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Sample records for concentrate factor viii

  1. Factor VIII assay

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003678.htm Factor VIII assay To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  2. Blood coagulation factor VIII

    Indian Academy of Sciences (India)

    Factor VIII (FVIII) functions as a co-factor in the blood coagulation cascade for the proteolytic activation of factor X by factor IXa. Deficiency of FVIII causes hemophilia A, the most commonly inherited bleeding disorder. This review highlights current knowledge on selected aspects of FVIII in which both the scientist and the ...

  3. Human parvovirus B19 infection in hemophiliacs first infused with two high-purity, virally attenuated factor VIII concentrates.

    Science.gov (United States)

    Azzi, A; Ciappi, S; Zakvrzewska, K; Morfini, M; Mariani, G; Mannucci, P M

    1992-03-01

    Human parvovirus B19 can be transmitted by coagulation factor concentrates and is highly resistant to virucidal methods. To evaluate whether the additional removal of virus by chromatographic methods during the manufacture of high-purity concentrates reduces the risk of B19 transmission, we have prospectively evaluated the rate of anti-B19 seroconversion in two groups of susceptible (anti-B19 negative) hemophiliacs infused with high-purity, heated (pasteurized) or solvent-detergent-treated factor VIII concentrates. Both products infected a relatively high proportion of patients (nine of 20).

  4. The new albumin-free recombinant factor VIII concentrates for treatment of hemophilia: do they represent an actual incremental improvement?

    Science.gov (United States)

    Josephson, Cassandra D; Abshire, Thomas

    2004-07-01

    The goal of eliminating the low levels of infectious disease risk from hemophilia treatment has resulted in the development of multiple generations of recombinant factor VIII (rFVIII) products. The ideal product should be devoid of human and animal proteins, which may transmit infectious agents. These products should also maintain molecular integrity, hemostatic efficacy, similar immunogenicity, and acceptable side effect profiles as compared to plasma-derived factor VIII. Currently available first-, second-, and third-generation rFVIII products include Recombinate; Kogenate FS/Helixate FS and ReFacto; and Advate, respectively. During the evolution of rFVIII products, either full-length or B-domain-deleted factor VIII were transfected into immortalized cell lines. The B-domain-deleted product, ReFacto, has resulted in an additional method to monitor factor VIII levels. The third-generation products offer the theoretical advantage of being produced without human and/or animal proteins. Upon initial introduction into the marketplace, the newer products have a higher cost. However, when analyzing historical trends, the prices of these products are almost equivalent to first-generation products within 3 years of licensure. Thus, the initial cost of the product may be a minimal issue in the medical decision process when selecting rFVIII replacement therapy.

  5. A post-marketing safety and efficacy assessment of a monoclonal antibody purified high-purity factor VIII concentrate.

    Science.gov (United States)

    Hay, C R; Lee, C A; Savidge, G

    1996-01-01

    The identification of infrequent side-effects of clotting factor concentrates, undetected by clinical trials, is facilitated by post-marketing surveillance. We present a post-marketing surveillance study in which 97 patients with haemophilia A, attending three haemophilia centres, were treated over a median follow-up period of 284 days (range 1-1074), and a total follow-up period of 30,080 days, with a pasteurized immunoaffinity purified factor VIII concentrate (Monoclate-P, Armour, Collegeville, USA). 5216 infusions, using 10,527,000 units of Monoclate-P, were carried out, mostly for routine haemarthroses or prophylaxis. No new inhibitors were observed during the study. At the start of the study 60/97 were HIV seropositive, 67/97 HBs antibody positive, 12 HbsAb negative and the remainder HBsAb positive before the study period. 13/14 tested were HAV seropositive at the beginning of the study. One patient became HAV seropositive during the study period, an infection thought to be community acquired. No other seroconversions were observed. Only one mild transfusion reaction was observed. This study confirms the safety and efficacy of Monoclate-P. Post-marketing surveillance or nationally organized pharmaco-vigilance should be practiced more widely to enable identification of low-frequency side-effects of treatment.

  6. Factoring in Factor VIII With Acute Ischemic Stroke.

    Science.gov (United States)

    Siegler, James E; Samai, Alyana; Albright, Karen C; Boehme, Amelia K; Martin-Schild, Sheryl

    2015-10-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. © The Author(s) 2015.

  7. Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia a

    NARCIS (Netherlands)

    C.L. Eckhardt (Corien); A.S. van Velzen (Alice); M.A.D. Peters (Marjolein); J. Astermark (Jan); P.P. Brons; G. Castaman (Giancarlo); M.H. Cnossen (Marjon); N. Dors (N.); C. Escuriola-Ettingshausen (Carmen); K. Hamulyák (K.); D.P. Hart (Daniel); C.R.M. Hay (Charles R.); S. Haya (Saturnino); W.L. van Heerde; C. Hermans (Cédric); M. Holmström (Margareta); V. Jimenez-Yuste (Victor); R.D. Keenan (Russell); R. Klamroth (Robert); B.A.P. Laros-Van Gorkom (Britta); F.W.G. Leebeek (Frank); R. Liesner (Ri); A. Mäkipernaa (Anne); C. Male (Christoph); E.P. Mauser-Bunschoten (Eveline); M.G. Mazzucconi (Maria); S. McRae (Simon); K. Meijer (K.); M. Mitchell (Michael); M. Morfini (Massimo); M.R. Nijziel (Marten); J. Oldenburg (Jan); K. Peerlinck; P. Petrini (Pia); H. Platokouki (Helena); S.E. Reitter-Pfoertner (Sylvia); E. Santagostino (Elena); P. Schinco (Piercarla); F.J.W. Smiers (Frans); K.D. Siegmund (Kimberly); A. Tagliaferri (Annarita); T.T. Yee (Thynn); P.W. Kamphuisen (Pieter Willem); J.G. van der Bom (Anske); K. Fijnvandraat

    2013-01-01

    textabstractNeutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into

  8. The influence of prophylactic factor VIII in severe hemophilia A

    Science.gov (United States)

    Gissel, Matthew; Whelihan, Matthew F; Ferris, Lauren A; Mann, Kenneth G; Rivard, Georges E; Brummel-Ziedins, Kathleen E

    2013-01-01

    Introduction Hemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Aim To evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe hemophilia utilizing both empirical and computational models. Methods We investigated twenty-five clinically severe hemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. Results Due to prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from hemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk. PMID:21899664

  9. Prevalence of IgG antibodies to human parvovirus B19 in haemophilia children treated with recombinant factor (F)VIII only or with at least one plasma-derived FVIII or FIX concentrate: results from the French haemophilia cohort.

    Science.gov (United States)

    Gaboulaud, Valérie; Parquet, Armelle; Tahiri, Cedric; Claeyssens, Ségolène; Potard, Valérie; Faradji, Albert; Peynet, Jocelyne; Costagliola, Dominique

    2002-02-01

    Human parvovirus B19 (B19) has been transmitted by some brands of virally attenuated plasma-derived factor VIII (FVIII) or IX (FIX) concentrates. To quantify the differences of human parvovirus B19 risk transmission between albumin-stabilized recombinant factor and plasma-derived factor, we studied the prevalence of IgG antibodies to B19 (anti-B19) in 193 haemophiliac children between 1 and 6-years of age who had previously been treated with albumin-stabilized recombinant FVIII only (n = 104), and in children previously treated with solvent/detergent high-purity non-immunopurified and non-nanofiltered FVIII or IX concentrates (n = 89). Association between the prevalence of anti-B19 and the treatment group was analysed using multivariate logistic regression. Age, severity and type of haemophilia, number of cumulative days of exposure to factor VIII or IX, previous history of red blood cells or plasma transfusion were considered as potential confounding variables. A higher prevalence of anti-B19 was found in children previously treated with solvent/detergent high-purity non-immunopurified and non-nanofiltered FVIII or IX concentrates than in children treated with albumin- stabilized recombinant FVIII only (OR: 22.3; CI: 7.9-62.8), independently of the other factors studied.

  10. Development and characterization of recombinant ovine coagulation factor VIII.

    Directory of Open Access Journals (Sweden)

    Philip M Zakas

    Full Text Available Animal models of the bleeding disorder, hemophilia A, have been an integral component of the biopharmaceutical development process and have facilitated the development of recombinant coagulation factor VIII (fVIII products capable of restoring median survival of persons with hemophilia A to that of the general population. However, there remain several limitations to recombinant fVIII as a biotherapeutic, including invasiveness of intravenous infusion, short half-life, immunogenicity, and lack of availability to the majority of the world's population. The recently described ovine model of hemophilia A is the largest and most accurate phenocopy. Affected sheep die prematurely due to bleeding-related pathogenesis and display robust adaptive humoral immunity to non-ovine fVIII. Herein, we describe the development and characterization of recombinant ovine fVIII (ofVIII to support further the utility of the ovine hemophilia A model. Full-length and B-domain deleted (BDD ofVIII cDNAs were generated and demonstrated to facilitate greater biosynthetic rates than their human fVIII counterparts while both BDD constructs showed greater expression rates than the same-species full-length versions. A top recombinant BDD ofVIII producing baby hamster kidney clone was identified and used to biosynthesize raw material for purification and biochemical characterization. Highly purified recombinant BDD ofVIII preparations possess a specific activity nearly 2-fold higher than recombinant BDD human fVIII and display a differential glycosylation pattern. However, binding to the carrier protein, von Willebrand factor, which is critical for stability of fVIII in circulation, is indistinguishable. Decay of thrombin-activated ofVIIIa is 2-fold slower than human fVIII indicating greater intrinsic stability. Furthermore, intravenous administration of ofVIII effectively reverses the bleeding phenotype in the murine model of hemophilia A. Recombinant ofVIII should facilitate

  11. Successful Pregnancy in a Patient with Combined Deficiency of Factor V and Factor VIII.

    Science.gov (United States)

    El Adib, Ahmed Ghassan; Majdi, Farah; Dilai, Mohamed Othmane; Asmouki, Hamid; Bassir, Ahlam; Harou, Karam; Soumani, Abderraouf; Younous, Said; Mahmal, Lahoucine

    2014-01-01

    Inherited combined factor V and factor VIII deficiency (F5F8D) is autosomal recessive transmission disorder. Epistaxis, postsurgical bleeding, and menorrhagia are the most common symptoms. The risk of miscarriage and placental abruption is consequent. We report a case of successful pregnancy in a patient with F5F8D. 20-year-old woman, born of consanguineous parents, third gestate, first parity, two miscarriages, admitted for child birth of a spontaneous pregnancy estimated at 38 weeks and was diagnosed with F5F8D. At admission, patient was hemodynamically stable, with good obstetric conditions. The biologic results showed low levels of PT (52%), factor V (7%), and factor VIII (5%), and the activated partial thromboplastin time was prolonged (68,6%). Parturient was admitted in intensive care unit, maternal and fetal monitoring was performed. Fresh frozen plasma (FFP) and factor VIII concentrates were perfused at the induction of labor. Analgesia used fentanyl titration. The delivery gave birth to a newborn male, with Apgar 10/10 and 3000 g. The puerperium was simple without any important bleeding. Laboratory tests for the newborn were acceptable. Little literature is available on this subject and there are no guidelines available concerning pregnancy; we chose to prescribe a combination of factor VIII concentrate and FFP in pre-, per- and postpartum. The same protocol was successfully used in a patient before dental extraction and prostatectomy. Vaginal delivery is possible, as our case. Management by multidisciplinary team is recommended.

  12. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A.

    Science.gov (United States)

    Rangarajan, Savita; Walsh, Liron; Lester, Will; Perry, David; Madan, Bella; Laffan, Michael; Yu, Hua; Vettermann, Christian; Pierce, Glenn F; Wong, Wing Y; Pasi, K John

    2017-12-28

    Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue, and the central nervous system. Although successful gene transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding region has precluded improved outcomes with gene therapy in patients with hemophilia A. We infused a single intravenous dose of a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men with severe hemophilia A. Participants were enrolled sequentially into one of three dose cohorts (low dose [one participant], intermediate dose [one participant], and high dose [seven participants]) and were followed through 52 weeks. Factor VIII activity levels remained at 3 IU or less per deciliter in the recipients of the low or intermediate dose. In the high-dose cohort, the factor VIII activity level was more than 5 IU per deciliter between weeks 2 and 9 after gene transfer in all seven participants, and the level in six participants increased to a normal value (>50 IU per deciliter) that was maintained at 1 year after receipt of the dose. In the high-dose cohort, the median annualized bleeding rate among participants who had previously received prophylactic therapy decreased from 16 events before the study to 1 event after gene transfer, and factor VIII use for participant-reported bleeding ceased in all the participants in this cohort by week 22. The primary adverse event was an elevation in the serum alanine aminotransferase level to 1.5 times the upper limit of the normal range or less. Progression of preexisting chronic arthropathy in one participant was the only serious adverse event. No neutralizing antibodies to factor VIII were detected. The infusion of AAV5-hFVIII-SQ was associated with the sustained normalization of factor VIII activity level over a period of 1 year in six of seven participants who received a high dose, with

  13. Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

    Directory of Open Access Journals (Sweden)

    Nicholas B. Abt

    2014-01-01

    Full Text Available Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient’s plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered.

  14. Acquired high titre factor VIII inhibitor with underlying polyarteritis nodosa.

    Science.gov (United States)

    Snowden, J A; Hutchings, M; Spearing, R; Patton, W N

    1997-05-01

    We here present the case of a 70-year-old woman referred to our unit for investigation of bleeding. Investigations confirmed a high titre acquired Factor VIII inhibitor. In association there was relapse of systemic illness associated with anti-neutrophil cytoplasmic antibodies (atypical pattern) for which she had been treated five years previously. Immunosuppression was attempted, but it failed to have an impact both on the inhibitor titre and on the underlying disorder. The patient died from multi-organ failure and massive chest hemorrhage. Post-mortem showed necrotizing vasculitis of medium sized vessels at several sites, including the kidney, consistent with a diagnosis of polyarteritis nodosa. Although it is well recognised that Factor VIII inhibitors are found in conjunction with autoimmune disorders, this case is significant in that it is the first associated with histologically proven polyarteritis nodosa type vasculitis. The case illustrates the difficulties in the investigation and management of patients with acquired high titre Factor VIII inhibitors.

  15. Factor VIII-associated antigen in human lymphatic endothelium.

    Science.gov (United States)

    Nagle, R B; Witte, M H; Martinez, A P; Witte, C L; Hendrix, M J; Way, D; Reed, K

    1987-03-01

    Lymphatic vascular endothelium both on tissue section and in culture exhibits positivity for Factor VIII-associated antigen although staining is generally less intense and more spotty than in comparable blood vascular endothelium. Lymphatic endothelium also exhibits Weibel-Palade bodies. Neither marker, therefore, reliably distinguishes blood vascular endothelium from lymphatic endothelium.

  16. In vivo recovery and safety of human factor VIII product AAFACT in patients with haemophilia A

    NARCIS (Netherlands)

    Vossebeld, P. J. M.; Tissing, M. H.; van den Berg, H. M.; Leebeek, F. W. G.; de Goede-Bolder, A.; Novakova, I. R. O.; Gerrits, W. B. J.; Peters, M.; Koopman, M. M. W.; Faber, A.; Hiemstra, H.; Grob, P.; Strengers, P. F. W.

    2003-01-01

    AAFACT, a monoclonal purified, solvent/detergent treated human plasma-derived coagulation factor VIII concentrate obtained from plasma of voluntary, non-remunerated blood donors, is manufactured and marketed in the Netherlands by Sanquin Plasma Products since 1995. In a postmarketing surveillance

  17. 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

  18. Progress toward inducing immunologic tolerance to factor VIII

    OpenAIRE

    Scott, David W.; Pratt, Kathleen P.; Miao, Carol H.

    2013-01-01

    A major problem in treating hemophilia A patients with therapeutic factor VIII (FVIII) is that 20% to 30% of these patients produce neutralizing anti-FVIII antibodies. These antibodies block (inhibit) the procoagulant function of FVIII and thus are termed “inhibitors.” The currently accepted clinical method to attempt to eliminate inhibitors is immune tolerance induction (ITI) via a protocol requiring intensive FVIII treatment until inhibitor titers drop. Although often successful, ITI is ext...

  19. Characterization of five partial deletions of the factor VIII gene

    International Nuclear Information System (INIS)

    Youssoufian, H.; Antonarakis, S.E.; Aronis, S.; Tsiftis, G.; Phillips, D.G.; Kazazian, H.H. Jr.

    1987-01-01

    Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. By using cloned DNA probes, the authors have characterized the following five different partial deletions of the factor VIII gene from a panel of 83 patients with hemophilia A: (i) a 7-kilobase (kb) deletion that eliminates exon 6; (ii) a 2.5-kb deletion that eliminates 5' sequences of exon 14; (iii) a deletion of at least 7 kb that eliminates exons 24 and 25; (iv) a deletion of at least 16 kb that eliminates exons 23-25; and (v) a 5.5-kb deletion that eliminates exon 22. The first four deletions are associated with severe hemophilia A. By contrast, the last deletion is associated with moderate disease, possibly because of in-frame splicing from adjacent exons. None of those patients with partial gene deletions had circulating inhibitors to factor VIII. One deletion occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of the maternal grandfather. These observations demonstrate that de novo deletions of X-linked genes can occur in either male or female gametes

  20. Chromogenic Factor VIII Assays for Improved Diagnosis of Hemophilia A.

    Science.gov (United States)

    Rodgers, Susan; Duncan, Elizabeth

    2017-01-01

    Hemophilia A is an inherited bleeding disorder caused by a reduced level of factor VIII coagulant activity (FVIII:C) in blood. Bleeding episodes may occur spontaneously in the severe form of hemophilia or after trauma in the milder forms. It is important that patients are diagnosed correctly, which includes placing them into the correct severity category of the disorder so that appropriate treatment can be given. Diagnosis is made by determination of the amount of FVIII:C in the blood, usually using a one-stage factor VIII:C assay. However, approximately one third of patients with mild or moderate hemophilia will have much lower results by the chromogenic assay, with some of them having normal results by the one-stage assay. The chromogenic factor VIII assay is used in some specialized hemophilia reference centers and is recommended for the diagnosis of mild hemophilia A, as this assay is considered to better reflect the severity status of hemophilia patients than the one-stage assay.

  1. Home therapy with continuous infusion of factor VIII after minor surgery or serious haemorrhage.

    Science.gov (United States)

    Varon, D; Schulman, S; Bashari, D; Martinowitz, U

    1996-10-01

    Administration of factor VIII (F VIII) concentrates by continuous infusion is now routinely used at several haemophilia centers but almost exclusively for hospitalized patients. We evaluated various aspects of home therapy with continuous infusion of an immunoaffinity purified F VIII concentrate (Monoclate P®, Armour) in patients who would normally have been treated with high doses in bolus injections or with continuous infusion as in-patients. Twenty haemophilia A patients, eight after minor surgery and 12 for serious haemorrhage, received continuous infusion with undiluted F VIII by a minipump for a mean of 0.9 days in the hospital, followed by 3.3 days at home. Infusion bags were exchanged every 2.5 days. No haemorrhagic complications occurred, and five haemorrhages that had been resistant to treatment with bolus injections responded promptly to the continuous infusion. There were no technical problems and patient compliance and acceptance was good. We find this mode of therapy safe, efficacious and convenient for the patients as well as for the staff.

  2. A close insight to factor VIII inhibitor in the congenital hemophilia A.

    Science.gov (United States)

    Tabriznia-Tabrizi, Shamsoreza; Gholampour, Marzie; Mansouritorghabeh, Hassan

    2016-09-01

    Hemophilia A (HA) has an X-linked pattern of inheritance and is the most common of the hemorrhagic disorders. HA is caused by a decreased or deficiency of the functional clotting factor VIII (FVIII) and effects 1 in 5000-10,000 male births. The common treatment for hemophilia is replacement therapy by plasma-derived or recombinant FVIII. Approximately 20-30% of people with a severe type of HA develop an inhibitor and this phenomenon is the main challenge in the management of these patients. Genetic factors and environmental determinants contribute to inhibitor development. Here, the roles of various genetic and environmental factors such as the type of FVIII concentrate used, the number of exposure days, and peak treatment time will be discussed in detail. It seems this information is helpful for hematologists. A literature review was done in January 2016 on PubMed and Scopus using the following keywords:' h(a)emophilia A & factor VIII inhibitor', 'h(a)emophilia A & factor VIII alloantibody', 'h(a)emophilia A & inhibitor'. There was no time limitation; however, there was an English language limitation placed on the articles selected. Expert commentary: Influential genetic and environmental factors in developing inhibitors have been discussed. Most of the risk factors are related to previously untreated patients with hemophili.

  3. Acquired factor VIII inhibitor syndrome: A rare cause of hematuria

    Directory of Open Access Journals (Sweden)

    Muthuvel Seral Kannan

    2015-01-01

    Full Text Available A 50-year-old woman presented with gross hematuria for 1 month. Clinical examinations, laboratory investigations, ultrasound and contrast computed tomography were normal, except anemia. Cystoscopy revealed bloody efflux from the right side. Retrograde pyelogram showed filling defect in the renal pelvis and biopsy was inconclusive. Renal angiogram was normal. She developed ecchymosis on the right thigh and arm with elevated activated partial thromboplastin time. The partial thromboplastin time correction study and Bethesda study confirmed the presence of acquired factor VIII inhibitor (acquired hemophilia. With flexible ureterorenoscopy, the mass in the renal pelvis was removed and its histopathology revealed clotted blood. The patient was subsequently managed with steroids and Factor eight inhibitor bypass activity.

  4. Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor

    International Nuclear Information System (INIS)

    Repke, D.; Gemmell, C.H.; Guha, A.; Turitto, V.T.; Nemerson, Y.; Broze, G.J. Jr.

    1990-01-01

    The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a wall shear rate of 57, 300, or 1130 sec -1 . The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2 endash-to 3 endash fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia

  5. 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

  6. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, J.C.; Huang, M.; Roth, D.A.; Furie, B.C.; Furie, B. (Wyeth); (MBL)

    2008-06-03

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca{sup 2+} and two Cu{sup 2+} ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  7. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Chi Ki Ngo,J.; Huang, M.; Roth, D.; Furie, B.; Furie, B.

    2008-01-01

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca(2+) and two Cu(2+) ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  8. Diagnostic accuracy study of a factor VIII ELISA for detection of factor VIII antibodies in congenital and acquired haemophilia A.

    Science.gov (United States)

    Batty, Paul; Moore, Gary W; Platton, Sean; Maloney, James C; Palmer, Ben; Bowles, Louise; Pasi, K John; Rangarajan, Savita; Hart, Daniel P

    2015-10-01

    Antibody formation to factor VIII (FVIII) remains the greatest clinical and diagnostic challenge to the haemophilia-treating physician. Current guidance for testing for inhibitory FVIII antibodies (inhibitors) recommends the functional Nijmegen-Bethesda assay (NBA). A FVIII ELISA offers a complementary, immunological approach for FVIII antibody testing. It was the aim of this study to retrospectively evaluate the performance of a FVIII ELISA (index) for detection of FVIII antibodies, compared with the NBA (reference). All samples sent for routine FVIII antibody testing at two haemophilia Comprehensive Care Centres, were tested in parallel using the NBA and a solid-phase, indirect FVIII ELISA kit (Immucor). A total of 497 samples from 239 patients (severe haemophilia A=140, non-severe haemophilia A=85, acquired haemophilia A=14) were available for analysis. Sixty-three samples tested positive by the NBA (prevalence 12.7%, 95% confidence interval [CI], 9.9-15.9 %), with a median inhibitor titre of 1.2 BU/ml (range 0.7-978.0). The FVIII ELISA demonstrated a specificity of 94.0% (95%CI, 91.3-96.0), sensitivity of 77.8% (95%CI, 65.5-87.3), negative predictive value of 96.7% (95%CI, 94.5-98.2), positive predictive value 65.3% (95%CI, 53.5-76.0), negative likelihood ratio 0.2 (95%CI, 0.1-0.4), positive likelihood ratio 13.0 (95%CI, 8.7-19.3) and a diagnostic odds ratio of 54.9 (95%CI, 27.0-112.0). Strong positive correlation (r=0.77, pNBA (log adjusted) and FVIII ELISA optical density. In conclusion, FVIII ELISA offers a simple, specific, surveillance method enabling batch testing of non-urgent samples for the presence of FVIII antibodies.

  9. The F309S mutation increases factor VIII secretion in human cell line

    Directory of Open Access Journals (Sweden)

    Daianne Maciely Carvalho Fantacini

    2016-06-01

    Full Text Available ABSTRACT OBJECTIVES: The capacity of a human cell line to secrete recombinant factor VIII with a F309S point mutation was investigated, as was the effect of the addition of chemical chaperones (betaine and sodium-4-phenylbutyrate on the secretion of factor VIII. METHODS: This work used a vector with a F309S mutation in the A1 domain to investigate FVIII production in the HEK 293 human cell line. Factor VIII activity was measured by chromogenic assay. Furthermore, the effects of chemical drugs on the culture were evaluated. RESULTS: The addition of the F309S mutation to a previously described FVIII variant increased FVIII secretion by 4.5 fold. Moreover, the addition of betaine or sodium-4-phenylbutyrate increased the secretion rate of FVIIIΔB proteins in HEK 293 cells, but the same effect was not seen for FVIIIΔB-F309S indicating that all the recombinant protein produced had been efficiently secreted. CONCLUSION: Bioengineering factor VIII expressed in human cells may lead to an efficient production of recombinant factor VIII and contribute toward low-cost coagulation factor replacement therapy for hemophilia A. FVIII-F309S produced in human cells can be effective in vivo.

  10. Hemodialysis in a patient with severe hemophilia A and factor VIII inhibitor.

    Science.gov (United States)

    Gopalakrishnan, Natarajan; Usha, Thiruvengadam; Thopalan, Balasubramaniyan; Dhanapriya, Jeyachandran; Dineshkumar, Thanigachalam; Thirumalvalavan, Kaliaperumal; Sakthirajan, Ramanathan

    2016-10-01

    Hemophilia A is a hereditary X-linked recessive disease caused by mutations in the gene encoding factor VIII (FVIII), occurring in 1 out of 10,000 persons. Life expectancy and quality of life have dramatically improved recently in patients with hemophilia. Chronic kidney disease and need for renal replacement therapy in these patients are rare. The development of inhibitors to FVIII is the most serious complication of hemophilia and makes treatment of bleeds very challenging. We describe here a 28-year-old male patient with severe hemophilia A with presence of factor VIII inhibitor, who had end stage renal disease. Central venous access device was inserted along with infusion of factor eight inhibitor bypass activity before and after the procedure. He is currently on thrice weekly hemodialysis and doing well for 6 months without bleeding episodes. To our knowledge, hemophilia A with factor VIII inhibitor managed with hemodialysis has not been reported so far. © 2016 International Society for Hemodialysis.

  11. 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)

  12. 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

  13. 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

  14. Analysis of mutations in the entire coding sequence of the factor VIII gene

    Energy Technology Data Exchange (ETDEWEB)

    Bidichadani, S.I.; Lanyon, W.G.; Connor, J.M. [Glascow Univ. (United Kingdom)] [and others

    1994-09-01

    Hemophilia A is a common X-linked recessive disorder of bleeding caused by deleterious mutations in the gene for clotting factor VIII. The large size of the factor VIII gene, the high frequency of de novo mutations and its tissue-specific expression complicate the detection of mutations. We have used a combination of RT-PCR of ectopic factor VIII transcripts and genomic DNA-PCRs to amplify the entire essential sequence of the factor VIII gene. This is followed by chemical mismatch cleavage analysis and direct sequencing in order to facilitate a comprehensive search for mutations. We describe the characterization of nine potentially pathogenic mutations, six of which are novel. In each case, a correlation of the genotype with the observed phenotype is presented. In order to evaluate the pathogenicity of the five missense mutations detected, we have analyzed them for evolutionary sequence conservation and for their involvement of sequence motifs catalogued in the PROSITE database of protein sites and patterns.

  15. Idiopathic factor VIII inhibitor autoantibody in a man presented after accident.

    NARCIS (Netherlands)

    Mansouritorghabeh, H.; Lak, M.; Heerde, W.L. van

    2009-01-01

    Acquired hemophilia A is a rare but severe autoimmune bleeding disorder caused by autoantibodies against factor VIII activity and is a potentially life-threatening hemorrhagic disorder. The incidence of acquired hemophilia A has been estimated as 1.48 cases per million per year. The overall rate of

  16. Safety and Efficacy of BAY 94-9027, a Prolonged-Half-Life Factor VIII

    DEFF Research Database (Denmark)

    Reding, M T; Ng, H J; Poulsen, Lone Hvitfeldt

    2017-01-01

    BACKGROUND: BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) conjugates in a site-specific manner with polyethylene glycol. OBJECTIVE: Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A PATIEN...

  17. [Determinants of the elevated factor VIII activity in patients following venous thromboembolism].

    Science.gov (United States)

    Lech, Monika; Kościelniak, Barbara; Bryk, Agata; Undas, Anetta

    2016-01-01

    Activity of factor VIII (FVIII) increased above 150% of reference range predisposes to venous thromboembolism (VTE). The aim of this study was to identify predictors of increased FVIII activity in patients following VTE. 241 (38% men) patients presented due to objectively documented VTE episode at least 3 months ago were included in this study. FVIII activity was measured using a clotting assay on the analyzer BCS XP. Among 241 patients with VTE, activity of FVIII above 150% (FVIII ≥ 150%) was observed in 96 (40%). These patients were older (p = 0.035) and their concentrations of fibrinogen and C-reactive protein (CRP) were higher by 12% and 88% (p 200%) and this group was also older (p = 0.015), more patients in that group had obesity (p = 0.015), idiopathic VTE (p = 0.043), less of them had positive family history (p = 0.010) and they were characterized by fibrinogen and CRP increased by 28% (p 200% (p = 0.016). The activity of FVIII in patients after VTE episode is influenced by age, concentration of fibrinogen, bilirubin, hemoglobin, glucose, CRP and homocysteine. Our results suggest the role of environmental factors, mainly inflammatory response in maintaining elevated FVIII activity following VTE.

  18. Specific membrane binding of factor VIII is mediated by O-phospho-L-serine, a moiety of phosphatidylserine.

    Science.gov (United States)

    Gilbert, G E; Drinkwater, D

    1993-09-21

    Phosphatidylserine, a negatively charged lipid, is exposed on the platelet membrane following cell stimulation, correlating with the expression of factor VIII receptors. We have explored the importance of the negative electrostatic potential of phosphatidylserine vs chemical moieties of phosphatidylserine for specific membrane binding of factor VIII. Fluorescein-labeled factor VIII bound to membranes containing 15% phosphatidic acid, a negatively charged phospholipid, with low affinity compared to phosphatidylserine-containing membranes. Binding was not specific as it was inhibited by other proteins in plasma. Factor VIII bound to membranes containing 10% phosphatidylserine in spite of a varying net charge provided by 0-15% stearylamine, a positively charged lipid. The soluble phosphatidylserine moiety, O-phospho-L-serine, inhibited factor VIII binding to phosphatidylserine-containing membranes with a Ki of 20 mM, but the stereoisomer, O-phospho-D-serine, was 5-fold less effective. Furthermore, binding of factor VIII to membranes containing synthetic phosphatidyl-D-serine was 5-fold less than binding to membranes containing phosphatidyl-L-serine. Membranes containing synthetic phosphatidyl-L-homoserine, differing from phosphatidylserine by a single methylene, supported high-affinity binding, but it was not specific as factor VIII was displaced by other plasma proteins. O-Phospho-L-serine also inhibited the binding of factor VIII to platelet-derived microparticles with a Ki of 20 mM, and the stereoisomer was 4-fold less effective. These results indicate that membrane binding of factor VIII is mediated by a stereoselective recognition O-phospho-L-serine of phosphatidylserine and that negative electrostatic potential is of lesser importance.

  19. Potency determination of factor VIII and factor IX for new product labelling and postinfusion testing: challenges for caregivers and regulators.

    Science.gov (United States)

    Dodt, J; Hubbard, A R; Wicks, S J; Gray, E; Neugebauer, B; Charton, E; Silvester, G

    2015-07-01

    A workshop organized by the European Medicines Agency and the European Directorate for the Quality of Medicines and HealthCare was held in London, UK on November 28-29, 2013, to provide an overview of the current knowledge of the characterization of new factor VIII (FVIII) and factor IX (FIX) concentrates with respect to potency assays and testing of postinfusion material. The objective was to set the basis for regulatory authorities' discussion on the most appropriate potency assay for the individual products, and European Pharmacopoeia (Ph. Eur.) discussion on whether to propose revision of the Ph. Eur. monographs with respect to potency assays in the light of information on new FVIII and FIX concentrates. The workshop showed that for all products valid assays vs. the international concentrate standards were obtained and potency could be expressed in International Units. The Ph. Eur. chromogenic potency assay gave valid assay results which correlate with in vivo functionality of rFVIII products. For some modified rFVIII products and all modified rFIX products, one-stage clotting assay methods result in different potencies depending on the activated partial thromboplastin time reagent. As a consequence, monitoring of patients' postinfusion levels is challenging but it was pointed out that manufacturers are responsible for providing the users with appropriate information for use and laboratory testing of their product. Strategies to avoid misleading determination of patents' plasma levels, e.g. information on suitable assays, laboratory standards or correction factors were discussed. © 2015 John Wiley & Sons Ltd.

  20. Haemophilia A: Database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene

    Energy Technology Data Exchange (ETDEWEB)

    Tuddenham, E.G.D. (Clinical Research Centre, Harrow (United Kingdom)); Cooper, D.N. (Thrombosis Research Inst., London (United Kingdom)); Gitschier, J. (Univ. of California, San Francisco (United States)); Higuchi, M.; Kazazian, H.H.; Antonarakis, S.E. (Johns Hopkins Univ., Baltimore (United States)); Hoyer, L.W. (American Red Cross, Rockville (United States)); Yoshioka, A. (Nara Medical Coll., Kashihara City (Japan)); Peake, I.R. (Royal Hallamshire Hospital, Sheffield (United Kingdom)); Schwaab, R. (Inst. fuer Klinische Biochemie der Univ. Bonn (West Germany)); Lavergne, J.M. (Hopital de Bicetre (France)); Giannelli, F. (Guy' s Hospital, London (United Kingdom))

    1991-09-25

    Mutations at the factor VIII gene locus causing Haemophilia A have now been identified in many patients from a many ethnic groups. Earlier studies used biased methods which detected repetitive mutations at a few CG dinucleotides. More recently rapid gene scanning methods have uncovered an extreme diversity of mutations. Over 80 different point mutations, 6 insertions, 7 small deletions, and 60 large deletions have been characterized. Repetitive mutation has been proved for at least 16 CpG sites. All nonsense mutations cause severe disease. Most missense mutations appear to cause instability of the protein, but some are associated with production of dysfunctional factor VIII molecules, thereby localizing functionally critical regions of the cofactor. Variable phenotype has been observed in association with three of the latter class of genotype. This catalogue of gene lesions in Haemophilia A will be updated annually.

  1. Detection of Intracellular Factor VIII Protein in Peripheral Blood Mononuclear Cells by Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Gouri Shankar Pandey

    2013-01-01

    Full Text Available Flow cytometry is widely used in cancer research for diagnosis, detection of minimal residual disease, as well as immune monitoring and profiling following immunotherapy. Detection of specific host proteins for diagnosis predominantly uses quantitative PCR and western blotting assays. In this study, we optimized a flow cytometry-based detection assay for Factor VIII protein in peripheral blood mononuclear cells (PBMCs. An indirect intracellular staining (ICS method was standardized using monoclonal antibodies to different domains of human Factor VIII protein. The FVIII protein expression level was estimated by calculating the mean and median fluorescence intensities (MFI values for each monoclonal antibody. ICS staining of transiently transfected cell lines supported the method's specificity. Intracellular FVIII protein expression was also detected by the monoclonal antibodies used in the study in PBMCs of five blood donors. In summary, our data suggest that intracellular FVIII detection in PBMCs of hemophilia A patients can be a rapid and reliable method to detect intracellular FVIII levels.

  2. Construction of a mouse model of factor VIII deficiency by gene targeting

    Energy Technology Data Exchange (ETDEWEB)

    Bi, L.; Lawler, A.; Gearhart, J. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others

    1994-09-01

    To develop a small animal model of hemophilia A for gene therapy experiments, we set out to construct a mouse model for factor VIII deficiency by gene targeting. First, we screened a mouse liver cDNA library using a human FVIII cDNA probe. We cloned a 2.6 Kb partial mouse factor VIII cDNA which extends from 800 base pairs of the 3{prime} end of exon 14 to the 5{prime} end of exon 26. A mouse genomic library made from strain 129 was then screened to obtain genomic fragments covering the exons desired for homologous recombination. Two genomic clones were obtained, and one covering exon 15 through 22 was used for gene targeting. To make gene targeting constructs, a 5.8 Kb genomic DNA fragment covering exons 15 to 19 of the mouse FVIII gene was subcloned, and the neo expression cassette was inserted into exons 16 and 17 separately by different strategies. These two constructs were named MFVIIIC-16 and MFVIIIC-17. The constructs were linearized and transfected into strain 129 mouse ES cells by electroporation. Factor VIII gene-knockout ES cell lines were selected by G-418 and screened by genomic Southern blots. Eight exon 16 targeted cell lines and five exon 17 targeted cell lines were obtained. Three cell lines from each construct were injected into blastocysts and surgically transferred into foster mothers. Multiple chimeric mice with 70-90% hair color derived from the ES-cell genotype were seen with both constructs. Germ line transmission of the ES-cell genotype has been obtained for the MFVIIIC-16 construct, and multiple hemophilia A carrier females have been identified. Factor VIII-deficient males will be conceived soon.

  3. Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models

    OpenAIRE

    Siner, Joshua I.; Samelson-Jones, Benjamin J.; Crudele, Julie M.; French, Robert A.; Lee, Benjamin J.; Zhou, Shanzhen; Merricks, Elizabeth; Raymer, Robin; Nichols, Timothy C.; Camire, Rodney M.; Arruda, Valder R.

    2016-01-01

    Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645–1648) in the design of B-domain–deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by fu...

  4. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

    Science.gov (United States)

    Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

    2009-03-01

    Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

  5. 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

  6. Population pharmacokinetics of recombinant coagulation factor VIII-SingleChain in patients with severe hemophilia A.

    Science.gov (United States)

    Zhang, Y; Roberts, J; Tortorici, M; Veldman, A; St Ledger, K; Feussner, A; Sidhu, J

    2017-06-01

    Essentials rVIII-SingleChain is a unique recombinant factor VIII (FVIII) molecule. A population pharmacokinetic model was based on FVIII activity of severe hemophilia A patients. The model was used to simulate factor VIII activity-time profiles for various dosing scenarios. The model supports prolonged dosing of rVIII-SingleChain with intervals of up to twice per week. Background Single-chain recombinant coagulation factor VIII (rVIII-SingleChain) is a unique recombinant coagulation factor VIII molecule. Objectives To: (i) characterize the population pharmacokinetics (PK) of rVIII-SingleChain in patients with severe hemophilia A; (ii) identify correlates of variability in rVIII-SingleChain PK; and (iii) simulate various dosing scenarios of rVIII-SingleChain. Patients/Methods A population PK model was developed, based on FVIII activity levels of 130 patients with severe hemophilia A (n = 91 for ≥ 12-65 years; n = 39 for  85% and > 93% of patients were predicted to maintain FVIII activity level above 1 IU dL -1 , at all times with three-times-weekly dosing (given on days 0, 2, and 4.5) at the lowest (20 IU kg -1 ) and highest (50 IU kg -1 ) doses, respectively. For twice weekly dosing (days 0 and 3.5) of 50 IU kg -1 rVIII-SingleChain, 62-80% of patients across all ages were predicted to maintain a FVIII activity level above 1 IU dL -1 at day 7. Conclusions The population PK model adequately characterized rVIII-SingleChain PK, and the model can be utilized to simulate FVIII activity-time profiles for various dosing scenarios. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

  7. Nonneutralizing antibodies against factor VIII and risk of inhibitor development in severe hemophilia A.

    Science.gov (United States)

    Cannavò, Antonino; Valsecchi, Carla; Garagiola, Isabella; Palla, Roberta; Mannucci, Pier Mannuccio; Rosendaal, Frits R; Peyvandi, Flora

    2017-03-09

    The development of anti-factor VIII (FVIII) neutralizing antibodies (inhibitors) is the major complication in hemophilia A. Nonneutralizing antibodies (NNAs) have been detected in hemophilia patients and also in unaffected individuals. The aim of this study was to assess the prevalence of NNAs and to evaluate whether their presence is associated with the development of inhibitors in a cohort of previously untreated or minimally treated patients with hemophilia A; plasma samples of 237 patients with severe hemophilia A enrolled in the SIPPET trial were collected before any exposure to FVIII concentrates and analyzed for the presence of anti-FVIII NNAs. Patients were observed for the development of neutralizing antibodies. NNAs were found in 18 (7.6%) of 237 patients at screening, and there was a clear age gradient. Of those with NNAs, 7 patients subsequently developed an inhibitor for a cumulative incidence of 45.4% (95% confidence interval [CI], 19.5% to 71.3%); among the 219 patients without NNAs, 64 (29%) developed an inhibitor (cumulative incidence, 34.0%; 95% CI, 27.1%-40.9%). In Cox regression analyses, patients with NNAs at screening had an 83% higher incidence of inhibitor development than patients without NNAs (hazard ratio [HR], 1.83; 95% CI, 0.84-3.99). For high-titer inhibitors, the incidence rate had an almost threefold increase (HR, 2.74; 95% CI, 1.23-6.12). These associations did not materially change after adjustment. The presence of anti-FVIII NNAs in patients with severe hemophilia A who were not previously exposed to FVIII concentrates is associated with an increased incidence of inhibitors. © 2017 by The American Society of Hematology.

  8. Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy related hypertension and severe intrauterine growth retardation.

    Science.gov (United States)

    Witsenburg, C P J; Rosendaal, F R; Middeldorp, J M; Van der Meer, F J M; Scherjon, S A

    2005-01-01

    Recently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation. Plasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women. Mean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4). If the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.

  9. 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.

  10. Analysis of inversions in the factor VIII gene in Spanish hemophilia A patients and families

    Energy Technology Data Exchange (ETDEWEB)

    Domenech, M.; Tizzano, E.; Baiget, M. [Hospital de Sant Pau, Barcelona (Spain); Altisent, C. [Hospital Vall d`Hebron, Barcelona (Spain)

    1994-09-01

    Intron 22 is the largest intron of the factor VIII gene and contains a CpG island from which two additional transcripts originate. One of these transcripts corresponds to the F8A gene which have telomeric extragenic copies in the X chromosome. An inversion involving homologous recombination between the intragenic and the distal or proximal copies of the F8A gene has been recently described as a common cause of severe hemophilia A (HA). We analyzed intron 22 rearrangements in 195 HA patients (123 familial and 72 sporadic cases). According to factor VIII levels, our sample was classified as severe in 114 cases, moderate in 29 cases and mild in 52 cases. An intron 22 (F8A) probe was hybridized to Southern blots of BcII digested DNA obtained from peripheral blood. A clear pattern of altered bands identifies distal or proximal inversions. We detected an abnormal pattern identifying an inversion in 49 (25%) of the analyzed cases. 43% of severe HA patients (49 cases) showed an inversion. As expected, no inversion was found in the moderate and mild group of patients. We found a high proportion (78%) of the distal rearrangement. From 49 identified inversions, 33 were found in familial cases (27%), while the remaining 15 were detected in sporadic patients (22%) in support that this mutational event occurs with a similar frequency in familial or sporadic cases. In addition, we detected a significant tendency of distal inversion to occur more frequently in familial cases than in sporadic cases. Inhibitor development to factor VIII was documented in approximately 1/3 of the patients with inversion. The identification of such a frequent molecular event in severe hemophilia A patients has been applied in our families to carrier and prenatal diagnosis, to determine the origin of the mutation in the sporadic cases and to detect the presence of germinal mosaicism.

  11. Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A

    Science.gov (United States)

    Sherman, Alexandra; Biswas, Moanaro; Herzog, Roland W.

    2017-01-01

    Hemophilia A (coagulation factor VIII deficiency) is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies (“inhibitors”) remains. Overall, 20–30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response. New experimental therapies, such as gene and cell therapies, show promising results in pre-clinical studies in animal models of hemophilia. Examples include hepatic gene transfer with viral vectors, genetically engineered regulatory T cells (Treg), in vivo Treg induction using immune modulatory drugs, and maternal antigen transfer. Furthermore, an oral tolerance protocol is being developed based on transgenic lettuce plants, which suppressed inhibitor formation in hemophilic mice and dogs. Hopefully, some of these innovative approaches will reduce the risk of and/or more effectively eliminate inhibitor formation in future treatment of hemophilia A. PMID:29225598

  12. Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe hemophilia A, 2000-2011

    Science.gov (United States)

    Palmer, Benedict P.; Chalmers, Elizabeth A.; Hart, Daniel P.; Liesner, Ri; Rangarajan, Savita; Talks, Katherine; Williams, Michael; Hay, Charles R. M.

    2014-01-01

    The effect of recombinant factor VIII (rFVIII) brand on inhibitor development was investigated in all 407 severe hemophilia A previously untreated patients born in the United Kingdom (UK) between 1 January 2000 and 31 December 2011. Eighty-eight (22%) had been in the RODIN study. Information was extracted from the National Haemophilia Database. Because exposure days (EDs) were not known for some patients, time from first treatment was used as a surrogate for rFVIII exposure. An inhibitor developed in 118 (29%) patients, 60 high and 58 low titer, after a median (interquartile range) of 7.8 (3.3-13.5) months from first exposure and 16 (9-30) EDs. Of 128 patients treated with Kogenate Bayer/Helixate NexGen, 45 (35.2%, 95% confidence interval [CI] 27.4-43.8) developed an inhibitor compared with 42/172 (24.4%, 95% CI 18.6% to 31.4%) with Advate (P = .04). The adjusted hazard ratio (HR) (95% CI) for Kogenate Bayer/Helixate NexGen compared with Advate was 2.14 (1.12-4.10) (P = .02) for high titer and 1.75 (1.11-2.76) (P = .02) for all inhibitors. When excluding UK-RODIN patients, the adjusted HR (95% CI) for high-titer inhibitors was 2.00 (0.93-4.34) (P = .08). ReFacto AF was associated with a higher incidence of all, but not high-titer, inhibitors than Advate. These results will help inform debate around the relative immunogenicity and use of rFVIII brands. PMID:25339360

  13. Assessing patients' and caregivers' perspectives on stability of factor VIII products for haemophilia A

    DEFF Research Database (Denmark)

    DiBenedetti, D B; Coles, T M; Sharma, T

    2014-01-01

    Haemophilia A is a rare inherited bleeding disorder characterized by an inability of the blood to clot normally. Patients can experience spontaneous or trauma-induced joint and soft tissue bleeding and must keep coagulation factor VIII (FVIII) accessible at all times; thus, FVIII product storage...... challenges with storing FVIII products, especially storage away from home. More than half preferred storing FVIII products at room temperature vs. in the refrigerator for long periods of time. FVIII product accessibility, usage and storage affect disease management. Results support the need for more...... convenient and accessible FVIII products for patients in daily life and while travelling. In addition, the use of social media has potential value in recruiting this population....

  14. Analysis of factor VIII gene inversions in 164 unrelated hemophilia A families

    Energy Technology Data Exchange (ETDEWEB)

    Vnencak-Jones, L.; Phillips, J.A. III; Janco, R.L. [Vanderbilt Univ. School of Medicine, Nashville, TN (United States)] [and others

    1994-09-01

    Hemophilia A is an X-linked recessive disease with variable phenotype and both heterogeneous and wide spread mutations in the factor VIII (F8) gene. As a result, diagnostic carrier or prenatal testing often relies upon laborious DNA linkage analysis. Recently, inversion mutations resulting from an intrachromosomal recombination between DNA sequences in one of two A genes {approximately}500 kb upstream from the F8 gene and a homologous A gene in intron 22 of the F8 gene were identified and found in 45% of severe hemophiliacs. We have analyzed banked DNA collected since 1986 from affected males or obligate carrier females representing 164 unrelated hemophilia A families. The disease was sporadic in 37%, familial in 54% and in 10% of families incomplete information was given. A unique deletion was identified in 1/164, a normal pattern was observed in 110/164 (67%), and 53/164 (32%) families had inversion mutations with 43/53 (81%) involving the distal A gene (R3 pattern) and 10/53 (19%) involving the proximal A gene (R2 pattern). While 19% of all rearrangements were R2, in 35 families with severe disease (< 1% VIII:C activity) all 16 rearrangements seen were R3. In 18 families with the R3 pattern and known activities, 16 (89%) had levels < 1%, with the remaining 2 families having {le} 2.4% activity. Further, 18 referrals specifically noted the production of inhibitors and 8/18 (45%) had the R3 pattern. Our findings demonstrate that the R3 inversion mutation patterns is (1) only seen with VIII:C activity levels of {le} 2.4%, (2) seen in 46% of families with severe hemophilia, (3) seen in 45% of hemophiliacs known to have inhibitors, (4) not correlated with sporadic or familial disease and (5) not in disequilibrium with the Bcl I or Taq I intron 18 or ST14 polymorphisms. Finally, in families positive for an inversion mutation, direct testing offers a highly accurate and less expensive alternative to DNA linkage analysis.

  15. Factor VIII S373L: mutation at P1' site confers thrombin cleavage resistance, causing mild haemophilia A.

    Science.gov (United States)

    Johnson, D J; Pemberton, S; Acquila, M; Mori, P G; Tuddenham, E G; O'Brien, D P

    1994-04-01

    A novel CRM+ mutation, factor VIII position 373 serine to leucine substitution (FVIII 373-Leu) was identified during a survey of Factor VIII (FVIII) mutations. We have purified the variant protein from the patient's plasma in order to allow further characterisation of the molecule. The CRM+ plasma contained 120% Factor VIII antigen (FVIII:Ag) and 6% Factor VIII coagulant activity (FVIII:C). After purification the mutant FVIII was subjected to thrombin proteolysis, and was thereby activated 5.6-fold compared with 7-fold for wild type molecule. Subsequently, spontaneous inactivation of the mutant was much slower than noted for wild type FVIII. Western blot analysis using monoclonal antibodies demonstrated that thrombin cleavage of FVIII 373-Leu at positions 740 and 1689 were normal but that cleavage at position 372 was completely absent. Crystallographic coordinates of the active site of thrombin complexed to fibrinopeptide A were used to explore possible mechanistic reasons for the failure of thrombin to cleave the mutant FVIII at position 372. Steric hindrance between the mutant side chain and the side chain of the P1 residue was apparent. We conclude that the functional defect of FVIII 373-Leu results from the inability of thrombin to cleave the mutant at position 372-373, and propose that this is due to steric hindrance by the side chain of leucine 373, preventing correct formation of the enzyme substrate complex.

  16. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A

    NARCIS (Netherlands)

    Collins, P. W.; Blanchette, V. S.; Fischer, K.; Bjorkman, S.; Oh, M.; Fritsch, S.; Schroth, P.; Spotts, G.; Astermark, J.; Ewenstein, B.

    Background: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level <1 IU dL(-1).

  17. Tranexamic acid combined with recombinant factor VIII increases clot resistance to accelerated fibrinolysis in severe hemophilia A

    DEFF Research Database (Denmark)

    Hvas, Anne-Mette; Sørensen, Hanne Thykjær; Norengaard, Lisbeth

    2007-01-01

    examined whether the clot stability in hemophiliacs could be improved by treatment with tranexamic acid (TXA) in combination with recombinant factor VIII (rFVIII). PATIENTS/METHODS: Baseline blood samples were obtained from eight males with severe hemophilia A. Thereafter, a bolus injection of r...

  18. Evaluation of the biological differences of canine and human factor VIII in gene delivery: Implications in human hemophilia treatment

    Science.gov (United States)

    The canine is the most important large animal model for testing novel hemophilia A(HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, the different biological properties between cFVIII and human FVII...

  19. Desmopressin acetate as a haemostatic elevator in individuals with combined deficiency of factors V and VIII: a clinical trial.

    Science.gov (United States)

    Mansouritorghabeh, H; Shirdel, A

    2016-02-01

    ESSENTIALS: Combined factor V (FV) and factor VIII (FVIII) deficiency (CF5F8D) is an autosomal recessive coagulation disorder. Desmopressin acetate (DDAVP) was intravenously infused in 20 adult patients with CF5F8D. DDAVP can enhance FVIII levels but has no effect on FV levels in patients with CF5F8D. DDAVP can be substituted for FVIII concentrates in patients with CF5F8D. Combined factor V (FV) and FVIII deficiency (CF5F8D) is a rare inherited autosomal recessive double-gene disorder most frequently seen in the Middle East. Although affected individuals have deficiency of two coagulation factors (range 5-30%), their bleeding tendencies are similar to patients who have deficiency of a single coagulation factor at the same level. The mainstay of their treatment is infusion of FVIII concentrate and fresh frozen plasma. Here, the effect of intravenous infusion of desmopressin acetate (DDAVP) on elevation of coagulation FV and FVIII was investigated through a clinical trial in May 2015. In a registered controlled trial, DDAVP (dosage 0.3 μg kg(-1) ) was intravenously infused into 20 adult patients with CF5F8D over 20 min. After an hour, blood samples were collected and plasma levels of FV and FVIII were measured. This study revealed that DDAVP can enhance FVIII levels but has no effect on FV plasma concentration in patients with CF5F8D. Based on these findings, FVIII concentrates may be substituted for DDAVP in patients with CF5F8D. © 2015 International Society on Thrombosis and Haemostasis.

  20. Concentration factors for fish

    International Nuclear Information System (INIS)

    Feldt, W.; Lauer, R.; Melzer, M.; Siebert, W.

    1978-01-01

    Concentration factors are defined as operators allowing to calculate the specific activity of fish meat from a given concentration of an element in the water. This parameter depends among others from the content of stable isotopes and homologues in the different waters. If this parameter is reasonably to be used for model calculations it must be referred to water with all of its content substances, these calculations also being based on this type of 'water'. (orig.) [de

  1. 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

  2. Potential role of a new PEGylated recombinant factor VIII for hemophilia A

    Directory of Open Access Journals (Sweden)

    Wynn TT

    2016-06-01

    Full Text Available Tung Thanh Wynn,1 Burak Gumuscu,2,3 1Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Florida, Gainesville, FL, 2Pediatric Hematology-Oncology, Bon Secours Health System, St. Mary’s Hospital, Richmond, VA, 3Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Virginia, Charlottesville, VA, USA Abstract: Hemophilia A, a deficiency in the activity of coagulation factor (F VIII, is an X-linked bleeding disorder with an approximate incidence of one in 5,000 male infants. Bleeding-related complications often result in greater severity of disease, poor quality of life, surgical interventions for severe joint destruction, and shortened life span. With the availability of plasma-derived and recombinant FVIII products, the benefits of primary prophylaxis were demonstrated and is now the standard of care for patients with severe factor deficiencies. Current hemophilia research is focusing on the creation of new factor replacement therapies with longer half-lives; accessing alternative mechanisms to achieve desired hemostasis and enhance bypassing ­activity; and limiting the immunogenicity of the protein. PEGylation involves the covalent attachment of polyethylene glycol (PEG to a protein, peptide, or a small molecule drug. PEG effectively increases the molecular weight and size of the protein by creating a hydrophilic cloud around the molecule. This molecular change may reduce susceptibility of the molecule to proteolytic activity and degradation. It is also believed that PEGylation changes the surface charge of the protein that ultimately interferes with some receptor-mediated clearance processes. The half-life of PEGylated factor is more prolonged when compared to non-PEGylated full-length recombinant FVIII. The dawn of a new era in the care of hemophilia patients is upon us with the release of recombinant FVIII products with extended half-lives, and products with even more extended half

  3. 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.

  4. Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein.

    Science.gov (United States)

    McCue, Justin; Kshirsagar, Rashmi; Selvitelli, Keith; Lu, Qi; Zhang, Mingxuan; Mei, Baisong; Peters, Robert; Pierce, Glenn F; Dumont, Jennifer; Raso, Stephen; Reichert, Heidi

    2015-07-01

    Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8-15 log10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-α-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc. Copyright © 2015 Biogen. Published by Elsevier Ltd.. All rights reserved.

  5. Extracorporeal adsorption of anti-factor VIII allo-antibodies on randomly functionalized polystyrene resins.

    Science.gov (United States)

    Huguet, Hélène-Céline; Lasne, Dominique; Rothschild, Chantal; Siali, Rosa; Jozefonvicz, Jacqueline

    2004-02-01

    The occurrence of anti-factor VIII (FVIII) allo-antibodies is a severe complication of the treatment of haemophilia A patients, leading to the inhibition of transfused FVIII activity. The effective elimination of these inhibitory antibodies plays a decisive role in the management of affected patients. To achieve this, immunoadsorption devices employing synthetic adsorbers, which selectively eliminate inhibitors, are of interest in the treatment strategy of haemophilia A patients with inhibitors. Adsorbers consisting of polystyrene-based beads substituted with sulphonate and L-tyrosyl methylester groups, which mimic part of epitope of FVIII molecule recognized by inhibitors, exhibit selective binding capacities towards anti-FVIII antibodies. The adsorption of FVIII inhibitors was investigated by simulating an extracorporeal circulation of haemophilic plasma over these functionalized resins. These innovative adsorbers are able to remove around 25% of anti-FVIII antibodies in 15 minutes depending on the plasma tested. Furthermore, they do not modify the amount of essential plasmatic proteins or residual immunoglobulins G. Experiments which were carried out using different plasmas with various inhibitor titres demonstrate a good reproducibility regarding the adsorption capacity of the synthetic resin. The characteristics of adsorption are similar on either native or regenerated resins. Both the purely synthetic nature of the resin and its easy processability demonstrate the real advantages over currently available protocols. This synthetic adsorber is a major technological advance in selective removal of FVIII inhibitory antibodies.

  6. Transgenic rabbits as a model organism for production of human clotting factor VIII

    International Nuclear Information System (INIS)

    Vasicek, D.; Chrenek, P.; Makarevich, A.; Bauer, M.; Jurcik, R.; Suvegova, K.; Rafay, J.; Bulla, J.; Hetenyi, L.; Erickson, J.; Paleyanda, R.K.

    2005-01-01

    Human clotting factor VIII (hFVIII) is a very complex and large protein whose expression is difficult, as hFVIII requires extensive post-translational modification to be biologically active. This paper reports the generation of transgenic rabbits as a model species for testing the expression of hFVIII in the mammary gland. For micro-injection, a fusion gene construct was used, consisting of 2.5 kb murine whey acidic protein (mWAP) promoter, 7.2 kb cDNA of hFVIII, and 4.6 kb of 3' flanking sequences of the mWAP gene. from 130 micro-injected zygotes transferred into recipients, 30 offspring were delivered. The pups were screened for the transgene by PCR, using DNA isolated from the ear, and results were confirmed by Southern blot analysis. The transgene was identified in one female founder animal, and it was transmitted to the offspring in a Mendelian fashion, thus demonstrating stable integration of the gene construct into the germline of the transgenic rabbits. (author)

  7. Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models

    Science.gov (United States)

    Siner, Joshua I.; Samelson-Jones, Benjamin J.; Crudele, Julie M.; French, Robert A.; Lee, Benjamin J.; Zhou, Shanzhen; Merricks, Elizabeth; Raymer, Robin; Camire, Rodney M.; Arruda, Valder R.

    2016-01-01

    Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645–1648) in the design of B-domain–deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by furin is in fact deleterious to FVIII-BDD secretion and procoagulant activity. Inhibition of furin increases the secretion and decreases the intracellular retention of FVIII-BDD protein in mammalian cells. Our new variant (FVIII-ΔF), in which this recognition motif is removed, efficiently circumvents furin. FVIII-ΔF demonstrates increased recombinant protein yields, enhanced clotting activity, and higher circulating FVIII levels after adeno-associated viral vector–based liver gene therapy in a murine model of severe hemophilia A (HA) compared with FVIII-BDD. Moreover, we observed an amelioration of the bleeding phenotype in severe HA dogs with sustained therapeutic FVIII levels after FVIII-ΔF gene therapy at a lower vector dose than previously employed in this model. The immunogenicity of FVIII-ΔF did not differ from that of FVIII-BDD as a protein or a gene therapeutic. Thus, contrary to previous suppositions, FVIII variants that can avoid furin processing are likely to have enhanced translational potential for HA therapy. PMID:27734034

  8. Prediction of human pharmacokinetics of activated recombinant factor VII and B-domain truncated factor VIII from animal population pharmacokinetic models of haemophilia

    DEFF Research Database (Denmark)

    Larsen, Malte Selch; Juul, Rasmus Vestergaard; Groth, Andreas Velsing

    2018-01-01

    activated factor VII (rFVIIa) and recombinant factor VIII (rFVIII) in several experimental animal models using population PK modelling, and apply a simulation-based approach to evaluate how well the developed animal population PK models predict human PK. PK models were developed for rFVIIa and r...

  9. Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene

    Energy Technology Data Exchange (ETDEWEB)

    Young, M.; Antonarakis, S.E. [Univ. of Geneva (Switzerland); Inaba, Hiroshi [Tokyo Medical College (Japan)] [and others

    1997-03-01

    Although the molecular defect in patients in a Japanese family with mild to moderately severe hemophilia A was a deletion of a single nucleotide T within an A{sub 8}TA{sub 2} sequence of exon 14 of the factor VIII gene, the severity of the clinical phenotype did not correspond to that expected of a frameshift mutation. A small amount of functional factor VIII protein was detected in the patient`s plasma. Analysis of DNA and RNA molecules from normal and affected individuals and in vitro transcription/translation suggested a partial correction of the molecular defect, because of the following: (i) DNA replication/RNA transcription errors resulting in restoration of the reading frame and/or (ii) {open_quotes}ribosomal frameshifting{close_quotes} resulting in the production of normal factor VIII polypeptide and, thus, in a milder than expected hemophilia A. All of these mechanisms probably were promoted by the longer run of adenines, A{sub 10} instead of A{sub 8}TA{sub 2}, after the delT. Errors in the complex steps of gene expression therefore may partially correct a severe frameshift defect and ameliorate an expected severe phenotype. 36 refs., 6 figs.

