilia A plasma (90 U/dL VIII:Ag but 0 U/dL VIII:C) and analyzed the protein before and after thrombin activation by Western blotting with monoclonal antibodies (MoAbs). Normal or patient citrated plasma was ultracentrifuged, cryo-ethanol-precipitated and chromatographed on Sepharose 6B. The void volume fractions were reduced and subjected to ion exchange chromatography yielding material of specific activity approximately 1,000 U/mg protein (VIII:C or VIII:Ag). Factor VIII purified in this way from normal plasma is fully activatable by thrombin with proteolytic fragmentation as previously described by F. Rotblat et al (Biochemistry 24: 4294, 1985). Factor VIII 1,689-Cys has the normal distribution of factor VIII light and heavy chains prior to thrombin activation. After exposure to thrombin the heavy chain polypeptides were fully proteolysed but the light chain was totally resistant to cleavage. This is consistent with the demonstration in the patient's leucocyte DNA of a C to T transition in codon 1,689 converting Arg to Cys at the light chain thrombin cleavage site as previously described by J. Gitschier et al (Blood 72:1022, 1988). Uncleaved light chain of Factor VIII 1,689-Cys is not released from von Willebrand factor (vWF) by thrombin, but this is not the sole cause of the functional defect since the protein purified free of vWF has no coagulant activity. We conclude that the functional defect in factor VIII 1,689-Cys is a consequence of failure to release the acidic peptide from the light chain upon thrombin activation.

  12. Maternal age at delivery and order of birth are risk factors for type 1 diabetes mellitus in Upper Silesia, Poland.

    Science.gov (United States)

    Polańska, Joanna; Jarosz-Chobot, Przemysława

    2006-04-01

    Parental age and birth order as risk factors for childhood type 1 diabetes mellitus were investigated using data from the Regional Diabetic Center for Upper Silesia, Poland, in a population-based study of 398 children with type 1 DM aged 0-14 years born between 1979-1996. Noting differences in the proportions of children of different birth order between cases and controls, the data were stratified by birth order. For each stratum, odds ratios and their 95% confidence intervals were calculated to assess risks related to the mother's age. The homogeneity of the odds ratios related to the mother's age between strata was evaluated by the Mantel-Haenszel method. Risks related to mother's age and birth order were also estimated jointly by multivariable logistic regression. Decreased risk in later children compared with firstborns was noted. Increased maternal age was found to be a risk factor for type 1 DM. An increase in the mother's age by one year increases the risk of the child being affected by type 1 DM 1.07 times, and children born as the nth in the family are 1.59 times less exposed to the same risk than those born as the (n-1)th. Children of different birth order have different risks of being affected by type 1 DM. Increased maternal age at the time of delivery is a risk factor for type 1 DM in Upper Silesia, Poland. To avoid bias in estimating risks, the mother's age and child's sequence number should be analyzed jointly.

  13. Cerebrovascular diseases in a fixed population Hiroshima and Nagasaki with special reference to relationship between type and risk factors

    International Nuclear Information System (INIS)

    Lin, Chow-How; Shimizu, Yukiko; Kato, Hiroo; Robertson, T.L.; Furonaka, Hiroshi.

    1980-10-01

    A study was made of the incidence of cerebrovascular diseases, their chronological trend, and relationship between the disease types and risk factors on 16,491 subjects of Hiroshima and Nagasaki who underwent medical examination at least once between 1958 - 74, and who were free of cerebrovascular disease at the initial examination. During the 16-year period, 1,162 cases of cerebrovascular disease developed in this study population with the diagnosis definite in 621, and the annual incidence was 3.2 per 1,000 population. By type, there were 108 cases of cerebral hemorrhage, 469 cases of cerebral infarction, 33 cases of subarachnoid hemorrhage, and 11 cases of other unclassifiable types, with cerebral infarction occurring more frequently than cerebral hemorrhage at the ratio of 4.5 : 1. The incidence of cerebrovascular diseases increased with age in both types, but the proportion of younger subjects in cerebral hemorrhage was greater than that in cerebral infarction. A secular trend of declining incidence was noted for both cerebral hemorrhage and cerebral infarction. As a risk factor of cerebral hemorrhage, elevation of systolic and diastolic blood pressure was the most closely related to onset, and left ventricular hypertrophy on electrocardiogram (ECG) and proteinuria were also related. However, a tendency was seen for the risk to be somewhat higher the lower the levels of serum cholesterol. In cerebral infarction, aging, like systolic blood pressure, was a most important risk factor. Left ventricular hypertrophy on ECG, proteinuria, and diabetes could also be risk factors. However, the relation to blood pressure, especially diastolic blood pressure, was not so great as in the case of cerebral hemorrhage. (author)

  14. A new method for high yield purification of type beta transforming growth factor from human platelets

    NARCIS (Netherlands)

    Eijnden-van Raaij, A.J.M. van den; Koornneef, I.; Zoelen, E.J.J. van

    1988-01-01

    A new method was developed for the purification of type beta transforming growth factor from human platelets. This method is a three-step procedure including gel filtration, weak cation exchange HPLC and reverse phase HPLC. All steps are carried out at low pH using exclusively volatile acidic buffer

  15. Transcription factor 7-like 2 gene links increased in vivo insulin synthesis to type 2 diabetes

    NARCIS (Netherlands)

    S. Jainandunsing (Sjaam); Koole, H.R. (H. Rita); van Miert, J.N.I. (Joram N.I.); T. Rietveld (Trinet); J.L.D. Wattimena (Josias); E.J.G. Sijbrands (Eric); F.W.M. de Rooij (Felix)

    2018-01-01

    textabstractTranscription factor 7-like 2 (TCF7L2) is the main susceptibility gene for type 2 diabetes, primarily through impairing the insulin secretion by pancreatic β cells. However, the exact in vivo mechanisms remain poorly understood. We performed a family study and determined if the T risk

  16. Transforming growth factor type β can act as a potent competence factor for AKR-2B cells

    International Nuclear Information System (INIS)

    Goustin, A.S.; Nuttall, G.A.; Leof, E.B.; Ranganathan, G.; Moses, H.L.

    1987-01-01

    Transforming growth factor type β (TGFβ) is a pleiotropic regulator of cell growth with specific high-affinity cell-surface receptors on a large number of cells; its mechanism of action, however, is poorly defined. In this report, the authors utilized the mouse fibroblast line AKR-2B to explore the question of the temporal requirements during the cell cycle in regard to both the growth inhibitory and the growth stimulatory action of TGFβ. The results indicate that AKR-2B cells are most sensitive to the inhibitory action of TGFβ during early to mid-G 1 . In addition, TGFβ need be present only briefly in order to exert its inhibitory effect on EGF-induced DNA synthesis. Likewise, the stimulatory effect of TGFβ in the absence of EGF requires only an equally brief exposure to TGFβ. Use of homogeneous 125 I-labeled TGFβ in a cell-binding assay demonstrates that TGFβ bound to cell-surface receptors can readily exchange into the culture medium, helping to rule out the possibility that persistent receptor-bound TGFβ is the source of a continuous stimulus. The data indicate that TGFβ exposure induces a stable state in the cell similar to but distinct from the state of competence induced by platelet-derived growth factor (PDGF)

  17. Body Mass Index: A Risk Factor for Retinopathy in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Snježana Kaštelan

    2013-01-01

    Full Text Available The aim of the study was to investigate whether body mass index (BMI independently or in correlation with other risk factors is associated with diabetic retinopathy (DR progression. The study included 545 patients with type 2 diabetes. According to DR status, they were divided into three groups: group 1 (no retinopathy; n=296, group 2 (mild/moderate nonproliferative DR; n=118, and group 3 (severe/very severe NPDR or proliferative DR; n=131. Patients without DR were younger than those with signs of retinopathy at time of diabetes onset whilst diabetes duration was longer in groups with severe NPDR and PDR. DR progression was correlated with diabetes duration, BMI, HbA1c, hypertension, and cholesterol. Statistical analyses showed that the progression of retinopathy increased significantly with higher BMI (gr. 1: 26.50 ± 2.70, gr. 2: 28.11 ± 3.00, gr. 3: 28.69 ± 2.50; P<0.01. We observed a significant deterioration of HbA1c and a significant increase in cholesterol and hypertension with an increase in BMI. Correlation between BMI and triglycerides was not significant. Thus, BMI in correlation with HbA1c cholesterol and hypertension appears to be associated with the progression of DR in type 2 diabetes and may serve as a predictive factor for the development of this important cause of visual loss in developed countries.

  18. Factors associated with initiation of antihyperglycaemic medication in UK patients with newly diagnosed type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Sinclair Alan J

    2012-03-01

    Full Text Available Abstract Aim To assess the factors associated with antihyperglycaemic medication initiation in UK patients with newly diagnosed type 2 diabetes. Methods In a retrospective cohort study, patients with newly diagnosed type 2 diabetes were identified during the index period of 2003-2005. Eligible patients were ≥ 30 years old at the date of the first observed diabetes diagnosis (referred to as index date and had at least 2 years of follow-up medical history (N = 9,158. Initiation of antihyperglycaemic medication (i.e., treatment was assessed in the 2-year period following the index date. Adjusted Cox regression models were used to examine the association between time to medication initiation and patient age and other factors. Results Mean (SD HbA1c at diagnosis was 8.1% (2.3. Overall, 51% of patients initiated antihyperglycaemic medication within 2 years (65%, 55%, 46% and 40% for patients in the 30- th, 75th percentile time to treatment initiation was 63 (8, 257 days. Of the patients with HbA1c ≥ 7.5% at diagnosis, 87% initiated treatment within 2 years. These patients with a higher HbA1c also had shorter time to treatment initiation (adjusted hazard ratio (HR = 2.44 [95% confidence interval (CI: 1.61, 3.70]; p Conclusions In this UK cohort of patients with newly diagnosed type 2 diabetes, only 51% had antihyperglycaemic medication initiated over a 2-year period following diagnosis. Older patients were significantly less likely to have been prescribed antihyperglycaemic medications. Elevated HbA1c was the strongest factor associated with initiating antihyperglycaemic medication in these patients.

  19. DMPD: Type I interferon [corrected] gene induction by the interferon regulatory factorfamily of transcription factors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16979567 Type I interferon [corrected] gene induction by the interferon regulatory factorfamily...ng) (.svg) (.html) (.csml) Show Type I interferon [corrected] gene induction by the interferon regulatory factorfamily...orrected] gene induction by the interferon regulatory factorfamily of transcription factors. Authors Honda K

  20. Effect of centrifugation time on growth factor and MMP release of an experimental platelet-rich fibrin-type product.

    Science.gov (United States)

    Eren, Gülnihal; Gürkan, Ali; Atmaca, Harika; Dönmez, Ayhan; Atilla, Gül

    2016-07-01

    Platelet-rich fibrin (PRF) has a controlled release of growth factors due to the fibrin matrix structure. Different centrifugation protocols were suggested for PRF preparation. Since the derivation method of PRF can alter its contents, in the present study it is aimed to investigate the cell contents and transforming growth factor beta-1 (TGF-β1), platelet-derived growth factor (PDGF-AB), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and-8 release from experimental PRF-type membranes obtained with different centrifugation times at 400 gravity. Three blood samples were collected from 20 healthy non-smoker volunteers. One tube was used for whole blood analyses. The other two tubes were centrifuged at 400 g for 10 minutes (group A) or 12 minutes (group B). Each experimental PRF-type membrane was placed in Dulbecco's Modified Eagle's Medium (DMEM)and at 1, 24 and 72 hours, TGF-β1, PDGF-AB, VEGF, MMP-1 and -8 release amounts were analysed by enzyme-linked immunosorbent assay (ELISA). The blood cell count of membranes was determined by subtracting plasma supernatant and red blood cell (RBC) mixture from the whole blood cell counts. At 72 hours, the VEGF level of group B was statistically higher than that of group A (p = 0.040). The centrifugation time was not found to influence the release of other growth factors, enzymes and cell counts. Within the limits of the present study, it might be suggested that centrifugation time at a constant gravity has a significant effect on the VEGF levels released from experimental PRF-type membrane. It can be concluded that due to the importance of VEGF in the tissue healing process, membranes obtained at 12-minute centrifugation time may show a superior potential in wound healing.

  1. Tumour type and size are high risk factors for the syndrome of "cerebellar" mutism and subsequent dysarthria

    NARCIS (Netherlands)

    C.E. Catsman-Berrevoets (Coriene); H.R. van Dongen (Hugo); D. Paz y Geuze (Daniel); P.F. Paquier; M.H. Lequin (Maarten); P.G.H. Mulder (Paul)

    1999-01-01

    textabstractOBJECTIVE: "Cerebellar mutis" and subsequent dysarthria (MSD) is a documented complication of posterior fossa surgery in children. In this prospective study the following risk factors for MSD were assessed: type, size and site of the tumour; hydrocephalus at

  2. Polycystic ovary syndrome: cardiovascular risk factors according to specific phenotypes.

    Science.gov (United States)

    Aziz, Mubeena; Sidelmann, Johannes J; Faber, Jens; Wissing, Marie-Louise M; Naver, Klara V; Mikkelsen, Anne-Lis; Nilas, Lisbeth; Skouby, Sven O

    2015-10-01

    Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance. The objective of this cross-sectional study was to investigate the impact of insulin resistance and body mass index (BMI) on inflammatory and hemostatic variables associated with long-term risk of cardiovascular disease in women with PCOS. 149 premenopausal women with PCOS were recruited consecutively from April 2010 to February 2012 at three Danish University Hospitals. The study was conducted at the Department of Gynecology and Obstetrics, Herlev University Hospital, Denmark. PCOS was diagnosed in accordance with the Rotterdam criteria and the women were classified into four phenotypes according to BMI and insulin resistance measured by the homeostasis model assessment of insulin resistance index. Body composition was determined by dual-energy X-ray absorptiometry. Main outcome measures were the biomarkers C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor antigen. Normal weight insulin-resistant PCOS women were characterized by abdominal obesity and elevated levels of plasma PAI-1. Overweight/obese insulin-resistant PCOS women had increased levels of both PAI-1 and CRP. Of the three Rotterdam criteria, only hyperandrogenemia was significantly associated with the hemostatic risk marker of long-term cardiovascular disease risk. Surrogate risk markers for cardiovascular disease are elevated in women with PCOS, especially insulin-resistant and overweight/obese women. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  3. Psychosocial factors impacting on life transitions among young adults with type 2 diabetes

    DEFF Research Database (Denmark)

    Rasmussen, B; Maindal, Helle Terkildsen; Livingston, P

    2016-01-01

    and Danish young adults with T2DM and to identify unmet support needs during life transitions. Method: A qualitative approach was adopted using thematic content analysis of 26 in-depth semi-structured interviews. An inductive descriptive content analysis was undertaken using a comparative coding system......Background: Type 2 diabetes (T2DM) prevalence is increasing rapidly worldwide with a significant increase in young adults. There is limited information about psychosocial and service needs of this group. Aim: To explore similarities and differences in how psychosocial factors impact on Australian...

  4. Factors associated with numbers of remaining teeth among type 2 diabetes: a cross-sectional study.

    Science.gov (United States)

    Huang, Jui-Chu; Peng, Yun-Shing; Fan, Jun-Yu; Jane, Sui-Whi; Tu, Liang-Tse; Chang, Chang-Cheng; Chen, Mei-Yen

    2013-07-01

    To explore the factors associated with the numbers of remaining teeth among type 2 diabetes community residents. Promoting oral health is an important nursing role for patients with diabetes, especially in disadvantaged areas. However, limited research has been carried out on the relationship between numbers of remaining teeth, diabetes-related biomarkers and personal oral hygiene among diabetic rural residents. A cross-sectional, descriptive design with a simple random sample was used. This study was part of a longitudinal cohort study of health promotion for preventing diabetic foot among rural community diabetic residents. It was carried out in 18 western coastal and inland districts of Chiayi County in central Taiwan. In total, 703 participants were enrolled in this study. The findings indicated that a high percentage of the participants (26%) had no remaining natural teeth. Nearly three quarters (74%) had fewer than 20 natural teeth. After controlling for the potential confounding factors, multivariate analysis demonstrated that the factors determining numbers of remaining teeth were age (p teeth were less tooth-brushing with dental floss, abnormal ankle brachial pressure and poor glycemic control. This study highlights the importance of nursing intervention in oral hygiene for patients with type 2 diabetes. It is necessary to initiate oral health promotion activities when diabetes is first diagnosed, especially for older diabetic residents of rural or coastal areas who are poorly educated. © 2013 John Wiley & Sons Ltd.

  5. Prevalence of cardiovascular risk factors in youth with type 1 diabetes and elevated body mass index.

    Science.gov (United States)

    Redondo, Maria J; Foster, Nicole C; Libman, Ingrid M; Mehta, Sanjeev N; Hathway, Joanne M; Bethin, Kathleen E; Nathan, Brandon M; Ecker, Michelle A; Shah, Avni C; DuBose, Stephanie N; Tamborlane, William V; Hoffman, Robert P; Wong, Jenise C; Maahs, David M; Beck, Roy W; DiMeglio, Linda A

    2016-04-01

    The prevalence of cardiovascular risk factors in children with type 1 diabetes and elevated BMI in the USA is poorly defined. We aimed to test the hypothesis that children with type 1 diabetes who are overweight or obese have increased frequencies of hypertension, dyslipidemia, and micro-/macroalbuminuria compared to their healthy weight peers. We studied 11,348 children 2 to 18 years of age enrolled in T1D Exchange between September 2010 and August 2012 with type 1 diabetes for ≥1 year and BMI ≥ 5th age-/sex-adjusted percentile (mean age 12 years, 49 % female, 78 % non-Hispanic White). Overweight and obesity were defined based on Centers for Disease Control and Prevention criteria. Diagnoses of hypertension, dyslipidemia, and micro-/macroalbuminuria were obtained from medical records. Logistic and linear regression models were used to assess factors associated with weight status. Of the 11,348 participants, 22 % were overweight and 14 % obese. Hypertension and dyslipidemia were diagnosed in 1.0 % and 3.8 % of participants, respectively; micro-/macroalbuminuria was diagnosed in 3.8 % of participants with available data (n = 7,401). The odds of either hypertension or dyslipidemia were higher in obese than healthy weight participants [OR 3.5, 99 % confidence interval (CI) 2.0-6.1 and 2.2, 99 % CI 1.6-3.1, respectively]. Obese participants tended to be diagnosed with micro-/macroalbuminuria less often than healthy weight participants (OR 0.6, 99 % CI 0.4-1.0). Obese children with type 1 diabetes have a higher prevalence of hypertension and dyslipidemia than healthy weight children with type 1 diabetes. The possible association of obesity with lower micro-/macroalbuminuria rates warrants further investigation.

  6. Alteraciones de la hemostasia en la diabetes mellitus Alterations of hemostasis in the diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Patricia Caunedo Almagro

    2005-04-01

    Full Text Available La diabetes mellitus (DM se clasifica en 2 tipos de acuerdo con su patogénesis: la tipo 1 representa menos del 10 % del total de pacientes, la DM tipo 2 es más común dentro de la población de pacientes diabéticos. Se han encontrado múltiples alteraciones de la hemostasia en los pacientes con este padecimiento. Estudios realizados en plaquetas, coagulación sanguínea y fibrinólisis han permitido asegurar que estos trastornos son posiblemente un factor importante en el estado pretrombótico que presentan estos enfermos. Las investigaciones en las plaquetas han demostrado una hiperreactividad plaquetaria, un aumento de la actividad procoagulante de las plaquetas. Por otra parte, la mayoría de los autores coinciden en la actualidad en que la DM es un estado de hipercoagulabilidad,lo cual se basa en numerosas investigaciones sobre la enfermedad y el mecanismo de la coagulación que demuestran el aumento del fibrinógeno, factor VII y factor von Willebrand, así como de los marcadores de activación de este sistema. Además, se han demostrado alteraciones en el sistema fibrinolítico, como el aumento del inhibidor del activador del plasminógeno y del inhibidor de la fibrinólisis activado por trombina. En este trabajo se presentan algunos mecanismos que pudieran explicar las alteraciones en la hemostasia que posiblemente contribuyan al desarrollo de complicaciones trombóticas que se presentan en estos pacientes.Diabetes mellitus is classified into 2 types according to its pathogenesis: type 1 accounts for less than 10 % of the total of patients, whereas type 2 is the most common in the population of diabetic patients. Multiple alterations of hemostasis have been found among the patients suffering from this disease. The studies conducted in platelets, blood coagulation and fibrinolysis have allowed to assert that these disorders are probably an important factor in the prethrombotic state of these patients. The investigations carried out with

  7. Comparing the demographic factors of patient with limited and diffuse type of alopecia areata

    Directory of Open Access Journals (Sweden)

    Mina Daliri

    2010-09-01

    Full Text Available Background: Alopecia areata is a chronic inflammatory disease that involves the hair follicle. Clinically, patients with alopecia areata may have patchy or confluent hair loss on the scalp or body so we conduct a study to compare the demographic aspects of patient with limited and diffuse type of alopecia areata.Materials and Method: We conducted a descriptive-analyzing study in which 306 patient were chosen. The patients were divided into two groups of diffuse and limited Alopecia. Demographic factors including age, gender, disease onset were compared in two groups. Results: Out of 306 patients, 58.8 % were male and 41.2 % were female. 247 patients (80.7% suffered from limited type and 59 patients (19.2% suffered from diffuse type. The mean age of the onset of involvement in limited group was 21.9±12 yr and 15.8±12 yr in diffuse group. The mean duration of involvement in limited group was 18.7 months and 71 months in diffuse group. Conclusion: Diffuse type alopecia areata starts at lower age and has longer duration. Our study results were similar to the others. Like other studies, thyroid disorders and atopic dermatitis are positively correlative to the severity of disease

  8. Autoantibodies against complement components in systemic lupus erythematosus - role in the pathogenesis and clinical manifestations.

    Science.gov (United States)

    Hristova, M H; Stoyanova, V S

    2017-12-01

    Many complement structures and a number of additional factors, i.e. autoantibodies, receptors, hormones and cytokines, are implicated in the complex pathogenesis of systemic lupus erythematosus. Genetic defects in the complement as well as functional deficiency due to antibodies against its components lead to different pathological conditions, usually clinically presented. Among them hypocomplementemic urticarial vasculitis, different types of glomerulonephritis as dense deposit disease, IgA nephropathy, atypical haemolytic uremic syndrome and lupus nephritis are very common. These antibodies cause conformational changes leading to pathological activation or inhibition of complement with organ damage and/or limited capacity of the immune system to clear immune complexes and apoptotic debris. Finally, we summarize the role of complement antibodies in the pathogenesis of systemic lupus erythematosus and discuss the mechanism of some related clinical conditions such as infections, thyroiditis, thrombosis, acquired von Willebrand disease, etc.

  9. von Willebrand Disease

    Science.gov (United States)

    ... results from a physical exam and tests. Medical History Your doctor will likely ask questions about your ... a medical center that specializes in high-risk obstetrics and has a hematologist on staff for prenatal ...

  10. [Hand eczema. The clinical classification of the roles of exogenous and endogenous factors in each type].

    Science.gov (United States)

    Tamiya, Y

    1994-08-01

    Hand eczema is one of the most common dermatological disorders. Although it is a general term referring to eczematous dermatitis of the hands, it actually covers a wide range of diseases. The classification of hand eczema is controversial even now, as definitions of individual diseases have not yet been established. It is well-known that exogenous factors, such as chemicals or water, are associated with the occurrence of hand eczema. In this study, we focused on endogenous factors, especially personal or family history of atopy as a causative factor in hand eczema. According to exogenous and endogenous factors, we classified hand eczema into three types: atopic dermatitis, contact dermatitis and dysidrosis. This classification is useful because it makes the definition of each disease clear. Skin-humidity and sebum measurement are simple and rapid methods of determining personal atopy, skin condition and the effect of treatment on hand eczema patients.

  11. Types of Obesity and Its Association with the Clustering of Cardiovascular Disease Risk Factors in Jilin Province of China

    OpenAIRE

    Zhang, Peng; Wang, Rui; Gao, Chunshi; Song, Yuanyuan; Lv, Xin; Jiang, Lingling; Yu, Yaqin; Wang, Yuhan; Li, Bo

    2016-01-01

    Cardiovascular disease (CVD) has become a serious public health problem in recent years in China. Aggregation of CVD risk factors in one individual increases the risk of CVD and the risk increases substantially with each additional risk factor. This study aims to explore the relationship between the number of clustered CVD risk factors and different types of obesity. A multistage stratified random cluster sampling design was used in this population-based cross-sectional study in 2012. Informa...

  12. Absence of transforming growth factor-beta type II receptor is associated with poorer prognosis in HER2-negative breast tumours

    DEFF Research Database (Denmark)

    Paiva, C E; Drigo, S A; Rosa, F E

    2010-01-01

    BACKGROUND: The clinical relevance of transforming growth factor-beta (TGF-beta)-signalling pathway in breast carcinomas (BCs) remained elusive. This study aimed to evaluate the prognostic value of TGF-beta1 and transforming growth factor-beta type II receptor (TGF-betaRII) expression levels in t...

  13. Traditional risk factors as determinants of heart rate recovery in patients with diabetes mellitus type 2 without known coronary artery disease

    Science.gov (United States)

    Silaban, Sanny; Afif Siregar, A.; Hasan, H.; Aryfa Andra, C.

    2018-03-01

    The impact of Traditional risk factors on heart rate recovery (HRR) has not been studied in patients Diabetes Mellitus type 2 without known coronary artery disease (CAD). For this reason, we sought to determine the association between HRR as cardiac autonomic dysfunction marker and traditonal risk factors. The study was conducted with a cross-sectional study involving 89 patients with Type 2 Diabetes Mellitus without known having coronary artery disease. The data was taken through anamnese and laboratory tests, and subjects who met the criteria were tested for a treadmill exercise to assess heart rate recovery in the first minute. In bivariate analysis Dyslipidemia, Hypertension, smoker, age, duration of DM≥ 5 years, HbA1C ≥7.5, Peak Heart rate, functional capacity and ST depression ischemic have an association with heart rate recovery. In multivariate analysis patients with hyper triglyceride, smoker, overweight, duration of diabetes ≥ five years and HbA1C ≥ 7,5 have lower heart rate recovery significantly. Traditional risk factors are determinant factors for heart rate recovery in patients with Diabetes Mellitus type 2 without known coronary artery disease.

  14. Trp[superscript 2313]-His[superscript 2315] of Factor VIII C2 Domain Is Involved in Membrane Binding Structure of a Complex Between the C[subscript 2] Domain and an Inhibitor of Membrane Binding

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhuo; Lin, Lin; Yuan, Cai; Nicolaes, Gerry A.F.; Chen, Liqing; Meehan, Edward J.; Furie, Bruce; Furie, Barbara; Huang, Mingdong (Harvard-Med); (UAH); (Maastricht); (Chinese Aca. Sci.)

    2010-11-03

    Factor VIII (FVIII) plays a critical role in blood coagulation by forming the tenase complex with factor IXa and calcium ions on a membrane surface containing negatively charged phospholipids. The tenase complex activates factor X during blood coagulation. The carboxyl-terminal C2 domain of FVIII is the main membrane-binding and von Willebrand factor-binding region of the protein. Mutations of FVIII cause hemophilia A, whereas elevation of FVIII activity is a risk factor for thromboembolic diseases. The C2 domain-membrane interaction has been proposed as a target of intervention for regulation of blood coagulation. A number of molecules that interrupt FVIII or factor V (FV) binding to cell membranes have been identified through high throughput screening or structure-based design. We report crystal structures of the FVIII C2 domain under three new crystallization conditions, and a high resolution (1.15 {angstrom}) crystal structure of the FVIII C2 domain bound to a small molecular inhibitor. The latter structure shows that the inhibitor binds to the surface of an exposed {beta}-strand of the C2 domain, Trp{sup 2313}-His{sup 2315}. This result indicates that the Trp{sup 2313}-His{sup 2315} segment is an important constituent of the membrane-binding motif and provides a model to understand the molecular mechanism of the C2 domain membrane interaction.

  15. Determining The Factors Affecting Fruit Hardness of Different Peach Types with Meta Analysis

    Directory of Open Access Journals (Sweden)

    Hande Küçükönder

    2014-09-01

    Full Text Available The aim of this study is to determine the factor effective in determining the hardness of Caterina, Suidring, Royal Glory and Tirrenia peach types using meta analysis. In the study, the impact force (Fi and the contact time (tc were detected and the impulse values (I that are expressed as independent variable in the area under the curve were calculated in the measurements performed using the technique of a low-mass lateral impactor multiplicated with peach. Using the theory of elasticity, the independent variables were determined as Fmax (maximum impact force, contact time (tmax, Fmax/tmax, 1/tmax, 1/tmax2,5, Fmax/tmax 1.25 and Fmax2.5 parameters. The correlation coefficient values showing the relationship between these parameters and the dependent variable Magness-Taylor force (MT were calculated and were combined with meta-analysis by using the Hunter-Schmid and Fisher’s Z methods. The Cohen’s classification criterion was used in evaluating the resulting mean effect size (combined correlation value and in determining its direction. As a result of the meta-analysis, the mean effect size according to Hunter-Schmid method was found 0.436 (0.371-0.497 positively directed in 95% confidence interval, while it was found 0.468 (0.390-0.545 according to Fisher’s Z method. The effect sizes in both methods were determined “mid-level” according to the Cohen’s classification. When the significance level of the studies was analyzed with the Z test, all of the ones that taken into the meta analysis has been found statistically significant. As a result of the meta analysis in this study evaluating the relationship of peach types with the fruit hardness, the mean effect size has been found to reach “strong level”. Consequently, “maximum shock acceleration” was found to be a more effective factor comparing to the other factors in determining the the fruit hardness according to the results of meta analysis applied in both methods.

  16. Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Jeong HR

    2015-11-01

    Full Text Available Hye Rin Jeong, Seong Soo A AnDepartment of Bionano Technology, Gachon Medical Research Institute, Gachon University, Gyeonggi-do, Republic of KoreaAbstract: Human islet amyloid polypeptide (h-IAPP is a peptide hormone that is synthesized and cosecreted with insulin from insulin-secreting pancreatic β-cells. Recently, h-IAPP was proposed to be the main component responsible for the cytotoxic pancreatic amyloid deposits in patients with type 2 diabetes mellitus (T2DM. Since the causative factors of IAPP (or amylin oligomer aggregation are not fully understood, this review will discuss the various forms of h-IAPP aggregation. Not all forms of IAPP aggregates trigger the destruction of β-cell function and loss of β-cell mass; however, toxic oligomers do trigger these events. Once these toxic oligomers form under abnormal metabolic conditions in T2DM, they can lead to cell disruption by inducing cell membrane destabilization. In this review, the various factors that have been shown to induce toxic IAPP oligomer formation will be presented, as well as the potential mechanism of oligomer and fibril formation from pro-IAPPs. Initially, pro-IAPPs undergo enzymatic reactions to produce the IAPP monomers, which can then develop into oligomers and fibrils. By this mechanism, toxic oligomers could be generated by diverse pathway components. Thus, the interconnections between factors that influence amyloid aggregation (eg, absence of PC2 enzyme, deamidation, reduction of disulfide bonds, environmental factors in the cell, genetic mutations, copper metal ions, and heparin will be presented. Hence, this review will aid in understanding the fundamental causative factors contributing to IAPP oligomer formation and support studies for investigating novel T2DM therapeutic approaches, such as the development of inhibitory agents for preventing oligomerization at the early stages of diabetic pathology.Keywords: amyloid aggregation, causative factor, IAPP, islet

  17. Insulin Promoter Factor 1 variation is associated with type 2 diabetes in African Americans

    Directory of Open Access Journals (Sweden)

    Wang Xiaoqin

    2005-10-01

    Full Text Available Abstract Background Defective insulin secretion is a key defect in the pathogenesis of type 2 diabetes (T2DM. The β-cell specific transcription factor, insulin promoter factor 1 gene (IPF1, is essential to pancreatic development and the maintenance of β-cell mass. We hypothesized that regulatory or coding variants in IPF1 contribute to defective insulin secretion and thus T2DM. Methods We screened 71 Caucasian and 69 African American individuals for genetic variants in the promoter region, three highly conserved upstream regulatory sequences (PH1, PH2 and PH3, the human β-cell specific enhancer, and the two exons with adjacent introns. We tested for an association of each variant with T2DM Caucasians (192 cases and 192 controls and African Americans (341 cases and 186 controls. Results We identified 8 variants in the two populations, including a 3 bp insertion in exon 2 (InsCCG243 in African Americans that resulted in an in-frame proline insertion in the transactivation domain. No variant was associated with T2DM in Caucasians, but polymorphisms at -3766 in the human β-cell enhancer, at -2877 bp in the PH1 domain, and at -108 bp in the promoter region were associated with T2DM in African American subjects (p Conculsion The common alleles of regulatory variants in the 5' enhancer and promoter regions of the IPF1 gene increase susceptibility to type 2 diabetes among African American individuals, likely as a result of gene-gene or gene-environment interactions. In contrast, IPF1 is not a cause of type 2 diabetes in Caucasians. A previously described InsCCG243 variant may contribute to diabetes susceptibility in African American individuals, but is of low penetrance.