  10. Frequencies of VNTR and RFLP polymorphisms associated with factor VIII gene in Singapore

    Energy Technology Data Exchange (ETDEWEB)

    Fong, I.; Lai, P.S.; Ouah, T.C. [National Univ. of Singapore (Malaysia)] [and others

    1994-09-01

    The allelic frequency of any polymorphism within a population determines its usefulness for genetic counselling. This is important in populations of non-Caucasian origin as RFLPs may significantly differ among ethnic groups. We report a study of five intragenic polymorphisms in factor VIII gene carried out in Singapore. The three PCR-based RFLP markers studied were Intron 18/Bcl I, Intron 19/Hind III and Intron 22/Xba I. In an analysis of 148 unrelated normal X chromosomes, the allele frequencies were found to be A1 = 0.18, A2 = 0.82 (Bcl I RFLP), A1 = 0.80, A2 = 0.20 (Hind III RFLP) and A1 = 0.58, and A2 = 0.42 (Xba I RFLP). The heterozygosity rates of 74 females analyzed separately were 31%, 32% and 84.2%, respectively. Linkage disequilibrium was also observed to some degree between Bcl I and Hind III polymorphism in our population. We have also analyzed a sequence polymorphism in Intron 7 using hybridization with radioactive-labelled {sup 32}P allele-specific oligonucleotide probes. This polymorphism was not very polymorphic in our population with only 2% of 117 individuals analyzed being informative. However, the use of a hypervariable dinucleotide repeat sequence (VNTR) in Intron 13 showed that 25 of our of 27 (93%) females were heterozygous. Allele frequencies ranged from 1 to 55 %. We conclude that a viable strategy for molecular analysis of Hemophilia A families in our population should include the use of Intron 18/Bcl I and Intron 22/Xba I RFLP markers and the Intron 13 VNTR marker.

  11. Genotype and phenotype report on patients with combined deficiency of factor V and factor VIII in Iran.

    Science.gov (United States)

    Karimi, Mehran; Cairo, Andrea; Safarpour, Mohammad M; Haghpanah, Sezaneh; Ekramzadeh, Maryam; Afrasiabi, Abdolreza; Shahriari, Mahdi; Menegatti, Marzia

    2014-06-01

    Combined factor V (FV) and factor VIII (FVIII) deficiency is a rare autosomal recessive bleeding disorder characterized by mild-to-moderate bleeding. Epistaxis, postsurgical bleeding and menorrhagia are the most common symptoms. The aim of this study is to report the phenotype-genotype characterization carried out in patients affected with combined FV and FVIII deficiency from Iran. A cross-sectional study was conducted in Shiraz Hemophilia Center, southern Iran. Twelve cases, seven men and five women coming from eight families were included in our study after taking consent form. Coagulation activity for all patients was measured. All exons and intron-exon junctions of lectin mannose binding protein 1 (LMAN1) gene and multiple coagulation factor deficiency 2 genes were amplified by PCR, and subsequently sequenced by the Sanger method. Patients[Combining Acute Accent] age ranged from 6 to 59 years mean ± SD: 23.8 ± 15.4 years and median: 22 years. No patient presented with severe bleeding symptom. Only one patient had severe FV and FVIII deficiency (both factor levels stop codon. Larger studies are needed to calculate the correlation between factor levels, genetic and bleeding symptoms.

  12. Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A.

    Science.gov (United States)

    Young, G; Mahlangu, J; Kulkarni, R; Nolan, B; Liesner, R; Pasi, J; Barnes, C; Neelakantan, S; Gambino, G; Cristiano, L M; Pierce, G F; Allen, G

    2015-06-01

    Prophylactic factor replacement, which prevents hemarthroses and thereby reduces the musculoskeletal disease burden in children with hemophilia A, requires frequent intravenous infusions (three to four times weekly). Kids A-LONG was a phase 3 open-label study evaluating the safety, efficacy and pharmacokinetics of a longer-acting factor, recombinant factor VIII Fc fusion protein (rFVIIIFc), in previously treated children with severe hemophilia A (endogenous FVIII level of hemophilia A. © 2015 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

  13. Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients: results of the INSIGHT case-control study.

    Science.gov (United States)

    van Velzen, A S; Eckhardt, C L; Peters, M; Leebeek, F W G; Escuriola-Ettingshausen, C; Hermans, C; Keenan, R; Astermark, J; Male, C; Peerlinck, K; le Cessie, S; van der Bom, J G; Fijnvandraat, K

    2017-07-01

    Essentials Research suggests that intensive treatment episodes may increase the risk to develop inhibitors. We performed an international nested case-control study with 298 non-severe hemophilia A patients. Surgery and a high dose of factor VIII concentrate were associated with increased inhibitor risk. Physicians need to review arguments for factor VIII dose and elective surgery extra critically. Background Inhibitor development is a major complication of treatment with factor VIII concentrates in hemophilia. Findings from studies among severe hemophilia A patients suggest that intensive treatment episodes increase the risk of developing inhibitors. Objectives We set out to assess whether intensive treatment is also associated with an increased risk of inhibitor development among non-severe hemophilia A patients. Patients/Methods We performed a nested case-control study. A total of 75 inhibitor patients (cases) and 223 control patients were selected from 2709 non-severe hemophilia A patients (FVIII:C, 2-40%) of the INSIGHT cohort study. Cases and controls were matched for date of birth and cumulative number of exposure days (EDs) to FVIII concentrates. Conditional logistic regression was used to calculate both unadjusted and adjusted odds ratios (aOR); the latter were adjusted for a priori specified confounders. Results Peak treatment of 5 or 10 consecutive EDs did not increase inhibitor risk (aOR, 1.0; 95% confidence interval (CI), 0.4-2.5; and aOR, 1.8; CI, 0.6-5.5, respectively). Both surgical intervention (aOR, 4.2; CI, 1.7-10.3) and a high mean dose (> 45 IU kg -1 /ED) of FVIII concentrate (aOR, 7.5; CI, 1.6-35.6) were associated with an increased inhibitor risk. Conclusions Our findings suggest that high-dose FVIII treatment and surgery increase the risk of inhibitor development in non-severe hemophilia A. Together with the notion that non-severe hemophilia A patients are at a lifelong risk of inhibitor development, we suggest that in the future physicians

  14. Severe Hemophilia A in a Male Old English Sheep Dog with a C→T Transition that Created a Premature Stop Codon in Factor VIII

    Science.gov (United States)

    Lozier, Jay N; Kloos, Mark T; Merricks, Elizabeth P; Lemoine, Nathaly; Whitford, Margaret H; Raymer, Robin A; Bellinger, Dwight A; Nichols, Timothy C

    2016-01-01

    Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons. Comparing the results with the normal canine factor VIII sequence revealed a C→T transition in exon 12 of the factor VIII gene that created a premature stop codon at amino acid 577 in the A2 domain of the protein. In addition, 2 previously described polymorphisms that do not cause hemophilia were present at amino acids 909 and 1184. The hemophilia mutation creates a new TaqI site that facilitates rapid genotyping of affected offspring by PCR and restriction endonuclease analyses. This mutation is analogous to the previously described human factor VIII mutation at Arg583, which likewise is a CpG dinucleotide transition causing a premature stop codon in exon 12. Thus far, despite extensive treatment with factor VIII, this dog has not developed neutralizing antibodies (‘inhibitors’) to the protein. This novel mutation in a dog gives rise to severe hemophilia A analogous to a mutation seen in humans. This model will be useful for studies of the treatment of hemophilia. PMID:27780008

  15. Pathogen inactivation in fresh frozen plasma using riboflavin and ultraviolet light: Effects on plasma proteins and coagulation factor VIII

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    Stanojković Zoran

    2011-01-01

    Full Text Available Background/Aim. Riboflavin (vitamin B2 activated by ultraviolet (UV light, produces active oxygen which damages cell membrane and prevents replication of the carrier of diseases (viruses, bacteria, protozoa in all blood products. The aim of this study was to establish the influence of the process of photo inactivation in pathogens using riboflavin and UV rays on the concentration of coagulation factor VIII:C (FVIII:C and proteins in plasma that were treated before freezing. Methods. The examination included 20 units of plasma, separated from whole blood donated by voluntary blood donors around 6 hours from the moment of collection. The units were pooled and separated in to two groups: one consisted of 10 control units and the other of 10 experimental units. Experimental units of the plasma were treated by riboflavin (35 mL and UV rays (6.24 J/mL, 265-370 nm on Mirasol aparature (Caridian BCT Biotechnologies, USA in approximate duration of 6 minutes. Furthermore, 35 mL of saline solution was added to the control plasma. One sample for examining was taken from the control plasma (KG and two residual were taken from experimental plasma after the addition of riboflavin either before (EG1 or post illumination (EG2. Results. Comparing the mean values of FVIII:C (% we noticed statistically significantly higher level in the EG1 group than in the EG2 group (65.00 ± 4.52 vs 63.20 ± 4.73; t = 4.323, p = 0.002, while between the KG and experimental groups (EG1 and EG2 there was no statistically significant difference in the concentration of FVIII:C. There was a statistically significant decrease of albumin concentration (g/L in the EG2 group comparing to the KG (33.35 ± 0.94 vs 31.94 ± 0.84; t = 3.534, p = 0.002, but there was no mentioned difference in albumin concentration between the KG and the EG1, so as between the EG1 and the EG2. Conclusion. Plasma inactivated by riboflavin and UV rays (Mirasol PRT sistem, Caridian BCT, USA keeps all the

  16. 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.

  17. 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.

  18. Effects of Mg/Ga and V/III source ratios on hole concentration of N-polar (000\\bar{1}) p-type GaN grown by metalorganic vapor phase epitaxy

    Science.gov (United States)

    Nonoda, Ryohei; Shojiki, Kanako; Tanikawa, Tomoyuki; Kuboya, Shigeyuki; Katayama, Ryuji; Matsuoka, Takashi

    2016-05-01

    The effects of growth conditions such as Mg/Ga and V/III ratios on the properties of N-polar (000\\bar{1}) p-type GaN grown by metalorganic vapor phase epitaxy were studied. Photoluminescence spectra from Mg-doped GaN depended on Mg/Ga and V/III ratios. For the lightly doped samples, the band-to-acceptor emission was observed at 3.3 eV and its relative intensity decreased with increasing V/III ratio. For the heavily doped samples, the donor-acceptor pair emission was observed at 2.8 eV and its peak intensity monotonically decreased with V/III ratio. The hole concentration was maximum for the Mg/Ga ratio. This is the same tendency as in group-III polar (0001) growth. The V/III ratio also reduced the hole concentration. The higher V/III ratio reduced the concentration of residual donors such as oxygen by substituting nitrogen atoms. The surface became rougher with increasing V/III ratio and the hillock density increased.

  19. 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.

  20. Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs

    Science.gov (United States)

    Dumont, Jennifer A.; Liu, Tongyao; Low, Susan C.; Zhang, Xin; Kamphaus, George; Sakorafas, Paul; Fraley, Cara; Drager, Douglas; Reidy, Thomas; McCue, Justin; Franck, Helen W. G.; Merricks, Elizabeth P.; Nichols, Timothy C.; Bitonti, Alan J.; Pierce, Glenn F.

    2012-01-01

    Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency of dosing. rFVIIIFc has an ∼ 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs. The extension of rFVIIIFc half-life requires interaction of Fc with the neonatal Fc receptor (FcRn). In FcRn knockout mice, the extension of rFVIIIFc half-life is abrogated, and is restored in human FcRn transgenic mice. The Fc fusion has no impact on FVIII-specific activity. rFVIIIFc has comparable acute efficacy as rFVIII in treating tail clip injury in HemA mice, and fully corrects whole blood clotting time (WBCT) in HemA dogs immediately after dosing. Furthermore, consistent with prolonged half-life, rFVIIIFc shows 2-fold longer prophylactic efficacy in protecting HemA mice from tail vein transection bleeding induced 24-48 hours after dosing. In HemA dogs, rFVIIIFc also sustains partial correction of WBCT 1.5- to 2-fold longer than rFVIII. rFVIIIFc was well tolerated in both species. Thus, the rescue of FVIII by Fc fusion to provide prolonged protection presents a novel pathway for FVIII catabolism, and warrants further investigation. PMID:22246033

  1. Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

    Science.gov (United States)

    Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

    2017-05-01

    Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.

  2. Recurrent myocardial infarctions in a young football player secondary to thrombophilia, associated with elevated factor VIII activity

    Directory of Open Access Journals (Sweden)

    Vacek TP

    2014-10-01

    Full Text Available Thomas P Vacek, Shipeng Yu, Shahnaz Rehman, Blair P Grubb, Daniel Kosinski, Cherian Verghese, Ehab A Eltahawy, Shafiq Qaiser Department of Medicine, University of Toledo Medical Center, Toledo, OH, USAAbstract: Myocardial infarction (MI due to coronary atherosclerosis in young adults is uncommon; rare causes such as cocaine abuse, arterial dissection, and thromboembolism should be considered. A 21-year-old football player, and otherwise healthy African American man, developed chest pain during exercise while bench-pressing 400 lbs. Acute MI was diagnosed based on physical examination, electrocardiography findings, and elevated cardiac enzymes. Coronary arteriography showed a thrombus occluding the proximal left anterior descending artery (LAD. Aggressive antiplatelet therapy with aspirin, clopidogrel, and eptifibatide was pursued, in addition to standard post-MI care. This led to the successful resolution of symptoms and dissolution of the thrombus, demonstrated by repeat coronary arteriography. Five months later, he presented with similar symptoms during exercise after lifting heavy weights, and was found to have another acute MI. Coronary arteriography again showed a thrombus occluding the LAD. No evidence of coronary artery dissection or vasospasm was found. Only mild atherosclerotic plaque burden was observed on both occasions by intravascular ultrasound. A bare metal stent was placed at the site as it was thought this site had acted as a nidus for small plaque rupture and thrombus formation. Elevated serum factor VIII activity at 205% (reference range 60%–140% was found, a rare cause of hypercoagulability. Further workup revealed a patent foramen ovale during a Valsalva maneuver by transesophageal echocardiography. Both events occurred during weight lifting, which can transiently increase right heart pressure in a similar way to the Valsalva maneuver. In light of all the findings, we concluded that an exercise-related increase in factor

  3. Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice.

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    Marina E Fomin

    Full Text Available Liver sinusoidal endothelial cells (LSECs form a semi-permeable barrier between parenchymal hepatocytes and the blood. LSECs participate in liver metabolism, clearance of pathological agents, immunological responses, architectural maintenance of the liver and synthesis of growth factors and cytokines. LSECs also play an important role in coagulation through the synthesis of Factor VIII (FVIII. Herein, we phenotypically define human LSECs isolated from fetal liver using flow cytometry and immunofluorescence microscopy. Isolated LSECs were cultured and shown to express endothelial markers and markers specific for the LSEC lineage. LSECs were also shown to engraft the liver when human fetal liver cells were transplanted into immunodeficient mice with liver specific expression of the urokinase-type plasminogen activator (uPA transgene (uPA-NOG mice. Engrafted cells expressed human Factor VIII at levels approaching those found in human plasma. We also demonstrate engraftment of adult LSECs, as well as hepatocytes, transplanted into uPA-NOG mice. We propose that overexpression of uPA provides beneficial conditions for LSEC engraftment due to elevated expression of the angiogenic cytokine, vascular endothelial growth factor. This work provides a detailed characterization of human midgestation LSECs, thereby providing the means for their purification and culture based on their expression of CD14 and CD32 as well as a lack of CD45 expression. The uPA-NOG mouse is shown to be a permissive host for human LSECs and adult hepatocytes, but not fetal hepatoblasts. Thus, these mice provide a useful model system to study these cell types in vivo. Demonstration of human FVIII production by transplanted LSECs encourages further pursuit of LSEC transplantation as a cellular therapy for the treatment of hemophilia A.

  4. Milk fat globule-epidermal growth factor-factor VIII attenuates sepsis-induced acute kidney injury.

    Science.gov (United States)

    Cen, Cindy; Aziz, Monowar; Yang, Weng-Lang; Zhou, Mian; Nicastro, Jeffrey M; Coppa, Gene F; Wang, Ping

    2017-06-01

    Acute kidney injury (AKI) is most commonly caused by sepsis in critically ill patients, and it is associated with high morbidity and mortality. The pathophysiology of sepsis-induced AKI is generally accepted to include direct inflammatory injury, endothelial cell dysfunction, and apoptosis. Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein with a known role in the enhancement of apoptotic cell clearance and regulation of inflammation. We hypothesize that administration of recombinant mouse MFG-E8 (rmMFG-E8) can protect mice from kidney injuries caused by sepsis. Sepsis was induced in 8-wk-old male C57BL/6 mice by cecal ligation and puncture (CLP). rmMFG-E8 or phosphate-buffered saline (vehicle) was injected intravenously at a dosage of 20 μg/kg body weight at time of CLP (n = 5-8 mice per group). After 20 h, serum and renal tissue were harvested for various analyses. The renal injury markers blood urea nitrogen (BUN) and creatinine were determined by enzymatic and chemical reactions, respectively. The gene expression analysis was carried out by real-time quantitative polymerase chain reaction. At 20 h after CLP, serum levels of BUN and creatinine were both significantly increased in the vehicle group compared with the sham group, whereas the mice treated with rmMFG-E8 had a significant reduction in BUN and creatinine levels by 28% and 24.1%, respectively (BUN: 197.7 ± 23.6 versus 142.3 ± 20.7 mg/dL; creatinine: 0.83 ± 0.12 versus 0.63 ± 0.06 mg/dL; P sepsis through inhibiting the production of proinflammatory cytokines and chemokine, as well as through the activation of endothelial cells. Thus, MFG-E8 may have a therapeutic potential for treating AKI induced by sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Staining for factor VIII related antigen and Ulex europaeus agglutinin I (UEA-I) in 230 tumours. An assessment of their specificity for angiosarcoma and Kaposi's sarcoma.

    Science.gov (United States)

    Leader, M; Collins, M; Patel, J; Henry, K

    1986-11-01

    In this study we examined the staining reactivity of commercially available antisera to factor VIII related antigen (F VIII RAg) and Ulex europaeus agglutinin I (UEA-I) on sections from 230 formalin fixed paraffin embedded tumours. These included 196 sarcomas, 20 carcinomas and 14 angiomas. All angiomas showed positive staining for F VIII RAg; all carcinomas showed negative staining; the vasoformative areas of all angiosarcomas stained positively but only four of six angiosarcomas showed positive staining of their solid areas; of seven Kaposi's sarcomas, all showed positive staining of vessels and six showed positive staining of the spindle cell component. In the remaining 181 non-vascular sarcomas there was a false positive result in four tumours (2.2%), three of which had a history of irradiation. Pre-radiotherapy biopsies of these three tumours stained negatively with anti-F VIII RAg. UEA-I was demonstrated in all the angiomas studied, in all angiosarcomas (including the solid components) and in well-formed vessels of all Kaposi's sarcomas, but only in the spindle cell component of 3/6. However, there was an unacceptably high rate of false positive staining amongst the carcinomas and non-vascular sarcomas. In conclusion, F VIII RAg is a specific but not a sensitive marker of angiosarcomas; UEA-I is a sensitive but not a specific marker of angiosarcomas.

  6. Thrombomodulin as a marker for vascular tumors. Comparative study with factor VIII and Ulex europaeus I lectin.

    Science.gov (United States)

    Yonezawa, S; Maruyama, I; Sakae, K; Igata, A; Majerus, P W; Sato, E

    1987-10-01

    Thrombomodulin (TM) is a newly described endothelial cell-associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. Various vascular tumors were characterized with immunoperoxidase staining with the use of a polyclonal anti-TM serum. The staining patterns of TM were compared with those of Factor VIII-related antigen (FVIII-RAG) and Ulex europaeus agglutinin-I (UEA-I), which have been used as markers for endothelial cells. The results showed that TM is a specific and a highly sensitive marker for angiosarcomas in comparison with FVIII-RAG or UEA-I. In contrast, UEA-I is more sensitive for benign vascular tumors than TM or FVIII-RAG. The other mesenchymal tumors of nonvascular origin showed negative staining for three endothelial markers. These results indicate that TM is a new specific and sensitive tool for the diagnosis of angiosarcomas.

  7. Joint bleeds increase the inhibitor response to human factor VIII in a rat model of severe haemophilia A

    DEFF Research Database (Denmark)

    Löfgren, Karin Maria; Søndergaard, H.; Skov, Søren

    2016-01-01

    Introduction The most serious complication in haemophilia A (HA) replacement therapy with coagulation factor VIII (FVIII) is neutralizing antibodies, i.e. inhibitors. It has been hypothesized that danger signals generated during a bleed might have an adjuvant effect on the immune response to FVIII...... in on-demand treatment, increasing the inhibitor risk. Aim To compare the antibody response to treatment with recombinant human FVIII (rhFVIII) in relation to induced knee joint bleeds and treatment without concurrent bleeds in a HA rat model. Method HA rats were divided into two groups: one group (n...... = 10) receiving three needle induced knee joint bleeds 14 days apart and a control group (n = 9) receiving three sham procedures. Three hours after each injury/sham 50 IU kg−1 rhFVIII was administrated intravenously. Subsequently, both groups continued rhFVIII treatment for another 9 weeks. Binding...

  8. Targeting factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice.

    Science.gov (United States)

    Baumgartner, C K; Mattson, J G; Weiler, H; Shi, Q; Montgomery, R R

    2017-01-01

    Essentials Platelet-Factor (F) VIII gene therapy is a promising treatment in hemophilia A. This study aims to evaluate if platelet-FVIII expression would increase the risk for thrombosis. Targeting FVIII expression to platelets does not induce or elevate thrombosis risk. Platelets expressing FVIII are neither hyper-activated nor hyper-responsive. Background Targeting factor (F) VIII expression to platelets is a promising gene therapy approach for hemophilia A, and is successful even in the presence of inhibitors. It is well known that platelets play important roles not only in hemostasis, but also in thrombosis and inflammation. Objective To evaluate whether platelet-FVIII expression might increase thrombotic risk and thereby compromise the safety of this approach. Methods In this study, platelet-FVIII-expressing transgenic mice were examined either in steady-state conditions or under prothrombotic conditions induced by inflammation or the FV Leiden mutation. Native whole blood thrombin generation assay, rotational thromboelastometry analysis and ferric chloride-induced vessel injury were used to evaluate the hemostatic properties. Various parameters associated with thrombosis risk, including D-dimer, thrombin-antithrombin complexes, fibrinogen, tissue fibrin deposition, platelet activation status and activatability, and platelet-leukocyte aggregates, were assessed. Results We generated a new line of transgenic mice that expressed 30-fold higher levels of platelet-expressed FVIII than are therapeutically required to restore hemostasis in hemophilic mice. Under both steady-state conditions and prothrombotic conditions induced by lipopolysaccharide-mediated inflammation or the FV Leiden mutation, supratherapeutic levels of platelet-expressed FVIII did not appear to be thrombogenic. Furthermore, FVIII-expressing platelets were neither hyperactivated nor hyperactivatable upon agonist activation. Conclusion We conclude that, in mice, more than 30-fold higher levels of

  9. Association of peak factor VIII levels and area under the curve with bleeding in patients with haemophilia A on every third day pharmacokinetic-guided prophylaxis

    NARCIS (Netherlands)

    Valentino, L. A.; Pipe, S. W.; Collins, P. W.; Blanchette, V. S.; Berntorp, E.; Fischer, K.; Ewenstein, B. M.; Oh, M.; Spotts, G.

    2016-01-01

    Introduction: We previously showed that pharmacokinetic-guided prophylaxis (PKP) allows the dosing interval to be extended while maintaining a specific trough level. However, the associations of peak factor VIII (FVIII) levels and area under the curve (AUC) with breakthrough bleeding have not been

  10. BASIC FACTORS OF MARKET CONCENTRATION

    OpenAIRE

    V. Fyliuk

    2013-01-01

    The paper systemizes factors which reinforce trends towards market concentration in all economic systems. These factors include factors related to the general changes in economic environment such as globalization of the world economy, state structural and taxation policies, cycle of economic development and changes in consumer demand. They also include factors related to competition (intensification of competition, companies’ desire to monopolize market and present market structure) and scien...

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

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    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

  12. Factors Associated with the Time of Admission among Notified Dengue Fever Cases in Region VIII Philippines from 2008 to 2014.

    Science.gov (United States)

    Abello, Jason Echavez; Gil Cuesta, Julita; Cerro, Boyd Roderick; Guha-Sapir, Debarati

    2016-10-01

    In cases of Dengue fever, late hospital admission can lead to treatment delay and even death. In order to improve early disease notification and management, it is essential to investigate the factors affecting the time of admission of Dengue cases. This study determined the factors associated with the time of admission among notified Dengue cases. The study covered the period between 2008 and 2014 in Region VIII, Philippines. The factors assessed were age, sex, hospital sector, hospital level, disease severity based on the 1997 WHO Dengue classification, and period of admission (distinguishing between the 2010 Dengue epidemic and non-epidemic time). We analysed secondary data from the surveillance of notified Dengue cases. We calculated the association through chi-square test, ordinal logistic regression and linear regression at p value Dengue cases. The reported cases included a majority of children (70.09%), mild cases of the disease (64.00%), patients from the public sector (69.82%), and non-tertiary hospitals (62.76%). Only 1.40% of cases had a laboratory confirmation. The epidemic period in 2010 comprised 48.68% of all the admitted cases during this period. Late admission was more likely among adults than children (pDengue guidelines in order to standardize the admission criteria and time across hospitals.

  13. Factors Associated with the Time of Admission among Notified Dengue Fever Cases in Region VIII Philippines from 2008 to 2014.

    Directory of Open Access Journals (Sweden)

    Jason Echavez Abello

    2016-10-01

    Full Text Available In cases of Dengue fever, late hospital admission can lead to treatment delay and even death. In order to improve early disease notification and management, it is essential to investigate the factors affecting the time of admission of Dengue cases. This study determined the factors associated with the time of admission among notified Dengue cases. The study covered the period between 2008 and 2014 in Region VIII, Philippines. The factors assessed were age, sex, hospital sector, hospital level, disease severity based on the 1997 WHO Dengue classification, and period of admission (distinguishing between the 2010 Dengue epidemic and non-epidemic time. We analysed secondary data from the surveillance of notified Dengue cases. We calculated the association through chi-square test, ordinal logistic regression and linear regression at p value < 0.05. The study included 16,357 admitted Dengue cases. The reported cases included a majority of children (70.09%, mild cases of the disease (64.00%, patients from the public sector (69.82%, and non-tertiary hospitals (62.76%. Only 1.40% of cases had a laboratory confirmation. The epidemic period in 2010 comprised 48.68% of all the admitted cases during this period. Late admission was more likely among adults than children (p<0.05. The severe type of the disease was more likely to be admitted late than the mild type (p<0.05. Late admission was also more likely in public hospitals than in private hospitals (p<0.05; and within tertiary level hospitals than non-tertiary hospitals (p<0.05. Late admission was more likely during the non-epidemic period than the 2010 epidemic period (p<0.05. A case fatality rate of 1 or greater was significantly associated with children, severe diseases, tertiary hospitals and public hospitals when admitted late (p<0.05. Data suggests that early admission among child cases was common in Region VIII. This behavior is encouraging, and should be continued. However, further study is needed

  14. Novel factor VIII variants with a modified furin cleavage site improve the efficacy of gene therapy for hemophilia A.

    Science.gov (United States)

    Nguyen, G N; George, L A; Siner, J I; Davidson, R J; Zander, C B; Zheng, X L; Arruda, V R; Camire, R M; Sabatino, D E

    2017-01-01

    Essentials Factor (F) VIII is an inefficiently expressed protein. Furin deletion FVIII variants were purified and characterized using in vitro and in vivo assays. These minimally modified novel FVIII variants have enhanced function. These variants provide a strategy for increasing FVIII expression in hemophilia A gene therapy. Background The major challenge for developing gene-based therapies for hemophilia A is that human factor VIII (hFVIII) has intrinsic properties that result in inefficient biosynthesis. During intracellular processing, hFVIII is predominantly cleaved at a paired basic amino acid cleaving enzyme (PACE) or furin cleavage site to yield a heterodimer that is the major form of secreted protein. Previous studies with B-domain-deleted (BDD) canine FVIII and hFVIII-R1645H, both differing from hFVIII by a single amino acid at this site, suggested that these proteins are secreted mainly in a single polypeptide chain (SC) form and exhibit enhanced function. Objective We hypothesized that deletion(s) of the furin site modulates FVIII biology and may enhance its function. Methods A series of recombinant hFVIII-furin deletion variants were introduced into hFVIII-BDD [Δ1645, 1645-46(Δ2), 1645-47(Δ3), 1645-48(Δ4), or Δ1648] and characterized. Results In vitro, recombinant purified Δ3 and Δ4 were primarily SC and, interestingly, had 2-fold higher procoagulant activity compared with FVIII-BDD. In vivo, the variants also have improved hemostatic function. After adeno-associated viral (AAV) vector delivery, the expression of these variants is 2-4-fold higher than hFVIII-BDD. Protein challenges of each variant in mice tolerant to hFVIII-BDD showed no anti-FVIII immune response. Conclusions These data suggest that the furin deletion hFVIII variants are superior to hFVIII-BDD without increased immunogenicity. In the setting of gene-based therapeutics, these novel variants provide a unique strategy to increase FVIII expression, thus lowering the vector dose, a

  15. Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A.

    Science.gov (United States)

    Arai, M; Higuchi, M; Antonarakis, S E; Kazazian, H H; Phillips, J A; Janco, R L; Hoyer, L W

    1990-01-15

    The molecular defect responsible for moderate and severe hemophilia A has been identified for two unrelated patients with the CRM-positive form of this disorder (factor VIII activity of 0.02 and 0.05 U/mL with factor VIII antigen of 0.87 and 2.20 U/mL). In both cases, the immunopurified dysfunctional factor VIII protein is abnormal, in that the 80 Kd light chain is not cleaved by thrombin at arginine-1689. The basis for this failure was identified by polymerase chain reaction amplification of exon 14 of the variant factor VIII genes and direct sequencing of the amplified products. In both cases, a single base substitution (C to T) was identified that produces an arginine to cysteine substitution at amino acid residue 1689. These data identify the molecular defects of the two identical factor VIII variant proteins. The dysfunctional factor VIII has been designated "Factor VIII-East Hartford," the residence of the patient in whom the defect was first identified.

  16. 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.

  17. Limit of detection and threshold for positivity of the Centers for Disease Control and Prevention assay for factor VIII inhibitors.

    Science.gov (United States)

    Miller, C H; Boylan, B; Shapiro, A D; Lentz, S R; Wicklund, B M

    2017-10-01

    Essentials Immunologic methods detect factor VIII (FVIII) antibodies in some inhibitor-negative specimens. Specimens were tested by modified Nijmegen-Bethesda assay (NBA) and fluorescence immunoassay. The NBA with preanalytical heat inactivation detects FVIII inhibitors down to 0.2 NBU. IgG 4 frequency validates the established threshold for positivity of ≥ 0.5 NBU for this NBA. Background The Bethesda assay for measurement of factor VIII inhibitors called for quantification of positive inhibitors by using dilutions producing 25-75% residual activity (RA), corresponding to 0.4-2.0 Bethesda units, with the use of 'more sensitive methods' for samples with RA closer to 100% being recommended. The Nijmegen modification (Nijmegen-Bethesda assay [NBA]) changed the reagents used but not these calculations. Some specimens negative by the NBA have been shown to have FVIII antibodies detectable with sensitive immunologic methods. Objective To examine the performance at very low inhibitor titers of the Centers for Disease Control and Prevention (CDC)-modified NBA (CDC-NBA), which includes preanalytic heat inactivation to liberate bound anti-FVIII antibodies. Methods Specimens with known inhibitors were tested with the CDC-NBA. IgG 4 anti-FVIII antibodies were measured by fluorescence immunoassay (FLI). Results Diluted inhibitors showed linearity below 0.4 Nijmegen-Bethesda units (NBU). With four statistical methods, the limit of detection of the CDC-NBA was determined to be 0.2 NBU. IgG 4 anti-FVIII antibodies, which correlate most strongly with functional inhibitors, were present at rates above the background rate of healthy controls in specimens with titers ≥ 0.2 NBU and showed an increase in frequency from 14.3% at 0.4 NBU to 67% at the established threshold for positivity of 0.5 NBU. Conclusions The CDC-NBA can detect inhibitors down to 0.2 NBU. The FLI, which is more sensitive, demonstrates anti-FVIII IgG 4 in some patients with negative (NBA, supporting the need for

  18. Diagnostic and prognostic value of factor VIII binding antibodies in acquired hemophilia A: data from the GTH-AH 01/2010 study.

    Science.gov (United States)

    Werwitzke, S; Geisen, U; Nowak-Göttl, U; Eichler, H; Stephan, B; Scholz, U; Holstein, K; Klamroth, R; Knöbl, P; Huth-Kühne, A; Bomke, B; Tiede, A

    2016-05-01

    Essentials Factor VIII (FVIII) binding IgG detected by ELISA could be an alternative to the Bethesda assay. We studied the performance of anti-FVIII IgG ELISA in patients with acquired hemophilia and controls. Anti-FVIII IgG > 99th percentile of controls was highly sensitive and specific. Patients with high anti-FVIII IgG have a lower chance of achieving remission. Background Acquired hemophilia A is a severe bleeding disorder that requires fast and accurate diagnosis as it occurs often unexpectedly in previously healthy men and women of every age. The Nijmegen-modified Bethesda assay is the diagnostic reference standard for detecting neutralizing autoantibodies against factor VIII (FVIII), but is not widely available, not ideal for quantifying the complex type 2 inhibitors seen in acquired hemophilia, and suffers from high inter-laboratory variability. Objectives To assess the diagnostic and prognostic value of FVIII-binding antibodies as detected by ELISA compared with the Nijmegen Bethesda assay. Methods Samples from the time of first diagnosis and clinical data were available from 102 patients with acquired hemophilia enrolled in the prospective GTH-AH 01/2010 study. Controls (n = 102) were matched for gender and age. Diagnostic cut-offs were determined by receiver-operator curve analysis. The prognostic value was assessed in 92 of the 102 patients by Cox regression analysis of time to partial remission. Results Anti-FVIII IgG above the 99th percentile (> 15 arbitrary units per mL) revealed high sensitivity and specificity (both 0.99; 95% confidence interval, 0.95-1.0) for diagnosing acquired hemophilia. The likelihood of achieving partial remission was related to anti-FVIII IgG concentration ( 1050, 0.39). The Bethesda titer was only associated with the likelihood of partial remission when analyzed in the central laboratory, but not when data from local GTH study sites were used. Conclusion Although the Nijmegen-modified Bethesda assay is the reference

  19. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A.

    Science.gov (United States)

    Collins, P W; Blanchette, V S; Fischer, K; Björkman, S; Oh, M; Fritsch, S; Schroth, P; Spotts, G; Astermark, J; Ewenstein, B

    2009-03-01

    The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level break-through bleeding in patients with severe hemophilia A on prophylaxis. This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII safety and efficacy of a recombinant FVIII (Advate). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1). The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. These data have important implications for the management of patients with severe hemophilia.

  20. An Acquired Factor VIII Inhibitor in a Patient with HIV and HCV: A Case Presentation and Literature Review

    Directory of Open Access Journals (Sweden)

    S. B. Zeichner

    2013-01-01

    Full Text Available Introduction. Despite its low incidence, acquired factor VIII inhibitor is the most common autoantibody affecting the clotting cascade. The exact mechanism of acquisition remains unclear, but postpartum patients, those with autoimmune conditions or malignancies, and those with exposure to particular drugs appear most susceptible. There have been several case reports describing acquired FVIII inhibitors in patients receiving interferon alpha for HCV treatment and in patients being treated for HIV. To our knowledge, this is the first case of a patient with HCV and HIV who was not actively receiving treatment for either condition. Case Presentation. A 57-year-old Caucasian male with a history of HIV and HCV was admitted to our hospital for a several day history of progressively worsening right thigh bruising and generalized weakness. CTA of the abdominal arteries revealed large bilateral retroperitoneal hematomas. Laboratory studies revealed the presence of a high titer FVIII inhibitor. Conclusion. Our case of a very rare condition highlights the importance of recognizing and understanding the diagnosis of acquired FVIII inhibitor. Laboratory research and clinical data on the role of newer agents are needed in order to better characterize disease pathogenesis, disease associations, genetic markers, and optimal disease management.

  1. Quality control in the development of coagulation factor concentrates.

    Science.gov (United States)

    Snape, T J

    1987-01-01

    Limitation of process change is a major factor contributing to assurance of quality in pharmaceutical manufacturing. This is particularly true in the manufacture of coagulation factor concentrates, for which presumptive testing for poorly defined product characteristics is an integral feature of finished product quality control. The development of new or modified preparations requires that this comfortable position be abandoned, and that the effect on finished product characteristics of changes to individual process steps (and components) be assessed. The degree of confidence in the safety and efficacy of the new product will be determined by, amongst other things, the complexity of the process alteration and the extent to which the results of finished product tests can be considered predictive. The introduction of a heat-treatment step for inactivation of potential viral contaminants in coagulation factor concentrates presents a significant challenge in both respects, quite independent of any consideration of assessment of the effectiveness of the viral inactivation step. These interactions are illustrated by some of the problems encountered with terminal dry heat-treatment (72 h. at 80 degrees C) of factor VIII and prothrombin complex concentrates manufactured by the Blood Products Laboratory.

  2. Factor VIII (F8) inversions in severe hemophilia A: Male germ cell origin and diagnosis with RT-PCR

    Energy Technology Data Exchange (ETDEWEB)

    Antonarakis, S.E. [Geneva Medical School (Switzerland)]|[Johns Hopkins School of Medicine, Baltimore, MD (United States); Rossiter, J.P. [Johns Hopkins School of Medicine, Baltimore, MD (United States); Young, M. [Geneva Medical School (Switzerland)] [and others

    1994-09-01

    The Factor VIII (F8) gene, which is defective in hemophilia A, is located in the most telomeric megabase of Xq. Inversions due to intrachromosomal homologous recombination between mispaired copies of gene A located within intron 22 of the gene and about 500 kb telomeric to it account for nearly half of the cases of severe hemophilia A. We hypothesized that pairing of Xq with its homolog inhibits the inversion process, and that therefore the event originates predominantly in male germ cells. In all 21 informative cases in which the inversion originated in a maternal grandparent, DNA polymorphism analysis using markers within or very closely linked to F8, determined that it occurred in the male germline. In addition, all but one of 56 mothers of sporadic cases due to inversions were carriers. The data indicate that the F8 gene inversions leading to severe hemophilia A occur almost exclusively in male germ cells. The mean age of maternal grandfathers at the birth of their carrier daughters was 29.9 years (13 cases), i.e. not different from the mean paternal age in the general population, supporting the hypothesis that the inversions occur in meiosis. The inversions can be diagnosed by Southern blot analysis. For more rapid diagnosis we have used RT-PCR of RNA ectopically expressed in blood. Oligonucleotides were used to PCR amplify, after the initial RT reaction of RNA samples using random hexamers, either the normal transcript (F8 exons 21 to 24;312 bp product) or the novel abnormal transcript that is generated after the inversion. Both type 1 and 2 inversions can be recognized in affecteds and carriers by the presence of the diagnostic PcR product of 248 bp. Correct diagnoses were made in samples from 6 patients and 2 carriers with type 1 inversions, 2 patients and 2 carriers with type 2 inversions and 5 normal controls.

  3. Severe hemophilia A in a female by cryptic translocation: Order and orientation of factor VIII within Xq28

    Energy Technology Data Exchange (ETDEWEB)

    Migeon, B.R.; McGinniss, M.J.; Antonarakis, S.E.; Axelman, J.; Stasiowski, B.A.; Youssoufian, H.; Kearns, W.G.; Chung, A.; Pearson, P.L.; Kazazian, H.H. Jr. (Johns Hopkins Univ., Baltimore, MD (United States)); Muneer, R.S. (Univ. of Oklahoma, Norman (United States))

    1993-04-01

    The authors report studies of a female with severe hemophilia A resulting from a complex de novo translocation of chromosomes X and 17 (46,X,t(X; 17)). Somatic cell hybrids containing the normal X, the der(X), or the der(17) were analyzed for coagulation factor VIII (F8C) sequences using Southern blots and polymerase chain reaction. The normal X, always late replicating, contains a normal F8C gene, whereas the der(X) has no F8C sequences. The der(17) chromosome containing Xq24-Xq28 carries a functional G6PD locus and a deleted F8C allele that lacks exons 1--15. Also, it lacks the DXYS64-X locus, situated between the F8C locus and the Xq telomere. These results indicate that a cryptic breakpoint within Xq28 deleted the 5[prime] end of F8C, but left the more proximal G6PD locus intact on the der(17)chromosome. As the deleted segment includes the 5[prime] half of F8C as well as the subtelomeric DXYS64 locus, F8C must be oriented on the chromosome with its 5[prime] region closest to the telomere. Therefore, the order of these loci is Xcen-G6PD-3[prime]F8C-5[prime]F8C-DXYS64-Xqtel. The analysis of somatic cell hybrids has elucidated the true nature of the F8C mutation in the pro-band, revealing a more complex rearrangement (three chromosomes involved) than that expected from cytogenetic analysis, chromosome painting, and Southern blots. A 900-kb segment within Xq28 has been translocated to another autosome. Hemophilia A in this heterozygous female is due to the decapitation of the F8C gene on the der(17) and inactivation of the intact allele on the normal X. 27 refs., 5 figs., 1 tab.

  4. Transient B cell depletion or improved transgene expression by codon optimization promote tolerance to factor VIII in gene therapy.

    Directory of Open Access Journals (Sweden)

    Brandon K Sack

    Full Text Available The major complication in the treatment of hemophilia A is the development of neutralizing antibodies (inhibitors against factor VIII (FVIII. The current method for eradicating inhibitors, termed immune tolerance induction (ITI, is costly and protracted. Clinical protocols that prevent rather than treat inhibitors are not yet established. Liver-directed gene therapy hopes to achieve long-term correction of the disease while also inducing immune tolerance. We sought to investigate the use of adeno-associated viral (serotype 8 gene transfer to induce tolerance to human B domain deleted FVIII in hemophilia A mice. We administered an AAV8 vector with either human B domain deleted FVIII or a codon-optimized transgene, both under a liver-specific promoter to two strains of hemophilia A mice. Protein therapy or gene therapy was given either alone or in conjunction with anti-CD20 antibody-mediated B cell depletion. Gene therapy with a low-expressing vector resulted in sustained near-therapeutic expression. However, supplementary protein therapy revealed that gene transfer had sensitized mice to hFVIII in a high-responder strain but not in mice of a low-responding strain. This heightened response was ameliorated when gene therapy was delivered with anti-murine CD20 treatment. Transient B cell depletion prevented inhibitor formation in protein therapy, but failed to achieve a sustained hypo-responsiveness. Importantly, use of a codon-optimized hFVIII transgene resulted in sustained therapeutic expression and tolerance without a need for B cell depletion. Therefore, anti-CD20 may be beneficial in preventing vector-induced immune priming to FVIII, but higher levels of liver-restricted expression are preferred for tolerance.

  5. Obtenção e caracterização de anticorpo monoclonal murino anti-fator VIII da coagulação sangüínea Attainment and characterization of murine monoclonal anti-factor VIII antibodies

    Directory of Open Access Journals (Sweden)

    Rosana Rossi-Ferreira

    2006-06-01

    VIII human (FVIIIh by expanding clones and characterizing the antibodies by immunochemistry. Balb/c mice were immunized with FVIII both purified and from cryoprecipitation and the splenic cells of the animals were fused with myelomatous murine cells according to the method described by Kohler and Milstein to produce hybrids in a culture. A total of 1983 hybrids were tested and 105 were selected for cloning. Of these, 39 developed monoclonality and 7 of these clones were characterized through immunoblotting techniques. Three immunoglobulins from different classes, LAMB1-10A1A4, LAMB1-17A1A1 and LAMB1-24A2A1, were submitted to chromatography for purification. The purified immunoglobulin from the LAMB1-10A1A4 clone was adsorbed in the immunoaffinity column to purify the factor VIII concentrate coming from the plasmatic cryoprecipitate.

  6. Optimisation of the Factor VIII yield in mammalian cell cultures by reducing the membrane bound fraction

    DEFF Research Database (Denmark)

    Kolind, Mille Petersen; Nørby, Peder Lisby; Berchtold, Martin Werner

    2011-01-01

    and forms the tenase complex together with clotting Factor IX. In vitro, during serum free production of recombinant FVIII (rFVIII), production cells also expose PS, and since vWF is not present to hinder interaction of secreted rFVIII with PS, rFVIII is partly associated with the cell membrane...... of active membrane bound rFVIII to the culture medium. Moreover, the attachment of rFVIII to cell membranes of un-transfected HEK293 cells was studied in the presence of compounds that competes for interactions between rFVIII and PS. Competitive assays between iodinated rFVIII (¹²5I-rFVIII) and annexin V...... or ortho-phospho-L-serine (OPLS) demonstrated that annexin V and OPLS were able to reduce the membrane bound fraction of rFVIII by 70% and 30%, respectively. Finally, adding OPLS to CHO cells stably expressing FVIII increased the yield by 50%. Using this new knowledge, the recovery of rFVIII could...

  7. Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors.

    Science.gov (United States)

    Heimberger, Amy B; Crotty, Laura E; Archer, Gary E; Hess, Kenneth R; Wikstrand, Carol J; Friedman, Allan H; Friedman, Henry S; Bigner, Darell D; Sampson, John H

    2003-09-15

    The epidermal growth factor receptor (EGFR) is often amplified and structurally rearranged in malignant gliomas and other tumors such as breast and lung, with the most common mutation being EGFRvIII. In the study described here, we tested in mouse models a vaccine consisting of a peptide encompassing the tumor-specific mutated segment of EGFRvIII (PEP-3) conjugated to keyhole limpet hemocyanin [KLH (PEP-3-KLH)]. C57BL/6J or C3H mice were vaccinated with PEP-3-KLH and subsequently challenged either s.c. or intracerebrally with a syngeneic melanoma cell line stably transfected with a murine homologue of EGFRvIII. Control mice were vaccinated with KLH. To test its effect on established tumors, C3H mice were also challenged intracerebrally and subsequently vaccinated with PEP-3-KLH. S.c. tumors developed in all of the C57BL/6J mice vaccinated with KLH in Freund's adjuvant, and there were no long-term survivors. Palpable tumors never developed in 70% of the PEP-3-KLH-vaccinated mice. In the C57BL/6J mice receiving the PEP-3-KLH vaccine, the tumors that did develop were significantly smaller than those in the control group (P PEP-3-KLH vaccination did not result in significant cytotoxic responses in standard cytotoxicity assays; however, antibody titers against PEP-3 were enhanced. The passive transfer of sera from the immunized mice to nonimmunized mice protected 31% of the mice from tumor development (P PEP-3-KLH-vaccinated mice. Peptide vaccination was also sufficiently potent to have marked efficacy against intracerebral tumors, resulting in a >173% increase in median survival time, with 80% of the C3H mice achieving long-term survival (P = 0.014). In addition, C3H mice with established intracerebral tumor that received a single treatment of PEP-3-KLH showed a 26% increase in median survival time, with 40% long-term survival (P = 0.007). Vaccination with an EGFRvIII-specific peptide is efficacious against both s.c. and established intracerebral tumors. The

  8. The 1.7 Å X-ray crystal structure of the porcine factor VIII C2 domain and binding analysis to anti-human C2 domain antibodies and phospholipid surfaces.

    Directory of Open Access Journals (Sweden)

    Caileen M Brison

    Full Text Available The factor VIII C2 domain is essential for binding to activated platelet surfaces as well as the cofactor activity of factor VIII in blood coagulation. Inhibitory antibodies against the C2 domain commonly develop following factor VIII replacement therapy for hemophilia A patients, or they may spontaneously arise in cases of acquired hemophilia. Porcine factor VIII is an effective therapeutic for hemophilia patients with inhibitor due to its low cross-reactivity; however, the molecular basis for this behavior is poorly understood. In this study, the X-ray crystal structure of the porcine factor VIII C2 domain was determined, and superposition of the human and porcine C2 domains demonstrates that most surface-exposed differences cluster on the face harboring the "non-classical" antibody epitopes. Furthermore, antibody-binding results illustrate that the "classical" 3E6 antibody can bind both the human and porcine C2 domains, although the inhibitory titer to human factor VIII is 41 Bethesda Units (BU/mg IgG versus 0.8 BU/mg IgG to porcine factor VIII, while the non-classical G99 antibody does not bind to the porcine C2 domain nor inhibit porcine factor VIII activity. Further structural analysis of differences between the electrostatic surface potentials suggest that the C2 domain binds to the negatively charged phospholipid surfaces of activated platelets primarily through the 3E6 epitope region. In contrast, the G99 face, which contains residue 2227, should be distal to the membrane surface. Phospholipid binding assays indicate that both porcine and human factor VIII C2 domains bind with comparable affinities, and the human K2227A and K2227E mutants bind to phospholipid surfaces with similar affinities as well. Lastly, the G99 IgG bound to PS-immobilized factor VIII C2 domain with an apparent dissociation constant of 15.5 nM, whereas 3E6 antibody binding to PS-bound C2 domain was not observed.

  9. The pharmacokinetics of a B-domain truncated recombinant factor VIII, turoctocog alfa (NovoEight®), in patients with hemophilia A.

    Science.gov (United States)

    Jiménez-Yuste, V; Lejniece, S; Klamroth, R; Suzuki, T; Santagostino, E; Karim, F A; Saugstrup, T; Møss, J

    2015-03-01

    Turoctocog alfa (NovoEight(®)) is a human recombinant coagulation factor VIII (rFVIII) for the treatment of patients with hemophilia A. To evaluate the pharmacokinetics of turoctocog alfa in all age groups across clinical trials. Data from previously treated patients with severe hemophilia A (FVIII activity level of ≤ 1%) with no history of FVIII inhibitors, in a non-bleeding state, were included. The pharmacokinetics were assessed following a wash-out period and a subsequent single intravenous 50 IU kg(-1) dose of turoctocog alfa. Blood was sampled during a 48-h period postdose. Standard pharmacokinetic (PK) parameters were estimated on the basis of plasma FVIII activity vs. time (PK profiles) with non-compartmental methods. Furthermore, a population PK analysis was conducted. Data from 76 patients (aged 1-60 years) enrolled globally across six clinical trials were included, totaling 105 turoctocog alfa PK profiles. Single-dose PK results 3-6 months after the first dose of turoctocog alfa were comparable with the results obtained after the first dose. Similar PK characteristics were shown for different lots and strengths of the drug product. Overall, area under the plasma concentration (activity) curve from administration to infinity (AUC) and t1(/2) tended to increase with increasing age, with lower AUC and shorter t(1/2) being seen in children than in adolescents and adults. The PK profiles of turoctocog alfa and other commercially available plasma-derived FVIII and rFVIII products were similar in all age groups. The PK characteristics of turoctocog alfa have been thoroughly studied, and shown to be consistent over time, reproducible between different lots and strengths of drug product, and similar to those observed for other FVIII products. © 2014 International Society on Thrombosis and Haemostasis.

  10. 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.

  11. 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.

  12. Estudo citofotométrico da expressão do marcador tumoral Fator VIII e fatores prognósticos no adenocarcinoma gástrico Cytophotometric study of the expression of the tumoral marker Factor VIII and prognostic factors in gastrci adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Mary Tossa Nakamura

    2007-12-01

    ção III ou IV apresentaram índice de marcagem maiores do que aqueles com Bormann I ou II, porém sem correlação com a profundidade de invasão tumoral, grau de diferenciação, envolvimento nodal e padrão histológico. CONCLUSÕES: O presente estudo identificou e marcou 95,24% das amostras para o Fator VIII. Em relação aos fatores prognósticos não houve correlação significativa exceto entre o Fator VIII e a classificação de Bormann no qual o tipo III ou IV foi maior que o tipo I ou II.INTRODUCTION: Regarding gastric cancer, the incidence, diagnosis and therapeutic options showed improvement in the last decades, but prognosis remains gloomy, specially due the fact that most patients, already diagnosed present advanced tumors, metastatic and not liable to be surgically resected. Molecular biology is an area in science, which can give the answer to many questions and current scientific facts show that the this should be through detection of tumoral markers. The great advances in informatics refined cell image analysis by image cytophotometry makes it possible to study cell proliferation and angiogenesis in various tumor processes using immunohistochemistry and several markers. At present, studies are conducted to demonstrate the prognostic value of their expressions, however, in gastric adenocarcinoma the results have been divergent and studies are scarce. AIM: To identify and quantify the expression of cell proliferation markers using Ki-67 and of angiogenesis with Factor VIII in gastric adenocarcinoma using cytophotometry, and compare their expressions with factors such as Bormanns´ classification, tumor invasion depth, degree of differentiation, nodal involvement, histologic pattern and age. METHODS: Twenty-one patients with gastric adenocarcinoma identified between 1998 and 2006 were studied. Ki-67 and Factor VIII expressions were performed using immunohistochemistry with clone MIB-1 primary antibodies, monoclonal for Ki-67 and policlonal for Factor VIII

  13. Factors influencing erythrocyte choline concentrations.

    Science.gov (United States)

    Miller, B L; Jenden, D J; Tang, C; Read, S

    1989-01-01

    Choline concentrations in human erythrocytes increase after freezing and thawing, during incubation in Krebs-phosphate for 30 min or on storage at 0 degrees C for 3-24 hr. The increase is prevented by protein precipitation by 10% perchloric acid, 10% zinc hydroxide, 10% sodium tungstate or boiling in water. It is not prevented by EDTA (10 mM) and is increased by oleate (5 mM). We suggest that the increase is due to the action of phospholipase D on erythrocyte phospholipids.

  14. Endothelial cell markers in vascular neoplasms: an immunohistochemical study comparing factor VIII-related antigen, blood group specific antigens, 6-keto-PGF1 alpha, and Ulex europaeus 1 lectin.

    Science.gov (United States)

    Little, D; Said, J W; Siegel, R J; Fealy, M; Fishbein, M C

    1986-06-01

    Markers for endothelial cells including Ulex europaeus 1 lectin, blood group A, B, and H, and the prostaglandin metabolite 6-keto-PGF1 alpha were evaluated in paraffin secretions from formalin-fixed benign and malignant vascular neoplasms using a variety of immunohistochemical techniques, and results compared with staining for factor VIII-related antigen. Staining for Ulex appeared more sensitive than factor VIII-related antigen in identifying poorly differentiated neoplasms including haemangiosarcomas and spindle cell proliferations in Kaposi's sarcoma. Staining for blood group related antigens correlated with blood group in all cases. Ulex europaeus 1 lectin was the only marker for endothelial cells in lymphangiomas.

  15. Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

    Directory of Open Access Journals (Sweden)

    Cimino E

    2014-12-01

    Full Text Available Ernesto Cimino,1 Silvia Linari,2 Mara Malerba,3 Susan Halimeh,4 Francesca Biondo,5 Martina Westfeld5 1Dipartimento Medicina Clinica e Sperimentale, Universita’ degli Studi di Napoli Federico II, Naples, Italy; 2Agenzia per l’ Emofilia, AOU Careggi di Firenze, Florence, Italy; 3Fondazione Cà Granda Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi “A Bianchi Bonomi”, Milan, Italy; 4CRC Coagulation Research Centre GmbH, Duisburg, Germany; 5Pfizer Italia, Rome, Italy Introduction: Hemophilia A treatment involves replacing the deficient coagulation factor VIII. This process may involve multiple steps that might create a barrier to adherence. A new dual-chamber syringe (DCS; FuseNGo® was recently introduced with the aim of simplifying reconstitution. Aim: This study aimed to identify factors associated with adult patients’ preferences for different coagulation factor VIII reconstitution systems and to test ease of use and patient preference for the DCS. Methods: A cross-sectional survey of adults with hemophilia A in five European countries was conducted; a subset of subjects also participated in a practical testing session of the DCS. Results: Among the 299 survey participants, the device scenario requiring the least equipment and reconstitution steps (the DCS received a median preference rating of 71 out of 100 (0 being “the least desirable” and 100 “the most desirable” rating. This was significantly higher than the other scenarios (the next highest achieved a median of 50 points; P<0.001. Participants would be more likely to use this device prophylactically (P<0.001. Among the 98 participants who tested the DCS, 57% preferred this device over their current device, 26% preferred their current device, and 17% had no preference. The DCS was rated as easier to use than current treatment devices (median score 9/10 versus 7/10 for current treatment, P=0.001. Conclusion: The survey indicates that the prefilled DCS, Fuse

  16. Murine leukemia virus-derived retroviral vector has differential integration patterns in human cell lines used to produce recombinant factor VIII

    Directory of Open Access Journals (Sweden)

    Marcela Cristina Correa de Freitas

    2014-06-01

    Full Text Available OBJECTIVE: Nowadays recombinant factor VIII is produced in murine cells including in Chinese hamster ovary (CHO and baby hamster kidney cells (BHK. Previous studies, using the murine leukemia virus-derived retroviral vector pMFG-FVIII-P140K, modified two recombinant human cell lines, HepG2 and Hek293 to produce recombinant factor VIII. In order to characterize these cells, the present study aimed to analyze the integration pattern of retroviral vector pMFG-FVIII-P140K.METHODS: This study used ligation-mediated polymerase chain reaction to locate the site of viral vector integration by sequencing polymerase chain reaction products. The sequences were compared to genomic databases to characterize respective clones.RESULTS: The retroviral vector presented different and non-random profiles of integration between cells lines. A preference of integration for chromosomes 19, 17 and 11 was observed for HepG2FVIIIdB/P140K and chromosome 9 for Hek293FVIIIdB/P140K. In genomic regions such as CpG islands and transcription factor binding sites, there was no difference in the integration profiles for both cell lines. Integration in intronic regions of encoding protein genes (RefSeq genes was also observed in both cell lines. Twenty percent of integrations occurred at fragile sites in the genome of the HepG2 cell line and 17% in Hek293.CONCLUSION: The results suggest that the cell type can affect the profile of chromosomal integration of the retroviral vector used; these differences may interfere in the level of expression of recombinant proteins.

  17. Factors Affecting Tocopherol Concentrations in Soybean Seeds.

    Science.gov (United States)

    Carrera, Constanza S; Seguin, Philippe

    2016-12-21

    Soybean seeds contain several health-beneficial compounds, including tocopherols, which are used by the nutraceutical and functional food industries. Soybean tocopherol concentrations are, however, highly variable. Large differences observed in tocopherol concentrations among soybean genotypes together with the relatively simple biosynthetic pathway involving few genes support the feasibility of selecting for high-tocopherol soybean. Tocopherol concentrations are also highly influenced by environmental factors and field management. Temperature during seed filling and soil moisture appear to be the main factors affecting tocopherol concentrations; other factors such as soil fertility and solar radiation also affect concentrations and composition. Field management decisions including seeding date, row spacing, irrigation, and fertilization also affect tocopherols. Knowledge of factors affecting soybean tocopherols is essential to develop management strategies that will lead to the production of seeds with consistent target concentrations that will meet the needs of the nutraceutical and functional food industries.

  18. Milk fat globule-epidermal growth factor-factor VIII-derived peptide MSP68 is a cytoskeletal immunomodulator of neutrophils that inhibits Rac1.

    Science.gov (United States)

    Hendricks, Louie; Aziz, Monowar; Yang, Weng-Lang; Nicastro, Jeffrey; Coppa, Gene F; Symons, Marc; Wang, Ping

    2017-02-01

    Prolonged neutrophil infiltration leads to exaggerated inflammation and tissue damage during sepsis. Neutrophil migration requires rearrangement of their cytoskeleton. Milk fat globule-epidermal growth factor-factor VIII-derived short peptide 68 (MSP68) has recently been shown to be beneficial in sepsis-induced tissue injury and mortality. We hypothesize that MSP68 inhibits neutrophil migration by modulating small GTPase Rac1-dependent cytoskeletal rearrangements. Bone marrow-derived neutrophils (BMDNs) or whole lung digest isolated neutrophils were isolated from 8 to 10 wk old C57BL/6 mice by Percoll density gradient centrifugation. The purity of BMDN was verified by flow cytometry with CD11b/Gr-1 staining. Neutrophils were stimulated with N-formylmethionine-leucine-phenylalanine (f-MLP) (10 nM) in the presence or absence of MSP68 at 10 nM or cecal ligation and puncture (CLP) was used to induce sepsis, and MSP68 was administered at 1 mg/kg intravenously. Cytoskeletal organization was assessed by phalloidin staining, followed by analysis using fluorescence microscopy. Activity of the Rac1 GTPase in f-MLP or CLP-activated BMDN in the presence or absence of MSP68 was assessed by GTPase enzyme-linked immunosorbent assay. Mitogen-activated protein (MAP) kinase activity was determined by western blot densitometry. BMDN treatment with f-MLP increased cytoskeletal remodeling as revealed by the localization of filamentous actin to the periphery of the neutrophil. By contrast, cells pretreated with MSP68 had considerably reduced filamentous actin polymerization. Cytoskeletal spreading is associated with the activation of the small GTPase Rac1. We found BMDN-treated with f-MLP or that were exposed to sepsis by CLP had increased Rac1 signaling, whereas the cells pretreated with MSP68 had significantly reduced Rac1 activation (P Rac1-MAP kinase-mediated neutrophil motility. Thus, MSP68 is a novel therapeutic candidate for regulating inflammation and tissue damage caused

  19. 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.

  20. 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

  1. An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A.

    Science.gov (United States)

    Liu, Hongzhong; Wu, Runhui; Hu, Pei; Sun, Feifei; Xu, Lihong; Liang, Yali; Nepal, Sunil; Qu, Peng Roger; Huard, Francois; Korth-Bradley, Joan M

    2017-07-01

    Hemophilia A represents up to 80% of all hemophilia cases in China. In patients with this condition, bleeding can be prevented and controlled by administering clotting factor VIII (FVIII). Since their initial availability, recombinant FVIII products have undergone several iterations to enhance their safety. Moroctocog alfa albumin-free cell culture (AF-CC) is among the third generation of recombinant FVIII products and received regulatory approval in China in August 2012. The present study characterizes the single-dose pharmacokinetic parameters of FVIII activity (FVIII:C) after administration of moroctocog alfa (AF-CC) in male Chinese patients with hemophilia A. This multicenter, open-label, single-dose study enrolled 13 male Chinese patients diagnosed with severe hemophilia A (FVIII:C hemophilia A. The pharmacokinetic profile in older patients was similar to that previously reported with recombinant FVIII products in studies with a predominantly white population; younger patients had reduced exposure to FVIII:C. The single doses of moroctocog alfa (AF-CC) were well tolerated; 2 cases of transient, low-titer FVIII inhibitor development were observed. ClinicalTrials.gov identifier: NCT02461992. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  2. The effect of factor VIII deficiencies and replacement and bypass therapies on thrombus formation under venous flow conditions in microfluidic and computational models.

    Directory of Open Access Journals (Sweden)

    Abimbola A Onasoga-Jarvis

    Full Text Available Clinical evidence suggests that individuals with factor VIII (FVIII deficiency (hemophilia A are protected against venous thrombosis, but treatment with recombinant proteins can increase their risk for thrombosis. In this study we examined the dynamics of thrombus formation in individuals with hemophilia A and their response to replacement and bypass therapies under venous flow conditions. Fibrin and platelet accumulation were measured in microfluidic flow assays on a TF-rich surface at a shear rate of 100 s⁻¹. Thrombin generation was calculated with a computational spatial-temporal model of thrombus formation. Mild FVIII deficiencies (5-30% normal levels could support fibrin fiber formation, while severe (1 nM, but too low to support fibrin formation (<10 nM. In the absence of platelets, fibrin formation was not supported even at normal FVIII levels, suggesting platelet adhesion is necessary for fibrin formation. Individuals treated by replacement therapy, recombinant FVIII, showed normalized fibrin formation. Individuals treated with bypass therapy, recombinant FVIIa, had a reduced lag time in fibrin formation, as well as elevated fibrin accumulation compared to healthy controls. Treatment of rFVIIa, but not rFVIII, resulted in significant changes in fibrin dynamics that could lead to a prothrombotic state.

  3. PREDICTION OF STRESS CONCENTRATION FACTORS IN

    African Journals Online (AJOL)

    ES OBE

    consider the effect of brace spacing on strengths of tubular K joints without consideration of same effect on square section K Joints. This lack of studies design strengths of gapped square section K joints makes availability of information on stress concentration factors in same joints scarce. However, information on 'Hot Spot' ...

  4. On the application of concentration factor

    International Nuclear Information System (INIS)

    Shimizu, Makoto

    1981-01-01

    Concentration factor is used to estimate internal dose through consumption of fish and shellfish. The amount of nuclide intake is estimated as ''radioactivity in ambient water x concentration factor x consumption of fish and shellfish''. These parameters involved are usually treated as constants but these actually are variables. Here the significance of their variation on dose assessment is examined. Concentration factors are varied according to various environmental as well as biological factors. For example, Hg, Cs, and As in the muscle of Galeus nipponensis increase as total length increases and, on the contrary, Cu, Zn, Fe and Co show negative correlation with total length. We should examine these cases and determine what value should be used in dose assessment. More important is to build up models to interprete these phenomena totally. Significance of variation in ambient radioactivity was examined by a simulation of nuclide accumulation in biota exposed to intermittent release and compared with that to continuous release. Variations either within a day or within a year were not shown to have much effect. On the variations in sea food consumption, several examples were given. Problem to be solved is how to consider these variations on assessing internal dose due to fish consumption. In conclusion it is necessary to get more of such kind of informations on the variations of parameters. And also we should determine the precision of each parameter in the whole picture of dose assessment. (author)

  5. Assessment of the frequency of regulatory T cells (CD4+CD25+CD127-) in children with hemophilia A: relation to factor VIII inhibitors and disease severity.

    Science.gov (United States)

    El-Asrar, Mohamed Abo; Hamed, Ahmed El-Saeed; Darwish, Yasser Wagih; Ismail, Eman Abdel Rahman; Ismail, Noha Ali

    2016-01-01

    A rapidly growing evidence showed that regulatory T cells (Tregs) play a crucial role in tolerance to coagulation factors and may be involved in the pathogenesis of inhibitor formation in patients with hemophilia. We determined the percentage of Tregs (CD4CD25CD127) in 45 children with hemophilia A compared with 45 healthy controls, and assessed their relation to the clinical characteristics of patients and factor VIII (FVIII) inhibitors. Patients were studied stressing on frequency of bleeding attacks, joint pain, history of viral hepatitis, and the received therapy (FVIII precipitate/cryotherapy). FVIII activity and FVIII inhibitors were assessed with flow cytometric analysis of CD4CD25CD127 Tregs. According to residual FVIII activity levels, 30 patients (66.7%) had mild/moderate hemophilia A, whereas 15 (33.3%) patients had severe hemophilia A. The frequency of Tregs was significantly lower among all patients with hemophilia A compared with controls (2.59 ± 1.1 versus 3.73 ± 1.12%; P = 0.002). Tregs were significantly decreased among patients with FVIII inhibitors compared with the inhibitor-negative group (P hemophilia A had lower Tregs levels than those without (P = 0.34 and P = 0.011, respectively). A significant positive correlation was found between the percentage of Tregs and FVIII among hemophilia A patients. ROC curve analysis revealed that the cut-off value of Tregs at 1.91% could differentiate patients with and without FVIII inhibitors, with a sensitivity of 100% and a specificity of 91.3%. We suggest that alteration in the frequency of Tregs in young patients with hemophilia A may contribute to inhibitor formation and disease severity.

  6. Enhanced glycosylation of factor VIII:C in capillary endothelial cells following β-adrenoreceptor stimulation is not due to increased sugar transport

    International Nuclear Information System (INIS)

    Tavarez-Pagan, J.J.; Oliveira, C.M.; Banerjee, D.K.

    1990-01-01

    Factor VIII:C (Antihemophilia Factor A) in capillary endothelial cells from bovine adrenal medulla found to contain M r 200,000 and M r 46,000 dalton protein species when analyzed by SDS-PAGE under reduced condition. But the secretory FVIII:C under non-reduced condition gave rise to a protein of M r 270,000 dalton indicating that the heavy and light chains are held together by S-S bridge. Upon stimulation of these cells with β-agonist, isoproterenol (10 -7 M), a 2-fold increase in the ratio of [ 3 H]-mannose to [ 35 S]-methionine incorporation in immunoprecipitated FVIII:C was observed. In order to understand the molecular mechanism of this increase, a detail study of sugar transport was carried out. The transport of 2-deoxy-D-[ 3 H]-glucose in these cells was time and temperature dependent. Furthermore, inhibition of 2-deoxy-D-[ 3 H]-glucose uptake by cytochalasin B strongly supported for a carrier mediated process. However, when the transport studies were conducted in the presence of isoproterenol at 10 -5 M or 10 -7 M or 8 Br-cAMP (2 mM) no increase was observed. The kinetic studies indicated that the K m and V max for 2 deoxy-D-[ 3 H]-glucose were 0.24 mM and 0.88 nmol/mg protein/minute, respectively under normal conditions but these values were changed to 0.37 mM and 0.69 nmol/mg protein/minute when stimulated with isoproterenol (10 -7 M)

  7. Factor concentrates for the treatment of factor XIII deficiency.

    Science.gov (United States)

    Gootenberg, J E

    1998-11-01

    Factor XIII deficiency is a severe autosomal recessive bleeding disorder associated with a characteristic pattern of neonatal hemorrhage and a lifelong bleeding diathesis. Even relatively minor trauma can be followed by prolonged and recurrent bleeding. Intracranial hemorrhage is a frequent complication. With the development of safe and effective factor XIII concentrates, reliable prophylactic treatment is possible. Two plasma-derived, virus-inactivated factor XIII concentrates are currently in production. The first, Fibrogammin P, (Centeon LLC, King of Prussia, PA, USA; and Centeon Pharma GmbH, Marburg, Germany) is marketed in Europe, South America, South Africa, and Japan. It is distributed in the United States under a Food and Drug Administration Investigational New Drug Application. A second factor XIII concentrate (Bio Products Laboratory, Elstree, UK) is available for use only on a "named patient" compassionate basis in the United Kingdom. Patients with factor XIII deficiency who receive appropriately timed periodic infusions of such factor XIII concentrates are able to live normal lives, free from catastrophic bleeding episodes.

  8. Characterization of the anti-factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence-based immunoassay

    Science.gov (United States)

    Boylan, Brian; Rice, Anne S.; Dunn, Amy L.; Tarantino, Michael D.; Brettler, Doreen B.; Barrett, John C.; Miller, Connie H.

    2015-01-01

    Summary Background The development of neutralizing antibodies, referred to as inhibitors, against factor VIII (FVIII) is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestations associated with inhibitor development. Objective Assess HA patients' anti-FVIII antibody profiles as potential predictors of clinical outcomes. Methods A fluorescence immunoassay (FLI) was used to detect anti-FVIII antibodies in 491 samples from 371 HA patients. Results Assessments of antibody profiles showed that the presence of anti-FVIII IgG1, IgG2, or IgG4 correlated qualitatively and quantitatively with the presence of a FVIII inhibitor as reported by the Nijmegen-Bethesda assay (NBA). Forty-eight patients with a negative inhibitor history contributed serial samples to the study, including seven patients who had negative NBA titers initially and later converted to NBA-positive. The FLI detected anti-FVIII IgG1 in five of those seven patients prior to their conversion to NBA-positive. Five of 15 serial-sample patients who had a negative inhibitor history and a positive anti-FVIII IgG1 later developed an inhibitor, compared to 2 of 33 patients with a negative inhibitor history without anti-FVIII IgG1. Conclusions These data provide a rationale for future studies designed both to monitor the dynamics of anti-FVIII antibody profiles in HA patients as a potential predictor of future inhibitor development and to assess the value of the anti-FVIII FLI as a supplement to traditional inhibitor testing. PMID:25354263

  9. Comparison of Clot-based, Chromogenic, and Fluorescence Assays for Measurement of Factor VIII Inhibitors in the U.S. Hemophilia Inhibitor Research Study

    Science.gov (United States)

    Miller, Connie H.; Rice, Anne S.; Boylan, Brian; Shapiro, Amy D.; Lentz, Steven R.; Wicklund, Brian M.; Kelly, Fiona M.; Soucie, J. Michael

    2015-01-01

    Summary Background Detection and validation of inhibitors (antibodies) to hemophilia treatment products are important for clinical care, evaluation of product safety, and assessment of population trends. Methods Centralized monitoring for factor VIII (FVIII) inhibitors was conducted for patients in the Hemophilia Inhibitor Research Study using a previously reported modified Nijmegen-Bethesda clotting assay (NBA), a chromogenic Bethesda assay (CBA), and a novel fluorescence immunoassay (FLI). Results NBA and CBA were performed on 1005 specimens and FLI on 272 specimens. CBA was negative on 880/883 specimens (99.7%) with Nijmegen-Bethesda units (NBU)NBA and negative CBA, 58.1% were FLI-negative, 12.9% had evidence of lupus anticoagulant, and 35.5% had non-time-dependent inhibition. CBA and FLI were positive on 72.4% and 100% of 1.0–1.9 NBU specimens and 43.1% and 50.0% of 0.5–0.9 NBU specimens. FLI detected antibodies in 98.0% of CBA-positive and 81.6% of NBA-positive specimens (P=0.004). Among 21 new inhibitors detected by NBA, 5 (23.8%) with 0.7–1.3 NBU did not react in CBA or FLI. Among previously positive patients with 0.5–1.9 NBU, 7/25 (28%) were not CBA or FLI positive. FLI was positive on 36/169 NBU-negative specimens (21.3%). Conclusions FVIII specificity could not be demonstrated by CBA or FLI for 26% of inhibitors of 0.5–1.9 NBU; such results must be interpreted with caution. Low titer inhibitors detected in clot-based assays should always be repeated, with consideration given to evaluating their reactivity with FVIII using more specific assays. PMID:23601690

  10. Association of peak factor VIII levels and area under the curve with bleeding in patients with haemophilia A on every third day pharmacokinetic-guided prophylaxis.

    Science.gov (United States)

    Valentino, L A; Pipe, S W; Collins, P W; Blanchette, V S; Berntorp, E; Fischer, K; Ewenstein, B M; Oh, M; Spotts, G

    2016-07-01

    We previously showed that pharmacokinetic-guided prophylaxis (PKP) allows the dosing interval to be extended while maintaining a specific trough level. However, the associations of peak factor VIII (FVIII) levels and area under the curve (AUC) with breakthrough bleeding have not been investigated. The aim of this study was to analyse data from the PKP arm to determine whether peak FVIII levels, AUC and time with FVIII levels in a haemostatically effective range are independent predictors of bleeding during prophylaxis. Post hoc analysis of the association of FVIII levels and AUC with annualized bleeding rate in 34 patients on PKP. During 1 year of PKP, 131 bleeding episodes occurred in 24/34 patients. Average peak FVIII levels ranged from 24 to 168 IU dL(-1) , with higher values associated with a decreased risk for all bleeding (joint and non-joint; P 20 IU dL(-1) was 22%; median AUC was 1363. Both values were significantly associated with a lower ABR when targeting a 1% trough at 72 h. When PKP was administered every third day, higher peak FVIII levels, higher AUC and more time spent per week with FVIII levels >20 IU dL(-1) provided increased protection from joint and non-joint bleeding. These data highlight the potential impact of variability in individual pharmacokinetic and bleeding risk and support the need for high peak levels and AUC in some patients treated every third day. The findings do not necessarily apply to alternate-day or other prophylactic dosing regimens. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  11. Safety of PEGylated recombinant human full-length coagulation factor VIII (BAX 855) in the overall context of PEG and PEG conjugates.

    Science.gov (United States)

    Stidl, R; Fuchs, S; Bossard, M; Siekmann, J; Turecek, P L; Putz, M

    2016-01-01

    BAX 855 is a PEGylated human full-length recombinant factor VIII (rFVIII) based on licensed rFVIII (ADVATE). The applied PEGylation technology has been optimized to retain functionality of the FVIII molecule, improve its pharmacokinetic properties and allow less frequent injections while maintaining efficacy. The aim of this study was to confirm that the excellent safety profile of ADVATE remains unchanged after PEGylation. Non-clinical safety studies with BAX 855 and its respective unbound polyethylene glycol (PEG) were conducted in several species. The distribution of a single dose of radiolabelled BAX 855 was further investigated in rats. Publically available safety data on PEG alone and PEGylated biomolecules were summarized and reviewed for specific safety findings attributable to PEG or PEGylated biopharmaceuticals. Safety pharmacology studies in rabbits and macaques and repeated dose toxicity studies in rats and macaques identified no safety issues. Results of a distribution study in rats administered radiolabelled BAX 855 showed that radioactivity was completely excreted; urine was the major elimination route. A 28-day study in rats dosed with the unbound PEG constituent (PEG2ru20KCOOH) of BAX 855 showed no adverse or non-adverse effects. Safety data for PEG and PEG-protein conjugates indicate no safety concerns associated with PEG at clinically relevant dose levels. Although vacuolation of certain cell types has been reported in mammals, no such vacuolation was observed with BAX 855 or with the unbound PEG constituent. Non-clinical safety evaluation of PEG and BAX 855 identified no safety signals; the compound is now in clinical development for the treatment of patients with haemophilia A. © 2015 Baxalta Innovations GmbH. Haemophilia Published by John Wiley & Sons Ltd.

  12. The B-domain of factor VIII reduces cell membrane attachement to host cells in serum free conditions

    DEFF Research Database (Denmark)

    Kolind, Mille Petersen; Nørby, Peder Lisby; Flintegaard, Thomas Veje

    2010-01-01

    engineered extensively throughout the years to increase the low production yields that initially were obtained from mammalian cell cultures. The scope of this work was to investigate the interaction of rFVIII with the cell membrane surface of the producing cells in serum free medium. We wondered whether...... binding of rFVIII to the cell membrane could be a factor diminishing the production yield. We studied the contribution of the rFVIII B-domain to membrane attachment by transfecting several constructs containing increasing lengths of the B-domain into cells under serum free conditions. We found that 90......% of rFVIII is attached to the cell membrane of the producing cell when the rFVIII variant contains a short B-domain (21 aa). By increasing the length of the B-domain the membrane attached fraction can be reduced to 50% of the total expressed rFVIII. Further, our studies show that the N...

  13. Modeling of Body Weight Metrics for Effective and Cost-Efficient Conventional Factor VIII Dosing in Hemophilia A Prophylaxis

    Directory of Open Access Journals (Sweden)

    Alanna McEneny-King

    2017-10-01

    Full Text Available The total body weight-based dosing strategy currently used in the prophylactic treatment of hemophilia A may not be appropriate for all populations. The assumptions that guide weight-based dosing are not valid in overweight and obese populations, resulting in overdosing and ineffective resource utilization. We explored different weight metrics including lean body weight, ideal body weight, and adjusted body weight to determine an alternative dosing strategy that is both safe and resource-efficient in normal and overweight/obese adult patients. Using a validated population pharmacokinetic model, we simulated a variety of dosing regimens using different doses, weight metrics, and frequencies; we also investigated the implications of assuming various levels of endogenous factor production. Ideal body weight performed the best across all of the regimens explored, maintaining safety while moderating resource consumption for overweight and obese patients.

  14. The vestibulocochlear nerve (VIII).

    Science.gov (United States)

    Benoudiba, F; Toulgoat, F; Sarrazin, J-L

    2013-10-01

    The vestibulocochlear nerve (8th cranial nerve) is a sensory nerve. It is made up of two nerves, the cochlear, which transmits sound and the vestibular which controls balance. It is an intracranial nerve which runs from the sensory receptors in the internal ear to the brain stem nuclei and finally to the auditory areas: the post-central gyrus and superior temporal auditory cortex. The most common lesions responsible for damage to VIII are vestibular Schwannomas. This report reviews the anatomy and various investigations of the nerve. Copyright © 2013. Published by Elsevier Masson SAS.

  15. Review Blood coagulation factor VIII

    Indian Academy of Sciences (India)

    Unknown

    the development of inhibitors in patients with hemophilia A. 2. Lifespan. 2.1 FVIII gene .... intron 22 inversion is principally an error of DNA repli- cation during ..... Pittman D D, Wang J H and Kaufman R J 1992 Identification and functional ...

  16. Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: Family studies indicate a mutation type-dependent sex ratio of mutation frequencies

    Energy Technology Data Exchange (ETDEWEB)

    Becker, J.; Schmidt, W.; Olek, K. [Univ. of Bonn (Germany)] [and others

    1996-04-01

    The clinical manifestation of hemophilia A is caused by a wide range of different mutations. In this study the factor VIII genes of 147 severe hemophilia A patients-all exclusively from sporadic families-were screened for mutations by use of the complete panel of modern DNA techniques. The pathogenous defect could be characterized in 126 patients (85.7%). Fifty-five patients (37.4%) showed a F8A-gene inversion, 47 (32.0%) a point mutation, 14 (9.5%) a small deletion, 8 (5.4%) a large deletion, and 2 (1.4%) a small insertion. Further, four (2.7%) mutations were localized but could not be sequenced yet. No mutation could be identified in 17 patients (11.6%). Sixteen (10.9%) of the P identified mutations occurred in the B domain. Four of these were located in an adenosine nucleotide stretch at codon 1192, indicating a mutation hotspot. Somatic mosaicisms were detected in 3 (3.9%) of 76 patients` mothers, comprising 3 of 16 de novo mutations in the patients` mothers. Investigation of family relatives allowed detection of a de novo mutation in 16 of 76 two-generation and 28 of 34 three-generation families. On the basis of these data, the male:female ratio of mutation frequencies (k) was estimated as k = 3.6. By use of the quotients of mutation origin in maternal grandfather to patient`s mother or to maternal grandmother, k was directly estimated as k = 15 and k = 7.5, respectively. Considering each mutation type separately, we revealed a mutation type-specific sex ratio of mutation frequencies. Point mutations showed a 5-to-10-fold-higher and inversions a >10-fold- higher mutation rate in male germ cells, whereas deletions showed a >5-fold-higher mutation rate in female germ cells. Consequently, and in accordance with the data of other diseases like Duchenne muscular dystrophy, our results indicate that at least for X-chromosomal disorders the male:female mutation rate of a disease is determined by its proportion of the different mutation types. 68 refs., 1 fig., 5 tabs.

  17. 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.

  18. Polymorphisms in the F8 gene and MHC-II variants as risk factors for the development of inhibitory anti-factor VIII antibodies during the treatment of hemophilia a: a computational assessment.

    Directory of Open Access Journals (Sweden)

    Gouri Shankar Pandey

    Full Text Available The development of neutralizing anti-drug-antibodies to the Factor VIII protein-therapeutic is currently the most significant impediment to the effective management of hemophilia A. Common non-synonymous single nucleotide polymorphisms (ns-SNPs in the F8 gene occur as six haplotypes in the human population (denoted H1 to H6 of which H3 and H4 have been associated with an increased risk of developing anti-drug antibodies. There is evidence that CD4+ T-cell response is essential for the development of anti-drug antibodies and such a response requires the presentation of the peptides by the MHC-class-II (MHC-II molecules of the patient. We measured the binding and half-life of peptide-MHC-II complexes using synthetic peptides from regions of the Factor VIII protein where ns-SNPs occur and showed that these wild type peptides form stable complexes with six common MHC-II alleles, representing 46.5% of the North American population. Next, we compared the affinities computed by NetMHCIIpan, a neural network-based algorithm for MHC-II peptide binding prediction, to the experimentally measured values and concluded that these are in good agreement (area under the ROC-curve of 0.778 to 0.972 for the six MHC-II variants. Using a computational binding predictor, we were able to expand our analysis to (a include all wild type peptides spanning each polymorphic position; and (b consider more MHC-II variants, thus allowing for a better estimation of the risk for clinical manifestation of anti-drug antibodies in the entire population (or a specific sub-population. Analysis of these computational data confirmed that peptides which have the wild type sequence at positions where the polymorphisms associated with haplotypes H3, H4 and H5 occur bind MHC-II proteins significantly more than a negative control. Taken together, the experimental and computational results suggest that wild type peptides from polymorphic regions of FVIII constitute potential T-cell epitopes

  19. Structural Instability in Ice VIII under Pressure

    International Nuclear Information System (INIS)

    Besson, J.; Klotz, S.; Hamel, G.; Marshall, W.; Nelmes, R.; Loveday, J.

    1997-01-01

    Below 125K, tetragonal ice VIII remains in a metastable form at ambient pressure. This form has long been considered to be identical to ice VIII, although unexplained discrepancies exist between their vibrational spectra. Neutron diffraction studies reveal an isostructural phase transformation below 2GPa related to a weakening of the bonds between the two D 2 O sublattices of ice VIII. In this new phase, ice VIII ' , the tetragonal distortion is 20% larger than in ice VIII, which accounts for the differences between the vibrational frequencies of the two phases. copyright 1997 The American Physical Society

  20. 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.

  1. Studies of atmospheric pollutants concentration factors from La Reina reactor

    International Nuclear Information System (INIS)

    Vera, I.; Alegria, E.

    1983-01-01

    Results of an atmospheric diffusion model for pollutant gases re shown, in which the nuclear reactor of the La Reina Nuclear Centre is considered as the emitting source. The model uses a gaussian shape steady state cloud of concentration of pollutants and actual topographical and meteorological statistics data os the zone. Expected and maximum probable concentration factors are computed in a polar lattice in 16 wind directions. It was found that peaks for expected concentration factors and maximum probable concentration factors at ground level fall within the N and ESE directions at distances where hills or mountains reach the emitted cloud. A discussion of the practical value of these calculations is given. (Author)

  2. Studies of atmospheric pollutants concentration factors from La Reina reactor

    Energy Technology Data Exchange (ETDEWEB)

    Vera, I; Alegria, E [Comision Chilena de Energia Nuclear, Santiago. Div. de Seguridade Nuclear y Radioproteccion

    1983-11-01

    Results of an atmospheric diffusion model for pollutant gases are shown, in which the nuclear reactor of the La Reina Nuclear Centre is considered as the emitting source. The model uses a gaussian shape steady state cloud of concentration of pollutants and actual topographical and meteorological statistics data of the zone. Expected and maximum probable concentration factors are computed in a polar lattice in 16 wind directions. It was found that peaks for expected concentration factors and maximum probable concentration factors at ground level fall within the N and ESE directions at distances where hills or mountains reach the emitted cloud. A discussion of the practical value of these calculations is given.

  3. Transfer and concentration factors in laboratory and environmental conditions

    International Nuclear Information System (INIS)

    Paschoa, A.S.; Amaral, E.C.S.

    1993-01-01

    Environmental transfer factors, as well as concentration and accumulation factors, have been increasingly used in environmental dosimetric models. These models are often the basis for decision-making processes concerning radiological protection. However, the uncertainties associated with measured and default values of transfer and concentration factors are usually not taken into account in the decision making processes. In addition, laboratory-based values for these factors do not necessarily agree with site-specific and species-specific transfer and concentration factors. Soil-to-plant transfer factors and water-to-aquatic-organisms concentration factors are not only time and concentration-dependent, but also species-and site-specific environment-dependent. These uncertainties and dependencies may make the decision-making process, based on models, quite a difficult exercise. The current work examines, as an example, the time-dependent variations in the accumulation of 226 Ra in zooplankton in a laboratory experiment as compared with the concentration factor measured in a natural environment. In addition, the work reviews differences in 228 Ra and 226 Ra concentration factors for several plant families measured in a highly radioactive environment. (author). 9 refs, 3 figs, 3 tabs

  4. Studies on influence of environmental factors on concentration on concentration of radionuclides

    International Nuclear Information System (INIS)

    Anon.

    1974-01-01

    Environmental factors which seemed to influence the concentration of radionuclides to marine organisms including illumination, water temperature, coexisting stable elements, salt concentration, suspended matters in sea water and residue were studied. The influence of illumination was examined by algae using 137 Cs, 60 Co, 85 Sr, and 106 Ru as tracers, within 24 hours of illumination. The concentration of 137 Cs and 60 Co revealed remarkable increase of uptake in accordance with increasing illumination intensity, and 24 hours illumination showed 2 times concentration of that by 4 hours'. 85 Sr and 106 Ru showed no effect of illumination, and suggested their concentration was depending on adsorption to the surface. As for water temperature, the concentration factor of 65 Zn, 137 Cs obtained from fishes and shells by 22 0 C breeding was 2 times of that by 12 0 C breeding. Concerning the influence of coexisting stable elements, fishes and shells were examined by 54 Mn, 60 Co, and 65 Zn as tracers. When the stable elements concentration in sea water became 10 times the normal, concentration factor depending on adsorption and metabolism became respective one tenth and one second of the normal value. The influence of salt concentration was examined using 85 Sr, 65 Zn, and 137 Cs, and revealed that 28 to 40 per cent changes of salt level gave slight influence on concentration factor. In order to study the influence of suspended matters and quality of residue, 3 kinds of 106 Ru complex species were added. Concentration factor of Hijiki (Hijikia fusiforme) showed no remarkable difference between breeding in filtrated and non-filtrated sea water. However, clams living in the sand should be taken care of the concentration by the residue in the sea bottom. (Kanao, N.)

  5. Control of exogenous factors affecting plasma homovanillic acid concentration.

    Science.gov (United States)

    Davidson, M; Giordani, A B; Mohs, R C; Mykytyn, V V; Platt, S; Aryan, Z S; Davis, K L

    1987-04-01

    Measurements of plasma homovanillic acid (pHVA) concentrations appear to be a valid research strategy in psychiatric disorders in which a central dopamine (DA) abnormality has been implicated. This study provides guidance about the control of some of the exogenous factors affecting pHVA concentrations. Fasting for 14 hours eliminates the dietary effects on pHVA in healthy human subjects. Changing position, walking for 30 minutes, or smoking two cigarettes has no effect on pHVA concentrations.

  6. Factors influencing indoor concentrations of radon and daughter products

    International Nuclear Information System (INIS)

    Wang Hengde

    1985-01-01

    The correlation between indoor concentrations of 222 Rn and its daughters and some influencing factors is discussed and expressions of concentrations are derived with relation to radon exhalation rate from indoor surfaces, air exchange rate and daughter deposition velocities on indoor surfaces. Experimental methods for determining radon exhalation rate, air exchange rate and daughter deposition velocities are also mentioned

  7. Risk factors contributing to a low darunavir plasma concentration

    NARCIS (Netherlands)

    Daskapan, Alper; Stienstra, Ymkje; Kosterink, Jos G.W.; Bierman, Wouter F.W.; van der Werf, Tjip S.; Touw, Daan J.; Alffenaar, Jan Willem C.

    Darunavir is an efficacious drug; however, pharmacokinetic variability has been reported. The objective of this study was to find predisposing factors for low darunavir plasma concentrations in patients starting the once- or twice-daily dosage. Darunavir plasma concentrations from January 2010 till

  8. Status and trend analysis of prophylactic usage of recombinant factor VIII in Chinese pediatric patients with hemophilia A: ReCare - a retrospective, phase IV, non-interventional study.

    Science.gov (United States)

    Li, Changgang; Zhang, Xinsheng; Zhao, Yongqiang; Wu, Runhui; Hu, Qun; Xu, Vicky; Sun, Jing; Yang, Renchi; Li, Xiaojing; Zhou, Rongfu; Lian, Shinmei; Gu, Jian; Wu, Junde; Hou, Qingsong

    2017-09-01

    No study has reported the status and chronological trend of prophylactic recombinant factor VIII (rFVIII) use in Chinese pediatric patients with hemophilia A (HA). We aimed to analyze the status and trend of rFVIII-containing prophylaxis in Chinese pediatric patients with HA. ReCARE (Retrospective study in Chinese pediatric hemophilia A patients with rFVIII contained REgular prophylaxis) was a retrospective study conducted in 12 hemophilia treatment centers across China. The trend of prophylaxis was evaluated by determining the mean duration of prophylaxis, mean injection frequency (per week), mean dose of each injection (IU/kg), mean total dose injected/week (IU) and proportion of rFVIII consumption relative to factor VIII (FVIII) consumption over the study period. We analyzed 183 male pediatric patients with HA (mean age, 7.1 ± 4.23 years), who received intermittent prophylaxis between 1 November 2007 and 31 May 2013. The mean duration of prophylaxis with rFVIII increased from 16.72 weeks in 2008 to 32.77 in 2012. Per injection dose of rFVIII increased significantly from 2008 to 2013 (25.89 to 28.31 IU/kg, p < .001). An increase was also reported in the mean total FVIII consumed (699.97 ± 173.25 IU in 2008 and 891.30 ± 730.341 in 2013) and mean proportion of rFVIII used (33.33 ± 57.73% in 2008 to 85.50 ± 29.077% in 2013). Our data revealed an overall improvement in treatment dosage and duration with an increase in the number of patients receiving prophylaxis. The total proportion of rFVIII also increased gradually indicating the development of economy and safety awareness. The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02263066).

  9. Studies on influence of biological factors on concentration of radionuclides

    International Nuclear Information System (INIS)

    Anon.

    1974-01-01

    Biological factors influencing the concentration of radionuclides were studied from the points of uptake through digestive tract, food as pathways, and metabolic activities. The uptake of radionuclides by marine fishes through digestive tract was determined by whole body counter. 137 Cs, 65 Zn, 131 I, 54 Mn, 60 Co, 85 Sr, and 144 Ce were used as tracers and was given with solid feed. The feed given was excreated 24 to 48 hours later in small of middle sized fishes, and 20 to 48 hours later in large sized fishes. The uptake rate of 137 Cs and 65 Zn was high absorption of 20 to 80 per cent, that of 131 I, 60 Co and 54 Mn was not remarkable, and that of 85 Sr and 144 Ce was low absorption. The biological concentration of 137 Cs through pathways of food. In fishes taking up radionuclides through contaminated food, concentration factor increased in accordance with contamination level. In addition, radionuclides with small uptake but delayed excretion and those with high concentration rate could be the factors to decide the concentration factors of marine organisms. In order to study the relationship between metabolic activities and concentration, the uptake of one-year old fishes and adult fishes, and fishes fed and those non-fed were compared. One-year fishes took up large amount of 85 Sr during short period, however, concentration by metabolism in adult fishes was slow. Comparing feeding group and non-feeding group, the former showed 85 Sr concentration factor of 1.5 to 2 times that of the later, and the later showed 137 Cs concentration factor of 2 to 4 times that of the former. However, both uptake and excretion were rapid suggesting that taking food activated the metabolism of substances. (Kanao, N.)

  10. Soil-to-plant concentration factors for radiological assessments

    International Nuclear Information System (INIS)

    Ng, Y.C.; Thompson, S.E.; Colsher, C.S.

    1982-09-01

    This report presents the results of a literature review to derive soil-to-plant concentration factors to predict the concentration of a radionuclide in plants from that in soil. The concentration factor, B/sub v/ is defined as the ratio of the concentration of a nuclide in the edible plant part to that in dry soil. CR (the concentration ratio) is similarly defined to denote the concentration factor for dry feed consumed by livestock. B/sub v/ and CR values are used to assess the dose from radionuclides deposited onto soil and transferred into crop plants via roots. Approaches for deriving B/sub v/ and CR values are described, and values for food and feed are tabulated for individual elements. The sources of uncertainty are described, and the factors that contribute to the inherent variability of the B/sub v/ and CR values are discussed. Summary tables of elemental B/sub v/ and CR values and statistical parameters that characterize their distributions provide a basis for a systematic updating of many of the B/sub v/ values in Regulatory Guide 1.109. They also provide a basis for selecting B/sub v/ and CR values for other applications that involve the use of equilibrium models to predict the concentration of radionuclides in plants from that in soil

  11. An investigation of factors influencing indoor radon concentrations

    International Nuclear Information System (INIS)

    Majborn, B.; Soerensen, A.; Nielsen, S.P.; Boetter-Jensen, L.

    1988-05-01

    Variations in indoor radon concentrations and some influencing factors have been studied during a two-year period (1986-1987) in 16 almost identical single-family houses.The annual average radon concentration in the houses varied from about 50 to about 400 Bq/m 3 . Variations in soil characteristics and radon concentration in soil gas could not be directly related to the variations of the average indoor radon concentrations. Most of the houses showed a ''normal'' seasonal variation of the radon concentration with a maximum in the winter and minimum in the summer. A deviating seasonal variation was found in three of the houses. Hourly data obtained in one unoccupied house during a period of 2-1/2 months showed no or only weak correlations between the indoor radon concentration and meteorological factors. However, for most of the houses, the seasonal variation of the indoor radon concentration was well correlated with the average indoor-outdoor temperature difference on a 2-month basis. It was demonstrated that the radon concentration can be strongly reduced in the Risoe houses if a district-heating duct, which is connected to all the houses, is ventilated, so that a slightly lowered pressure is maintained in the duct. 5 taps., 24 ill. (author)

  12. Hemoglobin concentrations and associated factors in adolescentes from Recife, Brazil

    OpenAIRE

    Elisângela Barros Soares Mendonça; Lilian Ferreira Muniz; Ilma Kruze Grande de Arruda; Alcides da Silva Diniz

    2014-01-01

    OBJECTIVE: To estimate the prevalence of anemia and associated factors in adolescents from the city of Recife in Pernambuco state. METHODS: This is a cross-sectional study, involving a random sample of 256 adolescents of both genders, aged 13 to 18, whose hemoglobin concentrations were evaluated, along with their nutritional status and socioeconomic and demographic characteristics. RESULTS: The prevalence of inadequate hemoglobin concentrations was 10.2% [CI95%=6.7-14.5], reaching levels cons...

  13. Long-term efficacy and safety of prophylaxis with recombinant factor VIII in Chinese pediatric patients with hemophilia A: a multi-center, retrospective, non-interventional, phase IV (ReCARE) study.

    Science.gov (United States)

    Li, Changgang; Zhang, Xinsheng; Zhao, Yongqiang; Wu, Runhui; Hu, Qun; Xu, Weiqun; Sun, Jing; Yang, Renchi; Li, Xiaojing; Zhou, Rongfu; Lian, Shinmei; Gu, Jian; Wu, Junde; Hou, Qingsong

    2017-07-01

    The first recombinant factor VIII (rFVIII) product was launched in China in 2007. However, until now, no study has been conducted to describe the efficacy and safety of prophylaxis with rFVIII in Chinese pediatric patients with hemophilia A (HA). To summarize the efficacy and safety data on prophylaxis with rFVIII in Chinese pediatric patients with HA. ReCARE (Retrospective study in Chinese pediatric hemophilia A patients with rFVIII contained regular prophylaxis) was a retrospective study conducted in 12 hemophilia treatment centers (HTCs) across China. The primary endpoints included reduction in annualized bleeding rate (ABR); the secondary endpoints included evaluation of joint function (number and sites of target joints) using Gilbert score and Hemophilia Joint Health Score (HJHS), quality of life (QoL) and factors affecting treatment choices. Safety assessment of rFVIII was also conducted. We analyzed a total of 183 male pediatric patients (mean age, 7.1 ± 4.23 years) who received prophylaxis between 1 November 2007 and 31 May 2013. Compared with baseline, prophylaxis with rFVIII significantly reduced overall annualized joint bleed rate (AJBR) (p < .001) and ABR (p < .001). Inhibitor formation was reported in 5 (2.7%) patients and hemarthrosis was reported in 1 patient. The mean number of target joints was positively related to age (p < .001) and weight (p = .003) at baseline. Responses from survey questionnaires reported that effective bleeding control, joint protection, improvement in quality of life, favorable medical insurance policies, and economic capability were reasons for choosing prophylaxis. Prophylaxis with rFVIII reduced bleeding and number of target joints, even with a low-dose regimen, in Chinese pediatric patients with HA. Other than the efficacy and safety, factors such as poor disease control, improved economic stability and stable financial support made prophylaxis as an attractive treatment option. ClinicalTrials.gov ID

  14. Modifiable factors associated with copeptin concentration: a general population cohort.

    Science.gov (United States)

    van Gastel, Maatje D A; Meijer, Esther; Scheven, Lieneke E; Struck, Joachim; Bakker, Stephan J L; Gansevoort, Ron T

    2015-05-01

    Vasopressin plays an important role in maintaining volume homeostasis. However, recent studies suggest that vasopressin also may play a detrimental role in the progression of chronic kidney disease. It therefore is of interest to identify factors that influence vasopressin concentration, particularly modifiable ones. Cross-sectional analyses. Data used are from participants in a large general-population cohort study (Prevention of Renal and Vascular Endstage Disease [PREVEND]). Patients with a missing copeptin value (n=888), nonfasting blood sample (n=495), missing or assumed incorrect 24-hour urine collection (n=388), or heart failure (n=20) were excluded, leaving 6,801 participants for analysis. Identification of lifestyle- and diet-related factors that are associated with copeptin concentration. Copeptin concentration as surrogate for vasopressin. Copeptin was measured by an immunoluminometric assay as a surrogate for vasopressin. Associations were assessed in uni- and multivariable linear regression analyses. Median copeptin concentration was 4.7 (IQR, 2.9-7.6) pmol/L. When copeptin was studied as a dependent variable, the final stepwise backward model revealed associations with higher copeptin concentrations for lower 24-hour urine volume (P firm conclusions on cause-effect relationships. Important lifestyle- and diet-related factors associated with copeptin concentration are current smoking, alcohol use, protein and potassium intake, and particularly fluid and sodium intake. These data form a rationale to investigate whether intervening on these factors results in a lower vasopressin concentration with concomitant beneficial renal effects. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  15. Modifiable Factors Associated With Copeptin Concentration : A General Population Cohort

    NARCIS (Netherlands)

    van Gastel, Maatje D. A.; Meijer, Esther; Scheven, Lieneke E.; Struck, Joachim; Bakker, Stephan J. L.; Gansevoort, Ron T.

    Background: Vasopressin plays an important role in maintaining volume homeostasis. However, recent studies suggest that vasopressin also may play a detrimental role in the progression of chronic kidney disease. It therefore is of interest to identify factors that influence vasopressin concentration,

  16. Factors that influence an elemental depth concentration profile

    International Nuclear Information System (INIS)

    McHugh, J.A.

    1975-01-01

    The use of secondary ion mass spectrometry in concentration profiling is discussed. Two classes of factors that influence an elemental concentration profile are instrumental effects and ion-matrix effects. Instrumental factors that must be considered are: (1) uniformity of the primary ion current density, (2) constancy of the primary ion current, (3) redeposition, (4) memory, (5) primary ion beam tailing and the nonfocused component, (6) chemical purity of the primary ion beam, and (7) residual gas impurities. Factors which can be classified as ion matrix effects are: (1) the mean escape depth of secondary ions, (2) recoil implantation, (3) molecular ion interferences, (4) primary ion beam induced diffusion of matrix species, (5) nonuniform sputter removal of matrix layers, and (6) implanted primary ion chemical and lattice damage effects

  17. Current use of factor concentrates in pediatric cardiac anesthesia.

    Science.gov (United States)

    Guzzetta, Nina A; Williams, Glyn D

    2017-07-01

    Excessive bleeding following pediatric cardiopulmonary bypass is associated with increased morbidity and mortality, both from the effects of hemorrhage and the therapies employed to achieve hemostasis. Neonates and infants are especially at risk because their coagulation systems are immature, surgeries are often complex, and cardiopulmonary bypass technologies are inappropriately matched to patient size and physiology. Consequently, these young children receive substantial amounts of adult-derived blood products to restore adequate hemostasis. Adult and pediatric data demonstrate associations between blood product transfusions and adverse patient outcomes. Thus, efforts to limit bleeding after pediatric cardiopulmonary bypass and minimize allogeneic blood product exposure are warranted. The off-label use of factor concentrates, such as fibrinogen concentrate, recombinant activated factor VII, and prothrombin complex concentrates, is increasing as these hemostatic agents appear to offer several advantages over conventional blood products. However, recognizing that these agents have the potential for both benefit and harm, well-designed studies are needed to enhance our knowledge and to determine the optimal use of these agents. In this review, our primary objective was to examine the evidence regarding the use of factor concentrates to treat bleeding after pediatric CPB and identify where further research is required. PubMed, MEDLINE/OVID, The Cochrane Library and the Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched to identify existing studies. © 2017 John Wiley & Sons Ltd.

  18. Prophylaxis vs. on-demand treatment with BAY 81-8973, a full-length plasma protein-free recombinant factor VIII product: results from a randomized trial (LEOPOLD II).

    Science.gov (United States)

    Kavakli, K; Yang, R; Rusen, L; Beckmann, H; Tseneklidou-Stoeter, D; Maas Enriquez, M

    2015-03-01

    BAY 81-8973 is a new full-length human recombinant factor VIII product manufactured with technologies to improve consistency in glycosylation and expression to optimize clinical performance. To demonstrate superiority of prophylaxis vs. on demand therapy with BAY 81-8973 in patients with severe hemophilia A. In this multinational,randomized, open-label crossover study (LEOPOLD II;ClinicalTrials.gov identifier: NCT01233258), males aged 12–65 years with severe hemophilia A were randomized to twice-weekly prophylaxis (20-30 IU kg(-1)), 3-times-weekly prophylaxis (30-40 IU kg(-1)), or on-demand treatment with BAY 81-8973. Potency labeling for BAY 81-8973 was based on the chromogenic substrate assay or adjusted to the one-stage assay. Primary efficacy endpoint was annualized number of all bleeds (ABR). Adverse events (AEs)and immunogenicity were also assessed. Eighty patients (on demand, n = 21; twice-weekly prophylaxis, n = 28; 3-times-weekly prophylaxis, n = 31) were treated and analyzed. Mean ± SD ABR was significantly lower with prophylaxis (twice-weekly, 5.7 ± 7.2; 3-times-weekly, 4.3 ± 6.5; combined, 4.9 ± 6.8) vs. on-demand treatment (57.7 ± 24.6; P demand treatment (60.0). Median ABR was higher with twice-weekly vs. 3-times-weekly prophylaxis during the first 6-month treatment period (4.1 vs. 2.0) but was comparable in the second 6-month period (1.1 vs. 2.0). Few patients reported treatment-related AEs (4%); no treatment-related serious AEs or inhibitors were reported. Twice weekly or 3-times-weekly prophylaxis with BAY 81-8973 reduced median ABR by 97% compared with on-demand therapy, confirming the superiority of prophylaxis. Treatment with BAY 81-8973 was well tolerated.

  19. Development, upscaling and validation of the purification process for human-cl rhFVIII (Nuwiq®), a new generation recombinant factor VIII produced in a human cell-line.

    Science.gov (United States)

    Winge, Stefan; Yderland, Louise; Kannicht, Christoph; Hermans, Pim; Adema, Simon; Schmidt, Torben; Gilljam, Gustav; Linhult, Martin; Tiemeyer, Maya; Belyanskaya, Larisa; Walter, Olaf

    2015-11-01

    Human-cl rhFVIII (Nuwiq®), a new generation recombinant factor VIII (rFVIII), is the first rFVIII produced in a human cell-line approved by the European Medicines Agency. To describe the development, upscaling and process validation for industrial-scale human-cl rhFVIII purification. The purification process involves one centrifugation, two filtration, five chromatography columns and two dedicated pathogen clearance steps (solvent/detergent treatment and 20 nm nanofiltration). The key purification step uses an affinity resin (VIIISelect) with high specificity for FVIII, removing essentially all host-cell proteins with >80% product recovery. The production-scale multi-step purification process efficiently removes process- and product-related impurities and results in a high-purity rhFVIII product, with an overall yield of ∼50%. Specific activity of the final product was >9000 IU/mg, and the ratio between active FVIII and total FVIII protein present was >0.9. The entire production process is free of animal-derived products. Leaching of potential harmful compounds from chromatography resins and all pathogens tested were below the limit of quantification in the final product. Human-cl rhFVIII can be produced at 500 L bioreactor scale, maintaining high purity and recoveries. The innovative purification process ensures a high-purity and high-quality human-cl rhFVIII product with a high pathogen safety margin. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Low risk of inhibitor formation in haemophilia A patients following en masse switch in treatment to a third generation full length plasma and albumin-free recombinant factor VIII product (ADVATE®).

    LENUS (Irish Health Repository)

    Bacon, C L

    2011-05-01

    Previous studies have suggested that development of inhibitors in previously treated patients (PTPs) may be attributable to a switch in factor VIII (FVIII) therapeutic product. Consequently, it is widely recognized that inhibitor development must be assessed in PTPs following the introduction of any new FVIII product. Following a national tender process in 2006, all patients with haemophilia A in Ireland changed their FVIII treatment product en masse to a plasma and albumin-free recombinant full-length FVIII product (ADVATE(®)). In this study, we retrospectively reviewed the case records of Irish PTPs to evaluate risk of inhibitor formation following this treatment switch. One hundred and thirteen patients participated in the study. Most patients (89%) had severe haemophilia. Only one of 96 patients with no inhibitor history developed an inhibitor. Prior to the switch in his recombinant FVIII (rFVIII) treatment of choice, this child had only experienced three exposure days (EDs). Consequently, in total he had only received 6 EDs when his inhibitor was first diagnosed. In keeping with this lack of de novo inhibitor development, we observed no evidence of any recurrent inhibitor formation in any of 16 patients with previously documented inhibitors. Similarly, following a previous en masse switch, we have previously reported that changing from a Chinese hamster ovary cell-produced to a baby hamster kidney cell-produced rFVIII was also associated with a low risk of inhibitor formation in PTPs. Our cumulative findings from these two studies clearly emphasizes that the risk of inhibitor development for PTPs following changes in commercial rFVIII product is low, at least in the Irish population.

  1. Functional Role of Milk Fat Globule-Epidermal Growth Factor VIII in Macrophage-Mediated Inflammatory Responses and Inflammatory/Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Young-Su Yi

    2016-01-01

    Full Text Available Inflammation involves a series of complex biological processes mediated by innate immunity for host defense against pathogen infection. Chronic inflammation is considered to be one of the major causes of serious diseases, including a number of autoimmune/inflammatory diseases, cancers, cardiovascular diseases, and neurological diseases. Milk fat globule-epidermal growth factor 8 (MFG-E8 is a secreted protein found in vertebrates and was initially discovered as a critical component of the milk fat globule. Previously, a number of studies have reported that MFG-E8 contributes to various biological functions including the phagocytic removal of damaged and apoptotic cells from tissues, the induction of VEGF-mediated neovascularization, the maintenance of intestinal epithelial homeostasis, and the promotion of mucosal healing. Recently, emerging studies have reported that MFG-E8 plays a role in inflammatory responses and inflammatory/autoimmune diseases. This review describes the characteristics of MFG-E8-mediated signaling pathways, summarizes recent findings supporting the roles of MFG-E8 in inflammatory responses and inflammatory/autoimmune diseases, and discusses MFG-E8 targeting as a potential therapeutic strategy for the development of anti-inflammatory/autoimmune disease drugs.

  2. Stress Concentration Factor and Stress Intensity Factor with U-notch and Crack in the Beam

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Bo Seong; Lee, Kwang Ho [Kyungpook National Univ., Daegu (Korea, Republic of)

    2016-05-15

    The stress concentration factors and stress intensity factors for a simple beam and a cantilever are analyzed by using finite element method and photoelasticity. Using the analyzed results, the estimated graphs on stress concentration factors and stress intensity factors are obtained. To analyze stress concentration factors of notch, the dimensionless notch length H(height of specimen)/h=1.1-2 and dimensionless gap space r(radius at the notch tip)/h=0.1~0.5 are used, where h=H-c and c is the notch length. As the notch gap length increases and the gap decreases, the stress concentration factors increase. Stress concentration factors of a simple beam are greater than those of a cantilever beam. However, actually, the maximum stress values under a load, a notch length and a gap occur more greatly in the cantilever beam than in the simple beam. To analyze stress intensity factors, the normalized crack length α(crack length)/H=0.2~0.5 is used. As the length of the crack increases, the normalized stress intensity factors increase. The stress intensity factors under a constant load and a crack length occur more greatly in the cantilever beam than in the simple beam.

  3. Variance of indoor radon concentration: Major influencing factors

    Energy Technology Data Exchange (ETDEWEB)

    Yarmoshenko, I., E-mail: ivy@ecko.uran.ru [Institute of Industrial Ecology UB RAS, Sophy Kovalevskoy, 20, Ekaterinburg (Russian Federation); Vasilyev, A.; Malinovsky, G. [Institute of Industrial Ecology UB RAS, Sophy Kovalevskoy, 20, Ekaterinburg (Russian Federation); Bossew, P. [German Federal Office for Radiation Protection (BfS), Berlin (Germany); Žunić, Z.S. [Institute of Nuclear Sciences “Vinca”, University of Belgrade (Serbia); Onischenko, A.; Zhukovsky, M. [Institute of Industrial Ecology UB RAS, Sophy Kovalevskoy, 20, Ekaterinburg (Russian Federation)

    2016-01-15

    Variance of radon concentration in dwelling atmosphere is analysed with regard to geogenic and anthropogenic influencing factors. Analysis includes review of 81 national and regional indoor radon surveys with varying sampling pattern, sample size and duration of measurements and detailed consideration of two regional surveys (Sverdlovsk oblast, Russia and Niška Banja, Serbia). The analysis of the geometric standard deviation revealed that main factors influencing the dispersion of indoor radon concentration over the territory are as follows: area of territory, sample size, characteristics of measurements technique, the radon geogenic potential, building construction characteristics and living habits. As shown for Sverdlovsk oblast and Niška Banja town the dispersion as quantified by GSD is reduced by restricting to certain levels of control factors. Application of the developed approach to characterization of the world population radon exposure is discussed. - Highlights: • Influence of lithosphere and anthroposphere on variance of indoor radon is found. • Level-by-level analysis reduces GSD by a factor of 1.9. • Worldwide GSD is underestimated.

  4. Stress concentration factors for pressurized elliptic crossbores in blocks

    International Nuclear Information System (INIS)

    Badr, Elie A.

    2006-01-01

    Intersecting bore geometries are used in a number of industrial applications including heavy-walled pressure vessels containing oil holes for lubrication, ports for valves and fluid ends of reciprocating pumps. The bore intersection location is a stress concentration point where the maximum hoop stress can be many times the fluid pressure in the bores. Intersecting circular holes in heavy-walled cylinders and rectangular blocks have been extensively investigated. Specifically, stress/pressure concentration curves for intersecting circular bores in rectangular blocks were presented by Sorem et al. [Sorem JR, Shadley JR, Tipton SM. Design curves for maximum stresses in blocks containing pressurized bore intersections. ASME J Mech Des 1990; 113: 427-31.]. However, stress/pressure concentrations due to intersecting elliptic bores have not been broadly investigated. With the availability of computer numerical control (CNC) machinery, bores with elliptic crosssection can be produced with relative ease. In this paper, hoop stress concentration ratios are developed for elliptic crossbores in rectangular blocks. Results indicate that introducing elliptic crossbores, rather than circular ones, significantly reduces the hoop stress concentration factor at the crossbore intersection. Also, the presence of intersecting crossbores has a major effect on the fatigue life of pressure vessels [Badr EA, Sorem JR, Jr Tipton SM. Evaluation of the autofrettage effect on fatigue lives of steel blocks with crossbores using a statistical and a strain-based method. ASTM J Test Eval 2000; 28: 181-8.] and the reduction of hoop stress concentration is expected to enhance the fatigue life of pressure vessels containing crossbores

  5. Blood coagulation factor VIII: An overview

    Indian Academy of Sciences (India)

    Unknown

    Solvent, detergent and heat treatment. Hemofil-M. Baxter. Pooled human venous plasma. Immunoaffinity chromatography using murine monoclonal anti- body. Solvent and detergent. Monarc-M. American. Red Cross. Pooled human venous plasma. Immunoaffinity chromatography using murine monoclonal antibody.

  6. Hemoglobin concentrations and associated factors in adolescentes from Recife, Brazil

    Directory of Open Access Journals (Sweden)

    Elisângela Barros Soares Mendonça

    2014-10-01

    Full Text Available OBJECTIVE: To estimate the prevalence of anemia and associated factors in adolescents from the city of Recife in Pernambuco state. METHODS: This is a cross-sectional study, involving a random sample of 256 adolescents of both genders, aged 13 to 18, whose hemoglobin concentrations were evaluated, along with their nutritional status and socioeconomic and demographic characteristics. RESULTS: The prevalence of inadequate hemoglobin concentrations was 10.2% [CI95%=6.7-14.5], reaching levels considered as mild anemia (9 g/dL 0.05, nor with socioeconomic or demographic characteristics (p>0.05. CONCLUSION: Although the prevalence of anemia was low and classified as a mild health problem, preventive nutrition education involving the dissemination of healthy eating habits in schools and encouraging the consumption of iron-rich foods are strongly recommended.

  7. The Effect of Concentration Factor on Membrane Fouling

    Directory of Open Access Journals (Sweden)

    Appana Lok

    2017-09-01

    Full Text Available Bench-scale systems are often used to evaluate pretreatment methods and operational conditions that can be applied in full-scale ultrafiltration (UF systems. However, the membrane packing density is substantially different in bench and full-scale systems. Differences in concentration factor (CF at the solution–membrane interface as a result of packing density may impact the mass transfer and fouling rate and the applicability of bench-scale systems. The present study compared membrane resistance when considering raw water (CF = 1 and reject water (also commonly referred to as concentrate water (CF > 1 as feed in UF systems operated in deposition (dead-end mode. A positive relationship was observed between the concentration of the organic matter in the solution being filtered and resistance. Bench-scale trials conducted with CF = 1 water were more representative of full-scale operation than trials conducted with elevated CFs when considering membrane resistance and permeate quality. As such, the results of this study indicate that the use of the same feed water as used at full-scale (CF = 1 is appropriate to evaluate fouling in UF systems operated in deposition mode.

  8. Concentration factors of radionuclides in the marine organisms

    International Nuclear Information System (INIS)

    1996-03-01

    Parameters related to the bioconcentration of radionuclides in the marine were shown by 'Assessment and guideline to the target value of dose in the environment of the power light water reactor facilities' (Nuclear Safety Commission), but the guideline data did not contain Ru and Ce relating to the reprocessing plant. So that more new data than these of 'Technical Reports Series No. 247' (published by IAEA in 1985) were mainly collected. Especially the data of nuclides with poor data of concentration factors (CF) and natural radionuclides (Po-210, Pb-210) were gathered. These data were pigeonholed and many tables (element, kinds of organisms, experimental methods) were made by separating the general remarks from the original experimental reports. The contents of this report are given as under, history of concentration factor (CF), determination method of CF, CF calculation method, calculation models related to CF, tables of metabolic parameters, tables of CF, the present conditions of studies for uptake of radionuclides with long half-life into the marine organisms, CF abstract tables and trial calculation of human exposure by eating the marine organisms. (S.Y.)

  9. Meteorological factors for PM10 concentration levels in Northern Spain

    Science.gov (United States)

    Santurtún, Ana; Mínguez, Roberto; Villar-Fernández, Alejandro; González Hidalgo, Juan Carlos; Zarrabeitia, María Teresa

    2013-04-01

    Atmospheric particulate matter (PM) is made up of a mixture of solid and aqueous species which enter the atmosphere by anthropogenic and natural pathways. The levels and composition of ambient air PM depend on the climatology and on the geography (topography, soil cover, proximity to arid zones or to the coast) of a given region. Spain has particular difficulties in achieving compliance with the limit values established by the European Union (based on recommendations from the World Health Organization) for particulate matter on the order of 10 micrometers of diameter or less (PM10), but not only antropogenical emissions are responsible for this: some studies show that PM10 concentrations originating from these kinds of sources are similar to what is found in other European countries, while some of the geographical features of the Iberian Peninsula (such as African mineral dust intrusion, soil aridity or rainfall) are proven to be a factor for higher PM concentrations. This work aims to describe PM10 concentration levels in Cantabria (Northern Spain) and their relationship with the following meteorological variables: rainfall, solar radiation, temperature, barometric pressure and wind speed. Data consists of daily series obtained from hourly data records for the 2000-2010 period, of PM10 concentrations from 4 different urban-background stations, and daily series of the meteorological variables provided by Spanish National Meteorology Agency. The method used for establishing the relationships between these variables consists of several steps: i) fitting a non-stationary probability density function for each variable accounting for long-term trends, seasonality during the year and possible seasonality during the week to distinguish between work and weekend days, ii) using the marginal distribution function obtained, transform the time series of historical values of each variable into a normalized Gaussian time series. This step allows using consistently time series

  10. Concentration Factors of Norm in Sediment of Cisadane River

    International Nuclear Information System (INIS)

    Agus Gindo S; Lubis, Erwansyah

    2008-01-01

    The Concentration factor (Cf) in sediment of Cisadane river was investigated. The surface water and sediment was sampling at Gunung Sindur area (down stream) until Teluk Naga area (up stream). The results indicated that Cf values of gross-α, gross-β, gross-th, gross-U, 40 K, 226 Ra and 228 Th were 830 ± 87, 1800 ± 290, 2150 ± 50, 1415 ± 41, 37 ± 1, 22 ± 5 and 115 ± 56 respectively. With these Cf values, the radiological impact from liquid effluent release to Cisadane river that contains NORM from industrial activities for agriculture and fishery pathways are able to predicted. This investigation still has to be continued for other radionuclides. (author)

  11. 77 FR 64401 - Order of Succession for HUD Region VIII

    Science.gov (United States)

    2012-10-19

    ... Region VIII AGENCY: Office of Field Policy and Management, HUD. ACTION: Notice of Order of Succession... Field Offices (Region VIII). This Order of Succession supersedes all previous Orders of Succession for HUD Region VIII. DATES: Effective Date: October 9, 2012. FOR FURTHER INFORMATION CONTACT: Lawrence D...

  12. Concentration factors and aggregated transfer factors in selected bio-indicators from Sweden[Radioecology

    Energy Technology Data Exchange (ETDEWEB)

    Holm, E.; Samuelsson, C.; Holstensson, M. [Lund Univ. (Sweden)

    2006-04-15

    Previously most common has been to use lichens and mosses in the terrestrial environment and mussels and algae in the marine environment. Several plants are promising and less commonly used such as ferns (e.g. Bracken, Pteridium aquilinum) and the fresh water plant, Water horsetail (Equisetum fluviatile). These show high uptake of radiocaesium but also accumulate plutonium and americium. Even if the uptake of transuranic elements is low, this behaviour is rather unique for plants. On bases of available data we have calculated concentration factors Cf and aggregated transfer factors, ATF according to their definitions i.e. Bq kg{sup -1} (biota)/Bq kg{sup -1}(water) and Bq kg{sup -1} (biota)/Bq m{sup -2} respectively. For earlier samples the water concentrations can only roughly be estimated while deposition data are rather well known. For fresh water samples it is a little awkward to use concentration factors since the uptake generally is not from water. Therefore a kind of Aggregated Transfer Factor has also been calculated on basis of using the same areal deposition in sediments as on land. We have used dry weight concentrations for biota. Data are presented for samples of various bio-medicator organisms. (LN)

  13. [Ehler-Danlos syndrome type VIII].