  18. Influence of psychological factors on acute exacerbation of tension-type headache: Investigation by ecological momentary assessment.

    Science.gov (United States)

    Kikuchi, Hiroe; Yoshiuchi, Kazuhiro; Ando, Tetsuya; Yamamoto, Yoshiharu

    2015-09-01

    In this study, we investigated whether psychological factors were associated with subsequent acute exacerbation of tension-type headache (TTH) in a prospective and ecologically valid manner with computerized ecological momentary assessment. Eighteen women and five men with TTH wore watch-type computers that acted as an electronic diary for 1week. The subjects recorded momentary headache intensity, psychological stress, anxiety, and depressive mood with a visual analog scale of 0-100 approximately every 6h as well as when waking up, when going to bed, and at acute headache exacerbations. Multilevel logistic regression analysis with acute headache exacerbation occurrence as the outcome was conducted. Person-mean centering was applied to psychological factors to disaggregate between- and within-individual association. Momentary psychological stress was associated with subsequent increase in headache exacerbation within 3h [Odds Ratio (95% CI)=1.32 (1.07, 1.64) for 10-point increments] while the individual mean of psychological stress was not. These results support the possibility that psychological stress could trigger acute exacerbations of TTH. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Optimization of key factors of the electrostatic separation for crushed PCB wastes using roll-type separator

    International Nuclear Information System (INIS)

    Wu Jiang; Li Jia; Xu Zhenming

    2008-01-01

    For the electrostatic separation process, the separator is most crucial. As a classical one, the roll-type corona-electrostatic separator has some advantages in recycle of waste electrical and electronic equipment (WEEE). Some researches have been done in this field and shown that there was a complex correlation between its configuration and the efficiency of the separation. In this paper, a fractional factorial design (2 v 1-5 ) was built and 32 tests were performed on a roll-type corona-electrostatic separator. The sample of granular mixture got from crushed PCB wastes (size 0.3-0.45 mm, containing 25% metal and 75% nonmetal). The experimental data were discussed and used to analyze the factors' main effect, interaction and optimization of the process. Three liner-interaction mathematical models were derived to describe the mass of middling fraction (M), conductor fraction (C) and Nonconductor fraction (NC), respectively. The results show that the efficiency of the PCB waste electrostatic separation process has a significant correlation with not only factors' main effects, but also the interaction between them

  20. Patient and surgery related factors associated with fatigue type polyethylene wear on 49 PCA and DURACON retrievals at autopsy and revision

    Directory of Open Access Journals (Sweden)

    Ochsner Peter E

    2008-02-01

    Full Text Available Abstract Background Polyethylene wear is an important factor for longevity of total knee arthroplasty. Proven and suspicious factors causing wear can be grouped as material, patient and surgery related. There are more studies correlating design and/or biomaterial factors to in vivo wear than those to patient and surgery related factors. Many retrieval studies just include revision implants and therefore may not be representative. This study is aimed to correlate patient- and surgery- related factors to visual wear score by minimizing design influence and include both autopsy and revision implants. Comparison between the groups was expected to unmask patient and surgery-related factors responsible for wear. Methods The amount of joint side wear on polyethylene retrievals was measured using a modification of an established visual wear score. Fatigue type wear was defined as summation of the most severe wear modes of delamination, pitting and cracks. Analysis of patient and surgery related variables suspicious to cause wear included prospectively sampled patient activity which was measured by self reported walking capacity. Statistical analysis was done by univariate analysis of variance. Activity level and implantation time were merged to an index of use and correlated to the wear score. Results Wear score after comparable implantation time was significantly less in the autopsy group. Even so, fatigue type wear accounted for 84 and 93 % of total wear score on autopsy and revision implants respectively. A highly significant influence on wear score was found in time of implantation (p = 0.002, level of activity (p = 0.025 and inserts belonging to revision group (p = 0.006. No influence was found for the kind of patella replacement (p = 0.483. Body mass index and accuracy of component alignment had no significant influence on visual wear score. Fatigue-type wear in the medial compartment was closely correlated to the index of use in the autopsy (R2

  1. Trajectories of metabolic risk factors and biochemical markers prior to the onset of type 2 diabetes : the population-based longitudinal Doetinchem study

    NARCIS (Netherlands)

    Hulsegge, G; Spijkerman, A M W; van der Schouw, Y T; Bakker, Stephan J. L.; Gansevoort, R T; Smit, H A; Verschuren, W M M

    2017-01-01

    BACKGROUND: Risk factors often develop at young age and are maintained over time, but it is not fully understood how risk factors develop over time preceding type 2 diabetes. We examined how levels and trajectories of metabolic risk factors and biochemical markers prior to diagnosis differ between

  2. AN EPIDEMIOLOGICAL STUDY OF TYPE 2 DIABETES MELLITUS AND ITS RISK FACTORS IN RURAL AREA OF KATIHAR

    Directory of Open Access Journals (Sweden)

    Om Narayan Yadav

    2016-12-01

    Full Text Available BACKGROUND Type 2 diabetes mellitus is a chronic, debilitating disease characterised by insulin resistance, impaired insulin secretion and hyperglycaemia. It is the most prevalent metabolic condition and one amongst major health and socioeconomic problems worldwide. It represents more than 90% of total prevalence of diabetes in the world and is responsible for 9% of the global mortality corresponding to four million deaths per year. The aim of the study is to- 1. Determine the prevalence of diabetes mellitus type 2 in a rural population of age 30 years and above. 2. Study the association of various risk factors with diabetes mellitus type 2. MATERIALS AND METHODS A community-based cross-sectional study was carried out in population 30 years and above at Hazipur village in the district of Katihar in Bihar. During the study period of 1 st January to 31 st December 2015, in which 910 persons aged 30 years or more living in this village were included in study. RESULTS Total sample size in this study was 910 and out of this, 37 (4.06% were found to have type 2 diabetes mellitus. The prevalence of type 2 diabetes was 45.94% among sedentary and only 13.52% among heavy worker subjects. According to literacy of subjects, the prevalence among illiterate, primary, middle, secondary, higher secondary and above was 24.33%, 32.43%, 16.22%, 13.51% and 13.51%, respectively. Among vegetarians and non-vegetarians, the prevalence was 18.91% and 81.09%, respectively. Among subjects with type 2 DM, 54.06% were overweight and 72.97% were hypertensive. Smoking habit was found among 54.05% subjects. CONCLUSION This study shows that the prevalence of diabetes is high in the subjects having sedentary lifestyle, poor literacy status, overweight, non-vegetarians, hypertension and smoking habit. Control of type 2 diabetes mellitus mandates lifestyle modification and control of risk factors.

  3. Vitamin D deficiency: a new risk factor for type 2 diabetes?.

    Science.gov (United States)

    Mezza, T; Muscogiuri, G; Sorice, G P; Prioletta, A; Salomone, E; Pontecorvi, A; Giaccari, A

    2012-01-01

    Recent compelling evidence suggests a role of vitamin D deficiency in the pathogenesis of insulin resistance and insulin secretion derangements, with a consequent possible interference with type 2 diabetes mellitus. The mechanism of this link is incompletely understood. In fact, vitamin D deficiency is usually detected in obesity in which insulin resistance is also a common finding. The coexistence of insulin resistance and vitamin D deficiency has generated several hypotheses. Some cross-sectional and prospective studies have suggested that vitamin D deficiency may play a role in worsening insulin resistance; others have identified obesity as a risk factor predisposing individuals to exhibit both vitamin D deficiency and insulin resistance. The available data from intervention studies are largely confounded, and inadequate considerations of seasonal effects on 25(OH)D concentrations are also a common design flaw in many studies. On the contrary, there is strong evidence that obesity might cause both vitamin D deficiency and insulin resistance, leaving open the possibility that vitamin D and diabetes are not related at all. Although it might seem premature to draw firm conclusions on the role of vitamin D supplementation in reducing insulin resistance and preventing type 2 diabetes, this manuscript will review the circumstances leading to vitamin D deficiency and how such a deficiency can eventually independently affect insulin sensitivity. Copyright © 2012 S. Karger AG, Basel.

  4. Correction of X-ray diffraction profiles in linear-type PSPC by position factor

    International Nuclear Information System (INIS)

    Takahashi, Toshio

    1992-01-01

    PSPC (Position Sensitive Proportional Counter) makes it possible to obtain one-dimentional diffraction profiles without mechanical scanning. In a linear-type PSPC, the obtained profiles need correcting, because the position factor influences the intensity of the diffracted X-ray beam and the counting rate at each position on PSPC. The distances from the specimen are not the same at the center and at the edge of the detector, and the intensity decreases at the edge because of radiation and absorption. The counting rate varies with the incident angle of the diffracted beam at each position on PSPC. The position factor f i at channel i of the multichannel-analyser is given by f i = cos 4 α i ·exp{-μR(1/cosα i -1)} where R is the distance between the specimen and the center of PSPC, μ is the linear absorption coefficient and α i is the incident angle of the diffracted beam at channel i. The background profiles of silica gel powder were measured with CrKα and CuKα. The parameters of the model function were fitted to the profiles by the non-linear least squares method. The agreement between these parameters and the calculated values shows that the position factor can correct the measured profiles properly. (author)

  5. Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type 2 diabetes, cardiovascular diseases, and cancer

    DEFF Research Database (Denmark)

    Schwab, Ursula; Lauritzen, Lotte; Tholstrup, Tine

    2014-01-01

    of this systematic review (SR) was to assess the evidence of an effect of the amount and type of dietary fat on body weight (BW), risk factors, and risk of non-communicable diseases, that is, type 2 diabetes (T2DM), cardiovascular diseases (CVD), and cancer in healthy subjects or subjects at risk for these diseases...... suggestive. Evidence for a direct association between total fat intake and risk of T2DM was inconclusive, whereas there was limited-suggestive evidence from biomarker studies that LA is inversely associated with the risk of T2DM. However, there was limited-suggestive evidence in biomarker studies that odd......-chain SFA found in milk fat and fish may be inversely related to T2DM, but these associations have not been supported by controlled studies. The evidence for an association between dietary n-3 PUFA and T2DM was inconclusive. Evidence for effects of fat on major types of cancer was inconclusive regarding...

  6. Human Platelet Senescence Study.

    Science.gov (United States)

    1980-03-01

    ability to measure certain enzymes to their oxidation-reduc other enzymes which can be measured by o phosphatase , acid phosphatase , chymotryp...alkaline sin, trypsin, esterases (17)); M use of n A or wheat germ agglutinin in the second etect specific carbohydrate constituents. We have...Von Willebrand factor. Nurden and Caen also demonstrated that GPI was rich in sialic acid (5) and probably responsible for the platelets’ surface

  7. Dietary Adherence, Glycemic Control, and Psychological Factors Associated with Binge Eating Among Indigenous and Non-Indigenous Chileans with Type 2 Diabetes.

    Science.gov (United States)

    Herbozo, Sylvia; Flynn, Patricia M; Stevens, Serena D; Betancourt, Hector

    2015-12-01

    Despite the strong association between obesity and binge eating, limited research has examined the implications of binge eating on dietary adherence and psychological factors in ethnically diverse type 2 diabetes patients. This study investigated the prevalence of binge eating and its association with dietary adherence, glycemic control, and psychological factors among indigenous and non-indigenous type 2 diabetes patients in Chile. Participants were 387 indigenous (Mapuche) and non-indigenous (non-Mapuche) adults with type 2 diabetes. Self-report measures of binge eating, dietary adherence, diet self-efficacy, body image dissatisfaction, and psychological well-being were administered. Participants' weight, height, and glycemic control (HbA(1c)) were also obtained. Approximately 8 % of the type 2 diabetes patients reported binge eating. The prevalence among Mapuche patients was 4.9 %, and among non-Mapuche patients, it was 9.9 %. Compared to non-binge eaters, binge eating diabetes patients had greater body mass index values, consumed more high-fat foods, were less likely to adhere to their eating plan, and reported poorer body image and emotional well-being. Results of this study extend previous research by examining the co-occurrence of binge eating and type 2 diabetes as well as the associated dietary behaviors, glycemic control, and psychological factors among indigenous and non-indigenous patients in Chile. These findings may increase our understanding of the health challenges faced by indigenous populations from other countries and highlight the need for additional research that may inform interventions addressing binge eating in diverse patients with type 2 diabetes.

  8. Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis

    DEFF Research Database (Denmark)

    Knol, M J; Twisk, Jos W R; Beekman, Aartjan T F

    2006-01-01

    the latter association by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic. METHODS: Medline and PsycInfo were searched for articles published up to January 2005. All studies that examined the relationship between depression and the onset of type 2 diabetes were...... included. Pooled relative risks were calculated using fixed and random effects models. To explore sources of heterogeneity between studies, subgroup analyses and meta-regression analyses were performed. RESULTS: Nine studies met our inclusion criteria for this meta-analysis. The pooled relative risk was 1......AIMS/HYPOTHESIS: Evidence strongly suggests that depression and type 2 diabetes are associated, but the direction of the association is still unclear. Depression may occur as a consequence of having diabetes, but may also be a risk factor for the onset of type 2 diabetes. This study examined...

  9. Types and Factors Associated With Online Health Information Seeking Among College Men in Latino Fraternities: A Qualitative Study.

    Science.gov (United States)

    Chavarria, Enmanuel Antonio; Chaney, Elizabeth Hensleigh; Stellefson, Michael Leland; Chaney, J Don; Chavarria, Nikita; Dodd, Virginia Jones

    2017-11-01

    Despite the fact that a large percentage of Americans go online to seek health information, literature pertaining to online health information (OHI) seeking among college men in Latino fraternities (CMLF) has been nonexistent. Thus, the purpose of this study was to (a) identify the types of OHI that CMLF seek and (b) to determine the factors motivating OHI seeking among CMLF. Four 1- to 1.5-hour focus groups were conducted in two public universities in Florida with 41 college-aged Latino males in an established Latino fraternity. E-mails were used to recruit fraternity members. Qualitative analysis of the focus group transcripts identified that CMLF search for a variety of OHI types including searches on symptoms, diagnoses, weight loss, and treatments for conditions or diseases among other types of OHI. Factors motivating OHI seeking included informational needs of others and concerns for others, worries due to lack of health insurance, preoccupations with health condition, concerns over physical appearance, and clarification through social media. CMLF may be elicited to serve as information conduits to increase access to health information on chronic diseases for older non-English-speaking Latino adults. Lack of health insurance along with other factors in this segment of the population have led to self-diagnosis and self-treatment of illness. Thus, empirical research and health promotion on the potential risks due to self-diagnosing and self-treatment of illness is warranted among CMLF.

  10. Factors Associated with Utilization of Dipeptidyl-4 Inhibitors in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Retrospective Study

    Directory of Open Access Journals (Sweden)

    Hasniza Zaman Huri

    2014-01-01

    Full Text Available Dipeptidyl-4 (DPP-4 inhibitors are oral antidiabetic agents recently introduced to Malaysia. Thus, limited data is available on their utilization patterns and factors associated with their use. This study aims to analyse the utilization patterns of DPP-4 inhibitors, factors that influenced the choice of agent, and the rationale for treatment with DPP-4 inhibitors in patients with type 2 diabetes mellitus. This retrospective study was conducted to address the utilization pattern of DPP-4 inhibitors and factors that influence choice in type 2 diabetes mellitus patients. 299 subjects taking either sitagliptin or vildagliptin from September 2008 to September 2012 were included in the study. Sitagliptin was more frequently prescribed than vildagliptin. Of the patients prescribed DPP-4 inhibitors, 95% received combinations of these and other agents, whereas only 5% were prescribed DPP-4 inhibitors as monotherapy. Factors affecting the utilization of DPP-4 inhibitors included age (P=0.049 and concomitant use of beta blockers (P=0.045 and aspirin (P=0.008. Early identification of factors associated with DPP-4 inhibitors is essential to enhance quality use of the drugs.