    Science.gov (United States)

    Ciarloni, L; Perrigouard, C; Lipsker, D; Cribier, B

    2010-03-01

    Ehlers-Danlos syndrome (EDS) comprises a heterogeneous group of diseases involving genetic collagen fibre impairment. We describe a case of a patient presenting the rare type VIII, in which dermatitis ocre was associated with parodontal disease, and which was diagnosed late. A 29-year-old man consulted for a pretibial ulcer present for seven years, resulting from a post-traumatic haematoma that had failed to heal. In view of the longiliner morphology, it had previously been diagnosed as Marfan syndrome. Subsequently, edentation was observed as well as "alveolar bone fragility". Examination revealed a marfanoid morphotype, a pretibial ulcer set within long-standing bilateral dermatitis ocre and papyraceous scars, but no joint hyperlaxity or cutaneous hyperelasticity. The diagnosis was consequently corrected to EDS type VIII. Type VIII is a rare form of EDS, and the molecular mechanism is poorly understood. The involvement of parodontal connective tissue suggests impairment of collagen I and III proteins. It is important to identify this type of the disease since it involves parodontal disease for which early treatment is required in order to try to prevent edentation. The present case demonstrates the importance of diagnosis, which may be based upon appearance of bilateral dermatitis ocre from the age of 15 years associated with skin fragility. This sign is not part of the classical picture of Marfan syndrome, with which EDS type VIII is often confounded. Copyright 2009 Elsevier Masson SAS. All rights reserved.

  14. Risk factors associated with high linezolid trough plasma concentrations.

    Science.gov (United States)

    Morata, L; De la Calle, C; Gómez-Cerquera, J M; Manzanedo, L; Casals, G; Brunet, M; Cobos-Trigueros, N; Martínez, J A; Mensa, J; Soriano, A

    2016-06-01

    The major concern of linezolid is the adverse events. High linezolid trough serum concentration (Cmin) has been associated with toxicity. The aim of this study was to analyze factors associated with high Cmin. Main clinical characteristics of 104 patients treated with 600 mg/12 hours of linezolid were retrospectively reviewed. Samples were obtained just before the next dose after at least three doses and within the first 8 days of treatment. High Cmin was considered when it was >8 mg/L. Univariate and multivariate analysis were performed. 34.6% patients had a Cmin >8 mg/L, and they were older and had more frequently an estimated glomerular filtration by MDRD 8 was the renal function. Patients with an eGF 80 mL/min (OR: 4.273) and there was a trend towards a high Cmin in patients with eGF between 40-80 mL/min (OR: 2.109). High Cmin were frequent, especially in patients with MDRD <40 mL/min. Therapeutic drug monitoring could be useful to avoid toxicity in patients with renal dysfunction.

  15. Effect of source and environmental factors on Rn-222 air concentration

    International Nuclear Information System (INIS)

    Mamoon, A.

    2005-01-01

    Rn-222(radon) air concentration depends on several factors. Some of the factors are source related and other factors are environmentally related. Because high levels of radon concentrations in air have potential health effects, it is important to study the impact of the various factors affecting radon air concentration. Laboratory scale investigations of the various factors affecting radon air concentration were carried out under controlled conditions that allow variation of the various variables

  16. Effects of exposure to factor concentrates containing donations from identified AIDS patients

    International Nuclear Information System (INIS)

    Jason, J.; Holman, R.C.; Dixon, G.; Lawrence, D.N.; Bozeman, L.H.; Chorba, T.L.; Tregillus, L.; Evatt, B.L.

    1986-01-01

    The authors recipients of eight lots of factors VII and IX voluntarily withdrawn from distribution because one donor was known to have subsequently developed the acquired immunodeficiency syndrome with a nonexposed cohort matched by age, sex, and factor use. The factor VIII recipient cohorts did not differ in prevalence of antibody to human immunodeficiency virus (HIV), T-cell subset numbers, T-helper to T-suppressor ratios, or immunogloubulin levels. Exposed individuals had higher levels of immune complexes by C1q binding and staphylococcal binding assays and lower responses to phytohemagglutinin and concanavalin A. However, only the staphylococcal binding assay values were outside the normal range for our laboratory. Factor IX recipient cohorts did not differ in HIV antibody prevalence or any immune tests. Although exposed and nonexposed individuals did not differ from each other in a clinically meaningful fashion at initial testing, both the exposed and nonexposed cohorts had high rats of HIV seroprevalence. Market withdrawals were clearly insufficient means of limiting the spread of HIV in hemophilic patients; however, the currently available methods of donor screening and viral inactivation of blood products will prevent continued exposed within this population

  17. Radium concentration factors and their use in health and environmental risk assessment

    International Nuclear Information System (INIS)

    Meinhold, A.F.; Hamilton, L.D.

    1991-01-01

    Radium is known to be taken up by aquatic animals, and tends to accumulate in bone, shell and exoskeleton. The most common approach to estimating the uptake of a radionuclide by aquatic animals for use in health and environmental risk assessments is the concentration factor method. The concentration factor method relates the concentration of a contaminant in an organism to the concentration in the surrounding water. Site specific data are not usually available, and generic, default values are often used in risk assessment studies. This paper describes the concentration factor method, summarizes some of the variables which may influence the concentration factor for radium, reviews reported concentration factors measured in marine environments and presents concentration factors derived from data collected in a study in coastal Louisiana. The use of generic default values for the concentration factor is also discussed

  18. Factors influencing mercury concentrations in walleyes in northern Wisconsin lakes

    Science.gov (United States)

    Wiener, J.G.; Martini, R.E.; Sheffy, T.B.; Glass, G.E.

    1990-01-01

    The authors examined relations between mercury concentrations in walleyes Stizostedion vitreum and the characteristics of clear-water Wisconsin lakes, which spanned a broad range of pH values (5.0-8.1) and acid- neutralizing capacities (-9 to 1,017 mu eq/L). Total concentrations of mercury in axial muscle tissue of walleyes (total length, 25-56 cm) varied from 0.12 to 1.74 mu g/g wet weight. Concentrations were greatest in fish from the eight lakes with pH less than 7.0; concentrations in these fish equaled or exceeded 0.5 mu g/g in 88% of the samples analyzed and 1.0 mu g/g in 44%. In the five lakes with pH of 7.0 and above, concentrations exceeded 0.5 mu g/g in only 1 of 21 walleyes. Multiple regression revealed that lake pH and total length of fish accounted for 69% of the variation in mercury concentration in walleyes. Regression models with total length and either waterborne calcium or acid-neutralizing capacity as independent variables accounted for 67% of the variation in concentration.

  19. Lithium ionophore VIII as an extraordinarily effective receptor for the strontium cation: Experimental and theoretical study

    Czech Academy of Sciences Publication Activity Database

    Makrlík, E.; Novák, Vít; Vaňura, P.; Bouř, Petr

    2014-01-01

    Roč. 1061, Mar 5 (2014), s. 110-113 ISSN 0022-2860 Institutional support: RVO:61388963 Keywords : strontium cation * lithium ionophore VIII * complexation * extraction and stability constants * DFT calculations * structures Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.602, year: 2014

  20. Complexation of the cesium cation with lithium ionophore VIII: extraction and DFT study

    Czech Academy of Sciences Publication Activity Database

    Makrlík, E.; Novák, Vít; Vaňura, P.; Bouř, Petr

    2013-01-01

    Roč. 298, č. 3 (2013), s. 2065-2068 ISSN 0236-5731 Institutional support: RVO:61388963 Keywords : cesium cation * lithium ionophore VIII * complexation * extraction and stability constants * water-nitrobenzene system * DFT calculations * structures Subject RIV: CB - Analytical Chemistry , Separation Impact factor: 1.415, year: 2013

  1. Modeling the Factors Impacting Pesticide Concentrations in Groundwater Wells

    DEFF Research Database (Denmark)

    Aisopou, Angeliki; Binning, Philip John; Albrechtsen, Hans-Jørgen

    2015-01-01

    This study examines the effect of pumping, hydrogeology, and pesticide characteristics on pesticide concentrations in production wells using a reactive transport model in two conceptual hydrogeologic systems; a layered aquifer with and without a stream present. The pumping rate can significantly...... affect the pesticide breakthrough time and maximum concentration at the well. The effect of the pumping rate on the pesticide concentration depends on the hydrogeology of the aquifer; in a layered aquifer, a high pumping rate resulted in a considerably different breakthrough than a low pumping rate......, while in an aquifer with a stream the effect of the pumping rate was insignificant. Pesticide application history and properties have also a great impact on the effect of the pumping rate on the concentration at the well. The findings of the study show that variable pumping rates can generate temporal...

  2. Applicability of concentration factors for the heavy metals hazard identification

    International Nuclear Information System (INIS)

    Guzzi, Luigi

    2006-01-01

    The bioconcentration factor (BCF) and bioaccumulation factor (BAF) used as criteria for heavy metals hazards identification are inadequate. These considerations is based on the argument that the BCF-BAF model was developed and validated for xenobiotic synthetic organic substances and that does not recognize the complex internal metal dynamic of uptake, the internal sequestration, and the essentially of some heavy metals [it

  3. [Estimation of relation between homocysteine concentration and selected lipid parameters and adhesion molecules concentration in children with atherosclerosis risk factors].

    Science.gov (United States)

    Sierakowska-Fijałek, Anna; Baj, Zbigniew; Kaczmarek, Piotr; Stepień, Mariusz; Rysz, Jacek

    2008-10-01

    Atherosclerosis begins in childhood. At present among numerous risk factors of atherosclerosis the role of hiperhomocysteinemia in development of cardiovascular heart disease is taken under consideration. Atherogenic effect of homocystein is related to its cytotoxin action, conducting to endothelial dysfunction and damage. It is correlated with increase of the lipid levels in the blood serum and change of expression of the soluble forms of adhesion molecules. The aim of this study was to estimate relations between the homocystein serum concentration, expression of the selected adhesion molecules and the lipid levels in the blood serum in children with atherosclerosis risk factors. The group consisted of 670 children, 76 of them had atherosclerosis risk factors. In further examination 48 children have taken a part, whose parents were agreed for theirs participation in the program. The comparative group composed of 25 children without the risk factors. We determined total cholesterol (TC), triglycerides (TG), LDL cholesterol fraction (LDL-C), HDL cholesterol fraction (HDL-C), serum homocysteine concentration (Hcy), the expression of the soluble forms of adhesion molecules (sCAM): sP-selectin and sVCAM-1 (vascular cell adhesion molecule-1). Obesity, hypertension and lipid disorders in the shape of higher concentration of TC, LDL-C, TG and lower HDL-C were the most frequent risk factors in the investigated children. No significant differences in serum homocysteine concentration were observed between the investigated groups. However, its concentration was significantly higher in children with two atherosclerosis risk factors. No significant differences in expression of s-VCAM-1 were observed in the investigated groups, concentration of sP-selectin was significantly higher in children with atherosclerosis risk factors (phomocysteine and chosen adhesion molecules in children with atherosclerosis risk factors might potentially constitute the marker of early

  4. [Indoor volatile organic compounds: concentrations, sources, variation factors].

    Science.gov (United States)

    Palot, A; Charpin-Kadouch, C; Ercoli, J; Charpin, D

    2008-06-01

    Volatile organic compounds (V.O.C.) are part of urban air pollution and are also generated indoors from cleaning and maintenance products. VOC measurements are, on average, 10 times higher within homes than outside. Results of the national survey led by the Observatoire National de la Qualité de l'Air Intérieur demonstrated that up to 25% of French homes have very high or high concentrations of VOC. Indoor levels depend mainly on indoor sources. Aldehydes are included in many everyday life products. VOC originate from various household decorating and cleaning products. Some products are less detrimental to the environment and health and have special labelling. Indoor VOC levels also depend on the rate of air exchange and on household characteristics such as indoor temperature and humidity, age of the building, presence of smokers, and communication with a garage. The public may participate in maintaining good indoor air quality and the authorities should also improve regulations. VOC are part of everyday air pollution. Their sources and concentrations should be better monitored.

  5. Factors influencing suspended solids concentrations in activated sludge settling tanks.

    Science.gov (United States)

    Kim, Y; Pipes, W O

    1999-05-31

    A significant fraction of the total mass of sludge in an activated sludge process may be in the settling tanks if the sludge has a high sludge volume index (SVI) or when a hydraulic overload occurs during a rainstorm. Under those conditions, an accurate estimate of the amount of sludge in the settling tanks is needed in order to calculate the mean cell residence time or to determine the capacity of the settling tanks to store sludge. Determination of the amount of sludge in the settling tanks requires estimation of the average concentration of suspended solids in the layer of sludge (XSB) in the bottom of the settling tanks. A widely used reference recommends averaging the concentrations of suspended solids in the mixed liquor (X) and in the underflow (Xu) from the settling tanks (XSB=0. 5{X+Xu}). This method does not take into consideration other pertinent information available to an operator. This is a report of a field study which had the objective of developing a more accurate method for estimation of the XSB in the bottom of the settling tanks. By correlation analysis, it was found that only 44% of the variation in the measured XSB is related to sum of X and Xu. XSB is also influenced by the SVI, the zone settling velocity at X and the overflow and underflow rates of the settling tanks. The method of averaging X and Xu tends to overestimate the XSB. A new empirical estimation technique for XSB was developed. The estimation technique uses dimensionless ratios; i.e., the ratio of XSB to Xu, the ratio of the overflow rate to the sum of the underflow rate and the initial settling velocity of the mixed liquor and sludge compaction expressed as a ratio (dimensionless SVI). The empirical model is compared with the method of averaging X and Xu for the entire range of sludge depths in the settling tanks and for SVI values between 100 and 300 ml/g. Since the empirical model uses dimensionless ratios, the regression parameters are also dimensionless and the model can be

  6. Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography

    OpenAIRE

    Mousavi Hosseini, Kamran; Nasiri, Saleh

    2015-01-01

    Background: Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII conce...

  7. Melanin-concentrating hormone (MCH: a new sleep factor?

    Directory of Open Access Journals (Sweden)

    Pablo eTorterolo

    2011-03-01

    Full Text Available Neurons that utilize the neuropeptide melanin-concentrating hormone (MCH as a neuromodulator are mainly located in the lateral hypothalamus and the incerto-hypothalamic area, and have widespread projections throughout the brain. While the biological functions of this neuropeptide are exerted in humans through two metabotropic receptors, the MCHR1 and MCHR2, only the MCHR1 is present in rodents. Recently, it has been shown that the MCHergic system is involved in the control of sleep. We can summarize the experimental findings as follows:1. The areas related to the control of sleep and wakefulness have an important density of MCHergic fibers and receptors.2. MCHergic neurons are active during sleep, especially during REM sleep.3. Genetically-modified animals without MCH have less REM sleep, notably under conditions of negative energy balance. 4. Systemically administered MCHR1 antagonists reduce sleep. 5. Intraventricular microinjection of MCH increases both slow wave sleep (SWS and REM sleep; however, the increment in REM sleep is more pronounced.6. Microinjection of MCH into the dorsal raphe nucleus increases REM sleep time. REM seep is inhibited by immunoneutralization of MCH within this nucleus.7. Microinjection of MCH in the nucleus pontis oralis of the cat enhances REM sleep time and reduces REM sleep latency.All these data strongly suggest that MCH has a potent role in the promotion of sleep. Although both SWS and REM sleep are facilitated by MCH, REM sleep seems to be more sensitive to MCH modulation.

  8. Factors affecting yearly variations of indoor radon concentrations

    International Nuclear Information System (INIS)

    Steck, D.J.; Baynes, S.A.

    1996-01-01

    Since indoor radon exposures take place over many years while radon measurement periods are shorter, we are studying the yearly variation of indoor radon concentrations in approximately 100 houses located throughout Minnesota. Most houses were initially measured for one or more years in the late 1980's and for 5 consecutive years starting in 1990. Two houses have been monitored for 12 y. Each year, two alpha track detectors were placed on the two lowest livable levels. The year-to-year variations averaged about 35% (corrected for instrumental uncertainties) in both basements and first floors. The minimum observed variation was 5% and the maximum was 130%. Some homes have shown substantial variation associated with Structural modifications. While most homes show no obvious systematic trends, a few houses have shown temporal trends that may be associated with aging or climate. We are studying possible correlation between year-to-year radon variation, climatic variables (yearly-average and seasonal such as heating/cooling degree days, precipitation, soil moisture), and structural changes

  9. [AVS concentrations in Xinan Creek and the influencing factors].

    Science.gov (United States)

    Liu, Xiao-Bing; Wen, Yan-Mao; Li, Feng; Wu, Chang-Hua; Duan, Zhi-Peng

    2012-07-01

    Sediment and overlying water samples were collected at 10 sampling stations at Xinan Creek, a tidal river in Pearl River Delta, and analyzed for physical and chemical characteristics as well as microbial incicators, in order to reveal the main factors dominating the spatial distribution of acid volatile sulfide (AVS). The effects of Eh, SRB OC and TS on the spatial distribution of AVS were investigated and the impact of AVS on the toxicity of heavy metals in the studied area was evaluated. The results showed that the range of AVS was 0.207-41.453 micromol x g(-1), with an average of 6.684 micromol x g(-1), which is relatively high compared to the results in other studies. The AVS value of the surface layer was higher than the bottom layer in 5 stations. The AVS values in both the surface layer and the bottom layer were highly variable, the coefficients of variation being 93.61% and 153.09% , respectively. The analytical results revealed that TS was the factor with the greatest impact on the spatial distribution of AVS, and the order was TS > OC > Eh > SRB. Potential ecological risk of heavy metals existed in 60% of the smpling stations based on the value of Sigma (SEM5-AVS), however, with the criterion of [Sigma(SEM5-AVS)]/foc, none of them had inacceptable ecological risk. Furthermore, in terms of single species of heavy metals, there was certain risk of toxic effect for all the five heavy metals (Cd, Ni, Cu, Zn and Pb). The above mentioned results will provide valuable data for the in-depth study of the formation mechanism of AVS and helpful reference for environmental impact assessment and scientific rehabilitation of heavy metals in polluted rivers.

  10. The labour ward analgesic service at King Edward VIII Hospital ...

    African Journals Online (AJOL)

    The labour ward analgesic service at King Edward VIII. Hospital, Durban. D. A. ROCKE, C. C. ROUT, H. D. RUSSELL, S. SINGH. Abstract The provision of analgesic services to the labour ward at King Edward VIII Hospital was studied during a I-week period. Of249 patients, 113 (45%) received no analgesia whatsoever.

  11. The Validation Of Influence Factors To DDT Concentration In Soil

    International Nuclear Information System (INIS)

    Kamal, Zainul; Poernomo, Herry

    2000-01-01

    Determination concentration of DDT in humidified land's and rising intensity has been done. The amount of natural soil was filled in poliethylene tube, and the amount of humadified soil was filled in order poliethylene tube. The solution of DDT-C sub.14 with volume of 10 ml and activity of 10 muCi was increased in those tube respectively, the latter it was resident for many time under shine. Sample of soil was took first week to sixthweek, it was crushed to reach homogenous, then it was counted by liquid scintillation counter. The experiment result indicated that the DDT content in the unilluminated soil for 1 week is < 0.1 ppb, for 2 week is 0.19 n 0.01 ppb, for 3 week is 1.95 n 0.32 ppb, for 4 week is 14.07 n 0.14 ppb, for 5 week is 3.67 n 0.21 ppb and for 6 week is 2.28 n 0.09 ppb. The DDT content in the humidified soil without sun illumination for 1 week is 0.25 n 0.07 ppb, for 2 week is 6.34 n 0.19 ppb, for 3 week is 9.33 n 0.80 ppb, for 4 week is 12.36 n 0.17 ppb, for 5 week is 4.58 n 0.15 ppb and for 6 week is 2.01 n 0.55 ppb. The DDT content in the natural soil illuminated by VIS for 1 week is 0.74 n 0.08 ppb, for 2 week is 7.48 n 0.14 ppb, for 3 week is 4.06 n 0.28 ppb, for 4 week is 13.16 n 0.20 ppb, for 5 week is 5.00 n 0.70 ppb and for 6 week is 2.03 n 0.03 ppb

  12. Concentration factors 226Ra, 210Pb and 90Sr in the biota of the Sava river

    International Nuclear Information System (INIS)

    Vujnovicj, J.

    1977-01-01

    This work presents the results of identification of the concentration factor in the biota of the river Sava. Organisms of the water system have different abilities of concentration of radio nuclide. This ability is most highly expressed in plancton as the first link on the trophic chain. As the length of trat chain increases, the concentration of radionuclide in the organisms diminishes

  13. Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography.

    Science.gov (United States)

    Mousavi Hosseini, Kamran; Nasiri, Saleh

    2015-01-01

    Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). RESULTS of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII.

  14. One-electron spectrum of Xe VIII

    International Nuclear Information System (INIS)

    Roberts, J.R.; Knystautas, E.J.; Sugar, J.

    1979-01-01

    The spectrum of Xe VIII has been observed in a theta-pinch discharge. New line identifications were made that determine the energies of the 6s, 7s, 6p, and 5f terms relative to the 5s 2 S ground state and confirm the previously known 5p and 5d terms. An independent system of levels derived from the observed 4f-ng (n = 5,6) transitions was found. Its position relative to the ground state is obtained from a predicted value for the 5g effective quantum number n*. From the ns series (n=5--7) a value for the ionization enegy of 105.91 +- 0.05 eV was derived

  15. VIII International Meeting on Lorentzian Geometry

    CERN Document Server

    Flores, José; Palomo, Francisco; GeLoMa 2016; Lorentzian geometry and related topics

    2017-01-01

    This volume contains a collection of research papers and useful surveys by experts in the field which provide a representative picture of the current status of this fascinating area. Based on contributions from the VIII International Meeting on Lorentzian Geometry, held at the University of Málaga, Spain, this volume covers topics such as distinguished (maximal, trapped, null, spacelike, constant mean curvature, umbilical...) submanifolds, causal completion of spacetimes, stationary regions and horizons in spacetimes, solitons in semi-Riemannian manifolds, relation between Lorentzian and Finslerian geometries and the oscillator spacetime. In the last decades Lorentzian geometry has experienced a significant impulse, which has transformed it from just a mathematical tool for general relativity to a consolidated branch of differential geometry, interesting in and of itself. Nowadays, this field provides a framework where many different mathematical techniques arise with applications to multiple parts of mathem...

  16. VIII Brazilian Meeting on Simulational Physics (BMSP)

    International Nuclear Information System (INIS)

    Branco, N. S.; Figueiredo, W.; Plascak, J. A.; Santos, M.

    2016-01-01

    This special issue includes invited and selected articles of the VIII Brazilian Meeting on Simulational Physics (BMSP), held in Florianópolis, Santa Catarina, Brazil, from 3rd to 8th August, 2015. This is the eighth such meeting, and the second one to have contributed papers published in Journal of Physics: Conference Series (the other was the VII BMSP). The previous meetings in the BMSP series took place in the mountains of Minas Gerais, in the region of the Brazilian Pantanal, and in the shores of Paraíba. Now, for the first time, the Meeting was held in Florianópolis, with its pleasing shores, the capital of Santa Catarina state. The VIII BMSP brought together about 50 researchers from all over the world for a vibrant and productive conference. As in the previous meetings, the talks and posters highlighted recent advances in applications, algorithms, and implementation of computer simulation methods for the study of condensed matter, materials, and out of equilibrium, quantum and biologically motivated systems. We are sure that this meeting series will continue to be an important occasion for people working in simulational physics to exchange ideas and discuss the state of the art of this always expanding field. We are very glad to put together this special issue, and are most appreciative of the efforts of the editors of the Journal of Physics: Conference Series for making this publication possible. We are grateful for the outstanding work of the Florianopolis team, for the financial support of the Brazilian agencies CAPES and CNPq, and of the Federal Universities UFPB and UFSC. At last, but not least, we would like to acknowledge all of the authors for their written submissions. (paper)

  17. Factors affecting the concentration of outdoor particles indoors: Existing data and data needs

    International Nuclear Information System (INIS)

    McKone, T.E.; Thatcher, T.L.; Fisk, W.J.; Sextro, R.G.; Sohn, M.D.; Delp, W.W.; Riley, W.J.

    2002-01-01

    Accurate characterization of particle concentrations indoors is critical to exposure assessments. It is estimated that indoor particle concentrations depend strongly on outdoor concentrations. For health scientists, knowledge of the factors that control the relationship of indoor particle concentrations to outdoor levels is particularly important. In this paper, we identify and evaluate sources of data for those factors that affect the transport to and concentration of outdoor particles indoors. To achieve this goal, we (i) identify and assemble relevant information on how particle behavior during air leakage, HVAC operation, and particle filtration effects indoor particle concentration; (ii) review and evaluate the assembled information to distinguish data that are directly relevant to specific estimates of particle transport from those that are only indirectly useful; and (iii) provide a synthesis of the currently available information on building air-leakage parameters and their effect on indoor particle matter concentrations

  18. Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs.

    Science.gov (United States)

    Jungbluth, Pascal; Grassmann, Jan-Peter; Thelen, Simon; Wild, Michael; Sager, Martin; Windolf, Joachim; Hakimi, Mohssen

    2014-01-01

    In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2) whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-bb) respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7) and transforming growth factor β1 (TGF-β1) were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, pplatelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors.

  19. Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

    Science.gov (United States)

    Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V.; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N.; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I.; Fischer, Kathelijn; Gill, Joan C.; P’Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A.; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St. Ledger, Katie

    2016-01-01

    Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. PMID:27330001

  20. Design factors of sensors for the optical tracking systems of solar concentrators

    International Nuclear Information System (INIS)

    Klychev, Sh. I.; Fazylov, A. K.; Orlov, S. A.; Burbo, A. V.

    2011-01-01

    Basic diagrams for the sensors of the optical tracking systems of solar concentrators are considered, the design factors that determine their accuracy are analyzed, a new sensor design is suggested, and its optimal parameters are determined. (authors)

  1. Plasma fibrinogen and factor VII concentrations in adults after prenatal exposure to famine

    NARCIS (Netherlands)

    Roseboom, T. J.; van der Meulen, J. H.; Ravelli, A. C.; Osmond, C.; Barker, D. J.; Bleker, O. P.

    2000-01-01

    To assess the effect of maternal malnutrition during different stages of gestation on plasma concentrations of fibrinogen and factor VII, we investigated 725 people, aged 50 years, born around the time of the Dutch famine 1944-5. After adjustment for sex, plasma fibrinogen concentrations differed by

  2. Plasma concentrations of blood coagulation factor VII measured by immunochemical and amidolytic methods

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Gram, J; Jespersen, J

    2000-01-01

    Ever since the coagulant activity of blood coagulation factor VII (FVII:C) was identified as a risk indicator of cardiac death, a large number of studies have measured FVII protein concentrations in plasma. FVII protein concentrations are either measured immunologically with an ELISA method (FVII...

  3. The influence of biological and environmental factors on metallothionein concentration in the blood.

    Science.gov (United States)

    Kowalska, Katarzyna; Bizoń, Anna; Zalewska, Marta; Milnerowicz, Halina

    2015-01-01

    The concentration of metallothionein (MT), a low-molecular-weight protein, is regulated by many factors, primarily metals (zinc, cadmium, copper), cytokines, glucocorticoides and free radicals. These factors are determined by such aspects of human biology as gender, pregnancy and age, as well as by environmental factors including the use of oral contraceptives and cigarette smoking, all which may affect MT levels in the body. The aim of this study was to investigate the influence of these biological and environmental factors on MT concentrations in erythrocyte lysate and in plasma. MT concentrations were determined by a two-step direct enzyme-linked immunosorbent assay. Evaluation of exposure to cigarette smoking was performed by checking cotinine levels in the plasma of subjects. The studies showed higher MT concentrations in both the erythrocyte lysate and plasma of women when compared to men. Furthermore, pregnancy causes an increase of MT concentration in plasma, while oral contraceptives cause an elevated concentration of MT in erythrocyte lysate. Age impacts plasma MT concentrations in men, whereas it does not affect concentrations of MT in erythrocyte lysate. Copyright © 2014 Elsevier GmbH. All rights reserved.

  4. Concentration factors of 226 Ra in the mullet species Liza aurata

    International Nuclear Information System (INIS)

    Antovic, I.; Antovic, N.M.

    2011-01-01

    On the basis of measured 226 Ra activity concentrations in whole individuals of the mullet species Liza aurata, its muscles and skeleton, concentration factors for transfer of radium from water and sediment to this mullet species from the South Adriatic Sea, have been determined. (author) [sr

  5. Stress concentration factor and stress intensity factor on hard metals in connection with the wear characteristics

    International Nuclear Information System (INIS)

    Dawihl, W.; Altmeyer, G.

    1977-01-01

    Description of a method to determine stress intensity factors on hard metals by lapping in notches of different diameter. Dependence of the values of the stress intensity factors on the size of the notch base diameter. For tungsten carbide hard metals with 6% Co, determination of a final value of 250 Nmm -3 / 2 . Characterisation of the stress intensity factor governed by the surface roughness which is decisive for the assessment of the wear-resistant behaviour. (orig.) [de

  6. A study of some factors which are related to indoor radon concentrations in Greece

    International Nuclear Information System (INIS)

    Louizi, A.; Nikolopoulos, D.; Lobotesi, E.; Mavroudaki, E.; Koukouliou, V.K.; Chanioti, M.; Papadimitriou, D.; Yiakoumakis, M.; Proukakis, C.

    1997-01-01

    The Medical Physics Department of the University of Athens is conducting radon-222 measurements in Greek dwellings. It is well known that the concentration of radon gas indoors, are related to various factors. A study of these factors has started and first results are reported. (authors)

  7. Hierarchical modeling of indoor radon concentration: how much do geology and building factors matter?

    International Nuclear Information System (INIS)

    Borgoni, Riccardo; De Francesco, Davide; De Bartolo, Daniela; Tzavidis, Nikos

    2014-01-01

    Radon is a natural gas known to be the main contributor to natural background radiation exposure and only second to smoking as major leading cause of lung cancer. The main concern is in indoor environments where the gas tends to accumulate and can reach high concentrations. The primary contributor of this gas into the building is from the soil although architectonic characteristics, such as building materials, can largely affect concentration values. Understanding the factors affecting the concentration in dwellings and workplaces is important both in prevention, when the construction of a new building is being planned, and in mitigation when the amount of Radon detected inside a building is too high. In this paper we investigate how several factors, such as geologic typologies of the soil and a range of building characteristics, impact on indoor concentration focusing, in particular, on how concentration changes as a function of the floor level. Adopting a mixed effects model to account for the hierarchical nature of the data, we also quantify the extent to which such measurable factors manage to explain the variability of indoor radon concentration. - Highlights: • It is assessed how the variability of indoor radon concentration depends on buildings and lithologies. • The lithological component has been found less relevant than the building one. • Radon-prone lithologies have been identified. • The effect of the floor where the room is located has been estimated. • Indoor radon concentration have been predicted for different dwelling typologies

  8. Factors affecting water strider (Hemiptera: Gerridae) mercury concentrations in lotic systems

    Energy Technology Data Exchange (ETDEWEB)

    Jardine, T.D.; Kidd, K.A.; Cunjak, R.A.; Arp, P.A. [University of New Brunswick, St John, NB (Canada). Canadian Rivers Institute

    2009-07-15

    Water striders (Hemiptera: Gerridae) have been considered as a potential sentinel for mercury (Hg) contamination of freshwater ecosystems, yet little is known about factors that control Hg concentrations in this invertebrate. Striders were collected from 80 streams and rivers in New Brunswick, Canada, in August and September of 2004 through 2007 to assess the influence of factors such as diet, water chemistry, and proximity to point sources on Hg concentrations in this organism. Higher than average Hg concentrations were observed in the southwest and Grand Lake regions of the province, the latter being the location of a coal-fired power plant that is a source of Hg (similar to 100 kg annually), with elevated Hg concentrations in the lichen Old Man's Beard (Usnea spp.) in its immediate vicinity. Across all streams, pH and total organic carbon of water were relatively weak predictors of strider Hg concentrations. Female striders that were larger in body size than males had significantly lower Hg concentrations within sites, suggestive of growth dilution. There was no relationship between percent aquatic carbon in the diet and Hg concentrations in striders. For those striders feeding solely on terrestrial carbon, Hg concentrations were higher in animals occupying a higher trophic level. Mercury concentrations were highly variable in striders collected monthly over two growing seasons, suggesting short-term changes in Hg availability. These measurements highlight the importance of considering both deposition and postdepositional processes in assessing Hg bioaccumulation in this species.

  9. SHAPE EFFECT OF ANNULAR CONCENTRATOR IN ULTRASONIC SYSTEM ON AMPLIFICATION FACTOR OF VIBRATIONS AMPLITUDE

    Directory of Open Access Journals (Sweden)

    D. A. Stepanenko

    2016-01-01

    Full Text Available The paper contains a theoretical underpinning on creation of ultrasonic vibration concentrators based on annular elastic elements with non-circular (ellipse-like eccentric shape of internal contour. Shape of internal contour in polar coordinates is described by Fourier series relative to angular coordinate that consists of a constant term and first and second harmonics. An effect of geometric parameters of the concentrator on amplification factor and natural vibration frequencies has been investigated with the help of a finite element method. The paper reveals the possibility to control an amplification factor of annular concentrators while varying eccentricity of internal contour and mean value of cross-section thickness. The amplification factor satisfies a condition K < N, where N is thickness ratio of amplifier input and output sections, and it is decreasing with increase of vibration mode order. The similar condition has been satisfied for conical bar concentrator with the difference that in the case of bar concentrators an amplification is ensured due to variation of diameter and N will represent ratio of diameters. It has been proved that modification of internal contour shape makes it possible to carry out a wide-band tuning of natural frequencies of concentrator vibrations without alteration of its overall dimensions and substantial change of amplification factor, which is important for frequency matching of the concentrator and ultrasonic vibratory system. Advantages of the proposed concentrators include simplicity of design and manufacturing, small overall dimensions, possibility for natural frequency tuning by means of static load variation. The developed concentrators can find their application in ultrasonic devices and instruments for technological and medical purposes.

  10. Associations between toenail arsenic concentration and dietary factors in a New Hampshire population

    Directory of Open Access Journals (Sweden)

    Gruber Joann F

    2012-06-01

    Full Text Available Abstract Background Dietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown. Methods As part of a population-based case–control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We used general linear models to examine the associations between toenail arsenic and each dietary factor, taking into account potentially confounding effects. Results As expected, we found an inverse association between ln-transformed toenail arsenic and consumption of vitamin B12 (excluding supplements and animal protein. Unexpectedly, there were also inverse associations with numerous dietary lipids (e.g., total fat, total animal fat, total vegetable fat, total monounsaturated fat, total polyunsaturated fat, and total saturated fat. Finally, increased toenail arsenic concentrations were associated with increased consumption of long chain n-3 fatty acids. Conclusion In a relatively well-nourished population exposed to relatively low levels of arsenic via water, consumption of certain dietary lipids may decrease toenail arsenic concentration, while long chain n-3 fatty acids may increase toenail arsenic concentration, possibly due to their association with arsenolipids in fish tissue.

  11. Environmental parameters series. 3. Concentration factors of radionuclides in freshwater organisms

    International Nuclear Information System (INIS)

    1994-03-01

    This report outlines recent research activities of Radioactive Waste Management Center. Aiming to estimate the radiation dose of man exposed to radioactive materials in an environment, construction of a calculation model on the transfer of radionuclide in the environment was attempted. This issue, Environmental parameter series No.3 includes six reports on the factors related to environmental concentration for radionuclides. The title of the reports are as follows; Factors modifying the concentration factor (CF), Evaluation of accumulation of radionuclides in brackish water organisms, Dose assessment, CF derived from Japanese limnological data, Data table of CF and Metabolic parameters in relation to bioaccumulation of elements by organisms. In addition to collect and arrange the existing data, CF was calculated based on the concentration of stable elements in various lakes and rivers in Japan. (M.N.)

  12. Meteorological factors influencing on the radon concentrations in indoor and outdoor airs

    International Nuclear Information System (INIS)

    Kojima, Hiroshi

    1989-01-01

    Factors influencing radon concentrations in indoor and outdoor airs are discussed. A balance between source and loss is required in determining the radon concentration. Source refers to as the outdoor and indoor exhalation rate from the ground and the building materials. Loss is caused by turbulent diffusion outdoors and ventilation indoors. A significant factor influencing the exhalation rate of indoor and outdoor radon may be the change in atmospheric pressure. A drop of pressure feeds the high concentration air under the ground or building materials into the open air, and contributes to the increased exhalation rate. The exhalation rate of radon closely depends on the moisture content of the ground or building materials. Up to a certain level of moisture, the radon exhalation increases with increasing moisture content because the emanation power increases by a recoil effect of a fluid present in the internal pores of the materials. Beyond a certain level of moisture, the exhalation decreases rapidly because the pores are filled with water. Radon exhalated from the ground is spread out by turbulent diffusion. The turbulent diffusion may be related to wind velocity and the lapse rate of temperature. There is a remakable difference between indoor and outdoor radon concentrations. The ventilation rate of the house exerted a great effect upon the indoor radon concentration. The ventilation rate is influenced by meteorological factors together with human activities. Of such factors, wind velocity and temperature gradient between indoor and outdoor airs may be the most significant. The correlation coefficients between RaA or radon and some meteorological factors were calculated on the data from the long term measurements on radon and its decay products in and out of a house under normal living conditions. The changes in atmospheric pressure and wind velocity are found to be a significant factor in the variation of concentration of these nuclides. (N.K.)

  13. The feasibility of using concentrates containing factor IX for continuous infusion.

    Science.gov (United States)

    Schulman, S; Gitel, S; Zivelin, A; Katsarou, O; Mandalaki, T; Varon, D; Martinowitz, U

    1995-04-01

    We have investigated the feasibility of continuous infusion of undiluted factor IX (F IX) over several days using minipumps. The stabilities of seven different reconstituted F IX products were substantially better than those declared by the manufacturers. Several concentrates maintained factor activities 80% of baseline for the entire period of 4 weeks at 4-8d̀C as did one product at 20-23d̀A. At 37d̀C the latter concentrate was stable for at least 1 week. The stability seemed to correlate with the purity of the product. Analysis of two prothrombin comples concentrates by gel electrophoresis demonstrated degradation of prothrombin to prethrombin-1 and fragment 1 at 37d̀C and in one of the concentrates also at 20-23d̀C. In two F IX concentrates the corresponding analysis did not reveal any degradation. Four patients were treated with continuous infusion with a pure F IX concentrate (Mononine™, Armour) after surgery or for serious haemorrhage (two each) with good haemostatic effect, an initial progressive decrease of the F IX clearance, and no side-effects. Continuous infusion with F IX, using a minipump and undiluted reconstituted factor, is therefore feasible and effective, and can be conveniently prepared for several days at a time. Pure F IX products are more stable and probably safer for this purpose.

  14. Concentration and measuring Platinum Group Elements (PGE) Transfer Factor in soil and vegetations

    International Nuclear Information System (INIS)

    Adibah Sakinah Oyub

    2012-01-01

    This study was conducted to determine the concentration and to measure platinum group elements (PGE) transfer factor in environmental samples of roadside soil and vegetation. The use of vehicle catalytic converter has released platinum group elements (PGE) and other gases into the environment. Thus, roadside soil and plants were exposed to this element and has become the medium for the movement of this elements. Samples of roadside soil and vegetation were taken at various locations in UKM Bangi Toll and the concentration of platinum group elements (PGE) is determined using mass spectrometry-inductively coupled plasma (ICP-MS). Overall, the concentrations of platinum group elements (PGE), which is the element platinum (Pt) in soil was 0.016 ± 0.036 μgg -1 . While the concentration of the elements palladium (Pd) was 0.079 ± 0.019 μgg -1 and element rhodium (Rh) is at a concentration of 0.013 ± 0.020 μgg -1 . Overall, the transfer factor for the element platinum (Pt) is 1. While the transfer factor of the element palladium (Pd) is 0.96 and the element rhodium (Rh) is 1.11. In conclusion, the concentration of platinum group elements (PGE) in soils have increased. (author)

  15. Hierarchical modeling of indoor radon concentration: how much do geology and building factors matter?

    Science.gov (United States)

    Borgoni, Riccardo; De Francesco, Davide; De Bartolo, Daniela; Tzavidis, Nikos

    2014-12-01

    Radon is a natural gas known to be the main contributor to natural background radiation exposure and only second to smoking as major leading cause of lung cancer. The main concern is in indoor environments where the gas tends to accumulate and can reach high concentrations. The primary contributor of this gas into the building is from the soil although architectonic characteristics, such as building materials, can largely affect concentration values. Understanding the factors affecting the concentration in dwellings and workplaces is important both in prevention, when the construction of a new building is being planned, and in mitigation when the amount of Radon detected inside a building is too high. In this paper we investigate how several factors, such as geologic typologies of the soil and a range of building characteristics, impact on indoor concentration focusing, in particular, on how concentration changes as a function of the floor level. Adopting a mixed effects model to account for the hierarchical nature of the data, we also quantify the extent to which such measurable factors manage to explain the variability of indoor radon concentration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial.

    Science.gov (United States)

    Stasyshyn, O; Djambas Khayat, C; Iosava, G; Ong, J; Abdul Karim, F; Fischer, K; Veldman, A; Blackman, N; St Ledger, K; Pabinger, I

    2017-04-01

    Essentials rVIII-SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII-SingleChain showed excellent hemostatic efficacy and a favorable safety profile. Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients hemophilia A. Patients/Methods Patients could be assigned to prophylaxis or on-demand therapy by the investigator. For patients assigned to prophylaxis, the treatment regimen and dose were based on the bleeding phenotype. For patients receiving on-demand therapy, dosing was guided by World Federation of Hemophilia recommendations. The primary endpoint was treatment success, defined as a rating of 'excellent' or 'good' on the investigator's clinical assessment of hemostatic efficacy for all treated bleeding events. Results The study enrolled 84 patients (0 to 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children hemophilia A. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and

  17. Simulation of influence of some climatic factors on radiocarbon concentration in the Earth atmosphere

    International Nuclear Information System (INIS)

    Akhmetkereev, S.Kh.; Dergachev, V.A.

    1981-01-01

    The effect of different climatic factors on radiocarbon concentration in the Earth atmosphere is analyzed by modelling the exchange radiocarbon system. It is supposed that the exchange system consists of four reservoirs: long-lived surface vegetation and its remnants, the atmosphere, surface layer of the World ocean. It is shown that the variations of the ocean temperature and the variations in CO 2 amount in the atmosphere connected with it do not affect the atmosphere radiocarbon concentration. Variations in the square of sea ice on the time scale of >=1000 years could bring about variations in the 14 C concentration with the amplitude up to 1%. 14 C concentration in the atmosphere in the icing maximum 18 thousands of years ago was 7% higher than present concentration [ru

  18. Arsenic concentrations, related environmental factors, and the predicted probability of elevated arsenic in groundwater in Pennsylvania

    Science.gov (United States)

    Gross, Eliza L.; Low, Dennis J.

    2013-01-01

    Analytical results for arsenic in water samples from 5,023 wells obtained during 1969–2007 across Pennsylvania were compiled and related to other associated groundwater-quality and environmental factors and used to predict the probability of elevated arsenic concentrations, defined as greater than or equal to 4.0 micrograms per liter (µg/L), in groundwater. Arsenic concentrations of 4.0 µg/L or greater (elevated concentrations) were detected in 18 percent of samples across Pennsylvania; 8 percent of samples had concentrations that equaled or exceeded the U.S. Environmental Protection Agency’s drinking-water maximum contaminant level of 10.0 µg/L. The highest arsenic concentration was 490.0 µg/L.

  19. Radium concentration factors in passionfruit (Passiflora foetida) from the Alligator Rivers Region, Northern Territory, Australia

    International Nuclear Information System (INIS)

    Medley, Peter; Bollhöfer, Andreas; Parry, David; Martin, Paul

    2013-01-01

    In this study, uptake of Ra from soil into the edible fruit of the wild passionfruit species Passiflora foetida was investigated, using selective extraction from the soil samples. A wide range of environmental exposure conditions were represented by the locations that were sampled, including both natural soils, and soils influenced by past and present uranium mining activities. The bioavailable 226 Ra fraction in soils was found to be a better predictor of 226 Ra fruit activity concentrations than the total soil activity concentration, or any of the other fractions studied. Concentration Factors (CFs) derived using the bioavailable fraction varied by only a factor of 7 between different locations, whereas CFs derived using other fractions and total soil varied by up to two orders of magnitude. CFs were highest for those soils containing the lowest concentrations of Mg, Ca and Ba, and approached a saturation value at higher soil concentrations. This finding suggests that group II elements influence radium uptake, most likely the result of increased pressure on the plant to take up essential nutrient group II elements from soil with the lower concentrations, with Ra being taken up as an analogue element. It is also possible that at higher concentrations of bioavailable Ca and Mg in the soil, these ions will outcompete Ra for adsorption sites in the soil and/or on the root surfaces. The study also shows that 228 Ra can potentially be a significant contributor to ingestion doses and should also be considered when assessing committed effective doses from the ingestion of fruits. -- Highlights: • Fruit and soil samples were taken from wild growing native passionfruit plants. • The sampling locations were on natural and U mining impacted sites. • Sequential extraction of the soil was undertaken. • Radium-226, radium-228 and other key elements were measured. • Concentration factors show the lowest variability in the bioavailable fraction

  20. Characterization of the Factors that Influence Sinapine Concentration in Rapeseed Meal during Fermentation

    Science.gov (United States)

    Niu, Yanxing; Jiang, Mulan; Guo, Mian; Wan, Chuyun; Hu, Shuangxi; Jin, Hu; Huang, Fenghong

    2015-01-01

    We analyzed and compared the difference in sinapine concentration in rapeseed meal between the filamentous fungus, Trametes sp 48424, and the yeast, Saccharomyces cerevisiae, in both liquid and solid-state fermentation. During liquid and solid-state fermentation by Trametes sp 48424, the sinapine concentration decreased significantly. In contrast, the liquid and solid-state fermentation process by Saccharomyces cerevisiae just slightly decreased the sinapine concentration (P ≤ 0.05). After the solid-state fermented samples were dried, the concentration of sinapine in rapeseed meal decreased significantly in Saccharomyces cerevisiae. Based on the measurement of laccase activity, we observed that laccase induced the decrease in the concentration of sinapine during fermentation with Trametes sp 48424. In order to eliminate the influence of microorganisms and the metabolites produced during fermentation, high moisture rapeseed meal and the original rapeseed meal were dried at 90°C and 105°C, respectively. During drying, the concentration of sinapine in high moisture rapeseed meal decreased rapidly and we obtained a high correlation coefficient between the concentration of sinapine and loss of moisture. Our results suggest that drying and enzymes, especially laccase that is produced during the solid-state fermentation process, may be the main factors that affect the concentration of sinapine in rapeseed meal. PMID:25606856

  1. VIII International Congress of Engineering Physics

    International Nuclear Information System (INIS)

    2017-01-01

    The Physicist Engineering is a multidisciplinary profession in which an undergraduate student integrates and applies their knowledge of Physics, Mathematics, and Computing to adapt and innovate all kind of technologies, as well as to development and apply theoretical knowledge to different fields of science and engineering. A Physicist Engineer, supported by a solid preparation in science and engineering is available to study, analyze, identify, and solve problems in different fields of science and technology for industries, hospitals, research laboratories, institutes and governmental organizations focused on metrology, optics, energy, materials, instrumentation of sophisticated equipment. The Physicist Engineering bachelor degree is a national and international reference to encouraging all those students to apply knowledge through active participation in the operation, planning, and management of projects. The technological and scientific impact of a Physicist Engineering undergraduate and graduate students, as well as the tutorial of the research professor that are interested in Physics and Physics Engineering, may be found in a biennial event like the International Conference on Physicist Engineering, through the diffusion of both experimental and theoretical research and teaching. In order to promote and encourage strength academic goals among universities and research institutions, the International Conference on Physics Engineering Committee, integrated by a faculty meeting of the Universidad Autónoma Metropolitana, Campus Azcapotzalco, has decided to grant the VIII International Congress of Physics Engineering to the Universidad Autónoma de Yucatán, which is going to take place on Mérida, November 7 th to 11 th , 2016. This conference considers different topics as: Renewables Energies Engineering Materials Technology Nanotechnology Medical Physics Education in Physics Engineering Nuclear Engineering High Precision Instrumentation Atmosphere Physics

  2. [Concentration of selected angiogenic factors in serum and peritoneal fluid of women with endometriosis].

    Science.gov (United States)

    Gogacz, Marek; Gałczyński, Krzysztof; Romanek-Piva, Katarzyna; Winkler, Izabela; Rechberger, Tomasz; Adamiak-Godlewska, Aneta

    2015-03-01

    Endometriosis is a sex hormone-dependent and successively progressing gynecological disease, characterized by the presence of endometrial tissue outside the uterus. The etiology of endometriosis is known to be multifactorial, and its growth depends on immunological, hormonal, genetic and environmental factors. Angiogenesis plays a key role in implantation and growth of endometriotic lesions, as well as in adhesion formation. Physiologically angiogenesis is responsible for neoangiogenesis and recruitment of new capillaries from the already existing capillaries. It is well-documented that altered angiogenesis provokes improper follicular maturation, infertility recurrent miscarriages, ovarian hyperstimulation syndrome, and carcinogenesis. Factors stimulating angionesis include angiogenin, vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). The aim of the study was to analyze angiogenic factor concentration (angiogenin, VEGF, FGF) in blood serum and peritoneal fluid in patients with diagnosed endometriosis and idiopathic infertility. A total of 39 patients were recruited for the study including 19 patients (study group) diagnosed with endometriosis during the laparoscopic procedure and 20 patients (control group) with idiopathic infertility and no morphologic changes within the pelvis revealed during the laparoscopic procedure. All patients underwent laparoscopy during the follicular phase of the menstrual cycle. Vein blood sample was obtained before the procedure and during laparoscopy the entire peritoneal fluid was aspirated for further measurement of VEGF, FGF and angiogenin concentrations. Angiogenin concentration in peritoneal fluid was statistically higher in patient with idiopathic infertility in comparison to endometriosis (pendometriosis, but no statistical significance was found. VEGF and FGF concentration in blood serum and peritoneal fluid was similar in both groups (p>0.05). There were no significant differences between serum

  3. Chromosome VIII disomy influences the nonsense suppression efficiency and transition metal tolerance of the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Zadorsky, S P; Sopova, Y V; Andreichuk, D Y; Startsev, V A; Medvedeva, V P; Inge-Vechtomov, S G

    2015-06-01

    The SUP35 gene of the yeast Saccharomyces cerevisiae encodes the translation termination factor eRF3. Mutations in this gene lead to the suppression of nonsense mutations and a number of other pleiotropic phenotypes, one of which is impaired chromosome segregation during cell division. Similar effects result from replacing the S. cerevisiae SUP35 gene with its orthologues. A number of genetic and epigenetic changes that occur in the sup35 background result in partial compensation for this suppressor effect. In this study we showed that in S. cerevisiae strains in which the SUP35 orthologue from the yeast Pichia methanolica replaces the S. cerevisiae SUP35 gene, chromosome VIII disomy results in decreased efficiency of nonsense suppression. This antisuppressor effect is not associated with decreased stop codon read-through. We identified SBP1, a gene that localizes to chromosome VIII, as a dosage-dependent antisuppressor that strongly contributes to the overall antisuppressor effect of chromosome VIII disomy. Disomy of chromosome VIII also leads to a change in the yeast strains' tolerance of a number of transition metal salts. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Factors influencing concentrations of dissolved gaseous mercury (DGM) and total mercury (TM) in an artificial reservoir

    International Nuclear Information System (INIS)

    Ahn, Myung-Chan; Kim, Bomchul; Holsen, Thomas M.; Yi, Seung-Muk; Han, Young-Ji

    2010-01-01

    The effects of various factors including turbidity, pH, DOC, temperature, and solar radiation on the concentrations of total mercury (TM) and dissolved gaseous mercury (DGM) were investigated in an artificial reservoir in Korea. Episodic total mercury accumulation events occurred during the rainy season as turbidity increased, indicating that the TM concentration was not controlled by direct atmospheric deposition. The DGM concentration in surface water ranged from 3.6 to 160 pg/L, having a maximum in summer and minimum in winter. While in most previous studies DGM was controlled primarily by a photo-reduction process, DGM concentrations tracked the amount of solar radiation only in winter when the water temperature was fairly low in this study. During the other seasons microbial transformation seemed to play an important role in reducing Hg(II) to Hg(0). DGM increased as dissolved organic carbon (DOC) concentration increased (p-value < 0.01) while it increased with a decrease of pH (p-value < 0.01). - Long-term in-situ monitoring of TM and DGM concentrations with various factors was executed in a large artificial reservoir in this study.

  5. Physiological epidermal growth factor concentrations activate high affinity receptors to elicit calcium oscillations.

    Directory of Open Access Journals (Sweden)

    Béatrice Marquèze-Pouey

    Full Text Available Signaling mediated by the epidermal growth factor (EGF is crucial in tissue development, homeostasis and tumorigenesis. EGF is mitogenic at picomolar concentrations and is known to bind its receptor on high affinity binding sites depending of the oligomerization state of the receptor (monomer or dimer. In spite of these observations, the cellular response induced by EGF has been mainly characterized for nanomolar concentrations of the growth factor, and a clear definition of the cellular response to circulating (picomolar concentrations is still lacking. We investigated Ca2+ signaling, an early event in EGF responses, in response to picomolar doses in COS-7 cells where the monomer/dimer equilibrium is unaltered by the synthesis of exogenous EGFR. Using the fluo5F Ca2+ indicator, we found that picomolar concentrations of EGF induced in 50% of the cells a robust oscillatory Ca2+ signal quantitatively similar to the Ca2+ signal induced by nanomolar concentrations. However, responses to nanomolar and picomolar concentrations differed in their underlying mechanisms as the picomolar EGF response involved essentially plasma membrane Ca2+ channels that are not activated by internal Ca2+ store depletion, while the nanomolar EGF response involved internal Ca2+ release. Moreover, while the picomolar EGF response was modulated by charybdotoxin-sensitive K+ channels, the nanomolar response was insensitive to the blockade of these ion channels.

  6. Physiological epidermal growth factor concentrations activate high affinity receptors to elicit calcium oscillations.

    Science.gov (United States)

    Marquèze-Pouey, Béatrice; Mailfert, Sébastien; Rouger, Vincent; Goaillard, Jean-Marc; Marguet, Didier

    2014-01-01

    Signaling mediated by the epidermal growth factor (EGF) is crucial in tissue development, homeostasis and tumorigenesis. EGF is mitogenic at picomolar concentrations and is known to bind its receptor on high affinity binding sites depending of the oligomerization state of the receptor (monomer or dimer). In spite of these observations, the cellular response induced by EGF has been mainly characterized for nanomolar concentrations of the growth factor, and a clear definition of the cellular response to circulating (picomolar) concentrations is still lacking. We investigated Ca2+ signaling, an early event in EGF responses, in response to picomolar doses in COS-7 cells where the monomer/dimer equilibrium is unaltered by the synthesis of exogenous EGFR. Using the fluo5F Ca2+ indicator, we found that picomolar concentrations of EGF induced in 50% of the cells a robust oscillatory Ca2+ signal quantitatively similar to the Ca2+ signal induced by nanomolar concentrations. However, responses to nanomolar and picomolar concentrations differed in their underlying mechanisms as the picomolar EGF response involved essentially plasma membrane Ca2+ channels that are not activated by internal Ca2+ store depletion, while the nanomolar EGF response involved internal Ca2+ release. Moreover, while the picomolar EGF response was modulated by charybdotoxin-sensitive K+ channels, the nanomolar response was insensitive to the blockade of these ion channels.

  7. Folate intake, lifestyle factors, and homocysteine concentrations in younger and older women

    DEFF Research Database (Denmark)

    Rasmussen, Lone Banke; Ovesen, L.; Bulow, I.

    2000-01-01

    Background: An elevated total homocysteine (tHcy) concentration is considered to be an independent risk factor for cardiovascular diseases and has also been associated with an increased risk of neural tube defects. Objective: The objective of this study was to investigate folate intake, folate st...

  8. Effects of a concentrate of pea antinutritional factors on pea protein digestibility in piglets

    NARCIS (Netherlands)

    Guen, M.P. Le; Huisman, J.; Guéguen, J.; Beelen, G.; Verstegen, M.W.A.

    1995-01-01

    Four experiments were designed to investigate the apparent ileal digestibility of raw pea (Pisum sativum) and two of its components - an isolate of its proteins and a concentrate of its proteinaceous antinutritional factors (ANFs). Three varieties of peas were used: spring varieties Finale and

  9. Cross-system comparison of factors influencing chlorophyll-a concentration in Oregon estuaries

    Science.gov (United States)

    Water column chlorophyll-a (chla) is a proxy for phytoplankton biomass and is often used as a biological response indicator of eutrophication. Although watershed nutrient loading may influence chla concentration in estuaries, factors such as freshwater inflow, residence time, and...

  10. Modified Weibull theory and stress-concentration factors of polycrystalline graphite

    International Nuclear Information System (INIS)

    Ho, F.H.

    1980-12-01

    Stress concentration factors (SCF) due to geometric discontinuities in graphite specimens are observed to be much less than the theoretical SCF in an elastic material. In fact, the experimental SCF is always less than two and sometimes even less than one. A four parameter Weibull theory which recognizes the grain size effect is found to give an adequate explanation of the above observed discrepancies

  11. Leaf litter nitrogen concentration as related to climatic factors in Eurasian forests

    DEFF Research Database (Denmark)

    Liu, Chunjiang; Berg, Bjørn; Kutsch, Werner

    2006-01-01

    The aim of this study is to determine the patterns of nitrogen (N) concentrations in leaf litter of forest trees as functions of climatic factors, annual average temperature (Temp, °C) and annual precipitation (Precip, dm) and of forest type (coniferous vs. broadleaf, deciduous vs. evergreen, Pinus...... concentration and Temp and Precip by means of regression analysis. Leaf litter data from N2-fixing species were excluded from the analysis. Results: Over the Eurasian continent, leaf litter N concentration increased with increasing Temp and Precip within functional groups such as conifers, broadleaf, deciduous....... In the context of global warming, these regression equations are useful for a better understanding and modelling of the effects of geographical and climatic factors on leaf litter N at a regional and continental scale....

  12. Comparison of 3-Factor Prothrombin Complex Concentrate and Low-Dose Recombinant Factor VIIa for Warfarin Reversal

    OpenAIRE

    Chapman, Scott A; Irwin, Eric D; Abou-Karam, Nada M; Rupnow, Nichole M; Hutson, Katherine E; Vespa, Jeffrey; Roach, Robert M

    2014-01-01

    Introduction Prothrombin complex concentrate (PCC) and recombinant Factor VIIa (rFVIIa) have been used for emergent reversal of warfarin anticoagulation. Few clinical studies have compared these agents in warfarin reversal. We compared warfarin reversal in patients who received either 3 factor PCC (PCC3) or low-dose rFVIIa (LDrFVIIa) for reversal of warfarin anticoagulation. Methods Data were collected from medical charts of patients who received at least one dose of PCC3 (20 units/kg) or LDr...

  13. Lake variability: Key factors controlling mercury concentrations in New York State fish

    International Nuclear Information System (INIS)

    Simonin, Howard A.; Loukmas, Jefferey J.; Skinner, Lawrence C.; Roy, Karen M.

    2008-01-01

    A 4 year study surveyed 131 lakes across New York State beginning in 2003 to improve our understanding of mercury and gather information from previously untested waters. Our study focused on largemouth and smallmouth bass, walleye and yellow perch, common piscivorous fish shown to accumulate high mercury concentrations and species important to local fisheries. Fish from Adirondack and Catskill Forest Preserve lakes generally had higher mercury concentrations than those from lakes in other areas of the state. Variability between nearby individual lakes was observed, and could be due to differences in water chemistry, lake productivity or the abundance of wetlands in the watershed. We found the following factors impact mercury bioaccumulation: fish length, lake pH, specific conductivity, chlorophyll a, mercury concentration in the water, presence of an outlet dam and amount of contiguous wetlands. - Lake water chemistry variables, dams, and wetlands play major roles in determining fish mercury concentrations

  14. Source apportionment of ambient particle number concentrations in central Los Angeles using positive matrix factorization (PMF

    Directory of Open Access Journals (Sweden)

    M. H. Sowlat

    2016-04-01

    Full Text Available In this study, the positive matrix factorization (PMF receptor model (version 5.0 was used to identify and quantify major sources contributing to particulate matter (PM number concentrations, using PM number size distributions in the range of 13 nm to 10 µm combined with several auxiliary variables, including black carbon (BC, elemental and organic carbon (EC/OC, PM mass concentrations, gaseous pollutants, meteorological, and traffic counts data, collected for about 9 months between August 2014 and 2015 in central Los Angeles, CA. Several parameters, including particle number and volume size distribution profiles, profiles of auxiliary variables, contributions of different factors in different seasons to the total number concentrations, diurnal variations of each of the resolved factors in the cold and warm phases, weekday/weekend analysis for each of the resolved factors, and correlation between auxiliary variables and the relative contribution of each of the resolved factors, were used to identify PM sources. A six-factor solution was identified as the optimum for the aforementioned input data. The resolved factors comprised nucleation, traffic 1, traffic 2 (with a larger mode diameter than traffic 1 factor, urban background aerosol, secondary aerosol, and soil/road dust. Traffic sources (1 and 2 were the major contributor to PM number concentrations, collectively making up to above 60 % (60.8–68.4 % of the total number concentrations during the study period. Their contribution was also significantly higher in the cold phase compared to the warm phase. Nucleation was another major factor significantly contributing to the total number concentrations (an overall contribution of 17 %, ranging from 11.7 to 24 %, with a larger contribution during the warm phase than in the cold phase. The other identified factors were urban background aerosol, secondary aerosol, and soil/road dust, with relative contributions of approximately 12

  15. In vitro characterization of high purity factor IX concentrates for the treatment of hemophilia B.

    Science.gov (United States)

    Limentani, S A; Gowell, K P; Deitcher, S R

    1995-04-01

    This study employed sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and immunoblotting to assess the purity of seven high purity factor IX concentrates: Aimafix (Aima), AlphaNine-SD (Alpha Therapeutic), Factor IX VHP (Biotransfusion), Immunine (Immuno), Mononine (Armour Pharmaceutical), Nanotiv (Kabi Pharmacia), and 9MC (Blood Products Laboratory). The mean specific activity of these products ranged from 68 U factor IX/mg (Aimafix) to 246 U factor IX/mg (Mononine). SDS-PAGE analysis showed that the highest purity product, Mononine, had a single contaminating band under non-reducing conditions. Two additional bands were detected when this product was analyzed under reducing conditions. All other products had multiple contaminating bands that were more apparent under reducing than non-reducing conditions. The immunoblot for factor IX showed a dominant factor IX band for all products. In addition, visible light chain of factor IX was detected for AlphaNine-SD, Factor IX VHP, Immunine, Mononine, Nanotiv, and 9MC, suggesting that the factor IX in these products had undergone partial activation to factor IXa. Another contaminating band was visible at 49,500 for all of the products except 9MC. In addition to this band, high molecular weight contaminants were apparent for some products, most notably AlphaNine-SD. The identity of these bands is unknown. Immunoblotting failed to demonstrate factor VII as a contaminant of any of the high purity products, although factor VIIa could be detected in some lots of Immunine, Nanotiv, and 9MC by a clot-based assay. Factor X contaminated Aimafix, AlphaNine-SD, Factor IX VHP, Immunine, Nanotiv, and 9MC, but activation products of factor X were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation

    Directory of Open Access Journals (Sweden)

    Hajar Mazahery

    2015-06-01

    Full Text Available Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OHD concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OHD concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OHD response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OHD, aging, body mass index(BMI/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation and environment (season are other contributing factors. With the exception of baseline 25(OHD, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.