  11. Factors associated with anxiety and depression among type 2 diabetes outpatients in Malaysia: a descriptive cross-sectional single-centre study

    OpenAIRE

    Ganasegeran, Kurubaran; Renganathan, Pukunan; Manaf, Rizal Abdul; Al-Dubai, Sami Abdo Radman

    2014-01-01

    Objective To determine the prevalence and factors associated with anxiety and depression among type 2 diabetes outpatients in Malaysia. Design Descriptive, cross-sectional single-centre study with universal sampling of all patients with type 2 diabetes. Setting Endocrinology clinic of medical outpatient department in a Malaysian public hospital. Participants All 169 patients with type 2 diabetes (men, n=99; women, n=70) aged between 18 and 90 years who acquired follow-up treatment from the en...

  12. Mortality in patients with acute aortic dissection type A: analysis of pre- and intraoperative risk factors from the German Registry for Acute Aortic Dissection Type A (GERAADA).

    Science.gov (United States)

    Conzelmann, Lars Oliver; Weigang, Ernst; Mehlhorn, Uwe; Abugameh, Ahmad; Hoffmann, Isabell; Blettner, Maria; Etz, Christian D; Czerny, Martin; Vahl, Christian F

    2016-02-01

    Acute aortic dissection type A (AADA) is an emergency with excessive mortality if surgery is delayed. Knowledge about independent predictors of mortality on surgically treated AADA patients is scarce. Therefore, this study was conducted to identify pre- and intraoperative risk factors for death. Between July 2006 and June 2010, 2137 surgically treated patients with AADA were enrolled in a multicentre, prospective German Registry for Acute Aortic Dissection type A (GERAADA), presenting perioperative status, operative strategies, postoperative outcomes and AADA-related risk factors for death. Multiple logistic regression analysis was performed to identify the influence of different parameters on 30-day mortality. Overall 30-day mortality (16.9%) increased with age [adjusted odds ratio (OR) = 1.121] and among patients who were comatose (adjusted OR = 3.501) or those who underwent cardiopulmonary resuscitation (adjusted OR = 3.751; all P risk for death was (adjusted OR for one organ = 1.651, two organs = 2.440, three organs or more = 3.393, P 0.1). No significant risk factors, but relevant increases in mortality, were determined in patients suffering from hemiparesis pre- and postoperatively (each P risk factors for death in AADA, influencing the outcome of surgically treated AADA patients. Comatose and resuscitated patients have the poorest outcome. Cannulation sites and operative techniques did not seem to affect mortality. Short operative times are associated with better outcomes. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  13. Risk Factors for Six Types of Disability among the Older People in Thailand in 2002, 2007, and 2011

    OpenAIRE

    Khongboon, Pattaraporn; Pongpanich, Sathirakorn; Chapman, Robert S.

    2016-01-01

    Background. There is an important need to characterize risk factors for disability in Thailand, in order to inform effective prevention and control strategies. This study investigated factors associated with risk of 6 types of disability in Thailand’s ageing population in 2002, 2007, and 2011. Methods. Data came from the Cross-Sectional National Surveys of Older Persons in Thailand conducted by the National Statistical Office (NSO) in 2002, 2007, and 2011. Stratified two-stage sampling was em...

  14. Randomized controlled trial of cholecalciferol supplementation in chronic kidney disease patients with hypovitaminosis D

    DEFF Research Database (Denmark)

    Marckmann, Peter; Agerskov, Hanne; Thineshkumar, Sasikala

    2012-01-01

    . Treatment consisted of 40 000 IU of cholecalciferol orally per week. Plasma 25-hydroxyvitamin D (25-OHD), plasma 1,25-dihydroxyvitamin D (1,25-diOHD), plasma parathyroid hormone (PTH), serum phosphate, ionized serum calcium and serum fibroblast growth factor 23 (FGF-23) were analysed. We also investigated...... biomarkers related to cardiovascular disease (plasma D-dimer, plasma fibrinogen, plasma von Willebrand factor antigen and activity, plasma interleukin 6, plasma C-reactive protein, blood pressure, aortic augmentation index, aortic pulse wave velocity and 24-h urinary protein loss). Objective and subjective...

  15. Changes in Fundus Autofluorescence after Anti-vascular Endothelial Growth Factor According to the Type of Choroidal Neovascularization in Age-related Macular Degeneration.

    Science.gov (United States)

    Lee, Ji Young; Chung, Hyewon; Kim, Hyung Chan

    2016-02-01

    To describe the changes of fundus autofluorescence (FAF) in patients with age-related macular degeneration before and after intravitreal injection of anti-vascular endothelial growth factor according to the type of choroidal neovascularization (CNV) and to evaluate the correlation of FAF with spectral domain optical coherence tomography (SD-OCT) parameters and vision. This was a retrospective study. Twenty-one treatment-naïve patients with neovascular age-related macular degeneration were included. Study eyes were divided into two groups according to the type of CNV. Fourteen eyes were type 1 CNV and seven eyes were type 2 CNV. All eyes underwent a complete ophthalmologic examination, including an assessment of best-corrected visual acuity, SD-OCT, fluorescein angiography, and FAF imaging, before and 3 months after intravitreal anti-vascular endothelial growth factor injection. Gray scales of FAF image for CNV areas, delineated as in fluorescein angiography, were analyzed using the ImageJ program, which were adjusted by comparison with normal background areas. Correlation of changes in FAF with changes in SD-OCT parameters, including CNV thickness, photoreceptor inner and outer segment junction disruption length, external limiting membrane disruption length, central macular thickness, subretinal fluid, and intraretinal fluid were analyzed. Eyes with both type 1 and type 2 CNV showed reduced FAF before treatment. The mean gray scales (%) of type 1 and type 2 CNV were 52.20% and 42.55%, respectively. The background values were 106.72 and 96.86. After treatment, the mean gray scales (%) of type 1 CNV and type 2 CNV were changed to 57.61% (p = 0.005) and 57.93% (p = 0.008), respectively. After treatment, CNV thickness, central macular thickness, and inner and outer segment junction disruption length were decreased while FAF increased. FAF was noted to be reduced in eyes with newly diagnosed wet age-related macular degeneration, but increased after anti

  16. Upstream transcription factor 1 (USF1) in risk of type 2 diabetes: association study in 2000 Dutch Caucasians

    NARCIS (Netherlands)

    Meex, S.J.; Vliet-Ostaptchouk, J.V.; Kallen, van der C.J.H.; Greevenbroek, M.M.; Schalkwijk, C.G.; Feskens, E.J.M.; Blaak, E.E.; Wijmenga, C.; Hofker, M.H.; Stehouwer, C.D.; Bruin, T.W.

    2008-01-01

    Type 2 diabetes shares substantial genetic and phenotypic overlap with familial combined hyperlipidemia. Upstream stimulatory factor 1 (USF1), a well-established susceptibility gene for familial combined hyperlipidemia, is postulated to be such a shared genetic determinant. We evaluated two

  17. Evaluation of Acute Aortic Dissection Type a Factors and Comparison the Postoperative Clinical Outcomes between Two Surgical Methods.

    Science.gov (United States)

    Shemirani, Hasan; Mirmohamadsadeghi, Amir; Mahaki, Behzad; Farhadi, Sadaf; Badalabadi, Reza Mohseni; Bidram, Peyman; Badalabadi, Mehdi Mohseni

    2017-01-01

    Although aortic dissection is a rare disease, it causes high level of mortality. If ascending aorta gets involved in this disease, it is known as type A. According to small number of studies about this disease in Iran, this study conducted to detect the factors related to acute aortic dissection type A, its surgery consequences and the factors affecting them. In this historical cohort study, all patients having acute aortic dissection type A referring to Chamran Hospital from 2006 to 2012 were studied. The impact of two surgical methods including antegrade cerebral perfusion (ACP) and retrograde cerebral one (RCP) on surgical and long-term mortality and recurrence of dissection was determined. The relation of mortality rate and hemodynamic instability before surgery, age more than 70 years old, ejection fraction lower than 50%, prolonged cardiopulmonary bypass pump (CPBP) time and excessive blood transfusion, was assessed. Surgery and long-term mortality and recurrence of dissection were 35.3%, 30.8% and 30.4%. Surgical and long-term death in the patients being operated by ACP method was lower than those one being operated by RCP ( P RCP according to the surgical and long-term mortality.

  18. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer - correlation with traditional prognostic factors

    International Nuclear Information System (INIS)

    Lampelj, Maja; Arko, Darja; Cas-Sikosek, Nina; Kavalar, Rajko; Ravnik, Maja; Jezersek-Novakovic, Barbara; Dobnik, Sarah; Dovnik, Nina Fokter; Takac, Iztok

    2015-01-01

    Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients. 606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman’s rank correlation, Mann Whitney U test and χ 2 test for statistical analysis. Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002). Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated

  19. Ownership type and team climate in elderly care facilities: the moderating effect of stress factors.

    Science.gov (United States)

    Heponiemi, Tarja; Elovainio, Marko; Kouvonen, Anne; Noro, Anja; Finne-Soveri, Harriet; Sinervo, Timo

    2012-03-01

    This paper is a report of a study examining the association between ownership type and perceived team climate among older people care staff. In addition, we examined whether work stress factors (time pressure, resident-related stress, role conflicts and role ambiguity) mediated or moderated the above mentioned association. There has been a trend towards contracting out in older people care facilities in Finland and the number of private for-profit firms has increased. Studies suggest that there may be differences in employee well-being and quality of care according to the ownership type of older people care. Cross-sectional survey data was collected during the autumn of 2007 from 1084 Finnish female older people care staff aged 18-69 years were used. Team Climate Inventory was used to measure team climate. Ownership type was divided into four categories: for-profit sheltered homes, not-for-profit sheltered homes, public sheltered homes and not-for-profit nursing homes. Analyses of covariance were used to examine the associations. Team climate dimensions participative safety, vision and support for innovation were higher in not-for-profit organizations (both sheltered homes and nursing homes) compared to for-profit sheltered homes and public sheltered homes. Stress factors did not account for these associations but acted as moderators in a way that in terms of task orientation and participative safety employees working in for-profit organizations seemed to be slightly more sensitive to work-related stress than others. Our results suggest that for-profit organizations and public organizations may have difficulties in maintaining their team climate. In consequence, these organizations should focus more effort on improving their team climate. © 2011 Blackwell Publishing Ltd.

  20. Prevalence of Non-Volitional Sex Types and Associated Factors: A National Sample of Young People.

    Directory of Open Access Journals (Sweden)

    Nicole H T M Dukers-Muijrers

    Full Text Available Non-volitional sex (NVS in young people continues to be a major public health problem with long-term negative health outcomes. For the first time, the prevalence of different types of NVS and associated factors are compared between young people with same-sex sexual activities and those who have not.We obtained data from 10,401 young women and men (aged 12 to 25 years who participated in a population study on sexual health, the Netherlands. We calculated and compared the prevalence of six types of NVS between women who had sex with men (yWSM or women (yWSW, and men who had sex with women (yMSW or men (yMSM. In sexually experienced participants (n = 5986 logistic regression analyses were applied to assess associations with NVS by assault or penetration. Analyses were weighted to represent the Dutch population.The prevalence of NVS ranged from 1% to 61%, depending on type. Prevalence was higher for young women (any: 40.6% than men (any: 20.4%, and highest for yMSM and yWSW. Prevalence of NVS by assault or penetration was related to a range of socio-demographic, behavioral and social factors, which were largely similar regardless of sex or same-sex-experiences. The NVS perpetrators were in over 70% of cases known to the victim; 1 in 4 cases of NVS by penetration were accompanied by violence.A substantial proportion of young people in the Netherlands have experienced NVS. Medical professionals, educators and caregivers should integrate services to continue to address NVS by targeting young people's multifaceted risk profiles and evidenced based interventions for doing so are needed.

  1. Changes of plasma angiogenic factors during chronic resistance exercise in type 1 diabetic rats

    International Nuclear Information System (INIS)

    Esfahani, S.P.; Gharakhanlou, R.

    2012-01-01

    Objective: Exercise has several beneficial effects on cardiovascular system. However, the exact mechanism is unclear. The purpose of this study was to evaluate the effects of chronic resistance exercise on some plasma angiogenic factors in type 1 diabetic rats. Methodology: Thirty male Wistar rats were divided into three groups of control, diabetic and diabetic trained (n = 10 each). Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg). The rats in the trained group undertook one training session per day, 3 days/week, for 4 weeks. Blood samples were taken and the concentrations of plasma glucose, lipid profile, nitric oxide (NO), vascular endothelial growth factor (VEGF) and soluble form of VEGF receptor-1 (sFlt-1) were determined. Results: We found a significant reduction in plasma NO concentrations in diabetic rats compared to the controls (p 0.05). There were no significant differences in plasma VEGF and sFlt-1 concentrations between diabetic sedentary and trained groups (p > 0.05). Moreover, VEGF/sFlt-1 ratios in diabetic animals were lower than the control group and resistance exercise could not increase this ratio in diabetic animals (p > 0.05) Conclusion: Resistance exercise could not change plasma VEGF, sFlt-1 and VEGF/sFlt-1 ratio. However, it increased plasma NO concentrations in diabetic animals. More studies are needed to determine the effects of this type of exercise on the angiogenesis process. (author)

  2. Prevalence of nucleic acid sequences specific for human parvoviruses, hepatitis A and hepatitis E viruses in coagulation factor concentrates.

    Science.gov (United States)

    Modrow, S; Wenzel, J J; Schimanski, S; Schwarzbeck, J; Rothe, U; Oldenburg, J; Jilg, W; Eis-Hübinger, A M

    2011-05-01

    Due to their high resistance to inactivation procedures, nonenveloped viruses such as parvovirus B19, human bocavirus (HBoV), human parvovirus 4 (PARV4), hepatitis A (HAV) and hepatitis E virus (HEV) pose a particular threat to blood products. Virus transmission to patients treated with blood products presents an additional burden to disease. We determined the frequency and the amount of nucleic acid specific for nonenveloped viruses in recently manufactured preparations of commercial coagulation factor concentrates. At least three different batches of each of 13 different plasma-derived and recombinant coagulation factor products were tested for the presence and the amount of nucleic acid for parvovirus B19, HBoV, human parvovirus 4, hepatitis A virus and HEV by using quantitative polymerase chain reaction. Whereas none of the recombinant products tested positive for any of these viruses, parvovirus B19 DNA with amounts ranging between 2×10(1) and 1.3×10(3) genome equivalents/ml was detected in five plasma-derived products. In addition to parvovirus B19 genotype 1, genotypes 2 and 3 were observed in two batches of a factor VIII/von-Willebrand factor product. In two products (one factor VIII concentrate and one activated prothrombin complex concentrate), a combination of both genotypes 1 and 2 of parvovirus B19 was detected. The data show that nucleic acids from several relevant nonenveloped viruses are not found at detectable levels in coagulation factor concentrates. In some cases, parvovirus B19 DNA was detectable at low levels. Testing of the plasma pools for the full range of parvovirus genotypes is advocated for ensuring product safety. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

  3. Deficient leukemia inhibitory factor signaling in muscle precursor cells from patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Broholm, Christa; Brandt, Claus; Schultz, Ninna S

    2012-01-01

    The cytokine leukemia-inhibitory factor (LIF) is expressed by skeletal muscle and induces proliferation of muscle precursor cells, an important feature of skeletal muscle maintenance and repair. We hypothesized that muscle precursor cells from patients with type 2 diabetes had a deficient response...... nor proliferation rate was affected. In conclusion, although LIF and LIFR proteins were increased in muscle tissue and myoblasts from diabetic patients, LIF signaling and LIF-stimulated cell proliferation were impaired in diabetic myoblasts, suggesting a novel mechanism by which muscle function......RNA knockdown of suppressor of cytokine signaling (SOCS)3 in myoblast cultures established from healthy individuals and patients with type 2 diabetes. Myoblast proliferation rate was assessed by bromodeoxyuridine incorporation. LIF and LIFR proteins were increased in both muscle tissue and cultured myoblasts...