  17. Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation.

    Science.gov (United States)

    Mazahery, Hajar; von Hurst, Pamela R

    2015-06-25

    Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OH)D concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OH)D concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OH)D response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OH)D, aging, body mass index(BMI)/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation) and environment (season) are other contributing factors. With the exception of baseline 25(OH)D, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.

  18. Landscape factors and hydrology influence mercury concentrations in wading birds breeding in the Florida Everglades, USA.

    Science.gov (United States)

    Herring, Garth; Eagles-Smith, Collin A; Ackerman, Joshua T; Gawlik, Dale E; Beerens, James M

    2013-08-01

    The hydrology of wetland ecosystems is a key driver of both mercury (Hg) methylation and waterbird foraging ecology, and hence may play a fundamental role in waterbird exposure and risk to Hg contamination. However, few studies have investigated hydrological factors that influence waterbird Hg exposure. We examined how several landscape-level hydrological variables influenced Hg concentrations in great egret and white ibis adults and chicks in the Florida Everglades. The great egret is a visual "exploiter" species that tolerates lower prey densities and is less sensitive to hydrological conditions than is the white ibis, which is a tactile "searcher" species that pursues higher prey densities in shallow water. Mercury concentrations in adult great egrets were most influenced by the spatial region that they occupied in the Everglades (higher in the southern region); whereas the number of days a site was dry during the previous dry season was the most important factor influencing Hg concentrations in adult ibis (Hg concentrations increased with the number of days dry). In contrast, Hg concentrations in egret chicks were most influenced by calendar date (increasing with date), whereas Hg concentrations in ibis chicks were most influenced by chick age, region, and water recession rate (Hg concentrations decreased with age, were higher in the southern regions, and increased with positive water recession rates). Our results indicate that both recent (preceding two weeks) hydrological conditions, and those of the prior year, influence Hg concentrations in wading birds. Further, these results suggest that Hg exposure in wading birds is driven by complex relationships between wading bird behavior and life stage, landscape hydrologic patterns, and biogeochemical processes. Published by Elsevier B.V.

  19. Evaluation of impact factors on VOC emissions and concentrations from wooden flooring based on chamber tests

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chi-Chi [Department of Civil and Environmental Engineering, National University of Kaohsiung, No. 700, Kaohsiung University Rd., Kaohsiung (China); Yu, Kuo-Pin [Institute of Environmental and Occupational Health Sciences, National Yang-Ming University, No.155, Sec.2, Linong Street, Taipei (China); Zhao, Ping [Filtration Group Inc., 912 E. Washington Street, Joliet, IL 60433 (United States); Whei-May Lee, Grace [Graduate Institute of Environmental Engineering, National Taiwan University, 71, Chou-Shan Rd., Taipei (China)

    2009-03-15

    In this study, the impact factors of temperature, relative humidity (RH), air exchange rate, and volatile organic compound (VOC) properties on the VOC (toluene, n-butyl acetate, ethylbenzene, and m,p-xylene) specific emission rates (SERs) and concentrations from wooden flooring were investigated by chamber test for 8 days. The tested wood in this study is not common solid wood, but composite wood made of combined wood fibers. The experiments were conducted in a stainless-steel environmental test chamber coated with Teflon. The experimental results within 8 days of testing showed that, when the temperature increased from 15 to 30 C, the VOC SERs and concentrations increased 1.5-129 times. When the RH increased from 50% to 80%, the VOC concentrations and SERs increased 1-32 times. When the air change rate increased from 1 to 2 h{sup -1}, the VOC concentrations decreased 9-40%, while the VOC SERs increased 6-98%. The relations between the boiling points of the VOCs and each of the normalized VOC SERs and concentrations were linear with negative slopes. The relations between the vapor pressures of the VOCs and each of the normalized VOC SERs and concentrations were linear with positive slopes. At 15 C, RH50%, the relations between the diffusivities of VOCs and each of the normalized VOC equilibrium SERs and concentrations were linear with a positive slope. (author)

  20. Effect of subinhibitory concentrations of chlorogenic acid on reducing the virulence factor production by Staphylococcus aureus.

    Science.gov (United States)

    Li, Guanghui; Qiao, Mingyu; Guo, Yan; Wang, Xin; Xu, Yunfeng; Xia, Xiaodong

    2014-09-01

    Chlorogenic acid (CA) has been reported to inhibit several pathogens, but the influence of subinhibitory concentrations of CA on virulence expression of pathogens has not been fully elucidated. The aim of this study was to explore the effect of CA on the virulence factor production of Staphylococcus aureus. The minimum inhibitory concentration (MIC) of CA against S. aureus was determined using a broth microdilution method. Hemolysin assays, coagulase titer assays, adherence to solid-phase fibrinogen assays, Western blot, and real-time reverse transcriptase-polymerase chain reaction were performed to evaluate the effect of subinhibitory concentrations of CA on the virulence factors of S. aureus. MIC of CA against S. aureus ATCC29213 was found to be 2.56 mg/mL. At subinhibitory concentrations, CA significantly inhibited the hemolysis and dose-dependently decreased coagulase titer. Reduced binding to fibrinogen and decreased production of SEA were observed with treatment of CA at concentrations ranging from 1/16MIC to 1/2MIC. CA markedly inhibited the expression of hla, sea, and agr genes in S. aureus. These data demonstrate that the virulence expression of S. aureus could be reduced by CA and suggest that CA could be potentially developed as a supplemental strategy to control S. aureus infection and to prevent staphylococcal food poisoning.

  1. Rotating night shift work, sleep quality, selected lifestyle factors and prolactin concentration in nurses and midwives.

    Science.gov (United States)

    Bukowska, Agnieszka; Sobala, Wojciech; Peplonska, Beata

    2015-04-01

    The pattern of secretion of many hormones, including prolactin, is dependent on the circadian rhythm. Night shift work involves exposure to artificial light at night and sleep deficiency, which in turn can affect prolactin synthesis. The aim of this study was to evaluate a possible association between night shift work characteristics, sleep quality, lifestyle factors and prolactin concentration, using data from a cross-sectional study of nurses and midwives. A cross-sectional study was conducted among 327 nurses and midwives currently working on rotating night shifts, and 330 nurses and midwives working during the day (aged 40-60 years) (388 premenopausal and 269 postmenopausal). Information about night shift work characteristics, lifestyle, reproductive factors, sleep pattern and other covariates was collected through a face-to-face interview, and from a one-week work and sleep diary completed by the subjects. Weight and height were measured. Prolactin concentration was measured in the morning blood sample using the electrochemiluminesence immunoassay method. Associations were analyzed using linear regression models adjusted for important confounders. Analyses were carried out separately in pre- and postmenopausal women. None of the night shift work or sleep characteristics was significantly associated with prolactin concentration. Prolactin concentration was significantly (p night shift work is not associated with prolactin concentration. Smoking, parity, time of blood collection and age among postmenopausal women were significant determinants of prolactin.

  2. The correlation of prenatal zinc concentration and deficiency with anthropometric factors.

    Directory of Open Access Journals (Sweden)

    Parichehr Hanachi

    2014-03-01

    Full Text Available To determine the status of serum zinc in pregnant women in different gestational ages and correlation with socio-demographic and anthropometric factors in Iranian women referring to prenatal care public health clinics.We analyzed the zinc concentrations in plasma samples obtained at different gestational ages from 961 women and recorded BMI at the first trimester in pregnant women who were screened for a trial designed to evaluate the zinc concentration. Subjects were from different socio economical backgrounds and attended public health clinics for their prenatal care. All analyses were performed by SPSS (version 16. P values < 0.05 were considered significant.The results showed that after plasma zinc concentrations were adjusted with Parity, weight (early pregnancy, BMI (at early pregnancy, age and educational statues. Plasma zinc deficiency declined as gestational age progressed, however it was not significant. There was no significant correlation between zinc concentration, anthropometric, method of contraception and socio factors. However, there were significant relation between parity (p = 0.007 and weight at early pregnancy (p= 0.039 with serum zinc levels.We conclude that plasma zinc concentrations decreased during the late first trimester to the early third trimester and with parity. These findings may indicate that the deficient levels of zinc in the latter third of pregnancy suggest a tendency for insufficient maternal nutrition. However larger studies are required to support this finding.

  3. INFLUENCE OF HEXAVALENT CHROMIUM INITIAL CONCENTRATION ON RETARDATION FACTOR AND CONTAMINANT VELOCITY IN A SOIL MEDIA

    Directory of Open Access Journals (Sweden)

    K. SHIVA PRASHANTH KUMAR

    2016-02-01

    Full Text Available Sources of soil and ground water contamination are many and include many folds of accidental spills and leaks of toxic and hazardous chemicals. Preparation of ground water contamination model needs good understanding of the behavior of contaminant transport through soil media for predicting the level of contamination of ground water in the near future at the intended site conditions. Sorption is a natural process; due to its presence, the contaminant can move slowly as compared to the ground water and hence the effects of sorption must be taken into consideration while predicting the travel time of the contaminant to reach the ground water sources. This paper discusses the results of column test studies carried out in the laboratory under controlled conditions about the spreading of contaminant (Hexavalent chromium, Cr (VI through the clay mixed red soil at two different initial concentrations (800 mg/L and 4200 mg/L. The variations of the contaminant flow velocity and retardation factor for two different initial concentrations of contaminant were brought out and discussed. The contaminant flow velocity drastically coming down for a relative concentration of 0 to 0.2 and beyond this range, the contaminant flow velocity value is decreasing in a slow rate for both the lower and higher initial contaminant concentrations tested. At the lower relative concentration, the higher retardation factor was observed and it may be due to slowly filling the available sorption sites in the soil column.

  4. Thrombin generation assay as a possible tool for assessment of reduced activity of clotting factors induced by antiphospholipid antibodies and in-vitro evaluation of treatment options.

    Science.gov (United States)

    Livnat, Tami; Zivelin, Ariella; Tamarin, Ilia; Guetta, Victor; Salomon, Ophira

    2009-12-01

    Bleeding is a rare manifestation of antiphospholipid syndrome, unless associated with reduced clotting factors or severe thrombocytopenia. Accurate assessment of the autoantibodies in plasma is very important since the autoantibodies can lead to bleeding or thrombosis. The objective of the present study was to define the inhibitors causing reduced clotting activity in a patient with antiphospholipids antibodies and to assess the potential of thrombin generation assay to assist in establishment of optimal treatment in case of major bleeding. Levels of clotting factors as well as inhibitors to factors II, V, VII, VIII, IX, X and XI were defined. For detection of inhibitors to prothrombin crossed immunoelectrophoresis was used. IgG was purified by commercial protein A column. Thrombin generation was measured using a fluorometric assay in platelet-poor and platelet-rich plasma. Inhibitors toward the activity of factors V, VII, VIII, IX, X and XI were defined and also an inhibitor to prothrombin antigen. No thrombin generation was induced in the patient's plasma by recalcification even in the presence of recombinant factor VIIa or factor VIII inhibitor bypassing activity. In contrast, addition of platelets from either donor or patient or synthetic phospholipids normalized the thrombin generation. The thrombin generation model showed that the addition of platelets and no recombinant factor VIIa or factor VIII inhibitor bypassing activity would correct thrombin generation in vitro. On this basis, platelet concentrates were administered to a patient with bleeding caused by lupus anticoagulant and low clotting factors activity.

  5. Metabolic syndrome, alcohol consumption and genetic factors are associated with serum uric acid concentration.

    Directory of Open Access Journals (Sweden)

    Blanka Stibůrková

    Full Text Available Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals.The cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii selected genetic variants of the MTHFR (c.665C>T, c.1286A>C, SLC2A9 (c.844G>A, c.881G>A and ABCG2 genes (c.421C>A. A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables.The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations.Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.

  6. Beneficial Effects of Concentrated Growth Factors and Resveratrol on Human Osteoblasts In Vitro Treated with Bisphosphonates

    Directory of Open Access Journals (Sweden)

    Elisa Borsani

    2018-01-01

    Full Text Available Bisphosphonates are primary pharmacological agents against osteoclast-mediated bone loss and widely used in the clinical practice for prevention and treatment of a variety of skeletal conditions, such as low bone density and osteogenesis imperfecta, and pathologies, such as osteoporosis, malignancies metastatic to bone, Paget disease of bone, multiple myeloma, and hypercalcemia of malignancy. However, long-term bisphosphonate treatment is associated with pathologic conditions including osteonecrosis of the jaw, named BRONJ, which impaired bone regeneration process. Clinical management of BRONJ is controversy and one recent approach is the use of platelet concentrates, such as Concentrated Growth Factors, alone or together with biomaterials or antioxidants molecules, such as resveratrol. The aim of the present study was to investigate the in vitro effects of Concentrated Growth Factors and/or resveratrol on the proliferation and differentiation of human osteoblasts, treated or not with bisphosphonates. Human osteoblasts were stimulated for 3 days in complete medium and for 21 days in mineralization medium. At the end of the experimental period, the in vitro effect on osteoblast proliferation and differentiation was evaluated using different techniques such as MTT, ELISA for the quantification/detection of osteoprotegerin and bone morphogenetic protein-2, immunohistochemistry for sirtuin 1 and collagen type I, and the Alizarin Red S staining for the rate of mineralization. Results obtained showed that Concentrated Growth Factors and/or resveratrol significantly increased osteoblast proliferation and differentiation and that the cotreatment with Concentrated Growth Factors and resveratrol had a protective role on osteoblasts treated with bisphosphonates. In conclusion, these data suggest that this approach could be promised in the clinical management of BRONJ.

  7. Derived concentration factors for caesium-137 in edible species of North Sea fish

    International Nuclear Information System (INIS)

    Steele, A.K.

    1990-01-01

    Concentration factor (CF=Bq kg -1 fillet/Bg kg -1 filtered sea water) values for 137 Cs in fillets of cod (Gadus morhua), haddock (Merlanogrammus aeglefinus), plaice (Pleuronectes platessa) and whiting (Merlangius merlangius), were derived from fish and filtered seawater concentrations. Samples were collected in twelve sampling boxes in the North Sea over an eight-year period - 1978-1985. The range of results with species, between species, and between surveys are discussed. Mean CF values of 92, 58, 39 and 150 were found in cod, haddock, plaice and whiting respectively. These support the International Atomic Energy Authority recommended CF value of 100 for fish in generalised dose assessments. (author)

  8. Comercio Internacional mediterráneo en el siglo VIII a.C.

    Directory of Open Access Journals (Sweden)

    Paloma Cabrera Bonet

    2018-01-01

    Full Text Available The VIII century B.C. saw, for the first time after the breakdown of the system in the Late Bronze Age, the revival of a true intemational trade at a growing scale, especíally protagonized by Phoenicians and Greeks. In this article we analyze sorne aspects of this phenomenon, from the Aegean to the Far West, which made possíble, through a vaste network of trading routes, a large multinational ínteractíon. We understand the international trade as a key factor in the proccess of economic, social and political changes of the Mediterranean areas submerged in this complex "world-system".

  9. Elevated CSF Corticotropin-Releasing Factor Concentrations in Posttraumatic Stress Disorder

    Science.gov (United States)

    Bremner, J. Douglas; Licinio, Julio; Darnell, Adam; Krystal, John H.; Owens, Michael J.; Southwick, Steven M.; Nemeroff, Charles B.; Charney, Dennis S.

    2011-01-01

    Objective Corticotropin-releasing factor (CRF) and somatostatin both play important roles in mediating responses to acute and chronic stress. The purpose of this study was to measure CSF concentrations of CRF and somatostatin in patients with chronic combat-related post-traumatic stress disorder (PTSD) and comparison subjects. Method Lumbar punctures for collection of CSF were performed in Vietnam combat veterans with PTSD (N=11) and comparison subjects (N=17). CSF concentrations of CRF and somatostatin were compared between the two groups. Results CSF concentrations of CRF were higher in the PTSD patients than in the comparison subjects (mean=29.0 pg/ml, SD=7.8, versus mean=21.9 pg/ml, SD=6.0). This group difference remained significant after covariance for age. CSF somatostatin concentrations in PTSD patients were higher than those of the comparison subjects (mean=19.9 pg/ml, SD=5.4, versus mean=13.7 pg/ml, SD=8.0). However, covarying for age reduced the level of significance. Conclusions Higher CSF CRF concentrations in patients with PTSD may reflect alterations in stress-related neurotransmitter systems. The higher CSF CRF concentrations may play a role in disturbances of arousal in patients with PTSD. PMID:9137116

  10. More efficient reversal of dabigatran inhibition of coagulation by activated prothrombin complex concentrate or recombinant factor VIIa than by four-factor prothrombin complex concentrate.

    Science.gov (United States)

    Lindahl, Tomas L; Wallstedt, Maria; Gustafsson, Kerstin M; Persson, Egon; Hillarp, Andreas

    2015-03-01

    The number of patients on antithrombotic treatment due to atrial fibrillation and venous thromboembolism is increasing fast due to an aging population. A growing proportion will be treated with novel oral anticoagulants, the first in clinical use was the direct oral thrombin inhibitor dabigatran (Pradaxa®). A small percentage of the patients on dabigatran will experience serious bleeding or be in need of urgent surgery. The aim of this study was to test the effects of different hemostatic agents in potentially reversing the anticoagulant effects in vitro in blood or platelet-rich plasma (PRP) spiked with dabigatran. Whole blood or PRP was spiked with the active substance dabigatran, 200 μg/L. We measured clotting time being induced by 1.4 pmol/L tissue factor using the instrument ReoRox2™ and initial clot growth velocity from a tissue factor covered surface using the instrument Thrombodynamics Analyzer T-2™. Dabigatran prolonged clotting time 5-fold but reduced clot growth velocity only slightly. The reversing effects of prothrombin complex concentrates (PCC), activated PCC (APCC) and recombinant activated factor VII (rFVIIa) were then tested. APCC (1.8 U/mL) reduced the prolonged clotting time by 1/3, rFVIIa (2 μg/L) only slightly (n = 10-20). The reduction was not significant using Mann-Whitney test but significant using t-test with Bonferronis' correction for multiple comparisons, whereas PCC (0.56 U/mL) had no effect on clotting time. APCC doubled initial clot growth velocity, although even more in the absence of dabigatran. In conclusion, APCC and rFVIIa, but not PCC, seem to reverse, at least partially, some effects of dabigatran on coagulation parameters. Systematic evaluation of case reports, registries and, ultimately, randomized clinical trials are needed to elucidate potential benefit for patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Igor Zabel 14. VIII 1958 - 23. VII 2005

    Index Scriptorium Estoniae

    2005-01-01

    Igor Zabel oli Ida-Euroopa tuntumaid kunstiteoreetikuid ja kuraatoreid. Töötas 1986. aastast Ljubljana moodsa kunsti muuseumi kuraatorina. 9. VIII avatakse seal viimane I. Zabeli kureeritud näitus "Territories, Identities, Nets-Slovene Art 1995-2005"

  12. Extended analyses of Se VII and Se VIII

    International Nuclear Information System (INIS)

    Vankleef, Th.A.M.; Joshi, Y.N.

    1984-01-01

    Joshi et al. (1984) have conducted an analysis of the 3d8 4s-3d8 4p transitions in As VII. The present investigation is concerned with an analysis of similar transitions in Se VIII. The selenium spectrum was photographed in the 400-1200-A wavelength region on a variety of normal-incidence spectrographs. Attention is given to least-squares-fit (LSF) and Hartree-Fock (HF) parameter values for the 3d9 4d configuration of Se VII, LSF and HF parameter values for the 3d8 4s and 3d8 4p configurations of Se VIII, the energy and composition of the levels of the 3d9 4d configuration of Se VII, classified lines in Se VII, energy levels and composition of the 3d8 4s configuration and the revised and newly determined levels of the 3d8 4p configuration of Se VIII, and newly classified lines of Se VIII. 15 references

  13. Factors influencing indoor PM2.5 concentration in rural houses of northern China

    Science.gov (United States)

    Zhang, Xueyan; Chen, Bin

    2018-02-01

    In traditional houses in rural areas of Northern China, most traditional heating systems, heated by mini-stove in the kitchen, usually take agricultural residues as fuels resources. Besides, burning cave under the ground-floor of a rural house is also widely used. The higher PM2.5 concentration is crisis for human health. In this study, PM2.5 concentration, temperature, relative humidity inside and outside the houses have been measured, moreover the factors impact on I/O rate coefficient has been discussed. The results show that the I/O rate coefficient in the evening is 2.5 times greater than the I/O rate coefficient in the daytime. I/O rate coefficient of PM2.5 concentration is positive related to air temperature difference between indoor and outdoor. In addition, the impact of outdoor wind speed and predominant wind direction on the PM2.5 emission has been studied.

  14. Dabigatran and its reversal with recombinant factor VIIa and prothrombin complex concentrate

    DEFF Research Database (Denmark)

    Sølbeck, Sacha; Nilsson, Caroline U; Engström, Martin

    2014-01-01

    OBJECTIVE: Dabigatran is a new oral direct thrombin inhibitor. No specific antidote exists in the event of hemorrhage, but prothrombin complex concentrate (PCC) and recombinant activated factor VII (rFVIIa) are suggested therapies. Sonoclot is a bedside viscoelastic instrument for monitoring...... different Sonoclot cuvettes: Glassbead, kaolin and tissue factor (diluted) activated. RESULTS: The Sonoclot detected in vitro-induced anticoagulation due to dabigatran with the glassbead- and kaolin-activated cuvettes. There was no reversing effect of PCC, probably due to the presence of heparin in the PCC...

  15. Imaging shear stress distribution and evaluating the stress concentration factor of the human eye

    Science.gov (United States)

    Joseph Antony, S.

    2015-03-01

    Healthy eyes are vital for a better quality of human life. Historically, for man-made materials, scientists and engineers use stress concentration factors to characterise the effects of structural non-homogeneities on their mechanical strength. However, such information is scarce for the human eye. Here we present the shear stress distribution profiles of a healthy human cornea surface in vivo using photo-stress analysis tomography, which is a non-intrusive and non-X-ray based method. The corneal birefringent retardation measured here is comparable to that of previous studies. Using this, we derive eye stress concentration factors and the directional alignment of major principal stress on the surface of the cornea. Similar to thermometers being used for monitoring the general health in humans, this report provides a foundation to characterise the shear stress carrying capacity of the cornea, and a potential bench mark for validating theoretical modelling of stresses in the human eye in future.

  16. Iron concentrations in breast milk and selected maternal factors of human milk bank donors.

    Science.gov (United States)

    Mello-Neto, Julio; Rondó, Patrícia H C; Morgano, Marcelo A; Oshiiwa, Marie; Santos, Mariana L; Oliveira, Julicristie M

    2010-05-01

    The aim of this study was to evaluate the relationship between iron concentration in mature breast milk and characteristics of 136 donors of a Brazilian milk bank. Iron, vitamin A, zinc, and copper concentrations were assessed in human milk and maternal blood. Data were collected on maternal anthropometrics, obstetric, socioeconomic, demographic, and lifestyle factors. Iron, zinc, and copper in milk and zinc and copper in blood were detected by spectrophotometry. Vitamin A in milk and blood was determined by high-performance liquid chromatography. Hemoglobin was measured by electronic counting and serum iron and ferritin by colorimetry and chemoluminescence, respectively. Transferrin and ceruloplasmin were determined by nephelometry. According to multivariate linear regression analysis, iron in milk was positively associated with vitamin A in milk and with smoking but negatively associated with timing of breast milk donation (P milk of Brazilian donors may be influenced by nutritional factors and smoking.

  17. Hair mercury concentrations and associated factors in an electronic waste recycling area, Guiyu, China

    Energy Technology Data Exchange (ETDEWEB)

    Ni, Wenqing [Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong (China); Chen, Yaowen [Central Laboratory of Shantou University, Shantou 515063, Guangdong (China); Huang, Yue; Wang, Xiaoling [Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong (China); Zhang, Gairong [Central Laboratory of Shantou University, Shantou 515063, Guangdong (China); Luo, Jiayi [Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong (China); Wu, Kusheng, E-mail: kswu@stu.edu.cn [Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong (China)

    2014-01-15

    Objective: Toxic heavy metals are released to the environment constantly from unregulated electronic waste (e-waste) recycling in Guiyu, China, and thus may contribute to the elevation of mercury (Hg) and other heavy metals levels in human hair. We aimed to investigate concentrations of mercury in hair from Guiyu and potential risk factors and compared them with those from a control area where no e-waste processing occurs. Methods: A total of 285 human hair samples were collected from three villages (including Beilin, Xianma, and Huamei) of Guiyu (n=205) and the control area, Jinping district of Shantou city (n=80). All the volunteers were administered a questionnaire regarding socio-demographic characteristics and other possible factors contributed to hair mercury concentration. Hair mercury concentration was analyzed by hydride generation atomic fluorescence spectrometry (AFS). Results: Our results suggested that hair mercury concentrations in volunteers of Guiyu (median, 0.99; range, 0.18–3.98 μg/g) were significantly higher than those of Jinping (median, 0.59; range, 0.12–1.63 μg/g). We also observed a higher over-limit ratio (>1 μg/g according to USEPA) in Guiyu than in Jinping (48.29% vs. 11.25%, P<0.001). Logistic regression model showed that the variables of living house also served as an e-waste workshop, work related to e-waste, family income, time of residence in Guiyu, the distance between home and waste incineration, and fish intake were associated with hair mercury concentration. After multiple stepwise regression analysis, in the Guiyu samples, hair mercury concentration was found positively associated with the time residence in Guiyu (β=0.299, P<0.001), and frequency of shellfish intake (β=0.184, P=0.016); and negatively associated with the distance between home and waste incineration (β=−0.190, P=0.015) and whether house also served as e-waste workshop (β=−0.278, P=0.001). Conclusions: This study investigated human mercury exposure

  18. Hair mercury concentrations and associated factors in an electronic waste recycling area, Guiyu, China

    International Nuclear Information System (INIS)

    Ni, Wenqing; Chen, Yaowen; Huang, Yue; Wang, Xiaoling; Zhang, Gairong; Luo, Jiayi; Wu, Kusheng

    2014-01-01

    Objective: Toxic heavy metals are released to the environment constantly from unregulated electronic waste (e-waste) recycling in Guiyu, China, and thus may contribute to the elevation of mercury (Hg) and other heavy metals levels in human hair. We aimed to investigate concentrations of mercury in hair from Guiyu and potential risk factors and compared them with those from a control area where no e-waste processing occurs. Methods: A total of 285 human hair samples were collected from three villages (including Beilin, Xianma, and Huamei) of Guiyu (n=205) and the control area, Jinping district of Shantou city (n=80). All the volunteers were administered a questionnaire regarding socio-demographic characteristics and other possible factors contributed to hair mercury concentration. Hair mercury concentration was analyzed by hydride generation atomic fluorescence spectrometry (AFS). Results: Our results suggested that hair mercury concentrations in volunteers of Guiyu (median, 0.99; range, 0.18–3.98 μg/g) were significantly higher than those of Jinping (median, 0.59; range, 0.12–1.63 μg/g). We also observed a higher over-limit ratio (>1 μg/g according to USEPA) in Guiyu than in Jinping (48.29% vs. 11.25%, P<0.001). Logistic regression model showed that the variables of living house also served as an e-waste workshop, work related to e-waste, family income, time of residence in Guiyu, the distance between home and waste incineration, and fish intake were associated with hair mercury concentration. After multiple stepwise regression analysis, in the Guiyu samples, hair mercury concentration was found positively associated with the time residence in Guiyu (β=0.299, P<0.001), and frequency of shellfish intake (β=0.184, P=0.016); and negatively associated with the distance between home and waste incineration (β=−0.190, P=0.015) and whether house also served as e-waste workshop (β=−0.278, P=0.001). Conclusions: This study investigated human mercury exposure

  19. Rational and timely haemostatic interventions following cardiac surgery - coagulation factor concentrates or blood bank products.

    Science.gov (United States)

    Tang, Mariann; Fenger-Eriksen, Christian; Wierup, Per; Greisen, Jacob; Ingerslev, Jørgen; Hjortdal, Vibeke; Sørensen, Benny

    2017-06-01

    Cardiac surgery may cause a serious coagulopathy leading to increased risk of bleeding and transfusion demands. Blood bank products are commonly first line haemostatic intervention, but has been associated with hazardous side effect. Coagulation factor concentrates may be a more efficient, predictable, and potentially a safer treatment, although prospective clinical trials are needed to further explore these hypotheses. This study investigated the haemostatic potential of ex vivo supplementation of coagulation factor concentrates versus blood bank products on blood samples drawn from patients undergoing cardiac surgery. 30 adults were prospectively enrolled (mean age=63.9, females=27%). Ex vivo haemostatic interventions (monotherapy or combinations) were performed in whole blood taken immediately after surgery and two hours postoperatively. Fresh-frozen plasma, platelets, cryoprecipitate, fibrinogen concentrate, prothrombin complex concentrate (PCC), and recombinant FVIIa (rFVIIa) were investigated. The haemostatic effect was evaluated using whole blood thromboelastometry parameters, as well as by thrombin generation. Immediately after surgery the compromised maximum clot firmness was corrected by monotherapy with fibrinogen or platelets or combination therapy with fibrinogen. At two hours postoperatively the coagulation profile was further deranged as illustrated by a prolonged clotting time, a reduced maximum velocity and further diminished maximum clot firmness. The thrombin lagtime was progressively prolonged and both peak thrombin and endogenous thrombin potential were compromised. No monotherapy effectively corrected all haemostatic abnormalities. The most effective combinations were: fibrinogen+rFVIIa or fibrinogen+PCC. Blood bank products were not as effective in the correction of the coagulopathy. Coagulation factor concentrates appear to provide a more optimal haemostasis profile following cardiac surgery compared to blood bank products. Copyright © 2017

  20. 241-SY-101 strain concentration factor development via nonlinear analysis. Volume 1 of 1

    International Nuclear Information System (INIS)

    1997-01-01

    The 241-SY-101 waste storage tank at the Hanford-Site has been known to accumulate and release significant quantities of hydrogen gas. An analysis was performed to assess the tank's structural integrity when subjected to postulated hydrogen deflagration loads. The analysis addressed many nonlinearities and appealed to a strain-based failure criteria. The model used to predict the global response of the tank was not refined enough to confidently predict local peak strains. Strain concentration factors were applied at structural discontinuities that were based on steel-lined reinforced-concrete containment studies. The discontinuities included large penetrations, small penetrations, springline geometries, stud/liner connections, and the 1/2 inch to 3/8 inch liner thickness transition. The only tank specific strain concentration factor applied in the evaluation was for the 1/2 inch to 3/8 inch liner thickness change in the dome. Review of the tank drawings reveals the possibility that a 4 inches Sch. 40 pipe penetrates the dome thickness transition region. It is not obvious how to combine the strain concentration factors for a small penetration with that of a thickness transition to arrive at a composite strain concentration factor. It is the goal of this effort to make an approximate determination of the relative significance of the 4 inch penetration and the 1/2 inch to 3/8 inch thickness transition in the 241-SY-101 dome geometry. This is accomplished by performing a parametric study with three general finite-element models. The first represents the thickness transition only, the second represents a 4 inch penetration only, and the third combines the thickness transition with a penetration model

  1. Effect of Crack Tip Stress Concentration Factor on Fracture Resistance in Vacuum Environment

    Science.gov (United States)

    2015-01-20

    indicate: (1) in all alloys, the fracture resistance is highest for blunt-notches (smaller Kt), and is lowest for fatigue -sharpened precracked...paths are transgranular and the fracture mode is ductile void coalescence in all cases, irrespective of the stress concentration factor. 20-01-2015...because of corrosion and/or various loading conditions such as fatigue , fretting, abrasion, etc. Also, the geometry of the structure may cause an

  2. Silicon concentrator cells in a two-stage photovoltaic system with a concentration factor of 300x

    Energy Technology Data Exchange (ETDEWEB)

    Mohr, A.

    2005-06-15

    In this work a rear contacted silicon concentrator cell was developed for an application in a two stage concentrator photovoltaic system. This system was developed at Fraunhofer ISE some years ago. The innovation of this one-axis tracked system is that it enables a high geometrical concentration of 300x in combination with a high optical efficiency (around 78%) and a large acceptance angle of {+-}23.5 all year through. For this, the system uses a parabolic mirror (40.4x) and a three dimensional second stage consisting of compound parabolic concentrators (CPCs, 7.7x). For the concentrator concept and particularly for an easy cell integration, the rear line contacted concentrator (RLCC) cells with a maximum efficiency of 25% were developed and a hybrid mounting concept for the RLCC cells is presented. The optical performance of different CPC materials was tested and analysed in this work. Finally, small modules consisting of six series interconnected RLCC cells and six CPCs were integrated into the concentrator system and tested outdoor. A system efficiency of 16.2% was reached at around 800 W/m2 direct irradiance under realistic outdoor conditions. (orig.)

  3. Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition.

    Science.gov (United States)

    Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro

    2017-08-11

    Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 ( GluR2 ) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown. Therefore, we examined the effects of TBT on the activity of transcription factors that control GluR2 expression. Exposure of primary cortical neurons to 20 nM TBT for 3 h to 9 days resulted in a decrease in GluR2 mRNA expression. Moreover, TBT inhibited the DNA binding activity of nuclear respiratory factor-1 (NRF-1), a transcription factor that positively regulates the GluR2 . This result indicates that TBT inhibits the activity of NRF-1 and subsequently decreases GluR2 expression. In addition, 20 nM TBT decreased the expression of genes such as cytochrome c, cytochrome c oxidase (COX) 4, and COX 6c, which are downstream of NRF-1. Our results suggest that NRF-1 inhibition is an important molecular action of the neurotoxicity induced by low-concentration TBT.

  4. Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition

    Science.gov (United States)

    Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro

    2017-01-01

    Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 (GluR2) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown. Therefore, we examined the effects of TBT on the activity of transcription factors that control GluR2 expression. Exposure of primary cortical neurons to 20 nM TBT for 3 h to 9 days resulted in a decrease in GluR2 mRNA expression. Moreover, TBT inhibited the DNA binding activity of nuclear respiratory factor-1 (NRF-1), a transcription factor that positively regulates the GluR2. This result indicates that TBT inhibits the activity of NRF-1 and subsequently decreases GluR2 expression. In addition, 20 nM TBT decreased the expression of genes such as cytochrome c, cytochrome c oxidase (COX) 4, and COX 6c, which are downstream of NRF-1. Our results suggest that NRF-1 inhibition is an important molecular action of the neurotoxicity induced by low-concentration TBT. PMID:28800112

  5. Brain-derived neurotrophic factor (BDNF) plasma concentration in patients diagnosed with premature ovarian insufficiency (POI).

    Science.gov (United States)

    Czyzyk, Adam; Filipowicz, Dorota; Podfigurna, Agnieszka; Ptas, Paula; Piestrzynska, Malgorzata; Smolarczyk, Roman; Genazzani, Andrea R; Meczekalski, Blazej

    2017-05-01

    Premature ovarian insufficiency (POI) is defined as a cessation of function of ovaries in women younger than 40 years old. Brain-derived neurotrophic factor (BDNF) is a protein critically involved in neuronal growth and metabolism. BDNF also has been shown to be important regulator of oocyte maturation. Recent data show that BDNF can be potentially involved in POI pathology. The aim of the study was to assess the BDNF plasma concentrations in patients diagnosed with idiopathic POI. 23 women diagnosed with POI (age 31 ± 7 years) and 18 (age 31 ± 3) controls were included to the study, matched according to age and body mass index. The BDNF concentrations were measured using competitive enzyme-linked immunosorbent assay (ELISA). Hormonal and metabolic parameters were measured in all individuals, in controls in late follicular phase. The POI group demonstrated lower mean plasma concentrations of BDNF (429.25 ± 65.52 pg/ml) in comparison to healthy controls (479.75 ± 34.75 pg/ml, p = 0.0345). The BDNF plasma concentration correlated negatively (R = -0.79, p BDNF and progesterone in controls. In conclusion, POI patients show significantly lower BDNF plasma concentration and it correlates with the duration of amenorrhea. This observation brings important potential insights to the pathology of POI.

  6. Influence of thyroid hormones and transforming growth factor-β1 on cystatin C concentrations.

    Science.gov (United States)

    Kotajima, N; Yanagawa, Y; Aoki, T; Tsunekawa, K; Morimura, T; Ogiwara, T; Nara, M; Murakami, M

    2010-01-01

    Serum cystatin C concentrations are reported to increase in the hyperthyroid state. Serum concentrations of cystatin C and transforming growth factor-β1 (TGF-β1) were measured in patients with thyroid dysfunction, and the effects of 3,5,3'-tri-iodothyronine (T(3)) and TGF-β1 on cystatin C production in human hepatoblastoma (Hep G2) cells were studied. Serum concentrations of cystatin C and TGF-β1 were significantly higher in patients with Graves' disease compared with control subjects. Significantly positive correlations were observed between thyroid hormones and cystatin C, thyroid hormones and TGF-β1, and TGF-β1 and cystatin C in patients with thyroid dysfunction. Serum concentrations of cystatin C and TGF-β1 decreased after treatment for hyperthyroidism. Cystatin C mRNA levels and cystatin C secretion were increased by T(3) and TGF-β1 in cultured Hep G2 cells. These results suggest that serum cystatin C concentrations increase in patients with hyperthyroidism. The mechanisms for this may involve elevation of serum TGF-β1 levels and the stimulatory effects of T(3) and TGF-β1 on cystatin C production.

  7. Serum selenium concentration is associated with metabolic factors in the elderly: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Huang Hui-Ying

    2010-05-01

    Full Text Available Abstract Background Selenium is an essential micronutrient known for its antioxidant function. However, the association of serum selenium with lipid profiles and fasting glucose are inconsistent in populations with average intake of selenium. Furthermore, there were few studies conducted specifically for the elderly. This study examined the relationship of serum selenium concentration with serum lipids and fasting glucose in the Taiwanese elderly population. Methods This was a cross-sectional study of 200 males and females aged 65-85 years (mean 71.5 ± 4.6 years from Taipei, Taiwan. Serum selenium was measured by inductively coupled plasma-mass spectrometer. The association between serum selenium and metabolic factors was examined using a multivariate linear regression analysis after controlling several confounders. Results The mean serum selenium concentration was 1.14 μmol/L, without significant difference between sexes. Total cholesterol, triglycerides, and LDL cholesterol increased significantly with serum selenium concentration (P P P P Conclusions Total cholesterol, triglycerides, and LDL cholesterol, and fasting serum glucose concentrations increased significantly with serum selenium concentration in the Taiwanese elderly. The underlying mechanism warrants further research.

  8. Environmental Factors and Seasonality Affect the Concentration of Rotundone in Vitis vinifera L. cv. Shiraz Wine.

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    Pangzhen Zhang

    Full Text Available Rotundone is a sesquiterpene that gives grapes and wine a desirable 'peppery' aroma. Previous research has reported that growing grapevines in a cool climate is an important factor that drives rotundone accumulation in grape berries and wine. This study used historical data sets to investigate which weather parameters are mostly influencing rotundone concentration in grape berries and wine. For this purpose, wines produced from 15 vintages from the same Shiraz vineyard (The Old Block, Mount Langi Ghiran, Victoria, Australia were analysed for rotundone concentration and compared to comprehensive weather data and minimal temperature information. Degree hours were obtained by interpolating available temperature information from the vineyard site using a simple piecewise cubic hermite interpolating polynomial method (PCHIP. Results showed that the highest concentrations of rotundone were consistently found in wines from cool and wet seasons. The Principal Component Analysis (PCA showed that the concentration of rotundone in wine was negatively correlated with daily solar exposure and grape bunch zone temperature, and positively correlated with vineyard water balance. Finally, models were constructed based on the Gompertz function to describe the dynamics of rotundone concentration in berries through the ripening process according to phenological and thermal times. This characterisation is an important step forward to potentially predict the final quality of the resultant wines based on the evolution of specific compounds in berries according to critical environmental and micrometeorological variables. The modelling techniques described in this paper were able to describe the behaviour of rotundone concentration based on seasonal weather conditions and grapevine phenological stages, and could be potentially used to predict the final rotundone concentration early in future growing seasons. This could enable the adoption of precision irrigation and

  9. PARTICULATE MATTER CONCENTRATION AND EMISSION FACTOR IN THREE DIFFERENT LAYING HEN HOUSING SYSTEMS

    Directory of Open Access Journals (Sweden)

    Annamaria Costa

    2009-09-01

    Full Text Available The aim of this study was to evaluate PM10 concentration in three different laying hens houses (traditional battery cages with aerated open manure storage, aviary system and vertical tiered cages with manure belts with forced air drying and to evaluate particulate matter emission into atmosphere during one year of observation. Internal and external temperature and relative humidity, ventilation rate, PM10 concentration have been continuously monitored in order to evaluate particulate matter concentration changes during the day and the season and to define PM10 emission factors. PM10 concentration was corrected by gravimetric technique to lower measurements error. In the aviary system house, TSP and fine particulate matter (particles smaller than 2.5 micron concentration was measured. Average yearly PM10 concentration was remarkably higher in the aviary system house with 0.215 mg m-3 vs 108 mg m-3 for the ventilated belt house and vs 0.094 mg m-3 for the traditional battery cages house. In the Aviary system housing, TSP concentration was 0.444 mg m-3 and PM2.5 was 0.032 mg m-3, highlighting the existence of a severe working environment for men and animals. Recorded values for PM10 emission were 0.433 mg h-1 hen-1 for battery cages housing type, 0.081 mg h-1 hen-1 for ventilated belt cages house, values lower than those available in literature, while the aviary system housing type showed the highest PM10 emission (1.230 mg h-1 hen-1 with appreciable peaks during the morning, together with the increased animal activity and daily farmer operations, as feed administration, cleaning and droppings removal.

  10. Environmental Factors and Seasonality Affect the Concentration of Rotundone in Vitis vinifera L. cv. Shiraz Wine

    Science.gov (United States)

    Zhang, Pangzhen; Howell, Kate; Krstic, Mark; Herderich, Markus; Barlow, Edward William R.; Fuentes, Sigfredo

    2015-01-01

    Rotundone is a sesquiterpene that gives grapes and wine a desirable ‘peppery’ aroma. Previous research has reported that growing grapevines in a cool climate is an important factor that drives rotundone accumulation in grape berries and wine. This study used historical data sets to investigate which weather parameters are mostly influencing rotundone concentration in grape berries and wine. For this purpose, wines produced from 15 vintages from the same Shiraz vineyard (The Old Block, Mount Langi Ghiran, Victoria, Australia) were analysed for rotundone concentration and compared to comprehensive weather data and minimal temperature information. Degree hours were obtained by interpolating available temperature information from the vineyard site using a simple piecewise cubic hermite interpolating polynomial method (PCHIP). Results showed that the highest concentrations of rotundone were consistently found in wines from cool and wet seasons. The Principal Component Analysis (PCA) showed that the concentration of rotundone in wine was negatively correlated with daily solar exposure and grape bunch zone temperature, and positively correlated with vineyard water balance. Finally, models were constructed based on the Gompertz function to describe the dynamics of rotundone concentration in berries through the ripening process according to phenological and thermal times. This characterisation is an important step forward to potentially predict the final quality of the resultant wines based on the evolution of specific compounds in berries according to critical environmental and micrometeorological variables. The modelling techniques described in this paper were able to describe the behaviour of rotundone concentration based on seasonal weather conditions and grapevine phenological stages, and could be potentially used to predict the final rotundone concentration early in future growing seasons. This could enable the adoption of precision irrigation and canopy

  11. Aerosol surface area concentration: a governing factor in new particle formation in Beijing

    Directory of Open Access Journals (Sweden)

    R. Cai

    2017-10-01

    Full Text Available The predominating role of aerosol Fuchs surface area, AFuchs, in determining the occurrence of new particle formation (NPF events in Beijing was elucidated in this study. The analysis was based on a field campaign from 12 March to 6 April 2016 in Beijing, during which aerosol size distributions down to  ∼  1 nm and sulfuric acid concentrations were simultaneously monitored. The 26 days were classified into 11 typical NPF days, 2 undefined days, and 13 non-event days. A dimensionless factor, LΓ, characterized by the relative ratio of the coagulation scavenging rate over the condensational growth rate (Kuang et al., 2010, was applied in this work to reveal the governing factors for NPF events in Beijing. The three parameters determining LΓ are sulfuric acid concentration, the growth enhancement factor characterized by contribution of other gaseous precursors to particle growth, Γ, and AFuchs. Different from other atmospheric environments, such as in Boulder and Hyytiälä, the daily-maximum sulfuric acid concentration and Γ in Beijing varied in a narrow range with geometric standard deviations of 1.40 and 1.31, respectively. A positive correlation between the estimated new particle formation rate, J1.5, and sulfuric acid concentration was found with a mean fitted exponent of 2.4. However, the maximum sulfuric acid concentrations on NPF days were not significantly higher (even lower, sometimes than those on non-event days, indicating that the abundance of sulfuric acid in Beijing was high enough to initiate nucleation, but may not necessarily lead to NPF events. Instead, AFuchs in Beijing varied greatly among days with a geometric standard deviation of 2.56, whereas the variabilities of AFuchs in Tecamac, Atlanta, and Boulder were reported to be much smaller. In addition, there was a good correlation between AFuchs and LΓ in Beijing (R2 = 0.88. Therefore, it was AFuchs that fundamentally determined the occurrence of NPF events

  12. Factors affecting Escherichia coli concentrations at Lake Erie public bathing beaches

    Science.gov (United States)

    Francy, Donna S.; Darner, Robert A.

    1998-01-01

    The environmental and water-quality factors that affect concentrations of Escherichia coli (E. coli) in water and sediment were investigated at three public bathing beachesEdgewater Park, Villa Angela, and Sims Parkin the Cleveland, Ohio metropolitan area. This study was done to aid in the determination of safe recreational use and to help water- resource managers assess more quickly and accurately the degradation of recreational water quality. Water and lake-bottom sediments were collected and ancillary environmental data were compiled for 41 days from May through September 1997. Water samples were analyzed for E. coli concentrations, suspended sediment concentrations, and turbidity. Lake- bottom sediment samples from the beach area were analyzed for E. coli concentrations and percent dry weight. Concentrations of E. coli were higher and more variable at Sims Park than at Villa Angela or Edgewater Park; concentrations were lowest at Edgewater Park. Time-series plots showed that short-term storage (less than one week) of E. coli in lake-bottom sediments may have occurred, although no evidence for long-term storage was found during the sampling period. E. coli concentrations in water were found to increase with increasing wave height, but the resuspension of E. coli from lake-bottom sediments by wave action could not be adequately assessed; higherwave heights were often associated with the discharge of sewage containing E. coli during or after a rainfall and wastewater-treatment plant overflow. Multiple linear regression (MLR) was used to develop models to predict recreational water quality at the in water. The related variables included turbidity, antecedent rainfall, antecedent weighted rainfall, volumes of wastewater-treatment plant overflows and metered outfalls (composed of storm-water runoff and combined-sewer overflows), a resuspension index, and wave heights. For the beaches in this study, wind speed, wind direction, water temperature, and the prswimmers

  13. Decreased plasma concentrations of brain-derived neurotrophic factor (BDNF) in patients with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Podfigurna-Stopa, Agnieszka; Casarosa, Elena; Luisi, Michele; Czyzyk, Adam; Meczekalski, Blazej; Genazzani, Andrea Riccardo

    2013-09-01

    Functional hypothalamic amenorrhea (FHA) is a non organic, secondary amenorrhea related to gonadotropin-releasing hormone pulsatile secretion impairment. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays an important role in the growth, development, maintenance and function of several neuronal systems. The aim of the study was the evaluation of plasma BDNF concentrations in patients with the diagnosis of FHA. We studied 85 subjects diagnosed with FHA who were compared with 10 healthy, eumenorrheic controls with normal body mass index. Plasma BDNF and serum luteinizing hormone, follicle-stimulating hormone and estradiol (E2) concentrations were measured by immunoenzymatic method (enzyme-linked immunosorbent assay). Significantly lower concentration of plasma BDNF was found in FHA patients (196.31 ± 35.26 pg/ml) in comparison to healthy controls (407.20 ± 25.71 pg/ml; p < 0.0001). In the control group, there was a strong positive correlation between plasma BDNF and serum E2 concentrations (r = 0.92, p = 0.0001) but in FHA group it was not found. Role of BDNF in FHA is not yet fully understood. There could be found studies concerning plasma BDNF concentrations in humans and animals in the literature. However, our study is one of the first projects which describes decreased plasma BDNF concentration in patients with diagnosed FHA. Therefore, further studies on BDNF in FHA should clarify the role of this peptide.

  14. Factors Effecting the Total Volatile Organic Compound (TVOC Concentrations in Slovak Households

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    Ľudmila Mečiarová

    2017-11-01

    Full Text Available Thirty five Slovak households were selected for an investigation of indoor environmental quality. Measuring of indoor air physical and chemical factors and a questionnaire survey was performed during May 2017. The range of permissible operative temperature was not met in 11% of objects. Relative humidity met the legislative requirements in all monitored homes. Concentrations of total volatile organic compounds (TVOCs were significantly higher in the apartments than in the family houses. The average TVOC levels in the apartments and family houses were 519.7 µg/m3 and 330.2 µg/m3, respectively. Statistical analysis confirmed the effect of indoor air temperature, relative humidity and particulate matter (PM0.5 and PM1 on the levels of TVOCs. Higher TVOC levels were observed also in homes where it is not a common practice to open windows during cleaning activities. Other factors that had a statistically significant effect on concentrations of volatile organic compounds were heating type, attached garage, location of the apartment within residential building (the floor, as well as number of occupants. Higher TVOC concentrations were observed in indoor than outdoor environment, while further analysis showed the significant impact of indoor emission sources on the level of these compounds in buildings. The questionnaire study showed a discrepancy between objective measurement and subjective assessment in the household environment, and pointed to insufficient public awareness about volatile organic compounds (VOCs.

  15. Variations in the concentration factor of $sup 60$Co in the mussel, Mytilus edulis L

    Energy Technology Data Exchange (ETDEWEB)

    Amiard, J.C.; Le Lannou, M.

    1972-11-01

    From twenty-third meeting of the International Commission for Scientific Exploitation of the Mediterranean Sea; Athens, Greece 13 Nov 1972). Mussels, collected at various times during the year, were placed in aquariums operating in closed circuit in a room kept at 14 to 16 deg C. Solutions of /sup 60/Co in HCl were added to the aquariums and the mussels were introduced in the contaminated medium when the radioactivity of the water was stabilized. Under the experimental conditions used the radiocobalt introduced in the cation form evolved toward the anion form. The radioactivity of the flesh and the shells of the mussels was measured separately with the aid of a multichannel analyzer. The results were expressed in concentration factor with respect to the water. An increase of the concentration factor of the meat was noted when the concentration level of the water passed from 1 to 7 mu Ci/l. A lower content was found for the shell than for the meat. (JSR)

  16. Stress concentration factors for an internally pressurized circular vessel containing a radial U-notch

    International Nuclear Information System (INIS)

    Carvalho, E.A. de

    2005-01-01

    This paper evaluates the stress concentration factors for an internally pressurized cylinder containing a radial U-notch along its length. This work studies the cases where the external to internal radius ratio (Ψ) is equal to 1.26, 1.52, 2.00, and 3.00 and the notch radius to internal radius ratio (Φ) is fixed and equal to 0.026. The U-notch depth varies from 0.1 to 0.6 of the wall thickness. Results are also presented for a fixed size semi-circular notch. Hoop stresses at the external wall are presented, showing regions where the stress matches the nominal one and the favourable places to install strain sensors. The finite element method is used to determine the stress concentration factors (K t ) for the above described situations and for a special case where a varying semi-circular notch is present with Ψ=3.00. This notch depth varies from 0.013 to 0.3 of the wall thickness. It is pointed out that even relatively small notches introduce large stress concentrations and disrupt the hoop stress distribution all over the cross section. Results are also compared to an example found in the literature for semi-circular notches and K t curves for both cases present the same shape

  17. Dependence of soil-to-plant transfer factors of elements on their concentrations in soil

    International Nuclear Information System (INIS)

    Tsukada, Hirofumi; Watabe, Teruhisa.

    1996-01-01

    Transfer factors (TFs) of 31 stable elements from soil to plant were determined by neutron activation analysis. Soil and plant samples were collected from 112 farm fields in Aomori prefecture, Japan. The elements described are those that could be detected by this method, which include essential elements for plant growth and nonessential elements. Several of these elements were divided into two groups, each having different TF characteristics. In the first group of elements there was an inverse correlation between the TFs and the soil concentrations of the elements, especially for Cl, K and Ca. The concentrations of these elements in plants were independent of their soil concentrations. However, in the second group, especially Sc and Co, the TFs were independent of the soil concentrations of the elements. The fluctuation of TFs observed in this study was smaller than that previously reported. This may be attributed to the relatively narrow geographic area of the present study. In addition, the TFs for the stable elements in this study were generally one to three orders of magnitude lower than those compiled for radioactive isotopes in previous publications. (author)

  18. Total flavonoid concentrations of bryophytes from Tianmu Mountain, Zhejiang Province (China: Phylogeny and ecological factors.

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    Xin Wang

    Full Text Available The flavonoids in bryophytes may have great significance in phylogeny and metabolism research. However, to date there has been little research on bryophyte metabolites, especially flavonoids. To redress this somewhat, we determined flavonoid concentrations of bryophytes from Tianmu Mountain through a colorimetric assay and considered the factors influencing the results. This is the first time that the flavonoid contents of bryophytes have been examined in detail. The results revealed a range of total flavonoid concentrations in 90 samples collected from Tianmu Mountain from 1.8 to 22.3 mg/g (w/w. The total flavonoid contents of liverworts were generally higher than those of mosses; acrocarpous mosses had generally higher values than that of pleurocarpous mosses. The total flavonoid contents of bryophytes growing at lower light levels were general higher than those growing in full-sun. The total flavonoid contents of epiphytic bryophytes were highest, while those of aquatic bryophytes were the lowest. Total flavonoid contents of species growing at low-latitudes were much higher than those at high-latitude individuals. In conclusion, total flavonoid contents of bryophytes have some connection with plant phylogeny; more flavonoids might be contained in relatively primitive bryophytes. Meanwhile, the effects of ecological factors on total flavonoid contents of bryophytes exist; light and habitat (especially tree habitat and river habitat might be representative factor.

  19. Influence of environmental factors on the concentration of phenolic compounds in leaves of Lafoensia pacari

    Directory of Open Access Journals (Sweden)

    Bruno Leite Sampaio

    2011-09-01

    Full Text Available Lafoensia pacari A. St.-Hil., Lythraceae, a plant from the Cerrado known as pacari or dedaleiro, is widely used as an antipyretic, wound healing, anti-inflammatory, antidiarrheal and in the treatment of gastritis and cancer. Notable among the metabolite groups identified in leaves of L. pacari are the polyphenols, such as tannins and flavonoids, related to the pharmacological activities of pacari. Studies on the influence of environmental factors over production of major groups of secondary metabolites in pacari are important because they contribute data for its cultivation and harvest, and establish quantitative parameters of secondary metabolites in the plant drug. The objective of this study was to evaluate the influence of environmental factors on concentrations of phenolic metabolites in the leaves of L. pacari. Compounds quantified in the leaves were: total phenols, tannins by protein precipitation, hydrolysable tannins, total flavonoids, ellagic acid and mineral nutrients, while soil fertility was also analyzed, all over a period of one year. The data were analyzed using multivariate analysis, and the results suggest that metabolite concentrations in the leaves of this plant are influenced by seasonal factors, in particular the temperature and foliar micronutrients (Cu, Fe, Mn, Zn.

  20. Influence of environmental factors on the concentration of phenolic compounds in leaves of Lafoensia pacari

    Directory of Open Access Journals (Sweden)

    Bruno Leite Sampaio

    2011-12-01

    Full Text Available Lafoensia pacari A. St.-Hil., Lythraceae, a plant from the Cerrado known as pacari or dedaleiro, is widely used as an antipyretic, wound healing, anti-inflammatory, antidiarrheal and in the treatment of gastritis and cancer. Notable among the metabolite groups identified in leaves of L. pacari are the polyphenols, such as tannins and flavonoids, related to the pharmacological activities of pacari. Studies on the influence of environmental factors over production of major groups of secondary metabolites in pacari are important because they contribute data for its cultivation and harvest, and establish quantitative parameters of secondary metabolites in the plant drug. The objective of this study was to evaluate the influence of environmental factors on concentrations of phenolic metabolites in the leaves of L. pacari. Compounds quantified in the leaves were: total phenols, tannins by protein precipitation, hydrolysable tannins, total flavonoids, ellagic acid and mineral nutrients, while soil fertility was also analyzed, all over a period of one year. The data were analyzed using multivariate analysis, and the results suggest that metabolite concentrations in the leaves of this plant are influenced by seasonal factors, in particular the temperature and foliar micronutrients (Cu, Fe, Mn, Zn.

  1. Dissociation between plasma concentrations of thyroxine and insulin-like growth factor-I.

    Science.gov (United States)

    Dauncey, M J; Morovat, A; Rudd, B T; Shakespear, R A

    1990-09-01

    The relation between plasma concentrations of thyroxine (T4) and insulin-like growth factor-I (IGF-I) has been examined in young, growing pigs under controlled conditions of energy intake. Compared with euthyroid controls, plasma levels of IGF-I were significantly elevated (P less than 0.005) both in hypothyroid animals on the same food intake and in hyperthyroid animals on double the food intake. There was however no increase in IGF-I in a hyperthyroid group on the control level of intake. Contrary to previous reports in which energy intake was not controlled, it is concluded that there is no simple correlation between plasma concentrations of T4 and IGF-I.

  2. Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

    DEFF Research Database (Denmark)

    Pedersen, Henrik Duelund; Falk, Bo Torkel; Häggström, Jens

    2005-01-01

    Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations...... has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range...... of asymptomatic MR (median serum IGF-1: 76.7 µg/L; 25-75 percentile, 59.8-104.9 µg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated...

  3. Outcomes Following Three-Factor Inactive Prothrombin Complex Concentrate Versus Recombinant Activated Factor VII Administration During Cardiac Surgery.

    Science.gov (United States)

    Harper, Patrick C; Smith, Mark M; Brinkman, Nathan J; Passe, Melissa A; Schroeder, Darrell R; Said, Sameh M; Nuttall, Gregory A; Oliver, William C; Barbara, David W

    2018-02-01

    To compare outcomes following inactive prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa) administration during cardiac surgery. Retrospective propensity-matched analysis. Academic tertiary-care center. Patients undergoing cardiac surgery requiring cardiopulmonary bypass who received either rFVIIa or the inactive 3-factor PCC. Outcomes following intraoperative administration of rFVIIa (263) or factor IX complex (72) as rescue therapy to treat bleeding. In the 24 hours after surgery, propensity-matched patients receiving PCC versus rFVIIa had significantly less chest tube outputs (median difference -464 mL, 95% confidence interval [CI] -819 mL to -110 mL), fresh frozen plasma transfusion rates (17% v 38%, p = 0.028), and platelet transfusion rates (26% v 49%, p = 0.027). There were no significant differences between propensity-matched groups in postoperative stroke, deep venous thrombosis, pulmonary embolism, myocardial infarction, or intracardiac thrombus. Postoperative dialysis was significantly less likely in patients administered PCC versus rFVIIa following propensity matching (odds ratio = 0.3, 95% CI 0.1-0.7). No significant difference in 30-day mortality in patients receiving PCC versus rFVIIa was present following propensity matching. Use of rFVIIa versus inactive PCCs was significantly associated with renal failure requiring dialysis and increased postoperative bleeding and transfusions. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Subinhibitory concentrations of perilla oil affect the expression of secreted virulence factor genes in Staphylococcus aureus.