  4. Factors associated to the imposition of types of violence against women informed in sentry services

    Directory of Open Access Journals (Sweden)

    Luiza Jane Eyre de Souza Vieira

    2013-07-01

    Full Text Available OBJECTIVE: to identify the prevalence and the factors associated to the imposition of the different types of violence against women informed in sentry services. METHOD: transversal study accomplished through 939 notification forms of cases of violence against women, referring to the three years from 2006 to 2008 in Fortaleza, Ceará. Univariate and multiple analyses by logistic regression were realized. RESULT: the results showed a positive association between the imposition of types of violence against women with a schooling varying from illiterate to basic education and the aggression which had occurred other times. CONCLUSION: this knowledge contributes to the delineation of specific actions that aim at facing this problem, as well as generates subsidies for adequate attendance proposals and guidance for the victims who call on health services.

  5. A Practical and Time-Efficient High-Intensity Interval Training Program Modifies Cardio-Metabolic Risk Factors in Adults with Risk Factors for Type II Diabetes

    Directory of Open Access Journals (Sweden)

    Bethan E. Phillips

    2017-09-01

    Full Text Available IntroductionRegular physical activity (PA can reduce the risk of developing type 2 diabetes, but adherence to time-orientated (150 min week−1 or more PA guidelines is very poor. A practical and time-efficient PA regime that was equally efficacious at controlling risk factors for cardio-metabolic disease is one solution to this problem. Herein, we evaluate a new time-efficient and genuinely practical high-intensity interval training (HIT protocol in men and women with pre-existing risk factors for type 2 diabetes.Materials and methodsOne hundred eighty-nine sedentary women (n = 101 and men (n = 88 with impaired glucose tolerance and/or a body mass index >27 kg m−2 [mean (range age: 36 (18–53 years] participated in this multi-center study. Each completed a fully supervised 6-week HIT protocol at work-loads equivalent to ~100 or ~125% V˙O2 max. Change in V˙O2 max was used to monitor protocol efficacy, while Actiheart™ monitors were used to determine PA during four, weeklong, periods. Mean arterial (blood pressure (MAP and fasting insulin resistance [homeostatic model assessment (HOMA-IR] represent key health biomarker outcomes.ResultsThe higher intensity bouts (~125% V˙O2 max used during a 5-by-1 min HIT protocol resulted in a robust increase in V˙O2 max (136 participants, +10.0%, p < 0.001; large size effect. 5-by-1 HIT reduced MAP (~3%; p < 0.001 and HOMA-IR (~16%; p < 0.01. Physiological responses were similar in men and women while a sizeable proportion of the training-induced changes in V˙O2 max, MAP, and HOMA-IR was retained 3 weeks after cessation of training. The supervised HIT sessions accounted for the entire quantifiable increase in PA, and this equated to 400 metabolic equivalent (MET min week−1. Meta-analysis indicated that 5-by-1 HIT matched the efficacy and variability of a time-consuming 30-week PA program on V˙O2 max, MAP, and HOMA-IR.ConclusionWith a total time-commitment of

  6. Does high sugar consumption exacerbate cardiometabolic risk factors and increase the risk of type 2 diabetes and cardiovascular disease?

    Directory of Open Access Journals (Sweden)

    David E. Laaksonen

    2012-07-01

    Full Text Available Consumption of sugar has been relatively high in the Nordic countries; the impact of sugar intake on metabolic risk factors and related diseases has been debated. The objectives were to assess the effect of sugar intake (sugar-sweetened beverages, sucrose and fructose on association with type 2 diabetes, cardiovascular disease and related metabolic risk factors (impaired glucose tolerance, insulin sensitivity, dyslipidemia, blood pressure, uric acid, inflammation markers, and on all-cause mortality, through a systematic review of prospective cohort studies and randomised controlled intervention studies published between January 2000 and search dates. The methods adopted were as follows: the first search was run in PubMed in October 2010. A second search with uric acid as risk marker was run in April 2011. The total search strategy was rerun in April 2011 in SveMed+. An update was run in PubMed in January 2012. Two authors independently selected studies for inclusion from the 2,743 abstracts according to predefined eligibility criteria. The outcome was that out of the 17 studies extracted, 15 were prospective cohort studies and two were randomised controlled crossover trials. All of the studies included only adults. With respect to incident type 2 diabetes (nine studies, four of six prospective cohort studies found a significant positive association for sugar-sweetened beverage intake. In general, larger cohort studies with longer follow-up more often reported positive associations, and BMI seemed to mediate part of the increased risk. For other metabolic or cardiovascular risk factors or outcomes, too few studies have been published to draw conclusions. In conclusion, data from prospective cohort studies published in the years 2000–2011 suggest that sugar-sweetened beverages probably increase the risk of type 2 diabetes. For related metabolic risk factors, cardiovascular disease or all-cause mortality and other types of sugars, too few studies

  7. Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Tanaka, Hiroyuki; Takano, Kazuhiko; Iijima, Hiroaki; Kubo, Hajime; Maruyama, Nobuko; Hashimoto, Toshio; Arakawa, Kenji; Togo, Masanori; Inagaki, Nobuya; Kaku, Kohei

    2017-02-01

    Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients. Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days. Blood and urine samples were collected at predetermined time points. The primary endpoint was evaluation of correlations between changes from baseline in urine volume and factors that are known to affect urine volume and between actual urine volume and these factors. Canagliflozin transiently increased urine volume and urinary sodium excretion on Day 1 with a return to baseline levels thereafter. Canagliflozin administration increased urinary glucose excretion, which was sustained during repeated-dose administration. Plasma atrial natriuretic peptide (ANP) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels decreased, while plasma renin activity increased. On Day 1 of treatment, changes in sodium and potassium excretion were closely correlated with changes in urine output. A post hoc multiple regression analysis showed changes in sodium excretion and water intake as factors that affected urine volume change at Day 1. Furthermore, relative to that at baseline, canagliflozin decreased blood glucose throughout the day and increased plasma total GLP-1 after breakfast. Canagliflozin induced transient sodium excretion and did not induce water intake at Day 1; hence, natriuresis rather than glucose-induced osmotic diuresis may be a major factor involved in the canagliflozin-induced transient increase in urine output. In addition, canagliflozin decreased plasma ANP and NT-proBNP levels and

  8. The nuclear factor-erythroid 2-related factor/heme oxygenase-1 axis is critical for the inflammatory features of type 2 diabetes-associated osteoarthritis.

    Science.gov (United States)

    Vaamonde-Garcia, Carlos; Courties, Alice; Pigenet, Audrey; Laiguillon, Marie-Charlotte; Sautet, Alain; Houard, Xavier; Kerdine-Römer, Saadia; Meijide, Rosa; Berenbaum, Francis; Sellam, Jérémie

    2017-09-01

    Epidemiological findings support the hypothesis that type 2 diabetes mellitus (T2DM) is a risk factor for osteoarthritis (OA). Moreover, OA cartilage from patients with T2DM exhibits a greater response to inflammatory stress, but the molecular mechanism is unclear. To investigate whether the antioxidant defense system participates in this response, we examined here the expression of nuclear factor-erythroid 2-related factor (Nrf-2), a master antioxidant transcription factor, and of heme oxygenase-1 (HO-1), one of its main target genes, in OA cartilage from T2DM and non-T2DM patients as well as in murine chondrocytes exposed to high glucose (HG). Ex vivo experiments indicated that Nrf-2 and HO-1 expression is reduced in T2DM versus non-T2DM OA cartilage (0.57-fold Nrf-2 and 0.34-fold HO-1), and prostaglandin E 2 (PGE 2 ) release was increased in samples with low HO-1 expression. HG-exposed, IL-1β-stimulated chondrocytes had lower Nrf-2 levels in vitro , particularly in the nuclear fraction, than chondrocytes exposed to normal glucose (NG). Accordingly, HO-1 levels were also decreased (0.49-fold) in these cells. The HO-1 inducer cobalt protoporphyrin IX more efficiently attenuated PGE 2 and IL-6 release in HG+IL-1β-treated cells than in NG+IL-1β-treated cells. Greater reductions in HO-1 expression and increase in PGE 2 /IL-6 production were observed in HG+IL-1β-stimulated chondrocytes from Nrf-2 -/- mice than in chondrocytes from wild-type mice. We conclude that the Nrf-2/HO-1 axis is a critical pathway in the hyperglucidic-mediated dysregulation of chondrocytes. Impairments in this antioxidant system may explain the greater inflammatory responsiveness of OA cartilage from T2DM patients and may inform treatments of such patients. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Nutritional factors and preservation of C-peptide in youth with recently diagnosed type 1 diabetes: SEARCH Nutrition Ancillary Study.

    Science.gov (United States)

    Mayer-Davis, Elizabeth J; Dabelea, Dana; Crandell, Jamie L; Crume, Tessa; D'Agostino, Ralph B; Dolan, Lawrence; King, Irena B; Lawrence, Jean M; Norris, Jill M; Pihoker, Catherine; The, Natalie

    2013-07-01

    To test the novel hypothesis that nutritional factors previously associated with type 1 diabetes etiology or with insulin secretion are prospectively associated with fasting C-peptide (FCP) concentration among youth recently diagnosed with type 1 diabetes. Included were 1,316 youth with autoantibody-positive type 1 diabetes who participated in the SEARCH for Diabetes in Youth study (baseline disease duration, 9.9 months; SD, 6.3). Nutritional exposures included breastfeeding and age at introduction of complementary foods, baseline plasma long-chain omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), vitamin D, vitamin E, and, from a baseline food frequency questionnaire, estimated intake of the branched-chain amino acid leucine and total carbohydrate. Multiple linear regression models were conducted to relate each nutritional factor to baseline FCP adjusted for demographics, disease-related factors, and other confounders. Prospective analyses included the subset of participants with preserved β-cell function at baseline (baseline FCP ≥0.23 ng/mL) with additional adjustment for baseline FCP and time (mean follow-up, 24.3 months; SD, 8.2; n = 656). FCP concentration was analyzed as log(FCP). In adjusted prospective analyses, baseline EPA (P = 0.02), EPA plus DHA (P = 0.03), and leucine (P = 0.03) were each associated positively and significantly with FCP at follow-up. Vitamin D was unexpectedly inversely associated with FCP (P = 0.002). Increased intake of branched-chain amino acids and long-chain omega-3 fatty acids may support preservation of β-cell function. This represents a new direction for research to improve prognosis for type 1 diabetes.

  10. Associations between Familial Factor, Trait Conscientiousness, Gender and the Occurrence of Type 2 Diabetes in Adulthood: Evidence from a British Cohort.

    Directory of Open Access Journals (Sweden)

    Helen Cheng

    Full Text Available To investigate social, familial, and psychological factors in influencing the occurrence of type 2 diabetes in adulthood.Some 17,415 babies born in Great Britain in 1958 and followed up at 7, 11, 33, and 50 years of age. The prevalence of type 2 diabetes at age 50 years was the outcome measure.Some 5,032 participants with data on parental social class, childhood cognitive ability tests scores at age 11 years, educational qualifications at age 33 years, personality traits, occupational levels, and type 2 diabetes (all measured at age 50 years were included in the study. Available information also included whether cohort members' parents or siblings had diabetes. Using logistic regression analyses, results showed that sex (OR=0.63: 0.42-0.92, p<.05, family history (OR=3.40: 1.76-6.55, p<.01, and trait conscientiousness (OR=0.76: 0.64-0.90, p<.001 were all significantly and independently associated with the occurrence of type 2 diabetes in adulthood. It appears that the occurrence of type 2 diabetes is greater among men than women (4.3% vs 2.5%.Familial (genetic and non-genetic and psychological factors are significantly associated with the prevalence of type 2 diabetes in adulthood.

  11. Age modifies the risk factor profiles for acute kidney injury among recently diagnosed type 2 diabetic patients: a population-based study.

    Science.gov (United States)

    Chao, Chia-Ter; Wang, Jui; Wu, Hon-Yen; Huang, Jenq-Wen; Chien, Kuo-Liong

    2018-04-01

    The incidence of acute kidney injury (AKI) rises with age and is associated with multiple risk factors. Here, we compared the risk factors for AKI between younger and older incident diabetic patients to examine the trends in risk alteration for individual factors across different age groups. Between 2007 and 2013, we selected all incident type 2 diabetic adults from the Taiwan National Health Insurance registry, stratified based on age: young (< 65 years), old (≥ 65 but < 75 years), and older-old (≥ 75 years). All factors with potential renal influence (e.g., comorbidities, medications, and diagnostics/procedures) were recorded during the study period, with a nested case-controlled approach utilized to identify independent risk factors for AKI in each age group. Totally, 930,709 type 2 diabetic patients were categorized as young (68.7%), old (17.7%), or older-old (13.6%). Older-old patients showed a significantly higher incidence of AKI than the old and the young groups. Cardiovascular morbidities (hypertension, atrial fibrillation, acute coronary syndrome, and cerebrovascular disease) were shown to increase the risk of AKI, although the risk declined with increasing age. Chronic obstructive pulmonary disease and receiving cardiac catheterization elevated the risk of AKI preferentially in the older-old/old and older-old group, respectively, while the administration of angiotensin-converting enzyme/α-blocker and angiotensin receptor blocker/calcium channel blocker reduced the risk of AKI preferentially in the older-old and older-old/old group, respectively. In conclusion, our findings highlight the importance of devising age-specific risk factor panels for AKI in patients with recently diagnosed type 2 diabetes.

  12. The distressed (Type D) and Five-Factor Models of personality in young, healthy adults and their association with emotional inhibition and distress

    NARCIS (Netherlands)

    Svansdóttir, E.; van den Broek, K.C.; Karlsson, H.D.; Olason, D.T.; Thorgilsson, H.; Denollet, J.

    2013-01-01

    The distressed (Type D) personality (the combination of negative affectivity and social inhibition traits) has been associated with adverse health outcomes. This study investigated the validity of the Type D construct against the Five-Factor Model (FFM) of personality, and its association with

  13. Risk factors for the occurrence of undifferentiated carcinoma of nasopharyngeal type: A case-control study

    OpenAIRE

    Nešić Vladimir; Šipetić Sandra; Vlajinac Hristina; Stošić-Divjak Svetlana; Ješić Snežana

    2010-01-01

    Introduction. The incidence rate of nasopharyngeal carcinoma in Serbia is less than one per 100,000 citizens, which classifies it as a region with low incidence for this disease. Objective. The aim of this study was to test some hypotheses of the risk factors for undifferentiated carcinoma of nasopharyngeal type (UCNT) in the low incidence population. Methods. A case-control study was used for the research. The study included 45 cases with histopathological diagnosis of UCNT and 90 controls. ...

  14. Type D (distressed) personality in primary care patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Nefs, Giesje; Pouwer, Francois; Pop, Victor J M

    2012-01-01

    D Scale-14 (DS14) in type 2 diabetes patients. METHODS: 1553 primary care patients with type 2 diabetes were assessed for demographic, clinical, lifestyle and psychological characteristics in 2007. A subgroup (n=1012) completed the DS14 again 1 year later. RESULTS: The two-factor model of the Type D...... or physiological risk factors, but Type D women had a more sedentary lifestyle (p=.003). Type D patients experienced less social support and more stressful life events, loneliness, and more depressed mood, anhedonia and anxiety (p0......OBJECTIVE: In cardiovascular research, Type D personality (high negative affectivity and social inhibition) has been associated with a more than 3-fold increased risk of adverse health outcomes. This study examined the validity and clinical correlates of the Type D construct as assessed by the Type...

  15. Risk factors for diabetes, but not for cardiovascular disease, are associated with family history of Type 2 diabetes in subjects from central Mexico.

    Science.gov (United States)

    Zamora-Ginez, Irma; Pérez-Fuentes, Ricardo; Baez-Duarte, Blanca G; Revilla-Monsalve, Cristina; Brambila, Eduardo

    2012-03-01

    Independent of obesity, family history of type 2 diabetes mellitus (FHT2DM) is another important risk factor for developing diabetes. To establish the association among FHT2DM, risk factors for diabetes and cardiovascular disease in subjects from central Mexico. Clinical and biochemical studies were performed in 383 first-degree relatives of patients with type 2 diabetes and 270 subjects unrelated to patients with type 2 diabetes-all subjects were from the city of Puebla in central Mexico. Logistic regressions were used to assess the association between FHT2DM and metabolic parameters. Cardiovascular risk was classified by dyslipidemia and the Framingham Risk Score (FRS). FHT2DM was associated with risk factors for diabetes, such as increased fasting insulin levels (OR = 1.731, 95% CI = 1.041-2.877), decreased insulin sensitivity (OR = 1.951, 95% CI = 1.236-3.080) and pre-diabetes (OR = 1.63, 95% CI = 1.14-2.33). FHT2DH was not associated with risk factors for cardiovascular disease, such as dyslipidemia (OR = 1.12, 95% CI = 0.70-1.79) and FRS (OR = 0.74, 95% CI = 0.40-1.36) when adjusted for gender, age, smoking and obesity. Diabetic risk factors, but not cardiovascular disease risk factors, are associated with a positive family history of diabetes in subjects from central Mexico, independent of the presence of obesity.