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    Jiazhang Qiu

    Full Text Available BACKGROUND: The pathogenicity of staphylococcus aureus is dependent largely upon its ability to secrete a number of virulence factors, therefore, anti-virulence strategy to combat S. aureus-mediated infections is now gaining great interest. It is widely recognized that some plant essential oils could affect the production of staphylococcal exotoxins when used at subinhibitory concentrations. Perilla [Perilla frutescens (L. Britton], a natural medicine found in eastern Asia, is primarily used as both a medicinal and culinary herb. Its essential oil (perilla oil has been previously demonstrated to be active against S. aureus. However, there are no data on the influence of perilla oil on the production of S. aureus exotoxins. METHODOLOGY/PRINCIPAL FINDINGS: A broth microdilution method was used to determine the minimum inhibitory concentrations (MICs of perilla oil against S. aureus strains. Hemolysis, tumour necrosis factor (TNF release, Western blot, and real-time RT-PCR assays were performed to evaluate the effects of subinhibitory concentrations of perilla oil on exotoxins production in S. aureus. The data presented here show that perilla oil dose-dependently decreased the production of α-toxin, enterotoxins A and B (the major staphylococcal enterotoxins, and toxic shock syndrome toxin 1 (TSST-1 in both methicillin-sensitive S. aureus (MSSA and methicillin-resistant S. aureus (MRSA. CONCLUSIONS/SIGNIFICANCE: The production of α-toxin, SEA, SEB, and TSST-1 in S. aureus was decreased by perilla oil. These data suggest that perilla oil may be useful for the treatment of S. aureus infections when used in combination with β-lactam antibiotics, which can increase exotoxins production by S. aureus at subinhibitory concentrations. Furthermore, perilla oil could be rationally applied in food systems as a novel food preservative both to inhibit the growth of S. aureus and to repress the production of exotoxins, particularly staphylococcal enterotoxins.

  5. Synthesis of dispersive iron or iron–silver nanoparticles on engineered capsid pVIII of M13 virus with electronegative terminal peptides

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shuai; Nakano, Kazuhiko; Zhang, Shu-liang; Yu, Hui-min, E-mail: yuhm@tsinghua.edu.cn [Tsinghua University, Key Laboratory of Industrial Biocatalysis of the Ministry of Education, Department of Chemical Engineering (China)

    2015-10-15

    M13 is a filamentous Escherichia coli virus covered with five types of capsid proteins, in which pVIII with ∼2700 copies was around the cylindered surface and pIII with five copies located at one end of the phage particle. The pIII-engineered M13 phages with enhanced binding specificity toward Fe were screened after five rounds of biopanning, and the one containing ATPTVAMSLSPL peptide at pIII-terminus was selected for mediated synthesis of zero valent (ZV) Fe nanoparticles (NPs) with the wild M13 as control. Under a reducing environment, uniformly dispersed ZVFeNPs with diameter of 5–10 nm were both synthesized and the morphologies after annealing were confirmed to be face-centered cubic type. The synthesized FeNPs mediated by the two phages showed no significant difference, revealing that the pVIII capsid did dominant contribution to metal binding in comparison with the pIII. A novel pVIII-engineered M13 containing AAEEEDPAK at terminus, named as 4ED-pVIII-M13, was constructed and it carried one more negatively charged residue than the wild one (AEGDDPAK). Metal adsorption quantification showed that the binding affinity of the 4ED-pVIII-M13 toward Ag and Ni ions improved to 62 and 18 % from original 21 and 6 %, respectively. The binding affinity toward Fe remained constant (∼85 %). ZVFe–Ag bi-NPs were successfully synthesized through mediation of 4ED-pVIII-M13. Particularly, the Fe:Ag ratio in the bi-NPs was conveniently controlled through changing the molar concentration of FeCl{sub 2} and AgNO{sub 3} solution before reduction.

  6. Prophylactic use of factor IX concentrate in a Jehovah's Witness patient.

    Science.gov (United States)

    Bolliger, Daniel; Sreeram, Gautam; Duncan, Alexander; Molinaro, Ross J; Szlam, Fania; Chen, Edward P; Tanaka, Kenichi A

    2009-11-01

    In Jehovah's Witness patients, the use of red blood cells, platelets, and fresh frozen plasma is not optional. Various blood conservation techniques are available, but complex cardiac surgery remains a major challenge. The feasibility of fractions of "primary components" has not been fully considered in published case reports. For Jehovah's Witness patients who preoperatively give consent, factor IX concentrates may be acceptable for hemostatic therapy. We hereby describe a combination of "secondary components" to prevent excessive bleeding in a Jehovah's Witness patient undergoing complex replacement of the aortic arch.

  7. Factoring the brain signatures of anesthesia concentration and level of arousal across individuals.

    Science.gov (United States)

    Barttfeld, Pablo; Bekinschtein, Tristan A; Salles, Alejo; Stamatakis, Emmanuel A; Adapa, Ram; Menon, David K; Sigman, Mariano

    2015-01-01

    Combining resting-state functional magnetic resonance imaging (fMRI) connectivity and behavioral analysis during sedation, we factored out general effects of the anesthetic drug propofol and a specific index of conscious report, participants' level of responsiveness. The factorial analysis shows that increasing concentration of propofol in blood specifically decreases the connectivity strength of fronto-parietal cortical loops. In contrast, loss of responsiveness is indexed by a functional disconnection between the thalamus and the frontal cortex, balanced by an increase in connectivity strength of the thalamus to the occipital and temporal regions of the cortex.

  8. Concentration factors of stable elements and radionuclides in Po river fish

    International Nuclear Information System (INIS)

    Achilli, M.; Ciceri, G.; Bozzani, A.; Guzzi, L.; Queirazza, G.

    1988-01-01

    The concentration factors (CF) of stable Co, Cs, Mn, Fe, Zn and Sr in different fish from six stretches in the middle course of the Po river (N. Italy) have been investigated. The space-time variation in water has been followed for 14 months. The investigation has been undertaken to study CF variations in the same fish species as a function of the physico-chemical form of the different elements in water (dissolved, dissolved and exchangeable fraction of the particulate, total). CF values of 103 Ru, 131 I and 134 - 137 Cs were also investigated for Cyprinus carpio reared, with artificial food, in two semi-natural environments

  9. Sediment Ksub(d)s and concentration factors for radionuclides in the marine environment

    International Nuclear Information System (INIS)

    1985-01-01

    Both the biological and geochemical processes, which are dependent on the chemical form of the element in question, and the radioactive decay of the nuclide are important parameters in the models used for the calculation of dumping limits for radioactive wastes disposed of in the deep sea. The geochemical processes were not adequately represented in earlier models and only rough approximations of parameters were used in the calculations. This report provides an approach for the calculation of deep-sea sediment distribution coefficients and coastal sediment concentration factors for radionuclides in marine biological materials based, whenever possible, on field data

  10. Cystatin C and lactoferrin concentrations in biological fluids as possible prognostic factors in eye tumor development

    Directory of Open Access Journals (Sweden)

    Mariya A. Dikovskaya

    2013-08-01

    Full Text Available Objectives. To investigate the possible role of cystatin C in eye biological fluids locally and in serum and lactoferrin revealing anti-tumor activity in eye tumor development. Background. The increased number of eye tumors was registered recently not only in the countries with high insolation, but also in the northern countries including Russia (11 cases per million of population. Search for new biological markers is important for diagnosis and prognosis in eye tumors. Cystatin C, an endogenous inhibitor of cysteine proteases, plays an important protective role in several tumors. Lactoferrin was shown to express anti-tumor and antiviral activities. It was hypothesized that cystatin C and lactoferrin could serve as possible biomarkers in the diagnosis of malignant and benign eye tumors. Study design. A total of 54 patients with choroidal melanoma and benign eye tumors were examined (part of them undergoing surgical treatment. Serum, tear fluid and intraocular fluid samples obtained from the anterior chamber of eyes in patients with choroidal melanoma were studied. Methods. Cystatin C concentration in serum and eye biological fluids was measured by commercial ELISA kits for human (BioVendor, Czechia; lactoferrin concentration – by Lactoferrin-strip D 4106 ELISA test systems (Vector-BEST, Novosibirsk Region, Russia. Results. Cystatin C concentration in serum of healthy persons was significantly higher as compared to tear and intraocular fluids. In patients with choroidal melanoma, increased cystatin C concentration was similar in tear fluid of both the eyes. Lactoferrin level in tear fluid of healthy persons was significantly higher than its serum level. Significantly increased lactoferrin concentration in tear fluid was noted in patients with benign and malignant eye tumors. Conclusion. Increased level of cystatin C in tear fluid seems to be a possible diagnostic factor in the eye tumors studied. However, it does not allow us to differentiate

  11. Iron and obesity status-associated insulin resistance influence circulating fibroblast-growth factor-23 concentrations.

    Directory of Open Access Journals (Sweden)

    José Manuel Fernández-Real

    Full Text Available Fibroblast growth factor 23 (FGF-23 is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD. Circulating intact FGF-23 (iFGF-23 and C-terminal (CtFGF-23 concentrations (ELISA were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1; and in association with fat mass and bone mineral density (DEXA and atherosclerosis (intima media thickness, IMT in 78 subjects (52 women with a wide range of adiposity (Cohort 2. Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance.

  12. New study on the XeVIII spectrum

    International Nuclear Information System (INIS)

    Gallardo, M.; Raineri, M.; Giuliani, M.; Lagorio, C.; Padilla, S.; Sarmiento, R.; Reyna Almandos, J.G.

    2005-01-01

    Capillary light sources were used to observe the spectrum of seven-times-ionized xenon, XeVIII, in the 300-6000 A wavelength range. Twenty-eight energy levels belonging to the 5s-9s, 5d-9d, 5g-9g, 7i-10i, 9l, 5p-9p, 4f-9f, 6h-9h and 8k-10k configurations were adjusted and 38 new spectral lines were classified. The XeVIII ionization energy was determined with improved accuracy using the polarization model. The analysis was supported by Hartree-Fock calculations. The weighted oscillator strengths for all the observed spectral lines were also calculated considering the fitted values for the energy parameters

  13. Evidence for the formation of sodium hassate(VIII)

    International Nuclear Information System (INIS)

    Zweidorf, A. von; Angert, R.; Bruechle, W.; Buerger, S.; Eberhardt, K.; Eichler, R.; Hummrich, H.; Jaeger, E.; Kling, H.O.; Kratz, J.V.; Kuczewski, B.; Langrock, G.; Mendel, M.; Rieth, U.; Schaedel, M.; Schausten, B.; Schimpf, E.; Thoerle, P.; Trautmann, N.; Tsukada, K.; Wiehl, N.; Wirth, G.

    2004-01-01

    Hassium, element 108, was produced in the fusion reaction between 26 Mg and 248 Cm. The hassium recoils were oxidized in-situ to a highly volatile oxide, presumably HsO 4 , and were transported in a mixture of He and O 2 to a deposition and detection system. The latter consisted of 16 silicon PIN-photodiodes facing a layer of NaOH, which served, in the presence of a certain partial pressure of water in the transport gas, as reactive surface for the deposition of the volatile tetroxides. Six correlated α-decay chains of Hs were detected in the first 5 detectors centred around detection position 3. In analogy to OsO 4 , which forms Na 2 [OsO 4 (OH) 2 ], an osmate(VIII), with aqueous NaOH, HsO 4 presumably was deposited as Na 2 [HsO 4 (OH) 2 ], a hassate(VIII). (orig.)

  14. Henry VIII, McLeod syndrome and Jacquetta's curse.

    Science.gov (United States)

    Stride, P; Lopes Floro, K

    2013-01-01

    The mental decline of King Henry VIII from being a jovial, charismatic and athletic young man into an increasingly paranoid, brutal tyrant in later life, ever more concerned at his lack of one or more male heirs, has attracted many medical diagnostic theories. Previous hypotheses have included diabetes, syphilis and hypothyroidism, among others. However, these inadequately explain Henry's failure to produce a male heir, despite multiple pairings. The latest postulated diagnoses for Henry are the coexistence of both Kell blood group antigenicity (possibly inherited from Jacquetta Woodville, Henry's maternal great grandmother) causing related impaired fertility, and McLeod syndrome, causing psychotic changes. As the mutated McLeod protein of the syndrome significantly reduces the expression, effectively inactivating the Kell antigen, we critically review this theory, examining in detail the pathophysiology of these conditions and assessing the genealogy of Henry VIII and its effect in subsequent generations.

  15. New study on the XeVIII spectrum

    Energy Technology Data Exchange (ETDEWEB)

    Gallardo, M. [Centro de Investigaciones Opticas (CIOp) Casilla de Correo 124, 1900 La Plata (Argentina)]. E-mail: gallardom@ciop.unlp.edu.ar; Raineri, M. [Centro de Investigaciones Opticas (CIOp) Casilla de Correo 124, 1900 La Plata (Argentina)]. E-mail: monicar@ciop.unlp.edu.ar; Giuliani, M. [Dto. de Fisica, Fac. de C. Exactas y Naturales, Universidad Nacional de Mar del Plata Funes 3350 (7600) Mar del Plata (Argentina); Lagorio, C. [Dto. de Fisica, Fac. de C. Exactas y Naturales, Universidad Nacional de Mar del Plata Funes 3350 (7600) Mar del Plata (Argentina); Padilla, S. [Dto. de Fisica, Fac. de C. Exactas y Naturales, Universidad Nacional de Mar del Plata Funes 3350 (7600) Mar del Plata (Argentina); Sarmiento, R. [Dto. De Fisica, Universidad del Atlantico, A.A 1890 Barranquilla (Colombia); Reyna Almandos, J.G. [Centro de Investigaciones Opticas (CIOp) Casilla de Correo 124, 1900 La Plata (Argentina)]. E-mail: jreyna@ciop.unlp.edu.ar

    2005-10-15

    Capillary light sources were used to observe the spectrum of seven-times-ionized xenon, XeVIII, in the 300-6000 A wavelength range. Twenty-eight energy levels belonging to the 5s-9s, 5d-9d, 5g-9g, 7i-10i, 9l, 5p-9p, 4f-9f, 6h-9h and 8k-10k configurations were adjusted and 38 new spectral lines were classified. The XeVIII ionization energy was determined with improved accuracy using the polarization model. The analysis was supported by Hartree-Fock calculations. The weighted oscillator strengths for all the observed spectral lines were also calculated considering the fitted values for the energy parameters.

  16. The spectrum and term system of S VIII

    International Nuclear Information System (INIS)

    Bengtsson, P.; Jupen, C.; Engstroem, L.; Redfors, A.; Westerlind, M.

    1993-01-01

    The spectrum of seven times ionized sulfur, S VIII, has been observed in the wavelength range 50-1200 A. Both beam-foil and laser-produced plasma light sources have been used. 71 new lines representing the transitions 2p 5 -2p 4 3d, 2p 4 3s-3p, 3p-3d, 3d-4f, 4f-5g and 5g-6h have been identified and 100 energy levels, of which 46 are new, are now accurately established. The spectral analysis is supported by isoelectronic comparisons along the F I-sequence and by parametric least-squares fits of Slater integrals to the observed levels. The ionization potential in S VIII is determined to 2 651 899 ± 60 cm -1 and estimated ionization energies are derived for the isoelectronic elements between F I and Ar X. (orig.)

  17. Large-scale production and properties of human plasma-derived activated Factor VII concentrate.

    Science.gov (United States)

    Tomokiyo, K; Yano, H; Imamura, M; Nakano, Y; Nakagaki, T; Ogata, Y; Terano, T; Miyamoto, S; Funatsu, A

    2003-01-01

    An activated Factor VII (FVIIa) concentrate, prepared from human plasma on a large scale, has to date not been available for clinical use for haemophiliacs with antibodies against FVIII and FIX. In the present study, we attempted to establish a large-scale manufacturing process to obtain plasma-derived FVIIa concentrate with high recovery and safety, and to characterize its biochemical and biological properties. FVII was purified from human cryoprecipitate-poor plasma, by a combination of anion exchange and immunoaffinity chromatography, using Ca2+-dependent anti-FVII monoclonal antibody. To activate FVII, a FVII preparation that was nanofiltered using a Bemberg Microporous Membrane-15 nm was partially converted to FVIIa by autoactivation on an anion-exchange resin. The residual FVII in the FVII and FVIIa mixture was completely activated by further incubating the mixture in the presence of Ca2+ for 18 h at 10 degrees C, without any additional activators. For preparation of the FVIIa concentrate, after dialysis of FVIIa against 20 mm citrate, pH 6.9, containing 13 mm glycine and 240 mm NaCl, the FVIIa preparation was supplemented with 2.5% human albumin (which was first pasteurized at 60 degrees C for 10 h) and lyophilized in vials. To inactivate viruses contaminating the FVIIa concentrate, the lyophilized product was further heated at 65 degrees C for 96 h in a water bath. Total recovery of FVII from 15 000 l of plasma was approximately 40%, and the FVII preparation was fully converted to FVIIa with trace amounts of degraded products (FVIIabeta and FVIIagamma). The specific activity of the FVIIa was approximately 40 U/ micro g. Furthermore, virus-spiking tests demonstrated that immunoaffinity chromatography, nanofiltration and dry-heating effectively removed and inactivated the spiked viruses in the FVIIa. These results indicated that the FVIIa concentrate had both high specific activity and safety. We established a large-scale manufacturing process of human plasma

  18. Spatial and temporal variations in concentration factors in NW European seas - secondary use of monitoring data

    Energy Technology Data Exchange (ETDEWEB)

    Kershaw, P.J.; Mcmahon, C.A.; Rudjord, A.L.; Smedley, C.; Nawakowski, C.; Leonard, K.S. [Centre for Environment, Fisheries and Aquaculture Science (CEFAS), Lowestoft (United Kingdom)

    2004-07-01

    This paper presents new data on concentration factors (CFs: concentration kg-1 biota/concentration l-1 seawater) for several marine species-radionuclide pairs, in three regions: coastal waters of Ireland, eastern Irish Sea, coastal waters of Norway. The CFs were estimated using data from long-term monitoring programmes, obtained for radiological protection purposes. The practical constraints of using such data sources are discussed. CFs were obtained for Mytilus edulis (mussels), Nephrops norvegicus (Norway lobster/Dublin Bay prawn/scampi), Pleuronectes platessa (plaice), Cancer pagurus (edible crab), Littorina littoria (winkles) and Fucus vesiculosus, for one or more of the following radionuclides: {sup 99}Tc, {sup 137}Cs, {sup 239,240}Pu and {sup 241}Am. In general, there was a relatively high degree of variability in the values obtained, and it was not possible to discern systematic regional or time-dependent differences. However, for two datasets in the eastern Irish Sea ({sup 137}Cs in winkles and crabs) there was a statistically-significant increase in the CF over the 40 year monitoring period. In several cases the range of values obtained exceeded the range recommended by the IAEA. In 2002, the average {sup 99}Tc CF for F. vesiculosus from the eastern Irish Sea coastline was 26, significantly lower than the IAEA recommended valve (1 x 10{sup 3} - 1 x 10{sup 5}).The results are discussed in relation to the influence of contemporaneous discharges and the possible impact of re-mobilised radionuclides. (author)

  19. Safety of Factor XIII Concentrate: Analysis of More than 20 Years of Pharmacovigilance Data

    Science.gov (United States)

    Solomon, Cristina; Korte, Wolfgang; Fries, Dietmar; Pendrak, Inna; Joch, Christine; Gröner, Albrecht; Birschmann, Ingvild

    2016-01-01

    Background Plasma-derived factor XIII (FXIII) concentrate is an effective treatment for FXIII deficiency. We describe adverse drug reactions (ADRs) reported during pharmacovigilance monitoring of Fibrogammin®/Corifact® and review published safety data. Methods Postmarketing safety reports recorded by CSL Behring from June 1993 to September 2013 were analyzed. Clinical studies published during the same period were also reviewed. Results Commercial data indicated that 1,653,450,333 IU FXIII concentrate were distributed over the review period, equivalent to 1,181,036 doses for a 70 kg patient. 75 cases were reported (one/15,700 standard doses or 22,046,000 IU). Reports of special interest included 12 cases of possible hypersensitivity reactions (one/98,400 doses or 137,787,500 IU), 7 with possible thromboembolic events (one/168,700 doses or 236,207,200 IU), 5 of possible inhibitor development (one/236,200 doses or 330,690,100 IU), and 20 of possible pathogen transmission (one/59,100 doses or 82,672,500 IU). 19 pathogen transmission cases involved viral infection; 4 could not be analyzed due to insufficient data, but for all others a causal relationship to the product was assessed as unlikely. A review of published literature revealed a similar safety profile. Conclusion Assessment of ADRs demonstrated that FXIII concentrate carries a low risk of ADRs across various clinical situations, suggesting a favorable safety profile. PMID:27781024

  20. Influence of lyophilization factors and gelatin concentration on pore structures of atelocollagen/gelatin sponge biomaterial.

    Science.gov (United States)

    Yang, Longqiang; Tanabe, Koji; Miura, Tadashi; Yoshinari, Masao; Takemoto, Shinji; Shintani, Seikou; Kasahara, Masataka

    2017-07-26

    This study aimed to investigate influences of lyophilization factors and gelatin concentration on pore structures of ACG sponge. ACG sponges of different freezing temperatures (-30, -80 and -196 o C), freezing times (1, 2 and 24 h), gelatin concentrations (0.6%AC+0.15%G, 0.6%AC+0.6%G and 0.6%AC+2.4%G), and with 500 μM fluvastatin were fabricated. Pore structures including porosity and pore size were analyzed by scanning electron microscopy and ImageJ. The cytotoxic effects of ACG sponges were evaluated in vitro. Freezing temperature did not affect porosity while high freezing temperature (-30 o C) increased pore size. The high gelatin concentration group (0.6%AC+2.4%G) had decreased porosity and pore size. Freezing time and 500 μM fluvastatin did not affect pore structures. The cytotoxicity and cell proliferation assays revealed that ACG sponges had no cytotoxic effects on human mesenchymal stromal cell growth and proliferation. These results indicate that ACG sponge may be a good biomaterial scaffold for bone regeneration.

  1. Factors Influencing the Concentration of Certain Liposoluble Components in Cow and Goat Milk: A Review

    Directory of Open Access Journals (Sweden)

    Anamaria COZMA

    2014-09-01

    Full Text Available Milk fat contains a large number of fatty acids (FA and other liposoluble components that exhibit various effects on human health. The present article reviews some of the factors affecting FA, vitamin A and cholesterol concentrations in milk from dairy cow and goat. Milk fat composition is linked to many factors, both intrinsic (animal species, breed, lactation stage and extrinsic (environmental. The effect of animal species on milk fat composition is important, as reflected by higher concentrations of short- and medium-chain FA, vitamin A and cholesterol in goat than in cow milk. In a given ruminant species, the effects linked to breed are significant but limited and they can only be achieved over long periods of time. The lactation stage has an important effect on milk FA composition, mainly linked to body fat mobilisation in early lactation, but it only lasts a few weeks each year. Furthermore, changes in feeding have a marked influence on milk fat composition. Changing the forages in the diet of ruminants, pasture in particular, or supplementing lipids to the diet, represent an efficient mean to modify milk fat composition by decreasing saturated FA and cholesterol, and increasing cis-9,trans-11-CLA and vitamin A. Nutrition therefore constitutes a natural strategy to rapidly modulate milk FA, vitamin A and cholesterol composition, with the overall aim of improving the long-term health of consumers.

  2. Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review

    Science.gov (United States)

    Canestaro, William J.; Austin, Melissa A.; Thummel, Kenneth E.

    2015-01-01

    Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, have proven efficacy in both lowering low-density-lipoprotein levels and preventing major coronary events, making them one of the most commonly prescribed drugs in the United States. Statins exhibit a class-wide side effect of muscle toxicity and weakness, which has led regulators to impose both dosage limitations and a recall. This review focuses on the best-characterized genetic factors associated with increased statin muscle concentrations, including the genes encoding cytochrome P450 enzymes (CYP2D6, CYP3A4, and CYP3A5), a mitochondrial enzyme (GATM), an influx transporter (SLCO1B1), and efflux transporters (ABCB1 and ABCG2). A systematic literature review was conducted to identify relevant research evaluating the significance of genetic variants predictive of altered statin concentrations and subsequent statin-related myopathy. Studies eligible for inclusion must have incorporated genotype information and must have associated it with some measure of myopathy, either creatine kinase levels or self-reported muscle aches and pains. After an initial review, focus was placed on seven genes that were adequately characterized to provide a substantive review: CYP2D6, CYP3A4, CYP3A5, GATM, SLCO1B1, ABCB1, and ABCG2. All statins were included in this review. Among the genetic factors evaluated, statin-related myopathy appears to be most strongly associated with variants in SLCO1B1. PMID:24810685

  3. Factors Affecting Ballability of Mixture Iron Ore Concentrates and Iron Oxide Bearing Wastes in Metallurgical Processing

    Directory of Open Access Journals (Sweden)

    Mfon Udo

    2018-05-01

    Full Text Available Iron oxide bearing wastes (IROBEWAS are produced at every segment of processing stage of sinter, molten iron and steel production. They are hard to handle and in many cases are stockpiled only to be a source of environmental pollution but can be balled into pellets. Pellet of good ballability values are transportable and recyclable as they can withstand stress they will encounter without disintegrating back to dust. But ballability is affected by some factors like the grain sizes of the materials, the moisture and binder contents of the ball mix, wettability of the balled materials and the processing perimeters of the granulator. The objective of this research work is to investigate the factors affecting ballability of mixture of iron ore concentrates and iron oxide bearing wastes (IROBEWAS in metallurgical processing. The parameters under consideration were grain size of materials, the moisture contents, the speed of balling disc, IROBEWAS and Bentonite (Binder contents of the balled mix. This was carried out by balling different volume fractions of mix containing iron oxide concentrate and IROBEWAS using a balling disc and testing the resulting balls for green compressive strength using universal testing machine. It was found that the ballability of the mixture of iron ore concentrate and IROBEWAS increases as grain sizes of the materials reduce but increases as the moisture contents and IROBEWAS content increase up to an optimum value of moisture content in the mix before it starts to reduce. The ballability also increases as the speed of the granulator (Balling disc increases within the limit of this work. It was also observed that there was an increase in ballability with slight increase in bentonite content in the mix.

  4. Caesium concentration factors in wild herbivores and the fox (Vulpes vulpes L.)

    International Nuclear Information System (INIS)

    Lowe, V.P.W.; Horrill, A.D.

    1991-01-01

    A selection of wild animals was sampled in the winter of 1986/87. The sites chosen for sampling were based on information obtained from surveys carried out by The Institute of Terrestrial Ecology in the spring and autumn of 1986. Animals included deer, grouse, hares and rabbits, and foxes which were collected as a top carnivore in the food chain. Variation in concentration of caesium between species from the same area was unpredictable; rabbits never exceeded 200 Bq kg -1 (fresh wt) of 137 Cs in their flesh, even when adjacent to deer forests with over 1000 Bq kg -1 in the venison. The greatest complication arose from areas of peaty uplands where the pre-Chernobyl 137 Cs from weapons-testing was much higher than expected. This pre-Chernobyl contribution amounted to 630 Bq kg -1 in a red grouse from the Pennines, and 650 Bq kg -1 in a roe deer from near the Borders, being c. 60% of the total. Significant differences in concentration factors were found depending on species, food, sex, breeding condition and age. Contrasting the decrease of the two caesium isotopes in roe deer from forestry on peat with those from woodlands on mineral soils, it appeared that after an initial fall in concentration, the only decrease thereafter occurred on the mineral soils. Nowhere were radiocaesium concentrations high enough to cause concern amongst consumers of game and other wild animals, even when levels exceed 3000 Bq kg -1 (fresh wt) as they did in red deer, red grouse and the blue hare. (author)

  5. Vitreous vascular endothelial growth factor concentrations in proliferative diabetic retinopathy versus proliferative vitreoretinopathy.

    Science.gov (United States)

    Citirik, Mehmet; Kabatas, Emrah Utku; Batman, Cosar; Akin, Kadir Okhan; Kabatas, Naciye

    2012-01-01

    To assess vitreous vascular endothelial growth factor (VEGF) concentrations in proliferative diabetic retinopathy (PDR) in comparison to proliferative vitreoretinopathy (PVR). Vitreous samples were collected from 69 eyes of 69 patients with traumatic lens dislocation (n = 10), grade B PVR with rhegmatogenous retinal detachment (n = 13), grade C PVR with rhegmatogenous retinal detachment (n = 14), PDR with vitreous hemorrhage (n = 18), and PDR with vitreous hemorrhage and tractional retinal detachment (n = 14). Vitreous fluid samples were obtained at vitrectomy, and the levels of VEGF were measured by enzyme-linked immunosorbent assay. The mean vitreous level of VEGF was 15.14 ± 5.22 pg/ml in eyes with grade B PVR, 99.15 ± 38.58 pg/ml in eyes with grade C PVR, 4,534.01 ± 1,193.28 pg/ml in eyes with vitreous hemorrhage secondary to PDR, 5,157.29 ± 969.44 pg/ml in eyes with vitreous hemorrhage and tractional retinal detachment secondary to PDR, and 16.19 ± 5.76 pg/ml in eyes of the control group with traumatic lens dislocation. Vitreous VEGF concentrations were significantly higher in the patients with grade C PVR, PDR with vitreous hemorrhage and PDR with vitreous hemorrhage and tractional retinal detachment in comparison to the control patients (p < 0.05). A significant alteration was not observed in patients with grade B PVR (p = 0.55). Vitreous VEGF concentrations are increased in PDR and grade C PVR. The high VEGF concentrations could suggest a possible effect of VEGF on advanced PVR. Copyright © 2011 S. Karger AG, Basel.

  6. Investigation of the factors influencing radiocesium concentrations of fish inhabiting natural aquatic ecosystems

    International Nuclear Information System (INIS)

    Jinks, S.M.

    1975-01-01

    Distributions of radioactive and stable cesium were determined in water, sediment, and biota from eight different aquatic ecosystems between 1971 and 1973. The ecosystems included four lakes, fresh and brackish water regions of the Hudson River estuary, and two coastal marine sites. In the Hudson River estuary, the distribution of radiocesium between suspended and dissolved phases in water was found to be a function of salinity. Mean rates of deposition of suspended radiocesium into bottom sediment are calculated from the temporal changes in concentrations of the media, and observed depth distributions in sediment are semi-quantitatively described. Desorption by salt water is identified as the major mechanism for transport of radiocesium from bottom sediment in the lower estuary, and half-times for removal by this mechanism are estimated to be 1.5 to 2.0 years. Suspended-dissolved distributions of radiocesium in water, and depth distributions in sediment are also presented for lake and marine systems. Accumulation of radiocesium by fish is examined in relation to radiocesium distributions in water, sediment, and other biota, and to the chemical characteristics of each ecosystem. Radiocesium dissolved in water was the primary source to the fish in all ecosystems. Sediment inventories of 137 Cs constituted a secondary source which provided as much as 50 percent of the radiocesium in benthic feeding fish in the Hudson River. Dietary intake of 137 Cs is shown to be inversely related to the potassium concentration in the ambient water, and results in an inverse proportionality between the concentration factor in fish and the potassium concentrations in the different freshwater and estuarine ecosystems

  7. Factors affecting biotic mercury concentrations and biomagnification through lake food webs in the Canadian high Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Lescord, Gretchen L., E-mail: glescord@gmail.com [University of New Brunswick/Canadian Rivers Institute, 100 Tucker Park Rd, Saint John, NB E2L 4A6 (Canada); Kidd, Karen A. [University of New Brunswick/Canadian Rivers Institute, 100 Tucker Park Rd, Saint John, NB E2L 4A6 (Canada); Kirk, Jane L. [Environment Canada, Aquatic Contaminants Research Division, 867 Lakeshore Rd, Burlington, ON L7S 1A1 (Canada); O' Driscoll, Nelson J. [Acadia University, 15 University Ave, Wolfville, NS B4P 2R6 (Canada); Wang, Xiaowa; Muir, Derek C.G. [Environment Canada, Aquatic Contaminants Research Division, 867 Lakeshore Rd, Burlington, ON L7S 1A1 (Canada)

    2015-03-15

    In temperate regions of Canada, mercury (Hg) concentrations in biota and the magnitude of Hg biomagnification through food webs vary between neighboring lakes and are related to water chemistry variables and physical lake features. However, few studies have examined factors affecting the variable Hg concentrations in landlocked Arctic char (Salvelinus alpinus) or the biomagnification of Hg through their food webs. We estimated the food web structure of six high Arctic lakes near Resolute Bay, Nunavut, Canada, using stable carbon (δ{sup 13}C) and nitrogen (δ{sup 15}N) isotopes and measured Hg (total Hg (THg) in char, the only fish species, and methylmercury (MeHg) in chironomids and zooplankton) concentrations in biota collected in 2010 and 2011. Across lakes, δ{sup 13}C showed that benthic carbon (chironomids) was the dominant food source for char. Regression models of log Hg versus δ{sup 15}N (of char and benthic invertebrates) showed positive and significant slopes, indicting Hg biomagnification in all lakes, and higher slopes in some lakes than others. However, no principal components (PC) generated using all water chemistry data and physical characteristics of the lakes predicted the different slopes. The PC dominated by aqueous ions was a negative predictor of MeHg concentrations in chironomids, suggesting that water chemistry affects Hg bioavailability and MeHg concentrations in these lower-trophic-level organisms. Furthermore, regression intercepts were predicted by the PCs dominated by catchment area, aqueous ions, and MeHg. Weaker relationships were also found between THg in small char or MeHg in pelagic invertebrates and the PCs dominated by catchment area, and aqueous nitrate and MeHg. Results from these high Arctic lakes suggest that Hg biomagnification differs between systems and that their physical and chemical characteristics affect Hg concentrations in lower-trophic-level biota. - Highlights: • Mercury (Hg) in Arctic char and invertebrates

  8. Is a high serum copper concentration a risk factor for implantation failure?

    Science.gov (United States)

    Matsubayashi, Hidehiko; Kitaya, Kotaro; Yamaguchi, Kohei; Nishiyama, Rie; Takaya, Yukiko; Ishikawa, Tomomoto

    2017-08-10

    .88, respectively. Our single-center retrospective study suggests that high serum copper concentrations (high Cu/Zn ratio) are a risk factor for implantation failure.

  9. MILK WITH INCREASED CONCENTRATION OF MELATONIN PACKAGING FACTORS ON CONSUMER PURCHASE INTENTION

    Directory of Open Access Journals (Sweden)

    Maria Patricia Milagres

    2014-02-01

    Full Text Available The conjoint analysis of factors was used employed to develop a label for the packaging of milk with increased concentration of melatonin. Three factors were selected with three or two levels for the assembly of packaging: packaging design (“blue design with stars and pouring milk”, “white without drawing” and “blue stars with and without drawing”, name (“milk night “and” melatonin “ and informative text about getting natural melatonin by night milking, and the benefits of this compound (“with” and “without”. Twelve packaging designs were created based on a complete factorial arrangement. The designs were presented to 144 consumers who were asked to assess purchase intent of each package. For the joint analysis of factors, the ideal product or more likely to purchase for the most consumers would be blue with stars and packaging design of milk pouring, named milk night and in the presence of informational text, demonstrating that consumers like a package that brings the product and that contains information described. Therefore, the packaging has a major influence on consumer choice and can contribute positively or negatively to the acceptance of food.

  10. PM4 crystalline silica emission factors and ambient concentrations at aggregate-producing sources in California.

    Science.gov (United States)

    Richards, John R; Brozell, Todd T; Rea, Charles; Boraston, Geoff; Hayden, John

    2009-11-01

    The California Construction and Industrial Minerals Association and the National Stone, Sand, & Gravel Association have sponsored tests at three sand and gravel plants in California to compile crystalline silica emission factors for particulate matter (PM) of aerodynamic diameter of 4 microm or less (PM4) and ambient concentration data. This information is needed by industrial facilities to evaluate compliance with the Chronic Reference Exposure Level (REL) for ambient crystalline silica adopted in 2005 by the California Office of Environmental Health Hazard Assessment. The REL applies to PM4 respirable PM. Air Control Techniques, P.C. sampled for PM4 crystalline silica using a conventional sampler for PM of aerodynamic diameter of 2.5 microm or less (PM2.5), which met the requirements of 40 Code of Federal Regulations Part 50, Appendix L. The sample flow rate was adjusted to modify the 50% cut size to 4 microm instead of 2.5 microm. The filter was also changed to allow for crystalline silica analyses using National Institute for Occupational Safety and Health (NIOSH) Method 7500. The particle size-capture efficiency curve for the modified Appendix L instrument closely matched the performance curve of NIOSH Method 0600 for PM4 crystalline silica and provided a minimum detection limit well below the levels attainable with NIOSH Method 0600. The results of the tests indicate that PM4 crystalline silica emissions range from 0.000006 to 0.000110 lb/t for screening operations, tertiary crushers, and conveyor transfer points. The PM4 crystalline silica emission factors were proportional to the crystalline silica content of the material handled in the process equipment. Measured ambient concentrations ranged from 0 (below detectable limit) to 2.8 microg/m3. All values measured above 2 microg/m3 were at locations upwind of the facilities being tested. The ambient PM4 crystalline silica concentrations measured during this study were below the California REL of 3 microg/m3

  11. Ehlers-Danlos Syndrome Type VIII: A Rare Cause of Leg Ulcers in Young Patients

    Directory of Open Access Journals (Sweden)

    Sophie Ronceray

    2013-01-01

    Full Text Available Ehlers-Danlos syndrome type VIII (EDS-VIII is a very rare autosomal dominant disease characterized by early-onset periodontitis associated with features of Ehlers-Danlos syndrome. We report a 32-year-old man whose chronic leg ulcer led to the diagnosis of EDS-VIII. He had severe periodontitis with complete loss of permanent teeth and skin fragility with thin skin, atrophic scars, and brownish atrophic pretibial plaques. Leg ulcer is not a prominent feature of EDS-VIII. We suggest adding EDS-VIII to the list of rare diseases accounting for chronic leg ulcers, if this case report prompts others to report leg ulcers associated with EDS-VIII.

  12. Factors controlling temporal variability of near-ground atmospheric 222Rn concentration over central Europe

    Science.gov (United States)

    Zimnoch, M.; Wach, P.; Chmura, L.; Gorczyca, Z.; Rozanski, K.; Godlowska, J.; Mazur, J.; Kozak, K.; Jeričević, A.

    2014-09-01

    Concentration of radon (222Rn) in the near-ground atmosphere has been measured quasi-continuously from January 2005 to December 2009 at two continental sites in Europe: Heidelberg (south-west Germany) and Krakow (southern Poland). The atmosphere was sampled at ca. 30 and 20 m above the local ground. Both stations were equipped with identical instruments. Regular observations of 222Rn were supplemented by measurements of surface fluxes of this gas in the Krakow urban area, using two different approaches. The measured concentrations of 222Rn varied at both sites in a wide range, from less than 2.0 Bq m-3 to approximately 40 Bq m-3 in Krakow and 35 Bq m-3 in Heidelberg. The mean 222Rn content in Krakow, when averaged over the entire observation period, was 30% higher than in Heidelberg (5.86 ± 0.09 and 4.50 ± 0.07 Bq m-3, respectively). Distinct seasonality of 222Rn signal is visible in the obtained time series of 222Rn concentration, with higher values recorded generally during late summer and autumn. The surface 222Rn fluxes measured in Krakow also revealed a distinct seasonality, with broad maximum observed during summer and early autumn and minimum during the winter. When averaged over a 5-year observation period, the night-time surface 222Rn flux was equal to 46.8 ± 2.4 Bq m-2 h-1. Although the atmospheric 222Rn levels at Heidelberg and Krakow appeared to be controlled primarily by local factors, it was possible to evaluate the "continental effect" in atmospheric 222Rn content between both sites, related to gradual build-up of 222Rn concentration in the air masses travelling between Heidelberg and Krakow. The mean value of this build-up was equal to 0.78 ± 0.12 Bq m-3. The measured minimum 222Rn concentrations at both sites and the difference between them was interpreted in the framework of a simple box model coupled with HYSPLIT (Hybrid Single Particle Lagrangian Integrated Trajectory) analysis of air mass trajectories. The best fit of experimental data was

  13. Comparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers

    NARCIS (Netherlands)

    Levi, M. [=Marcel M.; Moore, K. T.; Castillejos, C. F.; Kubitza, D.; Berkowitz, S. D.; Goldhaber, S. Z.; Raghoebar, M.; Patel, M. R.; Weitz, J. I.; Levy, J. H.

    2014-01-01

    Four-factor prothrombin complex concentrates (PCCs), which contain factor II, FVII, FIX, and FX, have shown the potential to reverse the anticoagulant effect of rivaroxaban in healthy volunteers. The purpose of this study was to determine whether a three-factor PCC, which contains little FVII, has a

  14. Variability of in vivo recovery of factor IX after infusion of monoclonal antibody purified factor IX concentrates in patients with hemophilia B. The Mononine Study Group.

    Science.gov (United States)

    White, G C; Shapiro, A D; Kurczynski, E M; Kim, H C; Bergman, G E

    1995-05-01

    Monoclonal antibody purified factor IX concentrate, Mononine (Armour Pharmaceutical Company, Kankakee, Illinois, USA), is a recently developed replacement factor concentrate for the treatment of patients with hemophilia B. The pharmacokinetic properties of monoclonal antibody purified factor IX concentrate (MAb Factor IX concentrate) have been evaluated in only small samples of patients, and little is known about those factors that might influenced in vivo recovery of factor IX after infusion is a larger patient population. In vivo recovery of factor IX was therefore evaluated for 80 different indications in 72 patients who received MAb Factor IX concentrate for the management of spontaneous or trauma-induced bleeding, or as prophylaxis with surgery. The average recovery after infusions for presurgical pharmacokinetic analysis (mean +/- standard deviation) was 1.28 +/- 0.56 U/dl rise per U/kg infused (range 0.41-2.80), and the average recovery after all infusions for treatment was 1.23 +/- 0.49 U/dl rise per U/kg infused (range - 0.35-2.92). Recovery values for multiple MAb Factor IX doses in a given patient were also variable; the average recovery was 1.22 +/- 0.53 U/dl rise per U/kg given, and standard deviations ranged from 0.03 to 1.26. Patient age, weight, and MAb Factor IX concentrate dose minimally but significantly influenced factor IX recovery. There was no significant effect of either race, history of previous thrombotic complications during treatment with other replacement factor concentrates, or bleeding state on recovery. All of the patients treated with this preparation experienced excellent hemostasis, and no thrombotic complications were observed.

  15. Stress Concentration Factor of Expanded Aluminum Tubes Using Finite Element Modeling

    Directory of Open Access Journals (Sweden)

    L Mhamdi

    2013-06-01

    Full Text Available This paper discusses the development of semi-empirical relations for the maximum stress concentration factor (SCF around circular holes embedded in aluminum tubes under various expansion ratios and mandrel angles. Finite element models were developed to study the expansion of a typical aluminum tube with embedded holes of various sizes. An elastic perfectly-plastic material behaviour was used to describe the structural response of the tubes under expansion. Various hole-diameter-to-tubewall- thickness ratios, tube expansion ratios, and mandrel angles were considered to determine the stress state around the hole at zero and 90 degree locations from which the maximum SCF was determined. Semi-empirical relations for the maximum SCF using the Lagrange interpolation formulation were developed. The developed relations were found to predict the SCFs accurately.

  16. Concentration factors for 137Cs in Japanese coastal fish (1984-1990)

    International Nuclear Information System (INIS)

    Tateda, Yutaka; Koyanagi, Taku.

    1996-01-01

    Concentration factors (CFs; Bq kg -1 wet in fish muscle/Bq kg -1 in filtered seawater) for 137 Cs were determined in Japanese coastal fish collected from 1984 to 1990. 137 Cs/Cs (stable) atom ratios were also examined to clarify the distribution equilibrium of 137 Cs-between marine fish and seawater. The geometric mean of CF in Japanese coastal fish was 52±4 (standard error of the mean), with values ranging from 14 to 133. 137 Cs/Cs atom ratios both in marine fish and seawater indicate that the distribution of 137 Cs was in equilibrium between fish muscle and seawater. Therefore, CF values obtained in the present study can be regarded as equilibrated. Our results show that the CFs for 137 Cs in Japanese coastal fish were within the range of Japanese guidelines, but were below the recommended IAEA value. (author)

  17. 40 CFR Appendix Viii to Part 600 - Fuel Economy Label Formats

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Fuel Economy Label Formats VIII... POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Pt. 600, App. VIII Appendix VIII to Part 600—Fuel Economy Label Formats EC01MY92.117 EC01MY92.118 EC01MY92.119 EC01MY92.120...

  18. Controlling Factors of Mercury Wet Deposition and Precipitation Concentrations in Upstate New York

    Science.gov (United States)

    Ye, Z.; Mao, H.; Driscoll, C. T.

    2017-12-01

    Observations from the Mercury Deposition Network (MDN) at Huntington Wildlife Forest (HWF) suggested that a significant decline in Hg concentrations in precipitation was linked to Hg emission decreases in the United States, especially in the Northeast and Midwest, and yet Hg wet deposition has remained fairly constant over the past two decades. The present study was aimed to investigate how climatic, terrestrial, and anthropogenic factors had influenced the Hg wet deposition flux in upstate New York (NY). To achieve this, an improved Community Multiscale Air Quality (CMAQ) model was employed, which included state-of-the-art Hg and halogen chemistry mechanisms. A base simulation and five sensitivity simulations were conducted. The base simulation used 2010 meteorology, U.S. EPA NEI 2011, and GEOS-Chem output as initial and boundary conditions (ICs and BCs). The five sensitivity runs each changed one condition at the time as follows: 1-3) 2004, 2005, and 2007 meteorology instead of 2010, 4) NEI 2005 Hg anthropogenic emission out of NYS instead of NEI 2011, and 5) no in-state Hg anthropogenic emission. The study period of all the simulations was March - November 2010, and the domain covered the northeastern United States at 12 km resolution. As a result, compared with rural areas in NYS, Hg wet deposition and ambient Hg concentrations in urban areas were affected more significantly by in-state anthropogenic Hg emission. The in-state anthropogenic Hg emissions contributed up to 20% of Hg wet deposition at urban sites and cloud height, precipitation, wind speed and direction, and relative humidity, among which precipitation had the largest effects in most areas. Diluting effects were found in non-convective precipitation, which contributed 31-48% to changes in Hg concentration in precipitation.

  19. Nerve growth factor concentration and implications in photorefractive keratectomy vs laser in situ keratomileusis.

    Science.gov (United States)

    Lee, Hyung Keun; Lee, Kyung Sub; Kim, Hyeon Chang; Lee, Sung Ho; Kim, Eung Kweon

    2005-06-01

    To determine whether tear nerve growth factor (NGF) concentration correlates with corneal sensation and ocular surface dryness after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). Prospective, nonrandomized comparative clinical trial. Seventy eyes of 35 patients and 76 eyes of 38 patients underwent PRK and LASIK procedures to correct myopia and myopic astigmatism, respectively. Total tear protein level, tear NGF concentration, tear film breakup time (BUT) and Schirmer values were measured before and 1 day, 1 week, 1 month, 3 months, and 6 months after surgery. The postoperative mean tear NGF/total tear protein (NGF/tP) ratio increased in both PRK and LASIK patients compared with preoperative levels (P PRK than in LASIK subjects (P LASIK in the ablated zone was lower than the preoperative sensation (P PRK subjects. Mean BUT and Schirmer values were significantly lower in LASIK-treated eyes compared with PRK-treated eyes up to 6 months postoperatively (P PRK-treated and LASIK-treated eyes might be related to the difference in the early postoperative levels of NGF, which is a potent nerve growth stimulator.

  20. Thermoelectrical properties of the compounds ScM{sup VIII}Sb and YM{sup VIII}Sb (M{sup VIII} = Ni, Pd, Pt)

    Energy Technology Data Exchange (ETDEWEB)

    Oestreich, J; Probst, U; Richardt, F; Bucher, E [University of Konstanz, PO Box X916, D-78457 Konstanz (Germany)

    2003-02-05

    The research into new materials with good thermoelectric properties has revealed new compounds consisting of metallic elements (Bando Y, Suemitsu T, Takagi K, Tokushima H, Echizen Y, Katoh K, Umeo K, Maeda Y and Takabatake T 2000 J. Alloys Compounds 313 1-6, Ghelani N, Loo S, Chung D, Sportouch S, Nardi S, Kanatzidis M, Hogan T and Nolas G 2000 Mater. Res. Soc. 626 Z8.6.1). The half-Heusler compound ZrNiSn, in particular, shows promising thermoelectric properties and has been studied by many scientists during recent years (Uher C, Hu S, Yang J, Meisner G P and Morelli D T 1997 Proc. ICT'97: 16th Int. Conf. on Thermoelectrics pp 485-8, Romaka L P, Stadnyk Yu V, Goryn A M, Gorelenko Yu K and Skolozdra R V 1997 Proc. ICT'97: 16th Int. Conf. on Thermoelectrics pp 516-19, Hohl H, Ramirez A P, Goldmann C, Ernst G, Woelfing B and Bucher E 1998 J. Phys.: Condens. Matter 11 1697-709, Oestreich J, Kaefer W, Richardt F, Probst U and Bucher E 1999 Proc. 5th European Workshop on Thermoelectrics pp 192-5). In an effort to find new thermoelectric materials, the half-Heusler compounds of the groups ScM{sup VIII}Sb and YM{sup VIII}Sb (M{sup VIII} = Ni, Pd, Pt) were synthesized by arc melting and the thermoelectric properties were examined by standard characterization methods. Doping experiments showed that it is possible to change the electrical properties of the compounds while retaining the half-Heusler structure. Within the two groups, YPtSb showed the best thermoelectrical properties. At a temperature of 400 K the electrical conductivity of YPtSb is 748{omega}{sup -1} cm{sup -1} and the Seebeck coefficient is 116.3{mu}V K{sup -1}. The thermal conductivity at 400 K extrapolated using the Wiedemann-Franz law is 2.87 W K{sup -1} m{sup -1}. This leads to a dimensionless figure of merit of 0.14.

  1. Plasma triacylglycerol and coagulation factor concentrations predict the anticoagulant effect of dietary fish oil in overweight subjects

    DEFF Research Database (Denmark)

    Vanschoonbeek, Kristof; Feijge, Marion A H; Saris, Wim H M

    2007-01-01

    fish-oil effects. In study 1, 54 overweight subjects consumed 3.1 g (n-3) PUFA daily. In study 2, which involved 42 overweight patients with type 2 diabetes, 20 subjects consumed (n-3) PUFA, whereas 22 others ingested a preparation rich in (n-6) PUFA. Tissue factor-induced thrombin generation (thrombin...... potential) was determined as an integrated measure of plasma coagulant activity. In both studies, multivariate analysis indicated a strong clustering of fasting concentrations of triacylglycerols, prothrombin, factor V, factor VII, and factor X with one another at baseline. This cluster of factors......-induced lowering of triacylglycerol and coagulation factor V, VII, and X concentrations, and thrombin generation. We conclude that high fasting triacylglycerol concentrations predict high procoagulant activity and a lowering of thrombin potential with dietary fish oil....

  2. Updating Environmental Media Concentration Limits and Uncertainty factors in the ERICA Tool

    Energy Technology Data Exchange (ETDEWEB)

    Brown, J.E.; Hosseini, A. [Norwegian Radiation Protection Authority, P.O. Box 55, N-1332 Oesteraas (Norway); Alfonso, B.; Avila, R. [Facilia AB, S-167 51 Bromma (Sweden); Beresford, N.A. [Centre for Ecology and Hydrology, CEH-Lancaster, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA 1 4AP (United Kingdom); Copplestone, D. [Dept. Biological and Environmental Sciences, University of Stirling, Stirling, FK9 4LA (United Kingdom)

    2014-07-01

    Tiered approaches have become a standard means of structuring information in the process of conducting environmental risk assessments. For cases involving the assessment of impacts on wildlife from ionising radiation, the ERICA integrated approach and its supporting software (The ERICA Tool) provides such a structure, splitting the system into two generic screening tiers and a third site-specific tier. The first Tier is very simple, based around Environmental Media Concentration Limits, EMCLs, and requires minimal input from the assessor. The second Tier, although still a screening tier, calculates dose rates and requires more detailed input from the assessor allowing for scrutiny and editing of default parameters in the process. A key element of Tier 2 involves the application of Uncertainty Factors, UFs. Such factors reflect our knowledge concerning probability distribution functions and provide a way of incorporating conservatism into the assessment by considering high percentile values in underlying parameters. Following its launch in 2007, there have been significant developments regarding certain components of the ERICA integrated approach. Most notably, an extended international collation of concentration ratio data has precipitated the need to update parameter values in the Tools databases. In addition, more considered guidance has been developed with regards to filling knowledge gaps in the absence of transfer data. Furthermore, the efficacy of the methods used in assigning probability distribution functions has been questioned leading to an acknowledgement from the developers that the methods were not described in enough detail nor were the justifications for applying the selected approach provided in a convincing way. This has implications for the EMCL values which are derived probabilistically using parameters including concentration ratios. Furthermore, there are implications for UF derivation that relies upon a robust consideration of underlying

  3. Correlation of maternal factors and hemoglobin concentration during pregnancy Shiraz 2006

    Directory of Open Access Journals (Sweden)

    Marzieh Akbarzadeh

    2009-12-01

    Full Text Available Background: Anemia in pregnancy is a serious condition, contributing to maternal mortality, morbidity and fetal morbidity and its prevalence varies between 35-100% in developing countries. This investigation is conducted to survey the correlation of maternal factors and the changes in hemoglobin in pregnant women. Method: In this study, 108 healthy pregnant women with gestational age of 10 to 14 weeks, chosen by cluster random sampling were included. The women were followed in three visits: at the end of the first, second and third trimester. In addition, correlation of Hb concentration with maternal factors including BMI, age parity, hyperemesis, gestational age, pregnancy interval and weight gain was investigated. Results: There was no significant correlation between BMI, parity, pregnancy interval, severe nausea and vomiting and also maternal age with hemoglobin level during pregnancy. Moreover, Multiple regression models showed that adequate maternal weight gain (P<0.009 and high hemoglobin (p<0.0001 in the first trimester were positive predictors and late iron supplementation was negative predictor of hemoglobin in pregnancy (P<0.006. Conclusion: Our data demonstrated that adequate maternal weight gain, high hemoglobin in the first trimester and also late iron supplementation could be as predictors in clinical settings in this query.

  4. Factors Related to Blood Hydroxychloroquine Concentration in Patients With Systemic Lupus Erythematosus.

    Science.gov (United States)

    Yeon Lee, Ji; Lee, Jennifer; Ki Kwok, Seung; Hyeon Ju, Ji; Su Park, Kyung; Park, Sung-Hwan

    2017-04-01

    To identify factors associated with blood concentrations of hydroxychloroquine (HCQ) and its major metabolite, N-desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE; lupus) receiving long-term oral HCQ treatment. SLE patients who had been taking HCQ for more than 3 months were recruited. Various clinical characteristics, laboratory values, and SLE Disease Activity Index (SLEDAI) scores were examined. The concentrations of HCQ and DHCQ ([HCQ] and [DHCQ]) were measured by liquid chromatography mass spectrometry, and the relationship between [HCQ], [DHCQ], and [HCQ]:[DHCQ] ratio to various factors was investigated. In total, 189 SLE patients receiving long-term HCQ treatment were included in the analysis. The median (interquartile range [IQR]) [HCQ] was 515 (IQR 353-720) ng/ml, the median [DHCQ] was 417 (IQR 266-591) ng/ml, and the median [HCQ]:[DHCQ] ratio was 1.3 (range 1.0-1.7). [HCQ] was closely associated with [DHCQ] (r = 0.81, P < 0.0001). The weight-adjusted oral HCQ dose was strongly associated with both [HCQ] (P < 0.001) and [DHCQ] (P < 0.001). Time since last dose was associated with [HCQ] (P < 0.001). No statistically significant association was found between renal function or smoking and [HCQ] or [DHCQ]. Use of additional immunosuppressants increased both [HCQ] and [DHCQ] after adjusting for possible confounders (P = 0.04 and P = 0.03, respectively). The lower SLEDAI score was significantly related to higher [HCQ], after adjusting for age, sex, weight-adjusted HCQ dose, time since last dose, number of other immunosuppressants, and smoking status (P = 0.007). Various factors affected blood levels of [HCQ], [DHCQ], or the [HCQ]:[DHCQ] ratio of SLE patients receiving long-term oral HCQ treatment. Notably, higher [HCQ] was associated with a lower SLEDAI score in our typical outpatient clinic population with lupus. © 2016, American College of Rheumatology.

  5. Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia.

    Science.gov (United States)

    McCall-Hosenfeld, Jennifer S; Goldenberg, Don L; Hurwitz, Shelley; Adler, Gail K

    2003-04-01

    To determine activity of the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis in women with fibromyalgia (FM). Premenopausal women with FM (n = 24) and premenopausal healthy women (n = 27) were studied. IGF-1 was measured in 23 patients with FM and 25 controls. GH was measured during a stepped hypoglycemic hyperinsulinemic clamp procedure (blood glucose decreased from 90 to 40 mg/dl every 30 min in 10 mg/dl decrements) in 12 FM and 13 control subjects. IGF-1 concentrations were similar in the FM (200 +/- 71 ng/ml, mean +/- SD) and control (184 +/- 70 ng/ml) groups. By multiple variable analysis, IGF-1 was negatively associated with age (p = 0.0006), body mass index (BMI) (p = 0.006), and 24 h urinary free cortisol (p = 0.007) in healthy controls. Even after accounting for these factors, there was no association between FM and IGF-1. The average peak GH achieved during hypoglycemia was lower in patients with FM (range 5 to 58 ng/ml, median 13 ng/ml) versus controls (6 to 68 ng/ml, median 21 ng/ml) (p = 0.04). However, BMI was a significant predictor of average peak GH in FM (r = -0.62, p BMI, there was no significant association between FM subjects and the average peak GH (p = 0.20). In this sample of premenopausal women with FM, the activity of the GH-IGF-1 axis was similar to that of healthy controls. Increases in age and obesity were both strongly associated with lower activity of this axis, suggesting that these factors must be considered when studying activity of the GH-IGF-1 axis in FM.

  6. 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.

  7. A low serum bicarbonate concentration as a risk factor for mortality in peritoneal dialysis patients.

    Directory of Open Access Journals (Sweden)

    Tae Ik Chang

    Full Text Available BACKGROUND AND AIM: Metabolic acidosis is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, this relationship has not yet been determined in peritoneal dialysis (PD patients. METHODS: This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum bicarbonate (TA-Bic levels, we aimed to investigate whether a low serum bicarbonate concentration can predict mortality in these patients. RESULTS: Among the baseline parameters, serum bicarbonate level was positively associated with hemoglobin level and residual glomerular filtration rate (GFR, while it was negatively associated with albumin, C-reactive protein (CRP levels, peritoneal Kt/V urea, and normalized protein catabolic rate (nPCR in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. After adjustment for age, diabetes, coronary artery disease, serum albumin, ferritin, CRP, residual GFR, peritoneal Kt/V urea, nPCR, and percentage of lean body mass, TA-Bic level was associated with a significantly decreased risk of mortality (HR per 1 mEq/L increase, 0.83; 95% CI, 0.76-0.91; p < 0.001. In addition, compared to patients with a TA-Bic level of 24-26 mEq/L, those with a TA-Bic level < 22 and between 22-24 mEq/L conferred a 13.10- and 2.13-fold increased risk of death, respectively. CONCLUSIONS: This study showed that a low serum bicarbonate concentration is an independent risk factor for mortality in PD patients. This relationship between low bicarbonate levels and adverse outcome could be related to enhanced inflammation and a more rapid loss of RRF associated with metabolic acidosis. Large randomized clinical trials to correct acidosis are warranted to confirm our findings.

  8. Analysis and modelling of the factors controlling seed oil concentration in sunflower: a review

    Directory of Open Access Journals (Sweden)

    Andrianasolo Fety Nambinina

    2016-03-01

    Full Text Available Sunflower appears as a potentially highly competitive crop, thanks to the diversification of its market and the richness of its oil. However, seed oil concentration (OC – a commercial criterion for crushing industry – is subjected to genotypic and environmental effects that make it sometimes hardly predictable. It is assumed that more understanding of oil physiology combined with the use of crop models should permit to improve prediction and management of grain quality for various end-users. Main effects of temperature, water, nitrogen, plant density and fungal diseases were reviewed in this paper. Current generic and specific crop models which simulate oil concentration were found to be empirical and to lack of proper evaluation processes. Recently two modeling approaches integrating ecophysiological knowledge were developed by Andrianasolo (2014, Statistical and dynamic modelling of sunflower (Helianthus annuus L. grain composition as a function of agronomic and environmental factors, Ph.D. Thesis, INP Toulouse: (i a statistical approach relating OC to a range of explanatory variables (potential OC, temperature, water and nitrogen stress indices, intercepted radiation, plant density which resulted in prediction quality from 1.9 to 2.5 oil points depending on the nature of the models; (ii a dynamic approach, based on “source-sink” relationships involving leaves, stems, receptacles (as sources and hulls, proteins and oil (as sinks and using priority rules for carbon and nitrogen allocation. The latter model reproduced dynamic patterns of all source and sink components faithfully, but tended to overestimate OC. A better description of photosynthesis and nitrogen uptake, as well as genotypic parameters is expected to improve its performance.

  9. Influence of V/III growth flux ratio on trap states in m-plane GaN grown by ammonia-based molecular beam epitaxy

    International Nuclear Information System (INIS)

    Zhang, Z.; Arehart, A. R.; Hurni, C. A.; Speck, J. S.; Ringel, S. A.

    2012-01-01

    Deep level transient spectroscopy (DLTS) and deep level optical spectroscopy (DLOS) were utilized to investigate the behavior of deep states in m-plane, n-type GaN grown by ammonia-based molecular beam epitaxy (NH 3 -MBE) as a function of systematically varied V/III growth flux ratios. Levels were detected at E C - 0.14 eV, E C - 0.21 eV, E C - 0.26 eV, E C - 0.62 eV, E C - 0.67 eV, E C - 2.65 eV, and E C - 3.31 eV, with the concentrations of several traps exhibiting systematic dependencies on V/III ratio. The DLTS spectra are dominated by traps at E C - 0.14 eV and E C - 0.67 eV, whose concentrations decreased monotonically with increasing V/III ratio and decreasing oxygen impurity concentration, and by a trap at E C - 0.21 eV that revealed no dependence of its concentration on growth conditions, suggestive of different physical origins. Higher concentrations of deeper trap states detected by DLOS with activation energies of E C - 2.65 eV and E C - 3.31 eV in each sample did not display measureable sensitivity to the intentionally varied V/III ratio, necessitating further study on reducing these deep traps through growth optimization for maximizing material quality of NH 3 -MBE grown m-plane GaN.

  10. Three- versus four-factor prothrombin complex concentrate for the reversal of warfarin-induced bleeding

    Science.gov (United States)

    Holt, Tara; Taylor, Scott; Abraham, Prasad; Mcmillian, Wesley; Harris, Serena; Curtis, James; Elder, Tai

    2018-01-01

    Objective: The objective of this study was to evaluate the effectiveness of 3-factor prothrombin complex concentrate (3F-PCC) compared to 4-factor PCC (4F-PCC) in warfarin-associated bleeding. Methods: This multicenter, retrospective, cohort study analyzed data from patients admitted between May 2011 and October 2014 who received PCC for warfarin-associated bleeding. The primary outcome was the rate of international normalized ratio (INR) normalization, defined as an INR ≤1.3, after administration of 3F-PCC compared to 4F-PCC. Other variables of interest included the incidence of additional reversal agents, new thromboembolic events, and mortality. Results: A total of 134 patients were included in the analysis. The average dose of PCC administered was 24.6 ± 9.3 units/kg versus 36.3 ± 12.8 units/kg in the 3F-PCC and 4F-PCC groups, respectively, P < 0.001. Baseline INR in the 3F-PCC and 4F-PCC groups was 3.61 ± 2.3 and 6.87 ± 2.3, respectively P < 0.001. 4F-PCC had a higher rate of INR normalization at first INR check post-PCC administration compared to 3F-PCC (84.2% vs. 51.9%, P = 0.0001). Thromboembolic events, intensive care unit and hospital length of stay, and mortality were similar among both groups. Conclusion: The use of 4F-PCC leads to a more significant reduction in INR compared to 3F-PCC though no difference in mortality or length of stay was observed. Thromboembolism rates were similar among both groups. PMID:29619338

  11. Correlation of Stress Concentration Factors for T-Welded Connections – Finite Element Simulations and Fatigue Behavior

    Directory of Open Access Journals (Sweden)

    Gerardo Terán Méndez

    Full Text Available Abstract The stress concentration factors (SCFs in welded connections usually occur at zones with high stress levels. Stress concentrations reduce the fatigue behavior of welded connections in offshore structures and cracking can develop. By using the grinding technique, cracking can be eliminated. Stress concentration factors are defined as a ratio of maximum stress at the intersection to nominal stress on the brace. Defining the stress concentration factor is an important stage in the fatigue behavior of welded connections. Several approaches have evolved for designing structures with the classical S-N approach for estimating total life. This work correlates to the stress concentration factors of T-welded connections and the fatigue behavior. Stress concentration factors were computed with the finite element employing 3D T-welded connections with intact and grinding depth conditions. Then, T-welded connections were constructed with A36 plate steel and welded with E6013 electrodes to obtain the stress-life (S-N approach. The methodology from previous works was used to compute the SCF and fabricate the T-welded connections. The results indicated that the grinding process could restore the fatigue life of the T-welded connections for SCFs values in the range of 1.29. This value can be considered to be a low SCF value in T-welded connection. However, for higher SCF values, the fatigue life decreased, compromising and reducing the structural integrity of the T-welded connections.

  12. Concentration factors for Cs-137 in marine algae from Japanese coastal waters

    International Nuclear Information System (INIS)

    Tateda, Yutaka; Koyanagi, Taku.

    1994-01-01

    Concentration factors (CF: Bq·kg -1 in wet algae/Bq·kg -1 in filtered seawater) for Cs-137 in Japanese coastal algae, were investigated during 1984-1990. Cs-137/Cs (stable) atom ratios were also examined to clarify the distribution equilibrium of Cs-137 in marine algae and sea water. The CFs in marine algae were within the range of 5.4-92, and the geometric mean of CF was 28±2 (standard error) in Japanese coastal species. The CFs in edible species were within the range of 5.4-67, and the geometric means of CF was 26±4 (standard error). The values of Cs-137/Cs atom ratios in marine algae and sea water indicated that Cs-137 reached an equilibrium state in partition between algae and sea water. Therefore, the CF value obtained in the present study can be regarded as an equilibrated value. Our results showed that hte CF for Cs-137 in Japanese coastal algae were consistent with the Japanese guideline CFs, but were smaller than the recommended value by IAEA. (author)

  13. Environmental factors affecting the concentration of phenolic compounds in Myrcia tomentosa leaves

    Directory of Open Access Journals (Sweden)

    Leonardo L. Borges

    2013-02-01

    Full Text Available Myrcia tomentosa (Aubl. DC., Myrtaceae, found in Central Brazilian Cerrado and popularly known as "goiaba-brava", belongs to the Myrcia genus, which has several species with medicinal properties such as: hypoglycemic, diuretic, hypotensive, antidiarrheal, antimicrobial and antitumor. The present study aimed to analyzed the environmental influence on concentrations of phenolic metabolites in M. tomentosa leaves. Compounds assayed in the leaves were: total phenols, tannins by protein precipitation, hydrolysable tannins and total flavonoids and mineral nutrients, while soil fertility was also analyzed, all over during one year. The results were submitted to Pearson Correlation Analysis and stepwise Multiple Regression Analysis to investigate the relationship between phenolics and environment data. Analysis of variance and Cluster Analysis allowed indicated a high variability in samples from different sites. The results obtained suggests that content of phenolics from M. tomentosa leaves are influenced by environmental factors, particularly some foliar nutrients (N1, Ca1 and Mn1, soil nutrients (Ca s and Ks and Rainfall.

  14. Environmental factors affecting the concentration of phenolic compounds in Myrcia tomentosa leaves

    Directory of Open Access Journals (Sweden)

    Leonardo L. Borges

    2013-04-01

    Full Text Available Myrcia tomentosa (Aubl. DC., Myrtaceae, found in Central Brazilian Cerrado and popularly known as "goiaba-brava", belongs to the Myrcia genus, which has several species with medicinal properties such as: hypoglycemic, diuretic, hypotensive, antidiarrheal, antimicrobial and antitumor. The present study aimed to analyzed the environmental influence on concentrations of phenolic metabolites in M. tomentosa leaves. Compounds assayed in the leaves were: total phenols, tannins by protein precipitation, hydrolysable tannins and total flavonoids and mineral nutrients, while soil fertility was also analyzed, all over during one year. The results were submitted to Pearson Correlation Analysis and stepwise Multiple Regression Analysis to investigate the relationship between phenolics and environment data. Analysis of variance and Cluster Analysis allowed indicated a high variability in samples from different sites. The results obtained suggests that content of phenolics from M. tomentosa leaves are influenced by environmental factors, particularly some foliar nutrients (N1, Ca1 and Mn1, soil nutrients (Ca s and Ks and Rainfall.

  15. Hemodialysis decreases serum brain-derived neurotrophic factor concentration in humans.

    Science.gov (United States)

    Zoladz, Jerzy A; Śmigielski, Michał; Majerczak, Joanna; Nowak, Łukasz R; Zapart-Bukowska, Justyna; Smoleński, Olgierd; Kulpa, Jan; Duda, Krzysztof; Drzewińska, Joanna; Bartosz, Grzegorz

    2012-12-01

    In the present study we have evaluated the effect of a single hemodialysis session on the brain-derived neurotrophic factor levels in plasma [BDNF](pl) and in serum [BDNF](s) as well as on the plasma isoprostanes concentration [F(2) isoprostanes](pl), plasma total antioxidant capacity (TAC) and plasma cortisol levels in chronic kidney disease patients. Twenty male patients (age 69.8 ± 2.9 years (mean ± SE)) with end-stage renal disease undergoing maintenance hemodialysis on regular dialysis treatment for 15-71 months participated in this study. A single hemodialysis session, lasting 4.2 ± 0.1 h, resulted in a decrease (P = 0.014) in [BDNF](s) by ~42 % (2,574 ± 322 vs. 1,492 ± 327 pg ml(-1)). This was accompanied by an increase (P 0.05) in [BDNF](pl) and the platelets count were observed after a single dialysis session. Furthermore, basal [BDNF](s) in the chronic kidney disease patients was significantly lower (P = 0.03) when compared to the age-matched control group (n = 23). We have concluded that the observed decrease in serum BDNF level after hemodialysis accompanied by elevated [F(2)-Isoprostanes](pl) and decreased plasma TAC might be caused by enhanced oxidative stress induced by hemodialysis.

  16. 40 CFR Appendix Viii to Part 266 - Organic Compounds for Which Residues Must Be Analyzed

    Science.gov (United States)

    2010-07-01

    ... AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF SPECIFIC HAZARDOUS WASTES AND SPECIFIC TYPES OF HAZARDOUS WASTE MANAGEMENT FACILITIES Pt. 266, App. VIII Appendix VIII to Part 266... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Organic Compounds for Which Residues...

  17. 40 CFR Appendix Viii to Part 268 - LDR Effective Dates of Injected Prohibited Hazardous Wastes

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false LDR Effective Dates of Injected Prohibited Hazardous Wastes VIII Appendix VIII to Part 268 Protection of Environment ENVIRONMENTAL PROTECTION... to Part 268—LDR Effective Dates of Injected Prohibited Hazardous Wastes National Capacity LDR...

  18. Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling

    DEFF Research Database (Denmark)

    Hansen, N. U. B.; Willumsen, N.; Bülow Sand, Jannie Marie

    2016-01-01

    Objectives Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competitive...

  19. Effectiveness of Mind Mapping in English Teaching among VIII Standard Students

    Science.gov (United States)

    Hallen, D.; Sangeetha, N.

    2015-01-01

    The aim of the study is to find out the effectiveness of mind mapping technique over conventional method in teaching English at high school level (VIII), in terms of Control and Experimental group. The sample of the study comprised, 60 VIII Standard students in Tiruchendur Taluk. Mind Maps and Achievement Test (Pretest & Posttest) were…

  20. 4p-5s transitions in YVII, VIII, ZrVIII, IX, NbIX, X and MoX, XI

    International Nuclear Information System (INIS)

    Rahimullah, K.; Chaghtai, M.S.Z.; Khatoon, S.

    1976-01-01

    The spectra of Y VII, VIII, Zr VIII, IX, Nb X and Mo X, XI are studied for the first time and the 1971 analysis of Nb IX is improved. By analyses of the transitions 4s 2 4psup(k)-4s 2 4psup(k-1)5s all the levels of the configurations 4p 3 , 4p 2 5s, 4p 2 and 4p5s are established in the spectra concerned. (Auth.)

  1. Treatment of AVN Using Autologous BM Stem Cells and Activated Platelet-Derived Growth Factor Concentrates.

    Science.gov (United States)

    Nandeesh, Nagaraj H; Janardhan, Kiranmayee; Subramanian, Vignesh; Ashtekar, Abhishek Bhushan; Srikruthi, Nandagiri; Koka, Prasad S; Deb, Kaushik

    Avascular Necrosis (AVN) of hip is a devastating condition seen in younger individuals. It is the ischemic death of the constituents of the bone cartilage of the hip. The femoral head (FH) is the most common site for AVN. It results from interruption of the normal blood flow to the FH that fits into the hip socket. Earlier studies using autologous bone marrow stem cell concentrate injections have shown encouraging results with average success rates. The current study was designed to improve significantly the cartilage regeneration and clinical outcome. Total of 48 patients underwent autologous bone marrow stem cell and activated platelet-rich plasma derived growth factor concentrate (PRP-GFC) therapy for early and advanced stages AVN of femoral head in a single multi-specialty center. The total treatment was divided into three phases. In the phase I, all the clinical diagnostic measurements such as magnetic resonance imaging (MRI), computed tomography (CT) etc. with respect to the AVN patients and bone marrow aspiration from posterior iliac spine from the patients were carried out. In the phase II, isolation of stem cells and preparation from the patients were performed. Subsequently, in phase III, the stem cells and PRP- GFCs were transplanted in the enrolled patients. Ninety three percent of the enrolled AVN patients showed marked enhancement in the hip bone joint space (more than 3mm) after combined stem cells and PRP-GFC treatment as evidenced by comparison of the pre- and post-treatment MRI data thus indicative of regeneration of cartilage. The treated patients showed significant improvement in their motor function, cartilage regrowth (3 to 10mm), and high satisfaction in the two-year follow-up. Combination of stem cell and PRP-GFC therapy has shown promising cartilage regeneration in 45 out of 48 patients of AVN. This study clearly demonstrates the safety and efficacy of this treatment. Larger numbers of patients need to be evaluated to better understand the

  2. Individual and Interactive Influences of Anthropogenic and Ecological Factors on Forest PM2.5 Concentrations at an Urban Scale

    Directory of Open Access Journals (Sweden)

    Guoliang Yun

    2018-03-01

    Full Text Available Integration of Landsat images and multisource data using spatial statistical analysis and geographical detector models can reveal the individual and interactive influences of anthropogenic activities and ecological factors on concentrations of atmospheric particulate matter less than 2.5 microns in diameter (PM2.5. This approach has been used in many studies to estimate biomass and forest disturbance patterns and to monitor carbon sinks. However, the approach has rarely been used to comprehensively analyze the individual and interactive influences of anthropogenic factors (e.g., population density, impervious surface percentage and ecological factors (e.g., canopy density, stand age, and elevation on PM2.5 concentrations. To do this, we used Landsat-8 images and meteorological data to retrieve quantitative data on the concentrations of particulates (PM2.5, then integrated a forest management planning inventory (FMPI, population density distribution data, meteorological data, and topographic data in a Geographic Information System database, and applied a spatial statistical analysis model to identify aggregated areas (hot spots and cold spots of particulates in the urban area of Jinjiang city, China. A geographical detector model was used to analyze the individual and interactive influences of anthropogenic and ecological factors on PM2.5 concentrations. We found that particulate concentration hot spots are mainly distributed in urban centers and suburbs, while cold spots are mainly distributed in the suburbs and exurban region. Elevation was the dominant individual factor affecting PM2.5 concentrations, followed by dominant tree species and meteorological factors. A combination of human activities (e.g., population density, impervious surface percentage and multiple ecological factors caused the dominant interactive effects, resulting in increased PM2.5 concentrations. Our study suggests that human activities and multiple ecological factors

  3. Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men.

    Science.gov (United States)

    Zoladz, J A; Pilc, A; Majerczak, J; Grandys, M; Zapart-Bukowska, J; Duda, K

    2008-12-01

    It is believed that brain derived neurotrophic factor (BDNF) plays an important role in neuronal growth, transmission, modulation and plasticity. Single bout of exercise can increase plasma BDNF concentration [BDNF](p) in humans. It was recently reported however, that elevated [BDNF](p) positively correlated with risk factors for metabolic syndrome and type 2 diabetes mellitus in middle age group of subjects. On the other hand it is well established that endurance training decreases the risk of diabetes and development of metabolic syndrome. In the present study we have examined the effect of 5 weeks of moderate intensity endurance training on the basal and the exercise induced changes in [BDNF](p) in humans. Thirteen young, healthy and physically active men (mean +/- S.E: age 22.7 +/- 0.5 yr, body height 180.2 +/- 1.7 cm, body weight 77.0 +/- 2.5 kg, V(O2max) 45.29 +/- 0.93 ml x kg-1 x min(-1)) performed a five week endurance cycling training program, composed mainly of moderate intensity bouts. Before training [BDNF]p at rest have amounted to 10.3 +/- 1.4 pg x ml(-1). No effect of a single maximal incremental cycling up to V(O2max) on its concentration was found (10.9 +/- 2.3 pg x ml(-1), P=0.74). The training resulted in a significant (P=0.01) increase in [BDNF]p at rest to 16.8 +/- 2.1 pg x ml(-1), as well as in significant (P=0.0002) exercise induced increase in the [BDNF](p) (10.9 +/- 2.3 pg x ml(-1) before training vs. 68.4 +/- 16.0 pg x ml(-1) after training). The training induced increase in resting [BDNF](p) was accompanied by a slight decrease in insulin resistance (P=0.25), calculated using the homeostatic model assessment version 2 (HOMA2-IR), amounting to 1.40 +/- 0.13 before and 1.15 +/- 0.13 after the training. Moreover, we have found that the basal [BDNF](p) in athletes (n=16) was significantly higher than in untrained subjects (n=13) (29.5 +/- 9.5 pg x ml(-1) vs. 10.3 +/- 1.4 pg x ml(-1), P=0.013). We have concluded that endurance training of

  4. Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders

    DEFF Research Database (Denmark)

    Johansson, Pär I; Ostrowski, Sisse R

    2010-01-01

    Recombinant activated factor VII (rFVIIa, NovoSeven) was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX.......Recombinant activated factor VII (rFVIIa, NovoSeven) was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX....

  5. Placental growth factor concentration in maternal circulation decreases after fetal death: lessons from a case series study.

    Science.gov (United States)

    Beharier, Ofer; Shusterman, Eden; Szaingurten-Solodkin, Irit; Weintraub, Adi Y; Sheiner, Eyal; Swissa, Shani S; Gitler, Daniel; Hershkovitz, Reli

    2015-11-01

    Placental growth factor (PlGF) has been suggested as a possible biomarker for major placenta-related disorders such as preeclampsia and intrauterine growth restriction. However, experimental findings suggest that PlGF concentrations may be influenced by other factors besides the placenta. In the present study, we examined how acute fetal injury affects PlGF concentrations in maternal circulation. We therefore monitored PlGF concentrations in maternal circulation before and after feticide. A prospective comparative study was performed. Blood samples were drawn prospectively between January and July 2012, before and after feticide at predetermined time points in relation to the procedure (0, 30, 60, and 120 min). The levels of lactate dehydrogenase (LDH) in the maternal circulation were measured to detect acute tissue damage. PlGF concentrations were measured by standard human ELISA. Following feticide (60 and 120 min), PlGF concentrations decreased significantly compared to the concentrations before feticide. LDH concentrations did not change before and after feticide. Our finding, along with the detailed review of the literature described in our work, supports a new concept in which primary fetal distress can affect PlGF concentration in maternal circulation. A large-scale study is required to strengthen our finding.

  6. COMPENSATORY AND NON COMPENSATORY FACTORS WHICH INFLUENCE THE BUYING DECISION OF CULINARY PRODUCTS, CONCENTRATED SOUP CATEGORY, IN CONSUMERS FROM BARRANQUILLA

    Directory of Open Access Journals (Sweden)

    MARÍA MERCEDES BOTERO

    2005-10-01

    Full Text Available The aim of this research was to identify the main compensatory and non-compensatory factors influencing thepurchase of concentrated broth in consumers of the city of Barranquilla. This research compiles the data obtainedthrough 300 interviews applied to consumers of concentrated broth, who do their shopping in 41 supermarkets and8.000 general stores distributed along the city.The study demonstrated that brand and the flavor are the most important factors in buying concentrated broth.Additionally, customers usually buy the product that they previously have chosen, remaining loyal to their favoritebrand. This corroborates that non-compensatory factors such as memory, experience and tradition are determinantwhen choosing a product.

  7. Effects of maternal smoking and exposure to methylmercury on brain-derived neurotrophic factor concentrations in umbilical cord serum

    DEFF Research Database (Denmark)

    Spulber, Stefan; Rantamäki, Tomi; Nikkilä, Outi

    2010-01-01

    . The cohort consisted of 395 singleton births (206 boys and 189 girls), gestational age ranging from 38 to 42 weeks. Serum BDNF was measured by sandwich ELISA. Maternal smoking habits and other relevant factors were obtained by interviewing the mothers. The exposure to MeHg was estimated from Hg...... concentrations in cord blood, whereas exposure to PCB was estimated based on maternal serum concentrations. Only MeHg exposure affected the serum BDNF, which decreased in a concentration-dependent manner in girls born to nonsmoking mothers. Maternal smoking significantly increased BNDF in girls but not in boys....... For further statistical analyses, we used the serum BDNF concentration as a continuous outcome variable in supervised regression models. Serum BDNF concentration increased with gestational age, increased by maternal smoking, decreased slightly with MeHg exposure, and maternal smoking enhanced the decrease...

  8. Efeitos de humor no poema VIII de Catulo

    Directory of Open Access Journals (Sweden)

    Paulo Sérgio Vasconcellos

    1997-12-01

    Full Text Available Neste artigo apresenta-se uma contribuição ao estudo dos efeitos de humor no poema VIII de Catulo; de fato, além do metro dessa composição e de outros elementos criadores de distanciamento irônico que os estudiosos têm apontado, um outro aspecto de sua forma, ainda pouco percebido, guia a leitura para essa interpretação: o jogo, a maneira de anagrama imperfeito (o “hipograma”, ou, mais precisamente, “criptograma”, de Saussure, com os sons do nome da amada, aparentemente calado. E mais uma das maneiras com que o poeta elabora a jocosa diferença entre o que se diz e o que, sentido e reprimido, deixa-se, porém, transparecer.

  9. Energies and lifetimes of excited states in copperlike Kr VIII

    International Nuclear Information System (INIS)

    Livingston, A.E.; Curtis, L.J.; Schectman, R.M.; Berry, H.G.

    1980-01-01

    The spectrum of Kr VIII has been observed between 180 and 2000 A by using foil excitation of 2.5--3.5-MeV krypton ions. Twenty new transitions have been classified and eleven new excited-state energies have been determined within the n=4 --7 shells. The ionization potential is derived to be 1 015 800 +- 200 cm -1 . The excited-state energies and fine structures are compared with recent relativistic Hartree-Fock calculations. The 4p-state lifetime has been measured by performing a simultaneous analysis of decay data for the 4p level and for its dominant cascade-repopulating levels. The 4p lifetime is found to be 30% shorter than previously measured values and is in excellent agreement with the result of a recent multiconfiguration Hartree-Fock calculation. The source of the discrepancy between this result and earlier measurements is discussed

  10. Valor preditivo da expressão dos anticorpos Antifator VIII no carcinoma epidermóide do esôfago Predictive value of antifactor VIII antibody expression in squamous cell carcinoma of the esophagus

    Directory of Open Access Journals (Sweden)

    Sebastião Gonzaga Barbosa-Neto

    2007-12-01

    to progress knowledge on protein expression alterations for such neoplasia. AIM: To quantify protein expression implicated in the angiogenesis process and correlate to clinical-pathological features. METHODS: Using immunohistochemistry procedure, cytophotometric imaging by SAMBA, 29 sampled-tissue embedded in paraffin blocks of squamous cell carcinoma of the esophagus were analyzed. Clinical criteria, such as age and gender, as well as histophatological criteria, such as differentiated grade features, size and tumor location, were considered. Parameters evaluated were labeling index and optical density. The marker used in the present study was antifactor VIII. RESULTS: Verification on the expression of the marker in labeling index parameter was greater than optical density. Factor VIII presented homogeneous reading out. Labeling index was 80,17 + 10,40 (P=0,073 and optical density 51,25 + 11,02 (P=0,245. CONCLUSION: Protein expression reading analysis involved in angiogenesis process allows to define subgroups according to differentiated grade carcinoma, tumoral staging, size and tumor localization, although it does not allow association with gender and patient age. Optical density for factor VIII does not have statistical significant expression in any subgroup evaluated.

  11. Polymer and Concentrator Photovoltaic Technologies - Energy Return Factors and Area Efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Loefgren, Birger; Gustaf Zettergren

    2006-12-20

    Market diffusion of flat plate crystalline silicon photovoltaic (PV) technology has been induced by economical support schemes and has lead to reduced cost per produced kWh electricity. For further market penetration of the PV technology, a continued reduction of production cost is required. Two alternative approaches to achieve this are using less expensive materials or changing the active materials. The technologies of concentrator PV (CPV) systems and polymer PV (PPV) devices represent these two strategies. The potential energy performance of these technologies is studied in terms of the process primary energy requirements for manufacturing, how many times this energy is paid back during its lifetime and as the required land area for electricity generation. The study is an energy analysis incorporating the inherent uncertainties in technology development. Uncertainties are identified in data acquisition, in design choices, as induced by development and improvement, in performance and by different application scenarios. The future technology alternatives are defined in different ways for CPV and PPV. CPV parameters are derived from existing products and ideas for improvements and PPV parameters from the directions of research. This study shows that the invested energy in future CPV and PPV is potentially paid back up to about 90 and 170 times, respectively, under Arizona (CPV) and average European (PPV) solar irradiation conditions. However the result is highly dependent on configuration, inventory data and device performance. Thus, for certain design alternatives, data and performance, PPV production energy is far from paid back during its lifetime. For CPV the energy return factor is decreased to about 13 in the least beneficial case. Area efficiency is studied as the land area requirements for producing a net output electricity of 1 MWh during 25 years. With device efficiencies from 1 to 5 per cent and lifetimes from 1 to 5 years a PPV device requires from 2

  12. [The concentration of growth factors in patients with inherent and acquired shortenings of limbs bones].

    Science.gov (United States)

    Strogov, M V; Luneva, S N; Novikov, K I

    2013-04-01

    The article deals with the results of study of level of growth factors in blood serum of patients with inherent and post-traumatic shortenings of limbs' bones. The detection in blood serum the level of epidermal growth factor insulin-like growth factor I and angiopoetins is proposed to monitor in given patients the reparative bone formation.

  13. Characterization of air pollutant concentrations, fleet emission factors, and dispersion near a North Carolina interstate freeway across two seasons

    Science.gov (United States)

    Saha, Provat K.; Khlystov, Andrey; Snyder, Michelle G.; Grieshop, Andrew P.

    2018-03-01

    We present field measurement data and modeling of multiple traffic-related air pollutants during two seasons at a site adjoining Interstate 40, near Durham, North Carolina. We analyze spatial-temporal and seasonal trends and fleet-average pollutant emission factors and use our data to evaluate a line source dispersion model. Month-long measurement campaigns were performed in summer 2015 and winter 2016. Data were collected at a fixed near-road site located within 10 m from the highway edge, an upwind background site and, under favorable meteorological conditions, along downwind perpendicular transects. Measurements included the size distribution, chemical composition, and volatility of submicron particles, black carbon (BC), nitrogen oxides (NOx), meteorological conditions and traffic activity data. Results show strong seasonal and diurnal differences in spatial distribution of traffic sourced pollutants. A strong signature of vehicle emissions was observed within 100-150 m from the highway edge with significantly higher concentrations during morning. Substantially higher concentrations and less-sharp near-road gradients were observed in winter for many species. Season-specific fleet-average fuel-based emission factors for NO, NOx, BC, and particle number (PN) were derived based on up- and down-wind roadside measurements. The campaign-average NOx and PN emission factors were 20% and 300% higher in winter than summer, respectively. These results suggest that the combined effect of higher emissions and their slower downwind dispersion in winter dictate the observed higher downwind concentrations and wider highway influence zone in winter for several species. Finally, measurements of traffic data, emission factors, and pollutant concentrations were integrated to evaluate a line source dispersion model (R-LINE). The dispersion model captured the general trends in the spatial and temporal patterns in near-road concentrations. However, there was a tendency for the model

  14. Minimization of stress concentration factor in cylindrical pressure vessels with ellipsoidal heads

    International Nuclear Information System (INIS)

    Magnucki, K.; Szyc, W.; Lewinski, J.

    2002-01-01

    The paper presents the problem of stress concentration in a cylindrical pressure vessel with ellipsoidal heads subject to internal pressure. At the line, where the ellipsoidal head is adjacent to the circular cylindrical shell, a shear force and bending moment occur, disturbing the membrane stress state in the vessel. The degree of stress concentration depends on the ratio of thicknesses of both the adjacent parts of the shells and on the relative convexity of the ellipsoidal head, with the range for radius-to-thickness ratio between 75 and 125. The stress concentration was analytically described and, afterwards, the effect of these values on the stress concentration ratio was numerically examined. Results of the analysis are shown on charts

  15. Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition

    OpenAIRE

    Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro

    2017-01-01

    Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases ?-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 (GluR2) expression in cortical neurons and enhances neuronal vulnerability ...

  16. Factors affecting ANKOM™ fiber analysis of forage and browse varying in condensed tannin concentration.

    Science.gov (United States)

    Terrill, Thomas H; Wolfe, Richard M; Muir, James P

    2010-12-01

    Browse species containing condensed tannins (CTs) are an important source of nutrition for grazing/browsing livestock and wildlife in many parts of the world, but information on fiber concentration and CT-fiber interactions for these plants is lacking. Ten forage or browse species with a range of CT concentrations were oven dried and freeze dried and then analyzed for ash-corrected neutral detergent fiber (NDFom) and corrected acid detergent fiber (ADFom) using separate samples (ADFSEP) and sequential NDF-ADF analysis (ADFSEQ) with the ANKOM™ fiber analysis system. The ADFSEP and ADFSEQ residues were then analyzed for nitrogen (N) concentration. Oven drying increased (P < 0.05) fiber concentrations with some species, but not with others. For high-CT forage and browse species, ADFSEP concentrations were greater (P < 0.05) than NDFom values and approximately double the ADFSEQ values. Nitrogen concentration was greater (P < 0.05) in ADFSEP than ADFSEQ residues, likely due to precipitation with CTs. Sequential NDF-ADF analysis gave more realistic values and appeared to remove most of the fiber residue contaminants in CT forage samples. Freeze drying samples with sequential NDF-ADF analysis is recommended in the ANKOM™ fiber analysis system with CT-containing forage and browse species. Copyright © 2010 Society of Chemical Industry.

  17. The protein concentration of blood coagulation factor VII can be measured equally well in plasma and serum

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Overgaard, K; Gram, J

    1995-01-01

    In the Northwick Park Heart Study, the coagulant activity of factor VII (FVII:C) has been identified as a risk marker of ischaemic heart disease. In the fasting state, the protein concentration of FVII (FVII:Ag) might be an even better risk marker, because of the low coefficient of variation...

  18. Stress concentration factors for integral and pad reinforced nozzles in spherical pressure vessels subjected to radial load and moment

    International Nuclear Information System (INIS)

    Soliman, S.F.; Gill, S.S.

    1979-01-01

    Charts are presented giving the elastic stress concentration factors in spherical pressure vessels with pad and integral reinforcement for radial branches subjected to radial load and moment. The effect of all the geometrical parameters is discussed, including the limitations of thin shell theory on the validity of the results. (author)

  19. Can tissue element concentration patterns at the individual-species level indicate the factors underlying vegetation gradients in wetlands?

    Czech Academy of Sciences Publication Activity Database

    Rozbrojová, Zuzana; Hájek, M.

    2010-01-01

    Roč. 21, č. 2 (2010), s. 355-363 ISSN 1100-9233 Institutional research plan: CEZ:AV0Z60050516 Keywords : plant nutrient concentration * vegetation gradient * wetland vegetation Subject RIV: EF - Botanics Impact factor: 2.457, year: 2010

  20. Aqueous vascular endothelial growth factor and aflibercept concentrations after bimonthly intravitreal injections of aflibercept for age-related macular degeneration.

    Science.gov (United States)

    Sawada, Tomoko; Wang, Xiying; Sawada, Osamu; Saishin, Yoshitsugu; Ohji, Masahito

    2018-01-01

    Clinical evidence supports the efficacy of bimonthly aflibercept injection for age-related macular degeneration. The study aimed to evaluate aqueous vascular endothelial growth factor and aflibercept concentrations and the efficacy of bimonthly aflibercept in patients with age-related macular degeneration. This study is a prospective, interventional case series. Enrolled were 35 eyes with exudative age-related macular degeneration from 35 patients. Patients received three bimonthly intravitreal aflibercept without loading doses. We collected the aqueous humor just before each injection, measured vascular endothelial growth factor and aflibercept concentrations by enzyme-linked immunosorbent assay and measured best-corrected visual acuity and central retinal subfield thickness before and after the injections. Aqueous vascular endothelial growth factor and aflibercept concentrations were measured. The vascular endothelial growth factor concentration was 135.4 ± 60.5 pg/mL (mean ± standard deviation, range 60.6-323.4) at baseline and below the lowest detectable limit in all eyes at month 2 and in 32 eyes at month 4 (P age-related macular degeneration. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  1. Analysis of Factors Influencing Soil Salinity, Acidity, and Arsenic Concentration in a Polder in Southwest Bangladesh

    Science.gov (United States)

    Ayers, J. C.; Patton, B.; Fry, D. C.; Goodbred, S. L., Jr.

    2017-12-01

    Soil samples were collected on Polder 32 in the coastal zone of SW Bangladesh in wet (October) and dry (May) seasons from 2013-2017 and analyzed to characterize the problems of soil salinization and arsenic contamination and identify their causes. Soils are entisols formed from recently deposited, predominantly silt-sized sediments with low carbon concentrations typical of the local mangrove forests. Soluble (DI extract) arsenic concentrations were below the Government of Bangladesh limit of 50 ppb for drinking water. Soil acidity and extract arsenic concentrations exhibit spatial variation but no consistent trends. In October soil extract As is higher and S and pH are lower than in May. These observations suggest that wet season rainwater oxidizes pyrite, reducing soil S and releasing H+, causing pH to decrease. Released iron is oxidized to form Hydrous Ferric Oxyhydroxides (HFOs), which sorb As and increase extractable As in wet season soils. Changes in pH are small due to pH buffering by soil carbonates. Soil and rice paddy water salinities are consistently higher in May than October, reaching levels in May that reduce rice yields. Rice grown in paddies should be unaffected by salt concentrations in the wet season, while arsenic concentrations in soil may be high enough to cause unsafe As levels in produced rice.

  2. Variability of perfluoroalkyl substance concentrations in pregnant women by socio-demographic and dietary factors in a Spanish birth cohort.

    Science.gov (United States)

    Manzano-Salgado, Cyntia B; Casas, Maribel; Lopez-Espinosa, Maria-Jose; Ballester, Ferran; Martinez, David; Ibarluzea, Jesus; Santa-Marina, Loreto; Schettgen, Thomas; Vioque, Jesus; Sunyer, Jordi; Vrijheid, Martine

    2016-01-01

    Prenatal exposure to perfluoroalkyl substances (PFAS) might affect child health; but maternal determinants of PFAS exposure are unclear. We evaluated the socio-demographic and dietary factors of prenatal PFAS concentrations in a Spanish birth cohort. We analyzed perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in 1216 plasma samples collected during the 1(ST) trimester of pregnancy (2003-2008). We used multivariable linear regressions to assess the geometric mean (GM) ratios of PFAS concentrations by socio-demographic and dietary factors. We used analysis of variance (ANOVA) to assess the variability of PFAS concentrations by maternal factors. GM PFAS concentrations ranged from 0.55ng/mL for PFHxS to 5.77ng/mL for PFOS. Women born outside of Spain had lower PFAS concentrations (e.g. GM ratio for PFHxS 0.53[95%CI: 0.46, 0.60] than Spanish women. PFHxS and PFOA concentrations were higher in mothers from the regions of Sabadell (2.13[1.93, 2.35] and 1.73[1.60, 1.88], respectively) and Valencia (1.40[1.28, 1.54] and 1.42[1.31, 1.53], respectively) than Gipuzkoa. PFOA and PFNA concentrations decreased with parity (≥2 children: 0.79[0.67, 0.94] and 0.82[0.68, 0.99], respectively). Younger women (i.e. 6months compared to those who never breastfed (0.79[0.67, 0.94] and 0.82[0.71, 0.95], respectively). High intake of fish and shellfish during pregnancy (i.e. ≥5.6 servings/week) was associated with 11% (1.11[1.04, 1.18]) higher PFOS concentrations than the lowest intake group. Our ANOVA models explained 26% to 40% of PFAS concentrations variability. Prenatal PFAS concentrations were mainly determined by maternal country of birth, region of residence, previous breastfeeding and age. Fish and shellfish intake also contributed to PFOS and PFOA concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Plasma brain-derived neurotrophic factor concentration is a predictor of chronic kidney disease in patients with cardiovascular risk factors - Hyogo Sleep Cardio-Autonomic Atherosclerosis study.

    Directory of Open Access Journals (Sweden)

    Masafumi Kurajoh

    Full Text Available Brain-derived neurotrophic factor (BDNF has been shown to have protective effects against cardiovascular diseases and death through neural and non-neural pathways via tropomyosin-related kinase B signaling. However, it is not known whether plasma BDNF concentration is a predictor of chronic kidney disease (CKD.This study was conducted as a prospective cohort study as part of the Hyogo Sleep Cardio-Autonomic Atherosclerosis.We measured plasma BDNF concentration in 324 patients without CKD, defined as an estimated glomerular filtration rate (eGFR less than 60 ml/min/1.73m2, and with cardiovascular risk factors. As potential confounders, sleep condition, nocturnal hypertension, and autonomic function were quantitatively examined. The patients were followed for a median 37 months (range 2-59 months and occurrence of CKD was noted.Plasma BDNF concentration was significantly and independently associated with CKD development, which occurred in 38 patients (11.7%. Kaplan-Meier analysis revealed that patients with reduced plasma BDNF concentration exhibited a significantly (p = 0.029 greater number of CKD events as compared to those with a higher concentration. Moreover, comparisons of key subgroups showed that the risk of CKD in association with low plasma BDNF concentration was more prominent in patients with a greater reduction of nocturnal systolic blood pressure, better movement index, higher standard deviations of the NN(RR interval or average NN(RR interval for each 5-minute period, and without past cardiovascular disease events, smoking habit, or albuminuria.Plasma BDNF concentration is an independent predictor for development of CKD in patients with cardiovascular risk factors.

  4. Factors in Variability of Serial Gabapentin Concentrations in Elderly Patients with Epilepsy.

    Science.gov (United States)

    Conway, Jeannine M; Eberly, Lynn E; Collins, Joseph F; Macias, Flavia M; Ramsay, R Eugene; Leppik, Ilo E; Birnbaum, Angela K

    2017-10-01

    To characterize and quantify the variability of serial gabapentin concentrations in elderly patients with epilepsy. This study included 83 patients (age ≥ 60 yrs) from an 18-center randomized double-blind double-dummy parallel study from the Veterans Affairs Cooperative 428 Study. All patients were taking 1500 mg/day gabapentin. Within-person coefficient of variation (CV) in gabapentin concentrations, measured weekly to bimonthly for up to 52 weeks, then quarterly, was computed. Impact of patient characteristics on gabapentin concentrations (linear mixed model) and CV (linear regression) were estimated. A total of 482 gabapentin concentration measurements were available for analysis. Gabapentin concentrations and intrapatient CVs ranged from 0.5 to 22.6 μg/ml (mean 7.9 μg/ml, standard deviation [SD] 4.1 μg/ml) and 2% to 79% (mean 27.9%, SD 15.3%), respectively, across all visits. Intrapatient CV was higher by 7.3% for those with a body mass index of ≥ 30 kg/m 2 (coefficient = 7.3, p=0.04). CVs were on average 0.5% higher for each 1-unit higher CV in creatinine clearance (coefficient = 0.5, p=0.03) and 1.2% higher for each 1-hour longer mean time after dose (coefficient = 1.2, p=0.04). Substantial intrapatient variability in serial gabapentin concentration was noted in elderly patients with epilepsy. Creatinine clearance, time of sampling relative to dose, and obesity were found to be positively associated with variability. © 2017 Pharmacotherapy Publications, Inc.

  5. Pharmaceutical concentration variability at sewage treatment plant outlets dominated by hydrology and other factors.

    Science.gov (United States)

    Brunsch, Andrea F; Ter Laak, Thomas L; Rijnaarts, Huub; Christoffels, Ekkehard

    2018-04-01

    A study was conducted in which the effluent at four small to medium sized sewage treatment plants (STP) in North Rhine-Westphalia, Germany was monitored for three pharmaceutical compounds (carbamazepine, diclofenac, metoprolol) over a period of four years. Grab sampling and auto sampling campaigns were accomplished with respect to various weather conditions in the catchment area. Flow volumes and hydraulic retention times (HRT) from various sampling dates which provide information on processes causing emission changes were additionally taken into account. Monitoring results showed that concentration scattering in the effluent is related to HRT in the sewage treatment plants. Dilution effects following rain events in the catchment area were analysed for the three investigated substances. Short-term emission changes explained by dilution only could be well determined by the mathematical relation between discharge and concentration, and for carbamazepine to be solely determined by the dilution effects at all HRTs. For metoprolol, a clear decrease in concentrations was observed at HRTs above 80 h, and a significant contribution of biodegradation was supported by independent biodegradation tests. For three out of the four STPs, a decrease in concentrations of diclofenac was observed at hydraulic retention times above 80 h, indicating removal, whereas the relationship between concentration and HRT of the other STP could be explained by dilution only. The study shows that emissions can vary with weather conditions, hampering the assessment of emissions and estimation of concentrations in surface waters from generic removal rates only. Furthermore, it illustrates the importance of HRT of rather stable substances in wastewater treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Elevated platelet-derived growth factor-BB concentrations in premature neonates who develop chronic lung disease

    Directory of Open Access Journals (Sweden)

    Adcock Kim G

    2004-06-01

    Full Text Available Abstract Background Chronic lung disease (CLD in the preterm newborn is associated with inflammation and fibrosis. Platelet-derived growth factor-BB (PDGF-BB, a potent chemotactic growth factor, may mediate the fibrotic component of CLD. The objectives of this study were to determine if tracheal aspirate (TA concentrations of PDGF-BB increase the first 2 weeks of life in premature neonates undergoing mechanical ventilation for respiratory distress syndrome (RDS, its relationship to the development of CLD, pulmonary hemorrhage (PH and its relationship to airway colonization with Ureaplasma urealyticum (Uu. Methods Infants with a birth weight less than 1500 grams who required mechanical ventilation for RDS were enrolled into this study with parental consent. Tracheal aspirates were collected daily during clinically indicated suctioning. Uu cultures were performed on TA collected in the first week of life. TA supernatants were assayed for PDGF-BB and secretory component of IgA concentrations using ELISA techniques. Results Fifty premature neonates were enrolled into the study. Twenty-eight infants were oxygen dependent at 28 days of life and 16 infants were oxygen dependent at 36 weeks postconceptual age. PDGF-BB concentrations peaked between 4 and 6 days of life. Maximum PDGF-BB concentrations were significantly higher in infants who developed CLD or died from respiratory failure. PH was associated with increased risk of CLD and was associated with higher PDGF-BB concentrations. There was no correlation between maximum PDGF-BB concentrations and Uu isolation from the airway. Conclusions PDGF-BB concentrations increase in TAs of infants who undergo mechanical ventilation for RDS during the first 2 weeks of life and maximal concentrations are greater in those infants who subsequently develop CLD. Elevation in lung PDGF-BB may play a role in the development of CLD.

  7. The position of imidazopyridine and metabolic activation are pivotal factors in the antimutagenic activity of novel imidazo[1,2-a]pyridine derivatives.

    Science.gov (United States)

    El-Sayed, Wael M; Hussin, Warda A; Al-Faiyz, Yasair S; Ismail, Mohamed A

    2013-09-05

    The antimutagenic activity of eight novel imidazo[1,2-a]pyridine derivatives (I-VIII) against sodium azide (NaN3) and benzo[a]pyrene (B[a]P) was evaluated using the Salmonella reverse mutation assay. At non-toxic concentrations (12.5-50 µM), imidazopyridines I, II, III, and V with a terminal imidazopyridine group were mutagenic, while derivatives VII and VIII with a central imidazopyridine group were not mutagenic. Compounds IV, VII, and VIII exerted a moderate antimutagenic activity against NaN3 under pre-exposure conditions, and a strong activity (>40%) against B[a]P in the presence of S9 under both pre- and co-exposure conditions and mostly independent on the dose. Imidazopyridines possibly inhibited the microsomal-dependent activation of B[a]P. The demethylated derivative VII was the most active antimutagen. All imidazopyridines had a low to moderate antioxidant activity. The antibacterial activity of imidazopyridines was sporadic and moderate probably due to the failure of bacteria to convert imidazopyridines into active metabolites. The position of imidazopyridine was a pivotal factor in the mutagenic/antimutagenic activity. The strong antimutagenic compounds were dicationic planar compounds with a centered imidazo[1,2-a]pyridine spacer. With LD50 of 60 mg/kg in mice for both derivatives VII and VIII, it is safe to investigate the anticancer activity of these derivatives in animal models. © 2013 Elsevier B.V. All rights reserved.

  8. Tomato juices and tomato juice concentrates : a study of factors contributing to their gross viscosity

    NARCIS (Netherlands)

    Heutink, R.

    1986-01-01

    The gross viscosity of tomato juice and tomato juice concentrates was found to be determined primarily by the water insoluble solids (WIS) content. The serum viscosity did not contribute to gross viscosity. The WIS consisted of whole tomato cells, vascular bundles and skin fragments. In general the

  9. Modelling nutrient concentration to determine the environmental factors influencing grass quality

    CSIR Research Space (South Africa)

    Dudeni-Tlhone, N

    2010-10-01

    Full Text Available This paper uses the spatial and the least squares (Analysis of Covariance-ANCOVA) regression methods to evaluate the important environmental factors in estimating quality grass for grazing (based on the nitrogen (N) content in grass...

  10. US Subseabed Disposal Program radioecological data base: summaries of available radionuclide concentration factors and biological half-lives

    International Nuclear Information System (INIS)

    Gomez, L.S.; Marietta, M.G.; Jackson, D.W.

    1984-01-01

    The US Subseabed Disposal Program has compiled an extensive objective concentration factor and biological half-life data base from the international marine radioecological literature. A microcomputer-based data management system has been implemented to provide statistical and graphical summaries of these data. The data base is constructed in a manner which allows subsets to be sorted using a number of inter-study variables such as organism category, tissue/organ category, geographic location (for in situ studies), and several laboratory-related conditions (e.g., exposure time and exposure concentration). We discuss concentration factor data summaries for many elements. We also discuss summary material for biological half-life data. We discuss the results of our review with the estimates of mean concentration factors provided by the IAEA. It is proposed that this presentation scheme will enable those concerned with predictive assessment of radiation dose in the marine environment to make a more judicious selection of data for a given application. 7 references

  11. The effects of meteorological factors on airborne fungal spore concentration in two areas differing in urbanisation level

    Science.gov (United States)

    Oliveira, M.; Ribeiro, H.; Delgado, J. L.; Abreu, I.

    2009-01-01

    Although fungal spores are an ever-present component of the atmosphere throughout the year, their concentration oscillates widely. This work aims to establish correlations between fungal spore concentrations in Porto and Amares and meteorological data. The seasonal distribution of fungal spores was studied continuously (2005-2007) using volumetric spore traps. To determine the effect of meteorological factors (temperature, relative humidity and rainfall) on spore concentration, the Spearman rank correlation test was used. In both locations, the most abundant fungal spores were Cladosporium, Agaricus, Agrocybe, Alternaria and Aspergillus/Penicillium, the highest concentrations being found during summer and autumn. In the present study, with the exception of Coprinus and Pleospora, spore concentrations were higher in the rural area than in the urban location. Among the selected spore types, spring-autumn spores ( Coprinus, Didymella, Leptosphaeria and Pleospora) exhibited negative correlations with temperature and positive correlations both with relative humidity and rainfall level. On the contrary, late spring-early summer (Smuts) and summer spores ( Alternaria, Cladosporium, Epicoccum, Ganoderma, Stemphylium and Ustilago) exhibited positive correlations with temperature and negative correlations both with relative humidity and rainfall level. Rust, a frequent spore type during summer, had a positive correlation with temperature. Aspergillus/Penicillium, showed no correlation with the meteorological factors analysed. This knowledge can be useful for agriculture, allowing more efficient and reliable application of pesticides, and for human health, by improving the diagnosis and treatment of respiratory allergic disease.

  12. Factors influencing liver PCB concentrations in sparrowhawks (Accipiter nisus), kestrels (Falco tinnunculus) and herons (Ardea cinerea) in Britain

    Energy Technology Data Exchange (ETDEWEB)

    Wienburg, Claire L.; Shore, Richard F

    2004-11-01

    Large scale temporal and spatial changes in the exposure of terrestrial vertebrates to PCBs have been monitored in the UK by measuring liver residues in sparrowhawks (Accipiter nisus), kestrels (Falco tinnunculus) and grey herons (Ardea cinerea) from throughout the country. Residues in the three species are typically characterised by large intra- and inter-specific variation. Data for 306 sparrowhawks, 186 kestrels and 47 herons collected between 1992 and 1997 as part of a national Predatory Bird Monitoring Scheme were examined to determine how much of this variation was explained by body condition, age and sex, rather than other factors. In all three species, body condition was the single most important factor and accounted for up to 49% of the variation in PCB liver residues; starved birds had the highest liver concentrations. Age and sex were also significant but of lesser importance. Adult sparrowhawks and kestrels had liver PCB residues that were 2 to 10-fold higher than in first-year birds. Sex did not affect residue magnitude in a consistent manner. PCB concentrations in the liver were higher in males than females in both first-year and adult kestrels and in first-year sparrowhawks, but adult female sparrowhawks had similar PCB residues to adult males. Liver residues also varied seasonally. PCB concentrations in first-year sparrowhawks increased during the first year following fledging and a similar pattern was detected in adult female sparrowhawks following egg laying. When these physiological factors were taken into account, it was evident that while kestrels with high fat scores had significantly lower PCB concentrations than either sparrowhawks or herons, liver residues were similar in all three species when birds were in a starved condition. Overall during 1992-1997, the combined influence of body condition, age and sex explained more of the variation in liver PCB concentrations than species differences or other factors, such as geographical variation

  13. Sample pre-concentration with high enrichment factors at a fixed location in paper-based microfluidic devices.

    Science.gov (United States)

    Yeh, Shih-Hao; Chou, Kuang-Hua; Yang, Ruey-Jen

    2016-03-07

    The lack of sensitivity is a major problem among microfluidic paper-based analytical devices (μPADs) for early disease detection and diagnosis. Accordingly, the present study presents a method for improving the enrichment factor of low-concentration biomarkers by using shallow paper-based channels realized through a double-sided wax-printing process. In addition, the enrichment factor is further enhanced by exploiting the ion concentration polarization (ICP) effect on the cathodic side of the nanoporous membrane, in which a stationary sample plug is obtained. The occurrence of ICP on the shallow-channel μPAD is confirmed by measuring the current-voltage response as the external voltage is increased from 0 to 210 V (or the field strength from 0 to 1.05 × 10(4) V m(-1)) over 600 s. In addition, to the best of our knowledge, the electroosmotic flow (EOF) speed on the μPAD fabricated with a wax-channel is measured for the first time using a current monitoring method. The experimental results show that for a fluorescein sample, the concentration factor is increased from 130-fold in a conventional full-thickness paper channel to 944-fold in the proposed shallow channel. Furthermore, for a fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) sample, the proposed shallow-channel μPAD achieves an 835-fold improvement in the concentration factor. The concentration technique presented here provides a novel strategy for enhancing the detection sensitivity of μPAD applications.

  14. Time Transfer Experiment by TCE on the ETS-VIII Satellite

    National Research Council Canada - National Science Library

    Nakagawa, Fumimaru; Takahashi, Yasuhiro; Amagai, Jun; Tabuchi, Ryo; Hama, Shin'ichi; Hosokawa, Mizuhiko

    2007-01-01

    .... At NICT, we developed Time Comparison Equipment (TCE) both onboard ETS-VIII and in the Earth station for precise time transfer between the atomic clocks on the satellite and a ground reference clock...

  15. Class VIII Medical Materiel Controls in the U.S. European Command

    National Research Council Canada - National Science Library

    1991-01-01

    .... Class VIII medical materiel inventories are maintained as part of the U.S. war reserve stocks to ensure military readiness and to provide needed health care during wartime or contingencies. The U.S...

  16. Mechanistic aspects of Os(VIII) catalysed oxidation of loop diuretic ...

    Indian Academy of Sciences (India)

    furosemide by Ag(III) periodate complex in aqueous alkaline medium. SHWETA J .... Os(VIII) catalysed DPA oxidation, the order in [OH. −. ] ... Victoria-3170, Australia) connected to a rapid ..... follows. The furosemide, periodate and hydroxide ion.

  17. An analysis of factors affecting the high radon concentration in different types of houses

    Directory of Open Access Journals (Sweden)

    Gulan Ljiljana

    2017-01-01

    Full Text Available This paper presents an analysis of indoor radon measurements carried out in municipality of Zubin Potok, northwestern part of Kosovo and Metohija. Annual measurements in two rooms of each house were performed by solid state nuclear track detectors commercially known as Gammadata. Average indoor radon concentration in different type of houses varied from 29-326 Bq/m3. A different year of house's construction including various types of building materials were selected for survey. A detail analysis showed that the differences in radon concentration occur between various building materials used for construction, flooring level, type of room and behavior of inhabitants. It was found that building materials in some houses contribute additionally to indoor radon.

  18. Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors

    International Nuclear Information System (INIS)

    Chandrasekharan, Sabarinath; Kandasamy, Krishna Kumar; Dayalan, Pavithra; Ramamurthy, Viraragavan

    2013-01-01

    Highlights: •Estradiol (E2) at low dose induced cell proliferation in breast cancer cells. •E2 at high concentration induced cell stress in breast cancer cells. •Estrogen receptor physically interacts only with a few transcription factors. •Differential expression of genes with Oct-1 binding sites increased under stress. •Transcription factor binding sites showed distinct spatial distribution on genes. -- Abstract: Background: Breast cancer cells respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. The mechanism of this concentration dependent differential outcome is not well understood yet. Methodology: Meta-analysis of the expression data of MCF7 cells treated with low (1 nM) or high (100 nM) dose of estradiol (E2) was performed. We identified genes differentially expressed at the low or the high dose, and examined the nature of regulatory elements in the vicinity of these genes. Specifically, we looked for the difference in the presence, abundance and spatial distribution of binding sites for estrogen receptor (ER) and selected transcription factors (TFs) in the genomic region up to 25 kb upstream and downstream from the transcription start site (TSS) of these genes. Results: It was observed that at high dose E2 induced the expression of stress responsive genes, while at low dose, genes involved in cell cycle were induced. We found that the occurrence of transcription factor binding regions (TFBRs) for certain factors such as Sp1 and SREBP1 were higher on regulatory regions of genes expressed at low dose. At high concentration of E2, genes with a higher frequency of Oct-1 binding regions were predominantly involved. In addition, there were differences in the spatial distribution pattern of the TFBRs in the genomic regions among the two sets of genes. Discussion: E2 induced predominantly proliferative/metabolic response at low concentrations; but at high concentration, stress–rescue responses were induced

  19. Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors

    Energy Technology Data Exchange (ETDEWEB)

    Chandrasekharan, Sabarinath, E-mail: csab@bio.psgtech.ac.in [Department of Biotechnology, PSG College of Technology, Coimbatore 641004 (India); Kandasamy, Krishna Kumar [Max Planck Institute for Biology of Ageing, Cologne (Germany); Dayalan, Pavithra; Ramamurthy, Viraragavan [Department of Biotechnology, PSG College of Technology, Coimbatore 641004 (India)

    2013-08-02

    Highlights: •Estradiol (E2) at low dose induced cell proliferation in breast cancer cells. •E2 at high concentration induced cell stress in breast cancer cells. •Estrogen receptor physically interacts only with a few transcription factors. •Differential expression of genes with Oct-1 binding sites increased under stress. •Transcription factor binding sites showed distinct spatial distribution on genes. -- Abstract: Background: Breast cancer cells respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. The mechanism of this concentration dependent differential outcome is not well understood yet. Methodology: Meta-analysis of the expression data of MCF7 cells treated with low (1 nM) or high (100 nM) dose of estradiol (E2) was performed. We identified genes differentially expressed at the low or the high dose, and examined the nature of regulatory elements in the vicinity of these genes. Specifically, we looked for the difference in the presence, abundance and spatial distribution of binding sites for estrogen receptor (ER) and selected transcription factors (TFs) in the genomic region up to 25 kb upstream and downstream from the transcription start site (TSS) of these genes. Results: It was observed that at high dose E2 induced the expression of stress responsive genes, while at low dose, genes involved in cell cycle were induced. We found that the occurrence of transcription factor binding regions (TFBRs) for certain factors such as Sp1 and SREBP1 were higher on regulatory regions of genes expressed at low dose. At high concentration of E2, genes with a higher frequency of Oct-1 binding regions were predominantly involved. In addition, there were differences in the spatial distribution pattern of the TFBRs in the genomic regions among the two sets of genes. Discussion: E2 induced predominantly proliferative/metabolic response at low concentrations; but at high concentration, stress–rescue responses were induced

  20. Individual and environmental risk factors for high blood lead concentrations in Danish indoor shooters.

    Science.gov (United States)

    Grandahl, Kasper; Suadicani, Poul; Jacobsen, Peter

    2012-08-01

    International studies have shown blood lead at levels causing health concern in recreational indoor shooters. We hypothesized that Danish recreational indoor shooters would also have a high level of blood lead, and that this could be explained by shooting characteristics and the physical environment at the shooting range. This was an environmental case study of 58 male and female shooters from two indoor shooting ranges with assumed different ventilation and cleaning conditions. Information was obtained on general conditions including age, gender, tobacco and alcohol use, and shooting conditions: weapon type, number of shots fired, frequency of stays at the shooting range and hygiene habits. A venous blood sample was drawn to determine blood lead concentrations; 14 non-shooters were included as controls. Almost 60% of the shooters, hereof five out of 14 women, had a blood lead concentration above 0.48 micromol/l, a level causing long-term health concern. All controls had blood lead values below 0.17 micromol/l. Independent significant associations with blood lead concentrations above 0.48 micromol/l were found for shooting at a poorly ventilated range, use of heavy calibre weapons, number of shots and frequency of stays at the shooting range. A large proportion of Danish recreational indoor shooters had potentially harmful blood lead concentrations. Ventilation, amounts of shooting, use of heavy calibre weapons and stays at the shooting ranges were independently associated with increased blood lead. The technical check at the two ranges was performed by the Danish Technological Institute and costs were defrayed by the Danish Rifle Association. To pay for the analyses of blood lead, the study was supported by the The Else & Mogens Wedell-Wedellsborg Foundation. The Danish Regional Capital Scientific Ethics Committee approved the study, protocol number H-4-2010-130.

  1. Oral contraceptives increase insulin-like growth factor binding protein-1 concentration in women with polycystic ovarian disease.

    Science.gov (United States)

    Suikkari, A M; Tiitinen, A; Stenman, U H; Seppälä, M; Laatikainen, T

    1991-05-01

    Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. Seven women with PCOD and five healthy control subjects. An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD.

  2. Evaluation of correlating factors between 238U concentration measured in fine and course atmospheric particles

    International Nuclear Information System (INIS)

    Peixoto, Claudia Marques; Jacomino, Vanusa Maria Feliciano; Barreto, Alberto Avelar; Dias, Vagner Silva; Dias, Fabiana Ferrari

    2009-01-01

    Air quality is ever more important in function of the enormous proportion of human actions that have affected the environment over the last two centuries. Particulate material is one among many pollutants that can cause great risk to human health and the environment. It can be classified as: Total Suspended Particles (TSP), defined simply as particles with less than 50 μm aerodynamic diameter (one group of these particles can be inhaled and may cause health problems, while others may unfavorably affect the population's quality of life, interfering in environmental conditions and impairing normal community activities); and Inhalable Particles (PM 10 ), defined as those particles with less than 10 μm aerodynamic diameter. These particles penetrate the respiratory system and can reach pulmonary alveoli due to their small size, causing serious health damage. The Nuclear Technology Development Center (CDTN) has monitored air quality around its installations since 2000. CDTN's Environmental Monitoring Program (EMP) includes monitoring radioactivity levels contained in atmospheric TSP. In order to optimize its program, CDTN is carrying out a study to estimate the correlation between concentrations of particulate material measured in TSP and those measured in PM 10 , PI 2.5 and PI 1 , as well as determination of activity concentration for each controlled radionuclide in all parts. The objective of this study is to present preliminary results and report 238 U activity concentration results. (author)

  3. Utilization evaluation of factor concentration and frequencyof bleeds among patients with haemophilia "A" and haemophilia "B" in northwest Iran

    Directory of Open Access Journals (Sweden)

    Roya Dolatkhah

    2013-12-01

    Full Text Available Background Haemophilia A and B are X-linked bleeding disorders which result in decreased blood levels of coagulants. According to some studies, Hemophilia Severity Score (HSS is higher in severe Haemophilia A(HA than in severe Haemophilia B(HB. Objectives The aim of this study was comparison of bleed frequency and utilization of factor concentrate between HA and HB patients. Materials/Patients and Methods This is a single institution retrospective study, and we gathered information from records of our Hemophilia Clinic .Our samples consisted of 176 Haemophilia A and 35 Haemophilia B severe and moderate deficient patients. All of our patients used on-demand treatment with plasma derived factor concentrates. Chi-Square , one sample T and Mann-Whitney U tests were used. All the calculations were performed with MedCalc Statistical Software 12.1.4 version. Results Overall admission rates for patients with Haemophilia A were 3.125/patient/year and for Haemophilia B were 0.77/patient/year (P<0.05.The amount of factor concentrates used by our HA patient was 3731500IU of FVIII (21201.704 IU/patient/year, and 611000 IU of Factor IX , by patients with hemophilia B(17457.142 IU/patient/year.The difference in the usage of factor concentrate was not statistically significant (P=0.57. Conclusion The data suggest that the two inherited coagulation disorders (Haemophilia A and Haemophilia B have a different severity of clinical phenotype. Our findings correlate with findings by some other similar studies that have been published recently.