  16. Type A and type behaviors and factors related to job satisfaction among male white-collar workers.

    Science.gov (United States)

    Hagihara, A; Tarumi, K; Morimoto, K

    1998-01-01

    Numerous studies have examined the health effects of Type A behavior and job satisfaction/dissatisfaction, but we know very little about the relationship between aspects of the work environment related to job satisfaction and the Type A behavior pattern. In the present study, we analyzed data concerning work Stressors, private aspects of life, and job satisfaction among male white-collar workers (n=657) in a large steel company, and identified the respective aspects of the work environment related to job satisfaction among groups divided by Type A/B behavior patterns.We found that the nature of predictors for job satisfaction varied with the behavior type. "Being not busy at work" (pjob satisfaction among the Type A workers while "working less than 10 hours per day" (pjob satisfaction among the Type workers. "Work performance is evaluated" was a significant predictor of job satisfaction among all three behavior types (A, B, and A/B).Our results can provide information useful for the creation of programs to lower the level of job dissatisfaction and mental stress depending upon the behavior type of employees.

  17. Evolutionary history of the most speciose mammals: molecular phylogeny of muroid rodents.

    OpenAIRE

    Michaux, Johan; Reyes, A.; Catzeflis, F.

    2001-01-01

    Phylogenetic relationships between 32 species of rodents representing 14 subfamilies of Muridae and four subfamilies of Dipodidae were studied using sequences of the nuclear protein-coding genes Lecithin Cholesterol Acyl Transferase (LCAT) and von Willebrand Factor (vWF). An examination of some evolutionary properties of each data matrix indicates that the two genes are rather complementary, with lower rates of nonsynonymous substitutions for LCAT. Both markers exhibit a wide range of GC3 per...

  18. Direct linkage of mitochondrial genome variation to risk factors for type 2 diabetes in conplastic strains

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Hyakukoku, M.; Houštěk, Josef; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Mikšík, Ivan; Mothejzíková-Dudová, Kristýna; Pecina, Petr; Vrbacký, Marek; Drahota, Zdeněk; Vojtíšková, Alena; Mráček, Tomáš; Kazdová, L.; Oliyarnyk, O.; Wang, Ji.; Ho, Ch.; Qi, N.; Sugimoto, K.; Kurtz, T.

    2007-01-01

    Roč. 17, č. 9 (2007), s. 1319-1326 ISSN 1088-9051 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR(CZ) GA301/06/0028; GA ČR GA303/07/0781 Grant - others:GA UK(CZ) 24/2005; GA UK(CZ) 26/2005; National Institutes of Health(US) HL35018; National Institutes of Health(US) HL56028; National Institutes of Health(US) HL63709; EURATOOLS(XE) LSHG-CT-2005-019015 Institutional research plan: CEZ:AV0Z50110509 Source of funding: R - rámcový projekt EK Keywords : mitochondrial genome * conplastic strains * risk factors for type 2 diabetes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 11.224, year: 2007

  19. Protein Kinase A (PKA) Type I Interacts with P-Rex1, a Rac Guanine Nucleotide Exchange Factor

    Science.gov (United States)

    Chávez-Vargas, Lydia; Adame-García, Sendi Rafael; Cervantes-Villagrana, Rodolfo Daniel; Castillo-Kauil, Alejandro; Bruystens, Jessica G. H.; Fukuhara, Shigetomo; Taylor, Susan S.; Mochizuki, Naoki; Reyes-Cruz, Guadalupe; Vázquez-Prado, José

    2016-01-01

    Morphology of migrating cells is regulated by Rho GTPases and fine-tuned by protein interactions and phosphorylation. PKA affects cell migration potentially through spatiotemporal interactions with regulators of Rho GTPases. Here we show that the endogenous regulatory (R) subunit of type I PKA interacts with P-Rex1, a Rac guanine nucleotide exchange factor that integrates chemotactic signals. Type I PKA holoenzyme interacts with P-Rex1 PDZ domains via the CNB B domain of RIα, which when expressed by itself facilitates endothelial cell migration. P-Rex1 activation localizes PKA to the cell periphery, whereas stimulation of PKA phosphorylates P-Rex1 and prevents its activation in cells responding to SDF-1 (stromal cell-derived factor 1). The P-Rex1 DEP1 domain is phosphorylated at Ser-436, which inhibits the DH-PH catalytic cassette by direct interaction. In addition, the P-Rex1 C terminus is indirectly targeted by PKA, promoting inhibitory interactions independently of the DEP1-PDZ2 region. A P-Rex1 S436A mutant construct shows increased RacGEF activity and prevents the inhibitory effect of forskolin on sphingosine 1-phosphate-dependent endothelial cell migration. Altogether, these results support the idea that P-Rex1 contributes to the spatiotemporal localization of type I PKA, which tightly regulates this guanine exchange factor by a multistep mechanism, initiated by interaction with the PDZ domains of P-Rex1 followed by direct phosphorylation at the first DEP domain and putatively indirect regulation of the C terminus, thus promoting inhibitory intramolecular interactions. This reciprocal regulation between PKA and P-Rex1 might represent a key node of integration by which chemotactic signaling is fine-tuned by PKA. PMID:26797121

  20. Effect of 48-h food deprivation on the expressions of myosin heavy-chain isoforms and fiber type-related factors in rats.

    Science.gov (United States)

    Mizunoya, Wataru; Sawano, Shoko; Iwamoto, Yohei; Sato, Yusuke; Tatsumi, Ryuichi; Ikeuchi, Yoshihide

    2013-01-01

    The primary aim of this study was to examine the effects of 48-h food deprivation on rat skeletal muscle fiber type, according to myosin heavy-chain (MyHC) isoform composition and some metabolism-related factors in both slow-type dominant and fast-type dominant muscle tissues. Male Wistar rats (7 wk old) were treated with 48-h food deprivation or ad libitum feeding as control. After the treatment, the soleus muscle (slow-type dominant) and the extensor digitorum longus (EDL, fast-type dominant) were excised. We found that 48-h food deprivation did not affect MyHC composition in either the soleus or EDL, compared with fed rats by electrophoretic separation of MyHC isoforms. However, 48-h food deprivation significantly increased the mRNA expression of fast-type MyHC2B in the EDL muscle. Moreover, food deprivation increased fatty acid metabolism, as shown by elevated levels of related serum energy substrates and mRNA expression of mitochondrial uncoupling protein (UCP) 3 and lipoprotein lipase (LPL) in both the soleus and EDL. UCP3 and LPL are generally expressed at higher levels in slow-type fibers. Furthermore, we found that food deprivation significantly decreased the protein amounts of PGC1α and phosphorylated FOXO1, which are known as skeletal muscle fiber type regulators. In conclusion, 48-h food deprivation increased mRNA expression of fast-type MyHC isoform and oxidative metabolism-related factors in EDL, whereas MyHC composition at the protein level did not change in either the soleus or EDL.

  1. FACTORS ASSOCIATED WITH POOR GLYCEMIC CONTROL AMONG TYPE 2 DIABETES MELLITUS IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Rian Adi Pamungkas

    2017-07-01

    Full Text Available Background: Type 2 Diabetes mellitus becomes the public health problem in the wide world. Reasons for poor glycemic control in Type 2 diabetes are complex. Objective: To determine factors contributed to poor glycemic control among Indonesian patients with Type 2 Diabetes Methods: This was a cross sectional regression study. There were 70 respondents selected using purposive sampling. Pre-structured questionnaires were used to measure socio demographic, clinical characteristics, self-care management behaviors, medication adherence, barriers to adherence, and family support. Data were analyzed using chi-square and binary logistic regression. Results: Poor glycemic control was defined as HbA1c ≥7% or FBG ≥200 mg/dl. Findings of this study reported that 83% patients had or FBG ≥200 mg/dl, which confirmed as poor glycemic control. Logistic regression showed that increasing duration of diabetes (> 5 years, non-adherence to dietary behaviors recommendation through selecting healthy diet, arranging a meal plan, recognizing the amount calorie needs, managing dietary behaviors challenges, medication adherence, and family support were significantly influence poor glycemic control with increased odds ratio scores. Conclusion: The proportion of patients with poor glycemic control was raised. Increasing duration of diabetes, non- adherence to medication and dietary behaviors management, and lack of family support were associated with poor glycemic control. Thus, integration of diabetes self-management program with social support is needed to deal with patients’ need to achieve the great benefits in diabetes care.

  2. The predictive value of markers of fibrinolysis and endothelial dysfunction in the post thrombotic syndrome. A systematic review.

    Science.gov (United States)

    Rabinovich, Anat; Cohen, Jacqueline M; Kahn, Susan R

    2014-06-01

    The post thrombotic syndrome (PTS) develops in 20-40% of deep venous thrombosis (DVT) patients. Risk factors for PTS have not been well elucidated. Identification of risk factors would facilitate individualised risk assessment for PTS. We conducted a systematic review to determine whether biomarkers of fibrinolysis or endothelial dysfunction can predict the risk for PTS among DVT patients. Studies were identified by searching the electronic databases PubMed, EMBASE, Scopus and Web of science. We included studies published between 1990 and 2013, measured biomarker levels in adult DVT patients, and reported rates of PTS development. Fourteen studies were included: 11 investigated the association between D-dimer and PTS; three examined fibrinogen; two measured von Willebrand factor; one measured plasminogen activator inhibitor-1; one assessed ADAMTS-13 (A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats) and one measured factor XIII activity. Studies varied with regards to inclusion criteria, definition of PTS, time point and method of biomarker measurement. We were unable to meta-analyse results due to marked clinical heterogeneity. Descriptively, a significant association with PTS was found for D-dimer in four studies and factor XIII in one study. Further prospective research is needed to elucidate whether these markers might be useful to predict PTS development.

  3. Haemostatic disorders in reproductive age women with menorrhagia and effects on quality of life.

    Science.gov (United States)

    Hacioglu, Sibel; Karabulut, Aysun; Sari, Ismail; Keskin, Ali

    2016-11-01

    The aim of this study was to determine the frequency of haemostatic abnormalities in women with menorrhagia and to evaluate their effect on quality of life (QoL). The study population was composed of patients with menorrhagia seen in the outpatient clinic, having a score of >185 with a pictorial blood assessment chart. Structured questionnaires were used in the assessment of demographic characteristics and QoL, and patients were tested for bleeding disorders. Ninety women were recruited for the study. Bleeding disorders were detected in 40% of them: 11.1% had von Willebrand disease, 2.2% had low von Willebrand factor and 26.7% had platelet function disorders (PFD). In 22 (91.6%) cases with PFD the, defect was non-specific and impaired aggregation response to ristocetine (37.5%) was the most commonly detected problem. Bleeding disorders were not associated with any significant reduction in QoL (p > .05). Hereditary bleeding disorders may be the cause of unexplained menorrhagia even in the middle-aged women, but they had no prominent effect on QoL.

  4. Genetic risk factors for type 1 diabetes

    DEFF Research Database (Denmark)

    Pociot, Flemming; Lernmark, Åke

    2016-01-01

    Type 1 diabetes is diagnosed at the end of a prodrome of β-cell autoimmunity. The disease is most likely triggered at an early age by autoantibodies primarily directed against insulin or glutamic acid decarboxylase, or both, but rarely against islet antigen-2. After the initial appearance of one...... is generally needed. The pathogenesis can be divided into three stages: 1, appearance of β-cell autoimmunity, normoglycaemia, and no symptoms; 2, β-cell autoimmunity, dysglycaemia, and no symptoms; and 3, β-cell autoimmunity, dysglycaemia, and symptoms of diabetes. The genetic association with each one...... of the three stages can differ. Type 1 diabetes could serve as a disease model for organ-specific autoimmune disorders such as coeliac disease, thyroiditis, and Addison's disease, which show similar early markers of a prolonged disease process before clinical diagnosis....

  5. Prevalence of type I sensitization to alpha-gal in forest service employees and hunters: Is the blood type an overlooked risk factor in epidemiological studies of the alpha-Gal syndrome?

    Czech Academy of Sciences Publication Activity Database

    Cabezas Cruz, Alejandro; de la Fuente, J.

    2017-01-01

    Roč. 72, č. 12 (2017), s. 2044-2045 ISSN 0105-4538 Institutional support: RVO:60077344 Keywords : a-Gal * prevalence * blood type Subject RIV: EC - Immunology OBOR OECD: Immunology Impact factor: 7.361, year: 2016

  6. Higher prevalence of risk factors for type 2 diabetes mellitus and subsequent higher incidence in men

    DEFF Research Database (Denmark)

    Almdal, T.; Scharling, H.; Jensen, J.S.

    2008-01-01

    Background: This study investigates risk factors and the incidence of type 2 diabetes mellitus (type 2 DM) in both sexes of a northern European population. Methods: A total of 14,223 randomly selected men and women were studied from 1976 to 1978. Patients with diabetes (self-reported type 2 DM......, non-fasting blood glucose and triglycerides. Significantly more men (242, 5.4%) than women (152, 2.5%) developed type 2 DM. The odds ratio (OR) for developing diabetes with a BMI above 30 kg/m(2) compared to a BMI of 20-25 kg/m(2) was 8.1 in women and 6.3 in men; for a non-fasting plasma glucose of 8.......4-11.0 mmol/l compared to a plasma glucose of 5.5-6.4, the ORs were 7.8 in women and 4.7 in men. The OR for developing diabetes in persons with a non-fasting triglyceride level above 2.0 mmol/l compared to 1.0-2.0 mmol/l was 1.8 in both sexes; women with non -fasting triglycerides below 1.0 mmol/l had...

  7. Phenotypic and environmental factors associated with elevated autoantibodies at clinical onset of paediatric type 1 diabetes mellitus.

    Science.gov (United States)

    Ponsonby, Anne-Louise; Pezic, Angela; Cameron, Fergus J; Rodda, Christine; Ellis, Justine A; Kemp, Andrew S; Carlin, John; Dwyer, Terence

    2012-01-01

    To examine possible determinants of autoantibody levels at type 1 diabetes mellitus (T1DM) onset. We assessed levels of glutamic acid decarboxylase 65 islet cell antigen (GADA) and anti-insulin antibodies (IAA) in 247 incident T1DM cases presenting <15 years of age in Melbourne from 1st March 2008 to 30th June 2010. 58.9% (142/241) of cases were GADA seropositive and 42.3% (94/222) were IAA seropositive. Factors associated with elevated IAA antibodies included younger age and red hair phenotype. Factors associated with elevated GAD antibodies included lower birthweight and recent eczema. Intriguingly, low recent or past sun exposure was only associated with elevated GADA levels among children presenting at age <5 years, not older (difference in effect, p<0.05 for 4 of 5 associations). These findings show that environmental and phenotypic factors are associated with autoantibody levels at time of presentation for T1DM. We recommend such environmental and phenoytypic factors should be examined in further detail.

  8. Idiopathic Non-Cirrhotic Intrahepatic Portal Hypertension (NCIPH)—Newer Insights into Pathogenesis and Emerging Newer Treatment Options

    Science.gov (United States)

    Goel, Ashish; Elias, Joshua E.; Eapen, Chundamannil E.; Ramakrishna, Banumathi; Elias, Elwyn

    2014-01-01

    Chronic microangiopathy of portal venules results in idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH). Recent data suggest a role for vasoactive factors of portal venous origin in the pathogenesis of this ‘pure’ vasculopathy of the liver. Enteropathies (often silent), are an important ‘driver’ of this disease. NCIPH is under-recognized and often mis-labeled as cryptogenic cirrhosis. Liver biopsy is needed to prove the diagnosis of NCIPH. In these patients, with advancing disease and increased porto-systemic shunting, the portal venous vasoactive factors bypass the liver filter and contribute to the development of pulmonary vascular endothelial disorders—porto-pulmonary hypertension and hepato-pulmonary syndrome as well as mesangiocapillary glomerulonephritis. Prognosis in NCIPH patients is determined by presence, recognition and management of associated disorders. With better understanding of the pathogenesis of NCIPH, newer treatment options are being explored. Imbalance in ADAMTS 13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13): vWF (von-Willebrand factor) ratio is documented in NCIPH patients and may have a pathogenic role. Therapeutic interventions to correct this imbalance may prove to be important in the management of NCIPH. PMID:25755567

  9. Patient and Provider Factors Affecting Clinical Inertia in Patients With Type 2 Diabetes on Metformin Monotherapy.

    Science.gov (United States)

    Mahabaleshwarkar, Rohan; Gohs, Frank; Mulder, Holly; Wilkins, Nick; DeSantis, Andrea; Anderson, William E; Ejzykowicz, Flavia; Rajpathak, Swapnil; Norton, H James

    2017-08-01

    Our aim was to determine the extent of clinical inertia and the associated patient and provider factors in patients with type 2 diabetes on metformin monotherapy (MM) at a large integrated health care system in the United States. The study cohort included patients with type 2 diabetes aged 18 to 85 years, on MM between January 2009 and September 2013, who experienced MM failure (had an uncontrolled glycosylated hemoglobin [HbA 1c ] reading (≥8.0% [64 mmol/mol]) after at least 90 days of MM). Clinical inertia was defined as absence of treatment intensification with an add-on therapy within 180 days after the MM failure (index date). The impact of patient and provider factors on clinical inertia was determined using generalized estimating equations. The study cohort consisted of 996 patients; 58% were men and 59% were white, with a mean age of 53 (11.8) years. Of these, 49.8% experienced clinical inertia. Lower HbA 1c at index date, absence of liver diseases, absence of renal diseases, and greater provider age were associated with clinical inertia. The clinical inertia rate in a secondary analysis considering HbA 1c inertia. Considerable clinical inertia rates were observed in our real-world patient population, suggesting the need of interventions to reduce clinical inertia in clinical practice. Information about patient and provider factors affecting clinical inertia provided by this study could help healthcare policymakers plan and implement such interventions. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  10. Clinical Significance of von Willebrand Factor and Antithrombin in Diabetes Mellitus with Retinopathy%血管性血友病因子与抗凝血酶在糖尿病视网膜病变中的临床意义

    Institute of Scientific and Technical Information of China (English)

    张鹏; 汤荣华

    2012-01-01

    目的 探讨糖尿病微血管视网膜病变患者血管性血友病因子(vWF)、抗凝血酶(AT)的变化及临床意义.方法 将100例2型糖尿病患者分为两组,糖尿病无微血管视网膜病变并发症组53例,糖尿病微血管视网膜病变并发症组47例,设健康人群对照组50例.所有人群入院或体检时即采集静脉血,进行vWF:Ag、AT:A检测.结果 2型糖尿病无微血管视网膜病变并发症组患者血浆vWF:Ag含量较正常对照组增高(P<0.05),2型糖尿病微血管视网膜病变并发症组患者血浆vWF:Ag含量与2型糖尿病无微血管视网膜病变并发症组及正常对照组相比有显著性差异(P<0.05);且2型糖尿病微血管视网膜病变并发症组中背景性病变和增殖性病变患者血浆vWF:Ag含量比较有显著性差异(P<0.05).2型糖尿病无微血管视网膜病变并发症组患者血浆AT活性与正常对照组相比无显著性差异(P>0.05),2型糖尿病微血管视网膜病变并发症组患者血浆AT活性与2型糖尿病无微血管视网膜病变并发症组及正常对照组相比有显著性差异(P<0.05);且2型糖尿病微血管视网膜病变并发症组中背景性病变和增殖性病变患者血浆AT活性比较有显著性差异(P<0.05).结论 血浆vWF:Ag、AT:A的变化与糖尿病微血管视网膜病变的发生、发展有密切关系,监测其水平与活性对糖尿病微血管并发症的治疗和预防有重要的临床意义.%Objective To explore the changes of von Willebrand factor(vWF) and antithrombin(AT) in diabetic patients with retinopathy and its clinical implications. Methods 100 type 2 diabetes mellitus (T2DM) patients were divided into 2 groups,one group included 53 T2DM patients without retinopathy,another group included 47 T2DM patients with retinopathy, 50 healthy peoples were enrolled as control group. Venous blood was collected from all groups and vWF:Ag, AT; A were determined. Results The level of vWF;Ag in T2DM

  11. Beyond Type D personality

    DEFF Research Database (Denmark)

    Pelle, Aline J; Pedersen, Susanne S.; Szabó, Balázs M

    2009-01-01

    Type D personality has been associated with impaired health status in chronic heart failure (CHF), but other psychological factors may also be important.......Type D personality has been associated with impaired health status in chronic heart failure (CHF), but other psychological factors may also be important....

  12. Control of glycemia and other cardiovascular disease risk factors in older adults with type 2 diabetes mellitus: data from the Adult Diabetes Control and Management.

    Science.gov (United States)

    Sazlina, Shariff-Ghazali; Mastura, Ismail; Ahmad, Zaiton; Cheong, Ai-Theng; Adam, Bujang-Mohamad; Jamaiyah, Haniff; Lee, Ping-Yein; Syed-Alwi, Syed-Abdul-Rahman; Chew, Boon-How; Sriwahyu, Taher

    2014-01-01

    The aims of the present study were to assess the control of glycemia and other cardiovascular disease risk factors, and the association between age and these controls among older adults with type 2 diabetes in Malaysia. A cross-sectional study was carried out using cases notified to the Adult Diabetes Control and Management database between 1 January and 31 December 2009. A total of 10 363 people aged over 60 years with type 2 diabetes mellitus were included in the analyses. A standard online case report form was used to record demographic data, clinical factors (diabetes duration, comorbid condition and treatment modalities), cardiovascular disease risk factors, diabetes complications and laboratory assessments. The cardiovascular disease risk factors controls assessed included glycosylated hemoglobin (HbA(1c)) control of cardiovascular disease risk factors was suboptimal in older adults with type 2 diabetes. The oldest elderly were more likely to achieve target HbA(1c) (<7.0%) and triglycerides (<1.7 mmol/L) than older adults aged 60-69 years. © 2013 Japan Geriatrics Society.

  13. The Association of Bread and Rice with Metabolic Factors in Type 2 Diabetic Patients.

    Directory of Open Access Journals (Sweden)

    Mahdieh Akhoundan

    Full Text Available Carbohydrates are shown to have an important role in blood glucose control, type 2 diabetes and cardiovascular diseases risk. This is even more challenging when considering populations consuming refined grains diets. Bread and rice are staple foods which supply main proportion of Iranian calorie intake. This study was designed to investigate the effect of bread and rice intake on blood glucose control, lipid profile and anthropometric measurements in Iranian type 2 diabetic patients.426 patients with type 2 diabetes were included in this study. Anthropometric measurements were done using standard methods. Dietary information was assessed by a valid and reliable food frequency questionnaire (FFQ. Fasting blood glucose (FBG, glycated hemoglobin (HbA1c, serum triglycride (TG, total cholesterol (TC, low density lipoprotein (LDL and high density lipoprotein (HDL cholesterol were examined after 12-hour fasting.The results represented that people in the highest tertile compared to the lowest tertile of calorie adjusted total bread intake have higher FBG. FBG in the highest tertile of calorie adjusted total bread-rice intake was also significantly higher than the lowest. The association remained significant after adjusting for potential confounders. Rice intake showed no association with cardio-metabolic risk factors.We founded that higher total bread intake and total bread-rice intake were associated with FBG in type 2 diabetic patients whereas rice intake was not associated with glucose and lipid profile. This result should be confirmed in prospective studies, considering varieties, glycemic index (GI, glycemic load (GL and cooking method of bread and rice.

  14. Daintain/AIF-1 (Allograft Inflammatory Factor-1) accelerates type 1 diabetes in NOD mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yan-Ying, E-mail: biozyy@163.com [College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041 (China); Huang, Xin-Yuan [College of Life Science and Technology, Hubei Engineering University, Xiaogan 432000 (China); Chen, Zheng-Wang [Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Daintain/AIF-1 is over-expressed in the blood of NOD mice suffering from insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 stimulates white blood cell proliferation in NOD mice. Black-Right-Pointing-Pointer Daintain/AIF-1 increases blood glucose levels and triggers type 1 diabetes. Black-Right-Pointing-Pointer Daintain/AIF-1 accelerates insulitis, while its antibody prevents insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 enhances the levels of nitric oxide in the pancreases of NOD mice. -- Abstract: A large body of experimental evidence suggests that cytokines trigger pancreatic {beta}-cell death in type 1 diabetes mellitus. Daintain/AIF-1 (Allograft Inflammatory Factor-1), a specific marker for activated macrophages, is accumulated in the pancreatic islets of pre-diabetic BB rats. In the present study, we demonstrate that daintain/AIF-1 is released into blood and the levels of daintain/AIF-1 in the blood of type 1 diabetes-prone non-obese diabetic (NOD) mice suffering from insulitis are significantly higher than that in healthy NOD mice. When injected intravenously into NOD mice, daintain/AIF-1 stimulates white blood cell proliferation, increases the concentrations of blood glucose, impairs insulin expression, up-regulates nitric oxide (NO) production in pancreases and accelerates diabetes in NOD mice, while the antibody against daintain/AIF-1 delays or prevents insulitis in NOD mice. These results imply daintain/AIF-1 triggers type 1 diabetes probably via arousing immune cells activation and induction of NO production in pancreas of NOD mice.

  15. The Association of Bread and Rice with Metabolic Factors in Type 2 Diabetic Patients.

    Science.gov (United States)

    Akhoundan, Mahdieh; Shadman, Zhaleh; Jandaghi, Parisa; Aboeerad, Maryam; Larijani, Bagher; Jamshidi, Zahra; Ardalani, Hamidreza; Khoshniat Nikoo, Mohsen

    2016-01-01

    Carbohydrates are shown to have an important role in blood glucose control, type 2 diabetes and cardiovascular diseases risk. This is even more challenging when considering populations consuming refined grains diets. Bread and rice are staple foods which supply main proportion of Iranian calorie intake. This study was designed to investigate the effect of bread and rice intake on blood glucose control, lipid profile and anthropometric measurements in Iranian type 2 diabetic patients. 426 patients with type 2 diabetes were included in this study. Anthropometric measurements were done using standard methods. Dietary information was assessed by a valid and reliable food frequency questionnaire (FFQ). Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), serum triglycride (TG), total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol were examined after 12-hour fasting. The results represented that people in the highest tertile compared to the lowest tertile of calorie adjusted total bread intake have higher FBG. FBG in the highest tertile of calorie adjusted total bread-rice intake was also significantly higher than the lowest. The association remained significant after adjusting for potential confounders. Rice intake showed no association with cardio-metabolic risk factors. We founded that higher total bread intake and total bread-rice intake were associated with FBG in type 2 diabetic patients whereas rice intake was not associated with glucose and lipid profile. This result should be confirmed in prospective studies, considering varieties, glycemic index (GI), glycemic load (GL) and cooking method of bread and rice.

  16. Physiological and behavioral factors related to physical activity in black women with type 2 diabetes mellitus.

    Science.gov (United States)

    Allen, Nancy A; Melkus, Gail D; Chyun, Deborah A

    2011-10-01

    To describe relationships among physical activity (PA), physiological factors, and psychological factors in Black women with type 2 diabetes mellitus (T2DM). A cross-sectional design was used (N = 109). Data were collected on PA(activity/inactivity, TV hours, bed confinement), physiology (blood pressure, lipids, hemoglobin A1c), psychology (anxiety,emotional distress, physical functioning, bodily pain, vitality), and health care provider (HCP) support. Walking was the preferred PA; TV viewing averaged 3.7 hours/day, and 24% reported confinement to bed >1 week in the last year. Inactive women had greater physiological and psychological problems than active women. Women watching TV >2 hours/day had more physiological problems than women watching TV Women reporting >1 week of confinement to bed in the last year had more physiological and psychological problems than those confined to bed women with T2DM should promote walking, address TV viewing time, incorporate HCP’s role of PA counseling/support,and address several psychological factors.

  17. Effect of Elliptical High Intensity Interval Training on Metabolic Risk Factor in Pre- and Type 2 Diabetes Patients: A Pilot Study.

    Science.gov (United States)

    Fex, Annie; Leduc-Gaudet, Jean-Philippe; Filion, Marie-Eve; Karelis, Antony D; Aubertin-Leheudre, Mylène

    2015-07-01

    The purpose of the current study was to examine the impact of 12 weeks of elliptical high intensity interval training (HIIT) on metabolic risk factors and body composition in pre- and type 2 diabetes patients. Sixteen pre- (n = 8) and type 2 diabetes (n = 8) participants completed this study. Fasting blood glucose, HbA1c, anthropometric measurements, body composition (DXA), blood pressure, resting heart rate, VO2max, and dietary factors, as well as total and physical activity energy expenditure, were measured. The HIIT program on the elliptical was performed 3 times a week for 12 weeks. After the intervention, we observed a significant improvement for fasting blood glucose, waist and hip circumference, appendicular fat mass, leg lean body mass and appendicular lean body mass, systolic blood pressure, resting heart rate, and VO2max (P body composition in pre- and type 2 diabetes patients.

  18. Improvement of insulin sensitivity in response to exercise training in type 2 diabetes mellitus is associated with vascular endothelial growth factor A expression.

    Science.gov (United States)

    Wagner, Henrik; Fischer, Helene; Degerblad, Marie; Alvarsson, Michael; Gustafsson, Thomas

    2016-09-01

    Insulin sensitivity changes in response to exercise training demonstrate a large variation. Vascular endothelial growth factor A could promote increased insulin sensitivity through angiogenesis. We investigated associations between changes in expression of key genes and insulin sensitivity, aerobic capacity and glycaemic control following exercise training in diabetes mellitus type 2. Subjects with diabetes mellitus type 2 underwent 12 weeks of structured exercise. Euglycaemic clamp, exercise test and HbA1c were performed. Muscle biopsies were obtained for mRNA expression. A total of 16 subjects completed the study. Change in vascular endothelial growth factor A expression was positively associated with an increase in insulin sensitivity (p = 0.004) and with a decrease in HbA1c (p = 0.034). Vascular endothelial growth factor A receptor-1 expression showed similar associations. The variation in physical adaptation to exercise training in diabetes mellitus type 2 was associated with changes in expression of vascular endothelial growth factor A in muscle. This difference in induced gene expression could contribute to the variation in exercise training effects on insulin sensitivity. Measures of capillary blood flow need to be assessed in future studies. © The Author(s) 2016.

  19. Neighborhood level risk factors for type 1 diabetes in youth: the SEARCH case-control study

    Directory of Open Access Journals (Sweden)

    Liese Angela D

    2012-01-01

    Full Text Available Abstract Background European ecologic studies suggest higher socioeconomic status is associated with higher incidence of type 1 diabetes. Using data from a case-control study of diabetes among racially/ethnically diverse youth in the United States (U.S., we aimed to evaluate the independent impact of neighborhood characteristics on type 1 diabetes risk. Data were available for 507 youth with type 1 diabetes and 208 healthy controls aged 10-22 years recruited in South Carolina and Colorado in 2003-2006. Home addresses were used to identify Census tracts of residence. Neighborhood-level variables were obtained from 2000 U.S. Census. Multivariate generalized linear mixed models were applied. Results Controlling for individual risk factors (age, gender, race/ethnicity, infant feeding, birth weight, maternal age, number of household residents, parental education, income, state, higher neighborhood household income (p = 0.005, proportion of population in managerial jobs (p = 0.02, with at least high school education (p = 0.005, working outside the county (p = 0.04 and vehicle ownership (p = 0.03 were each independently associated with increased odds of type 1 diabetes. Conversely, higher percent minority population (p = 0.0003, income from social security (p = 0.002, proportion of crowded households (0.0497 and poverty (p = 0.008 were associated with a decreased odds. Conclusions Our study suggests that neighborhood characteristics related to greater affluence, occupation, and education are associated with higher type 1 diabetes risk. Further research is needed to understand mechanisms underlying the influence of neighborhood context.

  20. Le rôle du médecin anesthésiste-réanimateur dans la prise en ...

    African Journals Online (AJOL)

    La maladie de Von Willebrand (VWD) est la maladie hémorragique constitutionnelle de l'hémostase la plus fréquente. Elle est liée à un déficit, soit quantitatif, soit qualitatif en facteur willebrand (VWF). Elle se caractérise par son extrême hétérogénéité sur les plans clinique, phénotypique et génotypique. La grossesse et ...

  1. TACO: a general-purpose tool for predicting cell-type-specific transcription factor dimers.

    Science.gov (United States)

    Jankowski, Aleksander; Prabhakar, Shyam; Tiuryn, Jerzy

    2014-03-19

    Cooperative binding of transcription factor (TF) dimers to DNA is increasingly recognized as a major contributor to binding specificity. However, it is likely that the set of known TF dimers is highly incomplete, given that they were discovered using ad hoc approaches, or through computational analyses of limited datasets. Here, we present TACO (Transcription factor Association from Complex Overrepresentation), a general-purpose standalone software tool that takes as input any genome-wide set of regulatory elements and predicts cell-type-specific TF dimers based on enrichment of motif complexes. TACO is the first tool that can accommodate motif complexes composed of overlapping motifs, a characteristic feature of many known TF dimers. Our method comprehensively outperforms existing tools when benchmarked on a reference set of 29 known dimers. We demonstrate the utility and consistency of TACO by applying it to 152 DNase-seq datasets and 94 ChIP-seq datasets. Based on these results, we uncover a general principle governing the structure of TF-TF-DNA ternary complexes, namely that the flexibility of the complex is correlated with, and most likely a consequence of, inter-motif spacing.

  2. Academic Skills in Children with Early-Onset Type 1 Diabetes: The Effects of Diabetes-Related Risk Factors

    Science.gov (United States)

    Hannonen, Riitta; Komulainen, Jorma; Riikonen, Raili; Ahonen, Timo; Eklund, Kenneth; Tolvanen, Asko; Keskinen, Paivi; Nuuja, Anja

    2012-01-01

    Aim: The study aimed to assess the effects of diabetes-related risk factors, especially severe hypoglycaemia, on the academic skills of children with early-onset type 1 diabetes mellitus (T1DM). Method: The study comprised 63 children with T1DM (31 females, 32 males; mean age 9y 11mo, SD 4mo) and 92 comparison children without diabetes (40…

  3. Estudo de fatores pró-trombóticos e pró-inflamatórios na cardiomiopatia chagásica Study of pro-thrombotic and pro-inflammatory factors in chagas cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Leila Maria Magalhães Pessoa de Melo

    2010-10-01

    Full Text Available FUNDAMENTO: A relação entre atividade inflamatória e pró-trombótica na cardiomiopatia chagásica e em outras etiologias é obscura. OBJETIVO: Estudar o perfil de marcadores pró-trombóticos e pró-inflamatórios em pacientes com insuficiência cardíaca chagásica e compará-los com os de etiologia não chagásica. MÉTODOS: Coorte transversal. Critérios de inclusão: fração de ejeção do VE (FEVE um mês. Os pacientes foram divididos em dois grupos: grupo 1 (G1 - sorologias positivas para Chagas - e grupo 2 (G2 - sorologias negativas para Chagas. Fator pró-inflamatório: PCR ultrassensível. Fatores pró-trombóticos: fator trombina-antitrombina, fibrinogênio, antígeno do fator de von Willebrand, P-selectina plasmática e tromboelastograma. Amostra calculada para poder de 80%, assumindo-se diferença de 1/3 de desvio-padrão; p significativo se BACKGROUND: The relationship between inflammatory and prothrombotic activity in chagas cardiomyopathy and in other etiologies is unclear. OBJECTIVE: To study the profile of pro-thrombotic and pro-inflammatory markers in patients with Chagas' heart failure and compare them with patients of non-chagas etiology. METHODS: Cross-sectional cohort. Inclusion criteria: left ventricle ejection fraction (LVEF one month. The patients were divided into two groups: group 1 (G1 - seropositive for Chagas - and group 2 (G2 - seronegative for Chagas. Pro-inflammatory factor: Ultra-sensitive CRP. Pro-thrombotic factors: thrombin-antithrombin factor, fibrinogen, von Willebrand factor antigen, plasma P-selectin and thromboelastography. Sample calculated for 80% power, assuming a standard deviation difference of 1/3; significant p if it is < 0.05. Statistical analysis: Fisher's exact test for categorical variables; unpaired Student's t-test for parametric continuous variables and Mann-Whitney test for nonparametric continuous variables. RESULTS: Between January and June 2008, 150 patients were included, 80 in G1

  4. Factors associated with anxiety and depression among type 2 diabetes outpatients in Malaysia: a descriptive cross-sectional single-centre study.

    Science.gov (United States)

    Ganasegeran, Kurubaran; Renganathan, Pukunan; Manaf, Rizal Abdul; Al-Dubai, Sami Abdo Radman

    2014-04-23

    To determine the prevalence and factors associated with anxiety and depression among type 2 diabetes outpatients in Malaysia. Descriptive, cross-sectional single-centre study with universal sampling of all patients with type 2 diabetes. Endocrinology clinic of medical outpatient department in a Malaysian public hospital. All 169 patients with type 2 diabetes (men, n=99; women, n=70) aged between 18 and 90 years who acquired follow-up treatment from the endocrinology clinic in the month of September 2013. The validated Hospital Anxiety and Depression Scale (HADS), sociodemographic characteristics and clinical health information from patient records. Of the total 169 patients surveyed, anxiety and depression were found in 53 (31.4%) and 68 (40.3%), respectively. In multivariate analysis, age, ethnicity and ischaemic heart disease were significantly associated with anxiety, while age, ethnicity and monthly household income were significantly associated with depression. Sociodemographics and clinical health factors were important correlates of anxiety and depression among patients with diabetes. Integrated psychological and medical care to boost self-determination and confidence in the management of diabetes would catalyse optimal health outcomes among patients with diabetes.

  5. Improved survival and renal prognosis of patients with type 2 diabetes and nephropathy with improved control of risk factors

    DEFF Research Database (Denmark)

    Andrésdóttir, Gudbjörg; Jensen, Majken; Carstensen, Bendix

    2014-01-01

    OBJECTIVE: To evaluate long-term survival, development of renal end points, and decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and diabetic nephropathy (DN) after renin-angiotensin system (RAS) inhibition and multifactorial treatment of cardiovascular risk factors ha...

  6. The distressed (Type D) personality factor of social inhibition, but not negative affectivity, enhances eyeblink conditioning.

    Science.gov (United States)

    Allen, M T; Handy, J D; Blankenship, M R; Servatius, R J

    2018-06-01

    Recent work has focused on a learning diathesis model in which specific personality factors such as behavioral inhibition (BI) may influence associative learning and in turn increase risk for the development of anxiety disorders. We have found in a series of studies that individuals self-reporting high levels of BI exhibit enhanced acquisition of conditioned eyeblinks. In the study reported here, hypotheses were extended to include distressed (Type D) personality which has been found to be related to BI. Type D personality is measured with the DS-14 scale which includes two subscales measuring negative affectivity (NA) and social inhibition (SI). We hypothesized that SI, which is similar to BI, would result in enhanced acquisition while the effect of NA is unclear. Eighty nine participants completed personality inventories including the Adult Measure of Behavioral Inhibition (AMBI) and DS-14. All participants received 60 acquisition trials with a 500 ms, 1000 Hz, tone CS and a co-terminating 50 ms, 5 psi corneal airpuff US. Participants received either 100% CS-US paired trials or a schedule of partial reinforcement where 50% US alone trials were intermixed into CS-US training. Acquisition of CRs did not differ between the two training protocols. Whereas BI was significantly related to Type D, SI, and NA, only BI and SI individuals exhibited enhanced acquisition of conditioned eyeblinks as compared to non-inhibited individuals. Personality factors now including social inhibition can be used to identify individuals who express enhanced associative learning which lends further support to a learning diathesis model of anxiety disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Elevated fasting plasma cortisol is associated with ischemic heart disease and its risk factors in people with type 2 diabetes: the Edinburgh type 2 diabetes study.

    Science.gov (United States)

    Reynolds, Rebecca M; Labad, Javier; Strachan, Mark W J; Braun, Anke; Fowkes, F Gerry R; Lee, Amanda J; Frier, Brian M; Seckl, Jonathan R; Walker, Brian R; Price, Jackie F

    2010-04-01

    Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the metabolic syndrome, but whether circulating cortisol levels predict cardiovascular end points is less clear. People with type 2 diabetes are at increased cardiovascular disease risk and thus are suitable to study associations of plasma cortisol with cardiovascular risk. We aimed to assess whether altered HPA axis activity was associated with features of the metabolic syndrome and ischemic heart disease in people with type 2 diabetes. We conducted a cross-sectional cohort study in the general community, including 919 men and women aged 67.9 (4.2) yr with type 2 diabetes (the Edinburgh Type 2 Diabetes Study). We measured fasting morning plasma cortisol. Associations between cortisol levels, features of the metabolic syndrome, obesity, and ischemic heart disease were determined. Elevated plasma cortisol levels were associated with raised fasting glucose and total cholesterol levels (P cortisol levels were associated with prevalent ischemic heart disease (>800 vs. cortisol is also associated with a greater prevalence of ischemic heart disease, independent of conventional risk factors. Understanding the role of cortisol in the pathogenesis of ischemic heart disease merits further exploration.

  8. Differences in Factors Affecting Various Crash Types with High Numbers of Fatalities and Injuries in China

    Science.gov (United States)

    Wang, Kai; He, Jie; Ding, Jianxun; Shi, Qin; Wang, Changjun; Li, Pingfan

    2016-01-01

    Objectives Road traffic crashes that involve very high numbers of fatalities and injuries arouse public concern wherever they occur. In China, there are two categories of such crashes: a crash that results in 10–30 fatalities, 50–100 serious injuries or a total cost of 50–100 million RMB ($US8-16m) is a “serious road traffic crash” (SRTC), while a crash that is even more severe or costly is a “particularly serious road traffic crash” (PSRTC). The aim of this study is to identify the main factors affecting different types of these crashes (single-vehicle, head-on, rear-end and side impact) with the ultimate goal of informing prevention activities and policies. Methods Detailed descriptions of the SRTCs and PSRTCs that occurred from 2007 to 2014 were collected from the database “In-depth Investigation and Analysis System for Major Road Traffic Crashes” (IIASMRTC), which is maintained by the Traffic Management Research Institute of the Ministry of Public Security of China (TMRI). 18 main risk factors, which were categorized into four areas (participant, vehicle, road and environment-related) were chosen as potential independent variables for the multinomial logistic regression analysis. Comparisons were made among the single-vehicle, head-on, rear-end and side impact crashes in terms of factors affecting crash occurrence. Findings Five risk factors were significant for the six multinomial logistic regression models, which were location, vertical alignment, roadside safety rating, driver distraction and overloading of cargo. It was indicated that intersections were more likely to have side impact SRTCs and PSRTCs, especially with poor visibility at night. Overloaded freight vehicles were more likely to be involved in a rear-end crash than other freight vehicles. Driver distraction is an important risk factor for head-on crashes, while vertical alignment and roadside safety rating are positively associated with single-vehicle crashes. Conclusion Based

  9. CARDIOVASCULAR RISK FACTORS IN CHILDREN WITH TYPE 1 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Z ABDEYASDAN

    2003-12-01

    Full Text Available Introduction: Diabetes melliuts is a chronic, metabolic disease that involves the macro and micro vascular complications and one of its maer ascular cowplications is the cardio vascular disease, as ,the risk of cardiovascular disease is 2-4 folds in diabetic patients in comparison with non diabetic individuals. The researches have demonstrated that the risk factors of the cardio vascular disease are formed at childhood. Therefore the preventive measures must begin from early childhood. So the present study was planned with the goals to determine and compare the cardia-vascular risk factors in the diabetic children with type 1 of diabetes mellitus. Method: This was an analytic, cross sectional study that has been done in two groups (case-control. In this research, 148 children, suffering from the typel diabetes mellitus being supported by the metabolism and endocrine research center, were chosen in the continues case manner and for the control group, 148 children, matched with the study group (according to the age and the sex, at 6-18 years old from the schools in Isfahan city randomly and at 2-6 years from the neiborhoods of the case group. The data-gathering tool was the questionnaires includes lipid profile, blood pressure, weight and height. To analyze the data we used the analytic (t student and logistic regression and descriptive (mean and standard deviation statistic methods and SPSS. Results: Findings revealed that the means of Lipid profile, systolic blood pressure and body mass index had not statistically significant differences in the two groups. But the mean of diastolic blood pressure and the mean arterial blood pressure in the control group were more than the case group and this difference was significant. The mean, 75 and 95 percentiles for cholesterol and LDL in all the age groups, mean, 75 and 95 percentile for triglyceride in all the age groups except the age group of 1-4 years in the diabetic and non diabetic groups were

  10. N1421K mutation in the glycoprotein Ib binding domain impairs ristocetin- and botrocetin-mediated binding of von Willebrand factor to platelets

    DEFF Research Database (Denmark)

    Lanke, E.; Kristoffersson, A.C.; Isaksson, C.

    2008-01-01

    , moderately decreased plasma factor VIII (FVIII) and VWF levels, and disproportionately low-plasma VWF:RCo levels. The patients were found to be heterozygous for the novel N1421K mutation, caused by a 4263C > G transversion in exon 28 of the VWF gene coding for the A1 domain. Botrocetin- and ristocetin-mediated...... binding of plasma VWF to GPIb were reduced in the patients. In vitro mutagenesis and expression in COS-7 cells confirmed the impairment of the mutant in botrocetin- and ristocetin-mediated VWF binding to GPIb. VWF collagen binding capacity was unaffected in plasma from the heterozygous individuals as well...

  11. In silico particle margination in blood flow

    OpenAIRE

    Müller, Kathrin

    2015-01-01

    A profound knowledge of margination, the migration of blood components to the vessel wall in blood flow, is required in order to understand the genesis of various diseases, as e.g., cardiovascular diseases or bleeding disorders. Margination of particles is a pre-condition for potential adhesion. Adhesion to the vessel wall is required for platelets, the protein von Willebrand factor (VWF), but also for drug and imaging agent carriers in order to perform their particular tasks. In the haemosta...

  12. Pathogenesis of diabetic vascular disease: evidence for the role of reduced heparan sulfate proteoglycan

    DEFF Research Database (Denmark)

    Jensen, Tonny Joran

    1997-01-01

    that albuminuria is a marker of widespread vascular dysfunction. Increased transport of macromolecules across the vascular wall, elevated plasma levels of von Willebrand factor, and impaired fibrinolytic capacity have been demonstrated in albuminuric patients. The cause of this vascular vulnerability...... problems. What are the mechanisms of action of glycosaminoglycans at the molecular biology level, and how can we select compounds without anticoagulant activity suitable for long-term use in the prevention and treatment of late diabetic complications?...

  13. Early pregnancy clinical risk factors for preeclampsia in women with type 1 and type 2 diabete

    DEFF Research Database (Denmark)

    Nørgaard, Sidse Kjærhus; Vestergaard, Marianne; Ásbjörnsdóttir, Björg

    Aim: To assess the prevalence of pregnancy-induced hypertensive disorders and to identify early clinical, modifiable predictors of preeclampsia in women with type 1 and type 2 diabetes. Methods: A population-based cohort study of 494 women with pre-existing diabetes (307 type 1 and 187 type 2...... diabetes), included at their first antenatal visit at 11±6 gestational weeks (mean±SD) from 2012 to 2016. Predictors of preeclampsia present at first antenatal visit were sought identified. Results: At the first antenatal visit HbA1c was 6.9±2.3 % (51±10 mmol/mol) vs. 6.8±2.6 % (49±14 mmol/mol) and blood...... pressure 120±12/76±8 mmHg vs. 122±14/79±10 mmHg, (p=0.16/p=0.001) in women with type 1 and type 2 diabetes, respectively. Preeclampsia developed in 40 women at 36±3 gestational weeks with delivery 8±9 days later. The prevalence of preeclampsia was 8% (9% vs. 7%) and gestational hypertension 8% (9% vs. 6...

  14. Characterization of the coagulation profile in children with liver disease and extrahepatic portal vein obstruction or shunt.

    Science.gov (United States)

    Beattie, William; Magnusson, Maria; Hardikar, Winita; Monagle, Paul; Ignjatovic, Vera

    2017-03-01

    Chronic liver disease causes a disruption of procoagulant and anticoagulant factors, resulting in a fragile state, prone to increased rates of both bleeding and thrombosis. Currently, there is limited literature describing the changes observed in pediat