  4. Factors determining the concentration and chemical composition of particulate matter in the air of selected service facilities

    Science.gov (United States)

    Rogula-Kopiec, Patrycja; Pastuszka, Józef; Mathews, Barbara; Widziewicz, Kamila

    2018-01-01

    The link between increased morbidity and mortality and increasing concentrations of particulate matter (PM) resulted in great attention being paid to the presence and physicochemical properties of PM in closed rooms, where people spends most of their time. The least recognized group of such indoor environments are small service facilities. The aim of this study was to identify factors which determine the concentration, chemical composition and sources of PM in the air of different service facilities: restaurant kitchen, printing office and beauty salon. The average PM concentration measured in the kitchen was 5-fold (PM4, particle fraction ≥ 4 μm) and 5.3-fold (TSP, total PM) greater than the average concentration of these PM fractions over the same period. During the same measurement period in the printing office and in the beauty salon, the mean PM concentration was 10- and 4-fold (PM4) and 8- and 3-fold (TSP) respectively greater than the mean concentration of these PM fractions in outdoor air. In both facilities the main source of PM macro-components, especially organic carbon, were chemicals, which are normally used in such places - solvents, varnishes, paints, etc. The influence of some metals inflow from the outdoor air into indoor environment of those facilities was also recognized.

  5. Effects of low concentrations of glyphosate-based herbicide factor 540® on an agricultural stream freshwater phytoplankton community.

    Science.gov (United States)

    Smedbol, Élise; Gomes, Marcelo Pedrosa; Paquet, Serge; Labrecque, Michel; Lepage, Laurent; Lucotte, Marc; Juneau, Philippe

    2018-02-01

    Residual glyphosate from glyphosate based herbicides (GBH) are ubiquitously detected in streams draining agricultural fields, and may affect phytoplankton communities present in these ecosystems. Here, the effects of the exposure (96 h) of a phytoplankton community collected in an agricultural stream to various glyphosate concentrations (1, 5, 10, 50, 100, 500 and 1000 μg l -1 ) of Factor 540 ® GBH were investigated. The lowest GBH concentration of 1 μg l -1 reduced chlorophyll a and carotenoid contents. Low glyphosate concentrations, such as 5 and 10 μg l -1 , promoted changes in the community's structure and reduced the diversity of the main algal species. At glyphosate concentrations ranging from 50 to 1000 μg l -1 , the phytoplankton community's composition was modified and new main species appeared. The highest glyphosate concentrations (500 and 1000 μg l -1 ) affected the shikimate content, the lipid peroxidation and the activity of antioxidant enzymes (superoxide dismutase, catalase and ascorbate peroxidase). These results indicate that GBH can modify structural and functional properties of freshwater phytoplankton communities living in streams located in agricultural areas at glyphosate concentrations much inferior to the 800 μg l -1 threshold set by the Canadian guidelines for the protection of aquatic life. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  6. Reconstituting factor concentrates: Defining Evidence of Coaching Non-Experts (DEVICE) in haemophilia--a prospective randomized feasibility study.

    Science.gov (United States)

    Bidlingmaier, C; Kurnik, K; Hölscher, G; Kappler, M

    2007-09-01

    The introduction of new needleless devices as demanded by the US Department of Labor Occupational Safety and Health Administration (OSHA) has caused problems with the reconstitution of antihaemophilic factor in emergency situations. Our aim therefore was to evaluate the feasibility of a needleless device for reconstitution of antihaemophilic factor for non-haemophilia experts and to define evidence of the need for coaching these physicians via providing two additional photographs illustrating the two key points of the factor reconstitution process. Twenty-eight physicians of a tertiary care university children's hospital were randomized into two groups, either with no further explanation of the reconstitution device or with two additional photographs, showing the two key steps of the procedure. Reconstitution of dummy-factor concentrate was video-taped and evaluated by a blinded helper. Main outcome measure was the successful reconstitution of dummy-factor concentrate and procedure failure respectively. Of the group without explanation of the reconstitution device, only two of 14 physicians were able to reconstitute the dummy-factor concentrate. Of the group receiving two photographs, nine of 14 completed the task successfully (P = 0.0068). The needleless device is not self explaining to non-haemophilia physicians involved in emergency services. Coaching via short to the point instructions as provided by simple visual educational material therefore is crucial to enable these physicians to resolve the expensive emergency drug quickly and correctly. Companies concerned with the production of any devices to dissolve drugs, especially for treatment of rare diseases as haemophilia, therefore should take measures to simplify therapy.

  7. Serum brain-derived neurotrophic factor (BDNF) concentrations in pregnant women with post-traumatic stress disorder and comorbid depression.

    Science.gov (United States)

    Yang, Na; Gelaye, Bizu; Zhong, Qiuyue; Rondon, Marta B; Sanchez, Sixto E; Williams, Michelle A

    2016-12-01

    There is accumulating evidence for the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression. However, the role of BDNF in the pathophysiology of post-traumatic stress disorder (PTSD) remains controversial, and no study has assessed BDNF concentrations among pregnant women with PTSD. We examined early-pregnancy BDNF concentrations among women with PTSD with and without depression. A total of 2928 women attending prenatal care clinics in Lima, Peru, were recruited. Antepartum PTSD and depression were evaluated using PTSD Checklist-Civilian Version (PCL-C) and Patient Health Questionnaire-9 (PHQ-9) scales, respectively. BDNF concentrations were measured in a subset of the cohort (N = 944) using a competitive enzyme-linked immunosorbent assay (ELISA). Logistic regression procedures were used to estimate odds ratios (OR) and 95 % confidence intervals (95 % CI). Antepartum PTSD (37.4 %) and depression (27.6 %) were prevalent in this cohort of low-income pregnant Peruvian women. Approximately 19.9 % of participants had comorbid PTSD-depression. Median serum BDNF concentrations were lower among women with comorbid PTSD-depression as compared with women without either condition (median [interquartile range], 20.44 [16.97-24.30] vs. 21.35 [17.33-26.01] ng/ml; P = 0.06). Compared to the referent group (those without PTSD and depression), women with comorbid PTSD-depression were 1.52-fold more likely to have low (BDNF concentrations (OR = 1.52; 95 % CI 1.00-2.31). We observed no evidence of reduced BDNF concentrations among women with isolated PTSD. BDNF concentrations in early pregnancy were only minimally and non-significantly reduced among women with antepartum PTSD. Reductions in BDNF concentrations were more pronounced among women with comorbid PTSD-depression.

  8. Vitamin E concentration in human milk and associated factors: a literature review.

    Science.gov (United States)

    Lima, Mayara S R; Dimenstein, Roberto; Ribeiro, Karla D S

    2014-01-01

    To systematize information about vitamin E concentration in human milk and the variables associated with this composition in order to find possible causes of deficiency, supporting strategies to prevent it in postpartum women and infants. Studies published between 2004 and 2014 that assayed alpha-tocopherol in human milk of healthy women by high performance liquid chromatography were evaluated. The keywords used were "vitamin E", "alpha-tocopherol", "milk, human", "lactation", and equivalents in Portuguese, in the BIREME, CAPES, PubMed, SciELO, ISI Web of Knowledge, HighWire Press, Ingenta, and Brazilian Digital Library of Theses and Dissertations databases. Of the 41 publications found on the subject, 25 whose full text was available and met the inclusion criteria were selected. The alpha-tocopherol concentrations found in milk were similar in most populations studied. The variable phase of lactation was shown to influence vitamin E content in milk, which is reduced until the mature milk appears. Maternal variables parity, anthropometric nutritional status, socioeconomic status, and habitual dietary intake did not appear to affect the alpha-tocopherol levels in milk. However, the influence of the variables maternal age, gestational age, biochemical nutritional status in alpha-tocopherol, and maternal supplementation with vitamin E had conflicting results in the literature. Alpha-tocopherol concentration in milk decreases during lactation, until the mature milk appears. To confirm the influence of some maternal and child variables on milk vitamin E content, further studies with adequate design are needed. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  9. Diminished concentrations of insulin-like growth factor I in cystic fibrosis

    DEFF Research Database (Denmark)

    Laursen, Erik; Juul, A; Lanng, S

    1995-01-01

    Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data...

  10. Concentration factors of radionuclides and trace metals in Mytilus galloprovincialis in an estuarine ecosystem - North Aegean Sea - Greece

    International Nuclear Information System (INIS)

    Florou, H.; Catsiki, A.B.; Papaefthymiou, H.; Chaloulou, Ch.

    2004-01-01

    Mussels are worldwide recognized as pollution bio-indicator organisms (Mussel watch program of CIESM) because they accumulate pollutants in their tissues at elevated levels in terms of biological availability in the marine environment. In the present study, the levels of 137 Cs, Cr, Cu, Mn and Zn were measured in Mytilus galloprovincialis caught from Thermaikos gulf in North Aegean Sea Greece. The samples were collected seasonally from two aqua-cultures during the period 2000 2003. Measured and published concentrations of the above elements in seawater were used for the evaluation of concentration factors by applying a linear and a non-linear regression analysis. The variation in between the two stations and the seasonal evolution of bioaccumulation of the examined elements was also investigated. Some data on the concentrations of the measured elements in sediments from the area considered were evaluated as for determining the pollution conditions of the organism habitat. (author)

  11. Influence of concentration and hydrodynamic factors in sorption of iodine by anion-exchangers of the mass-transfer rate

    International Nuclear Information System (INIS)

    Sokolov, V.V.; Smirnov, N.N.

    1982-01-01

    An investigation of the joint influence of hydrodynamic and concentration factors in sorption of iodine by AV-17-8 and anion exchange resins on the mass-transfer coefficient is the subject of this report. The method of central composite rotatable experimental design was used for quantitative assessment and derivation of the appropriate equations. The investigation yielded the necessary regression equations satisfactorily describing the influence of all the factors in the mass-transfer coefficient. the optimal mass-transfer conditions were determined. On the basis of the values obtained, recommendations are made on the optimal hydrodynamic conditions of operation of equipment with pneumatic circulation of the ion-exchanger

  12. Spectra of the W VIII isoelectronic sequence: III. Re IX

    International Nuclear Information System (INIS)

    Ryabtsev, A N; Kononov, E Ya; Kildiyarova, R R; Tchang-Brillet, W-Ü L; Wyart, J-F; Champion, N; Blaess, C

    2015-01-01

    Rhenium spectra excited in vacuum spark sources of different setups and electric circuits were recorded on two high resolution vacuum spectrographs: a 10 m normal incidence spectrograph with a 3600 l mm −1 grating in the Meudon Observatory and a 3 m grazing incidence spectrograph with a 3600 l mm −1 grating in the Institute of Spectroscopy in Troitsk. A total of 112 lines in the region 146–244 Å were identified as transitions from the interacting excited even configurations 4f 12 5s 2 5p 6 5d + 4f 13 5s 2 5p 5 (5d + 6s) + 4f 14 5s 2 5p 4 (5d + 6s) to the low-lying odd configurations 4f 13 5s 2 5p 6 and 4f 14 5s 2 5p 5 . A change of the ground configuration from 4f 13 5s 2 5p 6 to 4f 14 5s 2 5p 5 in a comparison with the previous spectra of the isoelectronic sequence Hf VI–W VIII was observed. Fine structure splittings and relative positions of the odd terms were established, and 83 levels of the excited even configurations were found. (paper)

  13. Organohalogen pollutants in herring from the northern Baltic Sea: Concentrations, congener profiles and explanatory factors

    International Nuclear Information System (INIS)

    Koistinen, Jaana; Kiviranta, Hannu; Ruokojaervi, Paeivi; Parmanne, Raimo; Verta, Matti; Hallikainen, Anja; Vartiainen, Terttu

    2008-01-01

    Organohalogen contaminants were investigated in Baltic herring caught from three catchment areas in the Baltic Sea, off the coasts of Finland. Pools of both small and large herring were analysed for polychlorinated biphenyls (PCB), dibenzo-p-dioxins, dibenzofurans, naphthalenes, camphenes (toxaphene), polybrominated diphenyl ethers and the pesticide DDT and its metabolites. PCB concentrations per fresh weight in small herring were at the same level in all catchment areas, i.e. the Bothnian Bay, the Bothnian Sea and the Gulf of Finland, revealing no hot spots and reflecting most likely long term emissions and atmospheric deposition. Differences in the levels and/or congener profiles of other contaminants between catchment areas may be explained by point sources. Similar concentrations in small and large herring in the Gulf of Finland were possibly due to their common nutrition. In the other areas, differences between small and large herring most likely reflected their different food sources. - Sources of pollutants are reflected in levels and congener profiles of pollutants in Baltic herring

  14. Factors Affecting Element Concentrations in Eggshells of Three Sympatrically Nesting Waterbirds in Northern Poland.

    Science.gov (United States)

    Kitowski, Ignacy; Jakubas, Dariusz; Indykiewicz, Piotr; Wiącek, Dariusz

    2018-02-01

    Avian eggshells are convenient samples in biomonitoring studies, because they are easily accessible, especially from colonially or semicolonially breeding birds. In the present study, concentrations of 17 elements, including heavy metals and essential elements in post-hatch eggshells, were compared among three species of waterbirds of differing strategies for gaining reserves for egg production and diet: mallard, Anas platyrhynchos (ML, a capital breeder, mainly herbivorous), common tern, Sterna hirundo (CT, an income breeder, piscivorous) and black-headed gull, Chroicocephalus ridibundus (BHG, mixed strategy, omnivorous) and breeding sympatrically in three sites in North Poland. Analyses revealed that Fe, Zn, and Cu levels differed the most in the studied species, which may be explained by various contributions of fish, aquatic plants, and soil invertebrates in their diets. Generally, the studied species' eggshells accumulated amounts of elements comparable to those reported for other waterbirds without putting the growth and development of the embryo at risk. The only exception was very high levels of Cr in ML and CT, which may be explained by their foraging on aquatic organisms in waterbodies polluted by this element. Intersite differences in eggshell concentrations of Ni, Sr, Hg and Cr in CT (an income breeder) may be explained by the influence of local pollution sources (small factories, polluted river).

  15. A study on surveillance of environmental factors affecting the variation of indoor radon concentration

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Shin Ae; Kim, Ok Ja; Lee, Mi Kyeong; Cho, Eun Ok; Choi, Yun Sun; Choi, Jin Kyeong; Park, Seon Hye; Han, Hyeon Sun [Hankook Research, Seoul (Korea, Republic of)

    2000-03-15

    Before the main survey, a preliminary survey was carried out to decide the most suitable type of a radon detector the most appropriate places to install such a radon detector. To this end, three types of detectors were set up in 108 locations, approximately 3% of 3,000 to measure the radon levels, and 102 detectors(94%) were collected. As a result of the preliminary survey, Radtrack was chosen as a radon detector for the main survey, and bedrooms on the first floor of houses and the first floor of public buildings were decided to be the places for the first installment of detectors. It is most desirable to survey the radon concentrations in all houses nationwide. Considering the survey period and budgets, however, 3,000 spots were targeted for the main survey at the recommendation of the Korea Institute of Nuclear Safety in charge of this study. As it is important to maintain the same panels for a year to measure the radon concentrations at 3,000 locations, a total of 3,237 panels, 10% more than the target sample number, were surveyed considering the possible loss of panels during the survey period. The first radon detector was installed in each of 3,237 spots in December 1999, and collected three months later in March 2000, followed by the installment of the second detector.

  16. Diet and metabolic state are the main factors determining concentrations of perfluoroalkyl substances in female polar bears from Svalbard.

    Science.gov (United States)

    Tartu, Sabrina; Bourgeon, Sophie; Aars, Jon; Andersen, Magnus; Lone, Karen; Jenssen, Bjørn Munro; Polder, Anuschka; Thiemann, Gregory W; Torget, Vidar; Welker, Jeffrey M; Routti, Heli

    2017-10-01

    Perfluoroalkyl substances (PFASs) have been detected in organisms worldwide, including Polar Regions. The polar bear (Ursus maritimus), the top predator of Arctic marine ecosystems, accumulates high concentrations of PFASs, which may be harmful to their health. The aim of this study was to investigate which factors (habitat quality, season, year, diet, metabolic state [i.e. feeding/fasting], breeding status and age) predict PFAS concentrations in female polar bears captured on Svalbard (Norway). We analysed two perfluoroalkyl sulfonates (PFSAs: PFHxS and PFOS) and C 8 -C 13 perfluoroalkyl carboxylates (PFCAs) in 112 plasma samples obtained in April and September 2012-2013. Nitrogen and carbon stable isotope ratios (δ 15 N, δ 13 C) in red blood cells and plasma, and fatty acid profiles in adipose tissue were used as proxies for diet. We determined habitat quality based on movement patterns, capture position and resource selection functions, which are models that predict the probability of use of a resource unit. Plasma urea to creatinine ratios were used as proxies for metabolic state (i.e. feeding or fasting state). Results were obtained from a conditional model averaging of 42 general linear mixed models. Diet was the most important predictor of PFAS concentrations. PFAS concentrations were positively related to trophic level and marine diet input. High PFAS concentrations in females feeding on the eastern part of Svalbard, where the habitat quality was higher than on the western coast, were likely related to diet and possibly to abiotic factors. Concentrations of PFSAs and C 8 -C 10 PFCAs were higher in fasting than in feeding polar bears and PFOS was higher in females with cubs of the year than in solitary females. Our findings suggest that female polar bears that are exposed to the highest levels of PFAS are those 1) feeding on high trophic level sea ice-associated prey, 2) fasting and 3) with small cubs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Increasing Polymer Solar Cell Fill Factor by Trap-Filling with F4-TCNQ at Parts Per Thousand Concentration.

    Science.gov (United States)

    Yan, Han; Manion, Joseph G; Yuan, Mingjian; García de Arquer, F Pelayo; McKeown, George R; Beaupré, Serge; Leclerc, Mario; Sargent, Edward H; Seferos, Dwight S

    2016-08-01

    Intrinsic traps in organic semiconductors can be eliminated by trap-filling with F4-TCNQ. Photovoltaic tests show that devices with F4-TCNQ at parts per thousand concentration outperform control devices due to an improved fill factor. Further studies confirm the trap-filling pathway and demonstrate the general nature of this finding. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Air exchanges and indoor carbon dioxide concentration in Australian pig buildings: Effect of housing and management factors

    DEFF Research Database (Denmark)

    Banhazi, T. M.; Stott, P.; Rutley, D.

    2011-01-01

    There has been a growing interest in improving air quality within livestock buildings. However, the influence of housing and management factors on air exchange rates and indoor gas concentrations is not well understood. The aim of this study was to determine the effects of housing and management...... production, although these buildings may not always provide an optimal environment for pig production. (C) 2011 IAgrE. Published by Elsevier Ltd. All rights reserved....

  19. The importance of biological factors affecting trace metal concentration as revealed from accumulation patterns in co-occurring terrestrial invertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Hendrickx, Frederik; Maelfait, Jean-Pierre; Bogaert, Nicolas; Tojal, Catarina; Du Laing, Gijs; Tack, Filip M.G.; Verloo, Marc G

    2004-02-01

    As physicochemical properties of the soil highly influence the bioavailable fraction of a particular trace metal, measured metal body burdens in a particular species are often assumed to be more reliable estimators of the contamination of the biota. To test this we compared the Cd, Cu and Zn content of three spiders (generalist predators) and two amphipods (detritivores), co-occurring in seven tidal marshes along the river Schelde, between each other and with the total metal concentrations and the concentrations of four sequential extractions of the soils. Correlations were significant in only one case and significant sitexspecies interactions for all metals demonstrate that factors affecting metal concentration were species and site specific and not solely determined by site specific characteristics. These results emphasize that site and species specific biological factors might be of the utmost importance in determining the contamination of the biota, at least for higher trophic levels. A hypothetical example clarifies these findings. - Site and species specific biological factors are important in determining contamination of biota.

  20. INSIGHT in risk factors and treatment of inhibitors in nonsevere hemophilia A

    NARCIS (Netherlands)

    van Velzen, A.S.

    2016-01-01

    Hemophilia A is an inherited X-linked bleeding disorder that occurs in male offspring of carrier females. In these individuals a mutation in the F8 gene, located on the X-chromosome, causes a deficiency of the factor VIII protein, clotting factor VIII. The worldwide prevalence of hemophilia is 1 in

  1. Worldwide estimation of river concentrations of any chemical originating from sewage-treatment plants using dilution factors.

    Science.gov (United States)

    Keller, Virginie D J; Williams, Richard J; Lofthouse, Caryn; Johnson, Andrew C

    2014-02-01

    Dilution factors are a critical component in estimating concentrations of so-called "down-the-drain" chemicals (e.g., pharmaceuticals) in rivers. The present study estimated the temporal and spatial variability of dilution factors around the world using geographically referenced data sets at 0.5° × 0.5° resolution. Domestic wastewater effluents were derived from national per capita domestic water use estimates and gridded population. Monthly and annual river flows were estimated by accumulating runoff estimates using topographically derived flow directions. National statistics, including the median and interquartile range, were generated to quantify dilution factors. Spatial variability of the dilution factor was found to be considerable; for example, there are 4 orders of magnitude in annual median dilution factor between Canada and Morocco. Temporal variability within a country can also be substantial; in India, there are up to 9 orders of magnitude between median monthly dilution factors. These national statistics provide a global picture of the temporal and spatial variability of dilution factors and, hence, of the potential exposure to down-the-drain chemicals. The present methodology has potential for a wide international community (including decision makers and pharmaceutical companies) to assess relative exposure to down-the-drain chemicals released by human pollution in rivers and, thus, target areas of potentially high risk. © 2013 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

  2. Reduced serum concentrations of brain-derived neurotrophic factor (BDNF) in transsexual Brazilian men.

    Science.gov (United States)

    Fontanari, Anna Martha Vaitses; Costa, Angelo Brandelli; Aguiar, Bianca; Tusset, Cíntia; Andreazza, Tahiana; Schneider, Maiko; da Rosa, Eduarda Dias; Soll, Bianca Machado Borba; Schwarz, Karine; da Silva, Dhiordan Cardoso; Borba, André Oliveira; Mueller, Andressa; Massuda, Raffael; Lobato, Maria Inês Rodrigues

    2016-09-06

    Serum BDNF levels are significantly decreased in transsexual Brazilian women when compared to cis-sexual men. Since transsexual men are also exposed to chronic social stress and have a high prevalence of associated psychopathologies, it is plausible to inquire if BDNF serum levels are altered in transsexual men as well. Therefore, our objective was to evaluate differences in BDNF serum level of transsexual men when compared to cis-sexual men and women. Our sample comprises 27 transsexual men, 31 cis-sexual women and 30 cis-sexual men recruited between 2011 and 2015. We observed that BDNF serum concentration is decreased in transsexual men comparing to cis-sexual men and women. Cross-sex hormone treatment, chronic social stress or long-term gender dysphoria (GD) could explain the variation found in BDNF serum levels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Antepartal insulin-like growth factor concentrations indicating differences in the metabolic adaptive capacity of dairy cows.

    Science.gov (United States)

    Piechotta, Marion; Holzhausen, Lars; Araujo, Marcelo Gil; Heppelmann, Maike; Sipka, Anja; Pfarrer, Chistiane; Schuberth, Hans-Joachim; Bollwein, Heinrich

    2014-01-01

    Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-I(high) or IGF-I(low)), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 ± 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p 0.05). Thyroxine levels and ALS expression were higher in the IGF-I(high) cows compared to IGF-I(low) cows. Estradiol concentration tended to be greater in the IGF-I(low) group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study.

  4. Antepartal insulin-like growth factor concentrations indicating differences in the metabolic adaptive capacity of dairy cows

    Science.gov (United States)

    Holzhausen, Lars; Araujo, Marcelo Gil; Heppelmann, Maike; Sipka, Anja; Pfarrer, Chistiane; Schuberth, Hans-Joachim; Bollwein, Heinrich

    2014-01-01

    Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-Ihigh or IGF-Ilow), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 ± 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p 0.05). Thyroxine levels and ALS expression were higher in the IGF-Ihigh cows compared to IGF-Ilow cows. Estradiol concentration tended to be greater in the IGF-Ilow group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study. PMID:24962413

  5. Phenylketonuria is not a risk factor for changes of inflammation status as assessed by interleukin 6 and interleukin 8 concentrations.

    Science.gov (United States)

    Mozrzymas, Renata; Duś-Żuchowska, Monika; Kałużny, Łukasz; Wenska-Chyży, Ewa; Walkowiak, Jarosław

    2016-01-01

    High oxidative stress and a reduced potential for free radical scavenging in phenylketonuria (PKU) patients, a phenomenon confirmed in a few studies, may lead to systemic chronic inflammation. The aim of this study was to compare the inflammation status, as assessed by interleukin 6 and interleukin 8 concentrations, in patients with PKU and in healthy controls. Twenty patients with classical PKU, aged 18-34 years and under dietary control, were enrolled in the study. The control group comprised of 20 healthy subjects matched for age and sex. Interleukin 6 and 8 levels were measured by enzyme-linked immunosorbent assay (ELISA) kits in all study participants. IL-6 concentrations in the study group ranged from 0.74 pg/ml to 1.34 pg/ml. No significant differences were found between IL-6 concentration between the study group and the control group (p = 0.989). IL-8 concentrations ranged from 17.56 pg/ml to 20.87 pg/ml. The obtained results of IL-8 levels did not differ significantly between the study group and control group (p = 0.192). No significant correlation was observed between Phe blood levels and IL-6 or IL-8 concentrations in the study group (ρ respectively: -0.225, 0.177). In a multivariate analysis, neither IL-6 nor IL-8 concentrations were correlated with sex, age, BMI and Phe levels. Phenylketonuria is not a risk factor for changes of inflammation status as assessed by IL-6 and IL-8 concentrations.

  6. Increase of ozone concentrations, its temperature sensitivity and the precursor factor in South China

    Directory of Open Access Journals (Sweden)

    Y. C. Lee

    2014-08-01

    Full Text Available Concerns have been raised about the possible connections between the local and regional photochemical problem and global warming. The current study assesses the trend of ozone in Hong Kong and the Pearl River Delta (PRD in South China and investigates the interannual changes of sensitivity of ozone to air temperature, as well as the trends in regional precursors. Results reveal, at the three monitoring sites from the mid-1990s to 2010, an increase in the mean ozone concentrations from 1.0 to 1.6 µg m−3 per year. The increase occurred in all seasons, with the highest rate in autumn. This is consistent with trends and temperature anomalies in the region. The increase in the sensitivity of ozone to temperature is clearly evident from the correlation between ozone (OMI [Ozone Monitoring Instrument] column amount and surface air temperature (from the Atmospheric Infrared Sounder displayed in the correlation maps for the PRD during the prominently high ozone period of July–September. It is observed to have increased from 2005 to 2010, the latter being the hottest year on record globally. To verify this temporal change in sensitivity, the ground-level trends of correlation coefficients/regression slopes are analysed. As expected, results reveal a statistically significant upward trend over a 14-year period (1997–2010. While the correlation revealed in the correlation maps is in agreement with the corresponding OMI ozone maps when juxtaposed, temperature sensitivity of surface ozone also shows an association with ozone concentration, with R=0.5. These characteristics of ozone sensitivity are believed to have adverse implications for the region. As shown by ground measurements and/or satellite analyses, the decrease in nitrogen oxides (NO2 and NOx in Hong Kong is not statistically significant while NO2 of the PRD has only very slightly changed. However, carbon dioxide has remarkably declined in the whole region. While these observations concerning

  7. The use of autologous concentrated growth factors to promote syndesmosis fusion in the Agility total ankle replacement. A preliminary study.

    Science.gov (United States)

    Coetzee, J Chris; Pomeroy, Gregory C; Watts, J David; Barrow, Craig

    2005-10-01

    The Agility (DePuy, Warsaw, Indiana) total ankle replacement has been in use since 1984. One of the most common complications continues to be delayed union or nonunions of the distal tibiofibular syndesmosis. In the reported studies on the Agility ankle the delayed union and nonunion rate can be as high as 38%. Since 1999, 114 Agility total ankle replacements were done at two centers in the United States without the use of autologous concentrated growth factors. Since July of 2001, 66 Agility ankles were implanted with Symphony (DePuy, Warsaw, Indiana) augmented bone grafting. The standard operative technique was followed in all the patients. Prospective data was collected on all patients. The standard ankle radiographs were taken preoperatively and postoperative at 8 weeks, 12 weeks, 16 weeks, 6 months, and yearly. CT scans were obtained at 6 months if fusion at the syndesmosis was questionable. The Graphpad Instat software (Graphpad Software Inc., San Diego, CA) was used for statistical analysis. The two-tailed unpaired t-test was used, and the value ankle replacements without autologous concentrated growth factors 70 fused at 8 weeks (61%), 14 fused at 12 weeks (12%), 13 fused at 6 months (12%). There were 17 nonunions (15%); delayed unions (3 to 6 months) and nonunions, therefore, equaled 27%. The syndesmosis fused in 50 of the 66 ankle replacements (76%) that had autologous concentrated growth fractures at 8 weeks (76%); 12 fused at 3 months (18%), 2 fused at 6 months (3%), 2 had nonunions (3%). Delayed unions (3 to 6 months) and nonunions equaled 6%. There was a statistically significant improvement in the 8- and 12-week fusion rates, and a statistically significant reduction in delayed unions and nonunions. Autologous concentrated growth factors appear to make a significant positive difference in the syndesmosis union rate in total ankle replacements.

  8. Hair cortisol concentration is unaffected by basic military training, but related to sociodemographic and environmental factors.

    Science.gov (United States)

    Boesch, Maria; Sefidan, Sandra; Annen, Hubert; Ehlert, Ulrike; Roos, Lilian; Van Uum, Stan; Russell, Evan; Koren, Gideon; La Marca, Roberto

    2015-01-01

    The analysis of hair cortisol concentrations (HCC) is a promising new biomarker for retrospective measurement of chronic stress. The effect of basic military training (BMT) on chronic stress has not yet been reported. The aim of this study was to investigate the effect of 10-week BMT on HCC, while further exploring the role of known and novel covariates. Young healthy male recruits of the Swiss Army participated twice, 10 weeks apart, in data collection (1st examination: n = 177; 2nd examination: n = 105). On two occasions, we assessed HCC, perceived stress and different candidate variables that may affect HCC (e.g. socioeconomic status, meteorological data). Military training increased perceived stress from the first to the second examination, but did not affect HCC. In line with this, there was no correlation between HCC and perceived stress ratings. This could be interpreted as a missing influence of mainly physical stress (e.g. exercise) on HCC. In contrast, significant correlations were found between HCC and ambient temperature, humidity and education. Future studies should control for meteorological data and educational status when examining HCC.

  9. Source contributions to PM10 and arsenic concentrations in Central Chile using positive matrix factorization

    Science.gov (United States)

    Hedberg, Emma; Gidhagen, Lars; Johansson, Christer

    Sampling of particles (PM10) was conducted during a one-year period at two rural sites in Central Chile, Quillota and Linares. The samples were analyzed for elemental composition. The data sets have undergone source-receptor analyses in order to estimate the sources and their abundance's in the PM10 size fraction, by using the factor analytical method positive matrix factorization (PMF). The analysis showed that PM10 was dominated by soil resuspension at both sites during the summer months, while during winter traffic dominated the particle mass at Quillota and local wood burning dominated the particle mass at Linares. Two copper smelters impacted the Quillota station, and contributed to 10% and 16% of PM10 as an average during summer and winter, respectively. One smelter impacted Linares by 8% and 19% of PM10 in the summer and winter, respectively. For arsenic the two smelters accounted for 87% of the monitored arsenic levels at Quillota and at Linares one smelter contributed with 72% of the measured mass. In comparison with PMF, the use of a dispersion model tended to overestimate the smelter contribution to arsenic levels at both sites. The robustness of the PMF model was tested by using randomly reduced data sets, where 85%, 70%, 50% and 33% of the samples were included. In this way the ability of the model to reconstruct the sources initially found by the original data set could be tested. On average for all sources the relative standard deviation increased from 7% to 25% for the variables identifying the sources, when decreasing the data set from 85% to 33% of the samples, indicating that the solution initially found was very stable to begin with. But it was also noted that sources due to industrial or combustion processes were more sensitive for the size of the data set, compared to the natural sources as local soil and sea spray sources.

  10. Agnostic stacking of intergalactic doublet absorption: measuring the Ne VIII population

    Science.gov (United States)

    Frank, Stephan; Pieri, Matthew M.; Mathur, Smita; Danforth, Charles W.; Shull, J. Michael

    2018-05-01

    We present a blind search for doublet intergalactic metal absorption with a method dubbed `agnostic stacking'. Using a forward-modelling framework, we combine this with direct detections in the literature to measure the overall metal population. We apply this novel approach to the search for Ne VIII absorption in a set of 26 high-quality COS spectra. We probe to an unprecedented low limit of log N>12.3 at 0.47≤z ≤1.34 over a path-length Δz = 7.36. This method selects apparent absorption without requiring knowledge of its source. Stacking this mixed population dilutes doublet features in composite spectra in a deterministic manner, allowing us to measure the proportion corresponding to Ne VIII absorption. We stack potential Ne VIII absorption in two regimes: absorption too weak to be significant in direct line studies (12.3 13.7). We do not detect Ne VIII absorption in either regime. Combining our measurements with direct detections, we find that the Ne VIII population is reproduced with a power-law column density distribution function with slope β = -1.86 ^{+0.18 }_{ -0.26} and normalization log f_{13.7} = -13.99 ^{+0.20 }_{ -0.23}, leading to an incidence rate of strong Ne VIII absorbers dn/dz =1.38 ^{+0.97 }_{ -0.82}. We infer a cosmic mass density for Ne VIII gas with 12.3 value significantly lower that than predicted by recent simulations. We translate this density into an estimate of the baryon density Ωb ≈ 1.8 × 10-3, constituting 4 per cent of the total baryonic mass.

  11. Vascular Endothelial Growth Factor Concentration in Chronic Subdural Hematoma Fluid Is Related to Computed Tomography Appearance and Exudation Rate

    Science.gov (United States)

    Weigel, Ralf; Hohenstein, Axel

    2014-01-01

    Abstract Chronic subdural hematoma (CSH) is characterized by a net increase of volume over time. Major underlying mechanisms appear to be hemorrhagic episodes and a continuous exudation, which may be studied using labeled proteins to yield an exudation rate in a given patient. We tested the hypothesis that the concentration of vascular endothelial growth factor (VEGF) in hematoma fluid correlates with the rate of exudation. Concentration of VEGF was determined in 51 consecutive patients with CSH by the sandwich immune enzyme-linked immunosorbent assay technique. Mean values were correlated with exudation rates taken from the literature according to the appearance of CSH on computed tomography (CT) images. The CT appearance of each CSH was classified as hypodense, isodense, hyperdense, or mixed density. Mean VEGF concentration was highest in mixed-density hematomas (22,403±4173 pg/mL; mean±standard error of the mean; n=27), followed by isodense (9715±1287 pg/mL; n=9) and hypodense (5955±610 pg/mL; n=18) hematomas. Only 1 patient with hyperdense hematoma fulfilled the inclusion criteria, and the concentration of VEGF found in this patient was 24,200 pg/mL. There was a statistically significant correlation between VEGF concentrations and exudation rates in the four classes of CT appearance (r=0.98). The current report is the first to suggest a pathophysiological link between the VEGF concentration and the exudation rate underlying the steady increase of hematoma volume and CT appearance.With this finding, the current report adds another piece of evidence in favor of the pathophysiological role of VEGF in the development of CSH, including mechanisms contributing to hematoma growth and CT appearance. PMID:24245657

  12. 137Cs concentrations in northern Alaskan Eskimos, 1962-79: effects of ecological, cultural and political factors

    International Nuclear Information System (INIS)

    Hanson, W.C.

    1982-01-01

    Concentrations of worldwide fallout 137 Cs were measured in the lichen-caribou-Eskimo food chain of northern Alaska during the period 1962-79. Pronounced inputs of fallout occurred after major nuclear weapons tests in the atmosphere and 137 Cs was transmitted through the food chain to Eskimos with about a 2-yr delay due to environmental parameters. Caribou (Rangifer tarandus) meat sampled during spring harvest contained 4 times the 137 Cs concentration of lichens obtained from their winter range. Calculated caribou meat ingestion rates of Anaktuvuk Pass Eskimos during winter ranged from approximately equal to 1 kg/day in 1964 to 0.16 kg/day in 1977. Several environmental factors affected seasonal patterns and amounts of 137 Cs transferred through the food chain. Maximum 137 Cs concentrations of approximately equal to 20 nCi/kg body weight in Eskimos occurred in 1964 and have now decreased to approximately equal to 0.5 nCi/kg, largely because of cultural and political factors. Radiation doses from 137 Cs body burdens during the study period ranged from 60 mrad/yr in 1962 to approximately equal to 140 mrad/yr during the 1962-64 maxima and decreased to 8 mrad/yr in 1979. (author)

  13. On existence and properties of plutonium(VIII) derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Kiselev, Yu.M.; Dolzhenko, V.D.; Ermilov, A.Yu. [Moscow State Univ. (Russian Federation). Chemistry Dept.; Nikonov, M.V.; Myasoedov, B.F. [Russian Academy of Science, Moscow (Russian Federation). Inst. of Geochemistry and Analytical Chemistry; Tananaev, I.G. [Russian Academy of Science, Moscow (Russian Federation). Inst. of Physical Chemistry and Electrochemistry

    2014-04-01

    The existence of Pu(VIII) was shown in alkaline solutions and in nonpolar solvents (CCl{sub 4} and CHCl{sub 3}) on the ground of such experimental facts like extraction of plutonium species, obtained by means of ozonization of Pu(VI) alkaline solutions into CCl{sub 4} and CHCl{sub 3}; volatility of Pu compounds out of aqueous alkaline solutions, and the mentioned solvents. The product of interaction between PuO{sub 3}.0.8H{sub 2}O and XeF{sub 2} in CCl{sub 4} and CHCl{sub 3} was of the same chemical form for both cases and identical with the form of the product of volatility of Pu out of these organic solutions. The electronic absorbance spectra of these products in CCl{sub 4} and CHCl{sub 3} were fairly similar to the ones for OsO{sub 4} and RuO{sub 4}. The band of absorption in these spectra with the maximum at 332 nm corresponds to the charge transfer of metal-ligand type [π(O)→Pu], as the value of molar extinction coefficient e was found to be higher than 2 x 10{sup 3} L/mole cm. A satisfactory agreement between the energies for the transitions of PuO{sub 4} molecule designed by X{sub α}-SW method and experimental data was observed. A similar accordance was observed for the designed vibration frequency (DFT-method) with the one found as result of analysis of the vibration structure of the experimental spectra. (orig.)

  14. Separation method for ions of elements of the III., IV., VI. and VIII. groups of periodical system

    International Nuclear Information System (INIS)

    Marhol, M.

    1973-01-01

    The method is presented of separating the ions of the elements of the periodic system groups III, IV, and VIII by ion exchangers. The ions are complex-bonded to a new type of ion exchanger consisting of the polycondensates of phenol with aldehydes or ketones and containing an atom of phosphorus, arsenic or antimony with an atom of sulphur or oxygen in a complex bond. The polymers of compounds containing a double bond, e.g., of butadiene, polyvinyl alcohol, polyethylene, polypropylene, and the compounds of styrene with fural may also be used for this purpose. The method is demonstrated on a case of uranium and heavy metal concentration and the separation thereof from waste waters. (L.K.)

  15. Thermodynamics of mixtures containing amines. IX. Application of the concentration-concentration structure factor to the study of binary mixtures containing pyridines

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, Juan Antonio, E-mail: jagl@termo.uva.es [G.E.T.E.F. Dpto Termodinamica y Fisica Aplicada, Facultad de Ciencias, Universidad de Valladolid, Valladolid 47071 (Spain); Cobos, Jose Carlos; Garcia de la Fuente, Isaias; Mozo, Ismael [G.E.T.E.F. Dpto Termodinamica y Fisica Aplicada, Facultad de Ciencias, Universidad de Valladolid, Valladolid 47071 (Spain)

    2009-10-10

    Binary mixtures formed by a pyridine base and an alkane, or an aromatic hydrocarbon, or a 1-alkanol have been studied in the framework of the concentration-concentration structure factor, S{sub CC}(0), formalism. Deviations between experimental data and those provided by the DISQUAC model are discussed. Systems containing alkanes are characterized by homocoordination. In pyridine + alkane mixtures, S{sub CC}(0) decreases with the chain length of the longer alkanes, due to size effects. For a given alkane, S{sub CC}(0) also decreases with the number of CH{sub 3}- groups in the pyridine base. This has been interpreted assuming that the number of amine-amine interactions available to be broken upon mixing also decreases similarly, probably as steric hindrances exerted by the methyl groups of the aromatic amine increase with the number of these groups. Homocoordination is higher in mixtures with 3,5-dimethylpyridine than in those with 2,6-dimethylpyridine. That is, steric effects exerted by methyl groups in positions 3 and 5 are stronger than when they are in positions 2 and 6. Similarly, from the application of the DISQUAC (dispersive-quasichemical) model, it is possible to conclude that homocoordination is higher in systems with 3- or 4-methylpyridine than in those involving 2-methylpyridine. Systems including aromatic hydrocarbons are nearly ideal, which seems to indicate that there is no specific interaction in such solutions. Mixtures with 1-alkanols show heterocoordination. This reveals the existence of interactions between unlike molecules, characteristic of alkanol + amine mixtures. Methanol systems show the lowest S{sub CC}(0) values due, partially, to size effects. This explains the observed decrease of homocoordination in such solutions in the order: pyridine > 2-methylpyridine > 2,6-dimethylpyridine. Moreover, as the energies of the OH-N hydrogen bonds are practically independent of the pyridine base considered when mixed with methanol, it suggests that

  16. The Effect of Exercise Training on Resting Concentrations of Peripheral Brain-Derived Neurotrophic Factor (BDNF: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Adam Dinoff

    Full Text Available The mechanisms through which physical activity supports healthy brain function remain to be elucidated. One hypothesis suggests that increased brain-derived neurotrophic factor (BDNF mediates some cognitive and mood benefits. This meta-analysis sought to determine the effect of exercise training on resting concentrations of BDNF in peripheral blood.MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer-reviewed reports of peripheral blood BDNF concentrations before and after exercise interventions ≥ 2 weeks. Risk of bias was assessed using standardized criteria. Standardized mean differences (SMDs were generated from random effects models. Risk of publication bias was assessed using funnel plots and Egger's test. Potential sources of heterogeneity were explored in subgroup analyses.In 29 studies that met inclusion criteria, resting concentrations of peripheral blood BDNF were higher after intervention (SMD = 0.39, 95% CI: 0.17-0.60, p < 0.001. Subgroup analyses suggested a significant effect in aerobic (SMD = 0.66, 95% CI: 0.33-0.99, p < 0.001 but not resistance training (SMD = 0.07, 95% CI: -0.15-0.30, p = 0.52 interventions. No significant difference in effect was observed between males and females, nor in serum vs plasma.Aerobic but not resistance training interventions increased resting BDNF concentrations in peripheral blood.

  17. Contrasting food web factor and body size relationships with Hg and Se concentrations in marine biota.

    Directory of Open Access Journals (Sweden)

    Roxanne Karimi

    Full Text Available Marine fish and shellfish are primary sources of human exposure to mercury, a potentially toxic metal, and selenium, an essential element that may protect against mercury bioaccumulation and toxicity. Yet we lack a thorough understanding of Hg and Se patterns in common marine taxa, particularly those that are commercially important, and how food web and body size factors differ in their influence on Hg and Se patterns. We compared Hg and Se content among marine fish and invertebrate taxa collected from Long Island, NY, and examined associations between Hg, Se, body length, trophic level (measured by δ(15N and degree of pelagic feeding (measured by δ(13C. Finfish, particularly shark, had high Hg content whereas bivalves generally had high Se content. Both taxonomic differences and variability were larger for Hg than Se, and Hg content explained most of the variation in Hg:Se molar ratios among taxa. Finally, Hg was more strongly associated with length and trophic level across taxa than Se, consistent with a greater degree of Hg bioaccumulation in the body over time, and biomagnification through the food web, respectively. Overall, our findings indicate distinct taxonomic and ecological Hg and Se patterns in commercially important marine biota, and these patterns have nutritional and toxicological implications for seafood-consuming wildlife and humans.

  18. Diminished concentrations of insulin-like growth factor I in cystic fibrosis

    DEFF Research Database (Denmark)

    Laursen, Erik; Juul, A; Lanng, S

    1995-01-01

    on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean...... (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r......Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data...

  19. Contrasting Food Web Factor and Body Size Relationships with Hg and Se Concentrations in Marine Biota

    Science.gov (United States)

    Karimi, Roxanne; Frisk, Michael; Fisher, Nicholas S.

    2013-01-01

    Marine fish and shellfish are primary sources of human exposure to mercury, a potentially toxic metal, and selenium, an essential element that may protect against mercury bioaccumulation and toxicity. Yet we lack a thorough understanding of Hg and Se patterns in common marine taxa, particularly those that are commercially important, and how food web and body size factors differ in their influence on Hg and Se patterns. We compared Hg and Se content among marine fish and invertebrate taxa collected from Long Island, NY, and examined associations between Hg, Se, body length, trophic level (measured by δ15N) and degree of pelagic feeding (measured by δ13C). Finfish, particularly shark, had high Hg content whereas bivalves generally had high Se content. Both taxonomic differences and variability were larger for Hg than Se, and Hg content explained most of the variation in Hg:Se molar ratios among taxa. Finally, Hg was more strongly associated with length and trophic level across taxa than Se, consistent with a greater degree of Hg bioaccumulation in the body over time, and biomagnification through the food web, respectively. Overall, our findings indicate distinct taxonomic and ecological Hg and Se patterns in commercially important marine biota, and these patterns have nutritional and toxicological implications for seafood-consuming wildlife and humans. PMID:24019976

  20. Pengembangan Perangkat Pembelajaran Matematika Berbasis Problem Based Learning (PBL untuk Meningkatkan Kemampuan Pemecahan Masalah Peserta Didik Kelas VIII

    Directory of Open Access Journals (Sweden)

    Rizza Yustianingsih

    2017-09-01

    Full Text Available Abstrak. Berdasarkan hasil penelitian pendahuluan pada kelas VIII SMP di lapangan, masih ditemukan kemampuan pemecahan masalah matematis siswa dalam masalah nyata yang belum optimal dan aktivitas siswa tidak mendukung proses belajar mereka. Salah satu faktornya adalah tidak cocoknya perangkat pembelajaran yang dapat memudahkan pembelajar untuk memperbaiki pemecahan kemampuan matematika dan kemampuan belajar siswa. Dari situ, untuk mendasari melakukan pengembangan perangkat pembelajaran matematika, ada rencana rencana pembelajaran (RPP dan lembar kerja siswa (LKPD berbasis Problem Based Learning (PBL, yang dapat memberikan pengalaman belajar untuk belajar pemecahan masalah dan dapat memberikan efek potensial yang baik pada aktivitas siswa selama proses belajar. Data dikumpulkan melalui observasi, kuesioner, wawancara, dan uji kemampuan pemecahan masalah. Subyek penelitian ini adalah siswa kelas VIII SMP N 3 Sawahlunto. Pengembangan penelitian ini yang digunakan adalah mode Plomp yang terdiri dari tahap awal penelitian, tahap prototipe, dan tahap penilaian. Berdasarkan hasil analisis data, terlihat bahwa alat pembelajaran berdasarkan PBL telah memenuhi kriteria yang valid dalam hal isi dan konstruksi. Peralatan pelajaran telah dianggap praktis dalam hal pelaksanaan dan efisiensi penggunaan waktu oleh guru dan siswa. Alat pelajaran juga efektif dalam hal proses penguasaan presentasi siswa belajar setelah menggunakan pembelajaran berbasis perangkat berbasis pembelajaran lebih besar dari atau sama dengan 75% sedangkan dalam hal hasil rata-rata siswa telah aktif dalam belajar. Kata kunci: Perangkat Pelajaran Matematika, Pemecahan Masalah, PBL.   Abstract. Based on the results of preliminary studies at grade VIII SMP in the field, it is still  found a mathematical problem solving ability of students in real problem who have not optimally and students activities do not support their learning process. One of the  factor is unsuitable of learning tools

  1. Comparative Analysis of Cellular and Growth Factor Composition in Bone Marrow Aspirate Concentrate and Platelet-Rich Plasma

    Directory of Open Access Journals (Sweden)

    Hisashi Sugaya

    2018-01-01

    Full Text Available The purpose of this study was to quantify the stem cell and growth factor (GF contents in the bone marrow aspirate concentrate (BMAC and platelet-rich plasma (PRP prepared from whole blood using a protocol established in our laboratory. We examined 10 patients with osteonecrosis of the femoral head who were treated by autologous BMAC transplantation at our hospital between January 2015 and June 2015. We quantified CD34+ and CD31−CD45−CD90+CD105+ cells in BMAC and PRP by flow cytometry. Additionally, we measured various GFs, that is, basic fibroblast growth factor (b-FGF, platelet-derived growth factor-BB (PDGF-BB, vascular endothelial growth factor (VEGF, transforming growth factor-β1 (TGF-β1, and bone morphogenetic protein-2 (BMP-2 in BMAC and PRP using enzyme-linked immunosorbent assays and statistical analyses. CD34+ and CD31−45−90+105+ cells accounted for approximately 1.9% and 0.03% of cells in BMAC and no cells in PRP. The concentration of b-FGF was higher in BMAC than in PRP (P<0.001, whereas no significant differences in the levels of PDGF-BB, VEGF, TGF-β1, and BMP-2 were observed between the two types of sample. BMAC had an average of 1.9% CD34+ and 0.03% CD31−45−90+105+ cells and higher levels of b-FGF than those of PRP.

  2. Application of concentrated growth factors in reconstruction of bone defects after removal of large jaw cysts: The two cases report

    Directory of Open Access Journals (Sweden)

    Mirković Siniša

    2015-01-01

    Full Text Available Introduction. Coagulation and blood clot formation in bone defects is sometimes followed by retraction of a blood clot and serum extrusion, thus producing peripheral serum-filled spaces between bony wall and coagulum. This can result in a higher incidence of postoperative complications. Stabilization of blood coagulum, which enables successful primary healing, may be accomplished by autotransplantation, allotransplantation, xenotransplantation, or application of autologous platelet concentrate and concentrated growth factors (CGF. Case report. Two patients with large cystic lesions in the upper and lower jaw were presented. In both patients postoperative bony defects were filled with autologous fibrin rich blocks containing CGF. Postoperative course passed uneventfully. Conclusion. Application of fibrin rich blocks containing CGF is one of the possible methods for reconstruction of bone defects. CGF can be applied alone or mixed with a bone graft. The method is relatively simple, without risk of transmissible and allergic diseases and economically feasible.

  3. Biological and life-history factors affecting total mercury concentrations in Arctic charr from Heintzelman Lake, Ellesmere Island, Nunavut

    International Nuclear Information System (INIS)

    Velden, Shannon van der; Reist, James D.; Babaluk, John A.; Power, Michael

    2012-01-01

    A snapshot sample of Arctic charr (Salvelinus alpinus) from Heintzelman Lake (81°42′N, 66°56′W), Ellesmere Island, Canada was used to elucidate the biological and life-history factors potentially influencing individual total mercury (THg) concentrations. Migratory history was significant, with anadromous fish having a lower mean THg concentration (64 μg/kg ww) than the non-anadromous Arctic charr (117 μg/kg ww). The increase in individual THg concentration with age was shown to be independent of length-at-age when large and small individuals within the same age groups were compared. Similarly, the diets of individual Arctic charr were comparable regardless of size, and there was no apparent ontogenetic shift in diet that could explain differences in length-at-age or THg concentration among fast- and slow-growing groups of fish (i.e., fish of the same age but differing sizes). Maturity state was also not related to THg concentration, but appears to be related to differences in length-at-age, with slow-growing fish allocating more energy to reproduction than fast-growing conspecifics. The differences in THg concentration among individual Arctic charr were best explained by fish age. We suggest that the increase in mercury concentration with age can be altered by a shift in diet (e.g., to piscivory) or habitat (e.g., anadromy), but is otherwise unaffected by changes in size or length-at-age. -- Highlights: ► Total mercury concentrations ([THg]) were measured in Arctic charr from a single lake in the Canadian high Arctic. ► Anadromous Arctic charr had a significantly lower mean [THg] (64 μg/kg ww) than the non-anadromous fish (117 μg/kg ww). ► Length-at-age (i.e., average somatic growth rate) was not related to mean [THg] when same-age groups were compared. ► Prey resource use, determined by δ 13 C and δ 15 N isotopes and gut contents, was similar among fast- and slow-growing fish. ► Maturity state was not related to [THg], but the slow

  4. Lead and cadmium in human teeth from Jordan by atomic absorption spectrometry: Some factors influencing their concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Alomary, A. [Department of Chemistry, Yarmouk University, Irbid (Jordan)]. E-mail: ahmedalomary1000@hotmail.com; Al-Momani, I.F. [Department of Chemistry, Yarmouk University, Irbid (Jordan); Massadeh, A.M. [Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid (Jordan)

    2006-10-01

    The aim of this study was to measure the concentrations of lead (Pb) and cadmium (Cd) in human teeth and to investigate the affecting factors. Teeth samples (n = 268) were collected from people living in different cities in Jordan including Amman, Zarqa, Al-Mafraq and Irbid and analyzed for Pb and Cd using atomic absorption spectrometry (AAS). A questionnaire was used to gather information on each person, such as age, sex, place where the patient lives, smoking, presence of amalgam fillings inside the mouth, and whether the patient uses toothpaste or not. The mean concentrations of Pb and Cd were 28.91 {mu}g/g and 0.44 {mu}g/g, respectively. The results indicate that there is a clear relation between Pb and Cd concentrations and the presence of amalgam fillings, smoking, and place of living. Pb was sex-dependent, whereas Cd was not. Our results show that Pb and Cd concentrations in samples obtained from Al-Mafraq and Irbid are higher than those obtained from Amman and Zarqa. Pb was highest in Mafraq, whereas Cd was highest in Irbid. The Pb and Cd concentrations in teeth from smokers (means: Pb = 31.89 {mu}g/g, Cd = 0.49 {mu}g/g) were significantly higher than those from nonsmokers (means: Pb = 24.07 {mu}g/g, Cd = 0.37 {mu}g/g). Pb and Cd concentrations in teeth of patients with amalgam fillings (means: Pb = 31.02 {mu}g/g and Cd = 0.52 {mu}g/g) were significantly higher than those from patients without amalgam fillings (means: Pb = 26.87 {mu}g/g and Cd = 0.41 {mu}g/g). Our results show that brushing the teeth daily with toothpaste does not significantly decrease the concentration of both Pb and Cd. The mean concentrations of Pb and Cd do not vary significantly between the ages 20-30, 31-40, and 41-50, but both increased rapidly at age 51-60.

  5. Lead and cadmium in human teeth from Jordan by atomic absorption spectrometry: Some factors influencing their concentrations

    International Nuclear Information System (INIS)

    Alomary, A.; Al-Momani, I.F.; Massadeh, A.M.

    2006-01-01

    The aim of this study was to measure the concentrations of lead (Pb) and cadmium (Cd) in human teeth and to investigate the affecting factors. Teeth samples (n = 268) were collected from people living in different cities in Jordan including Amman, Zarqa, Al-Mafraq and Irbid and analyzed for Pb and Cd using atomic absorption spectrometry (AAS). A questionnaire was used to gather information on each person, such as age, sex, place where the patient lives, smoking, presence of amalgam fillings inside the mouth, and whether the patient uses toothpaste or not. The mean concentrations of Pb and Cd were 28.91 μg/g and 0.44 μg/g, respectively. The results indicate that there is a clear relation between Pb and Cd concentrations and the presence of amalgam fillings, smoking, and place of living. Pb was sex-dependent, whereas Cd was not. Our results show that Pb and Cd concentrations in samples obtained from Al-Mafraq and Irbid are higher than those obtained from Amman and Zarqa. Pb was highest in Mafraq, whereas Cd was highest in Irbid. The Pb and Cd concentrations in teeth from smokers (means: Pb = 31.89 μg/g, Cd = 0.49 μg/g) were significantly higher than those from nonsmokers (means: Pb = 24.07 μg/g, Cd = 0.37 μg/g). Pb and Cd concentrations in teeth of patients with amalgam fillings (means: Pb = 31.02 μg/g and Cd = 0.52 μg/g) were significantly higher than those from patients without amalgam fillings (means: Pb = 26.87 μg/g and Cd = 0.41 μg/g). Our results show that brushing the teeth daily with toothpaste does not significantly decrease the concentration of both Pb and Cd. The mean concentrations of Pb and Cd do not vary significantly between the ages 20-30, 31-40, and 41-50, but both increased rapidly at age 51-60

  6. Wet deposition of mercury in Qingdao, a coastal urban city in China: Concentrations, fluxes, and influencing factors

    Science.gov (United States)

    Chen, Lufeng; Li, Yanbin; Liu, Chang; Guo, Lina; Wang, Xiulin

    2018-02-01

    Mercury (Hg) is a global pollutant of public concern because of its high toxicity and capability for worldwide distribution via long-range atmospheric transportation. Wet atmospheric deposition is an important source of Hg in both terrestrial and aquatic environments. Concentrations of various Hg species in precipitation were monitored from March 2016 to February 2017 in a coastal urban area of Qingdao, and their wet deposition fluxes were estimated. The results showed that the volume-weighted mean (VWM) concentrations of total mercury (THg), reactive mercury (RHg), dissolved THg (DTHg), particulate THg (PTHg), total methylmercury (TMeHg), and dissolved and particulate MeHg (DMeHg and PMeHg) in Qingdao's precipitation were 13.6, 1.5, 5.4, 8.2, 0.38, 0.15, and 0.22 ng L-1, respectively, and their annual deposition fluxes were estimated to be 5703.0 (THg), 666.6 (RHg), 2304.0 (DTHg), 3470.4 (PTHg), 161.6 (TMeHg), 64.0 (DMeHg), and 95.7 (PMeHg) ng m-2 y-1, respectively. A relatively high proportion of MeHg in THg was observed in precipitation (3.0 ± 2.6%) possibly due to higher methylation and contributions from an oceanic source to MeHg in the precipitation. Obvious seasonal variations in Hg concentrations and deposition fluxes were observed in the precipitation in Qingdao. Correlation analyses and multiple regression analyses showed that SO2, pH, and NO3- were the controlling factors for THg in precipitation, whereas the MeHg concentration was primarily controlled by the SO2, WS, Cl-, and THg concentrations. PM2.5 and Cl- were the major controlling factors for PMeHg/TMeHg, whereas the TMeHg/THg ratio was mainly influenced by Cl-. The THg and MeHg fluxes were primarily controlled by precipitation, whereas Cl- was also an important factor for the MeHg wet deposition flux. The results of a 72-h backward trajectory analysis in the study region with the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model indicated that Hg deposition in Qingdao mainly

  7. A field study to evaluate the impact of different factors on the nutrient pollutant concentrations in green roof runoff.

    Science.gov (United States)

    Wang, Xiaochen; Zhao, Xinhua; Peng, Chenrui; Zhang, Xinbo; Wang, Jianghai

    2013-01-01

    The objectives of this study are to investigate the impact of different factors on the nutrient pollutant concentrations in green roof runoff and to provide reference data for the engineering design of dual substrate layer green roofs. The data were collected from eight different trays under three kinds of artificial rains. The results showed that except for total phosphorus, dual substrate layer green roofs behaved as a sink for most of the nutrient pollutants (significant at p green roof and the depth of the adsorption substrates. Compared with the influence of the substrates, the influence of the plant density and drainage systems was small.

  8. Calculation of the thermal utilisation factor in a cell made up of a given number of concentric media

    International Nuclear Information System (INIS)

    Amouyal, A.; Benoist, P.; Guionnet, Ch.

    1961-01-01

    The method of calculating the thermal utilisation factor, described in a previous report, is extended to the case of a cylindrical cell containing a given number of concentric media, certain of which may be empty. A collision by collision method is used in all but the peripheral medium, which may be treated by a theory of controlled diffusion. A programme for the IBM 650 calculator has been based on this method. Some numerical results are presented. An equivalent matrix formulation, due to C. Guionnet, is given as an appendix. (author) [fr

  9. Myosin VIII regulates protonemal patterning and developmental timing in the moss Physcomitrella patens.

    Science.gov (United States)

    Wu, Shu-Zon; Ritchie, Julie A; Pan, Ai-Hong; Quatrano, Ralph S; Bezanilla, Magdalena

    2011-09-01

    Plants have two classes of myosins. While recent work has focused on class XI myosins showing that myosin XI is responsible for organelle motility and cytoplasmic streaming, much less is known about the role of myosin VIII in plant growth and development. We have used a combination of RNAi and insertional knockouts to probe myosin VIII function in the moss Physcomitrella patens. We isolated Δmyo8ABCDE plants demonstrating that myosin VIII is not required for plant viability. However, myosin VIII mutants are smaller than wild-type plants in part due to a defect in cell size. Additionally, Δmyo8ABCDE plants produce more side branches and form gametophores much earlier than wild-type plants. In the absence of nutrient media, Δmyo8ABCDE plants exhibit significant protonemal patterning defects, including highly curved protonemal filaments, morphologically defective side branches, as well as an increase in the number of branches. Exogenous auxin partially rescues protonemal defects in Δmyo8ABCDE plants grown in the absence of nutrients. This result, together with defects in protonemal branching, smaller caulonemal cells, and accelerated development in the Δmyo8ABCDE plants, suggests that myosin VIII is involved in hormone homeostasis in P. patens.

  10. Practical experience and lessons learned through implementation of Appendix VIII performance demonstration requirements

    International Nuclear Information System (INIS)

    Ashwin, P.J.; Becker, F.L.; Latiolais, C.L.; Spanner, J.C.

    1996-01-01

    To provide the US nuclear industry with a uniform implementation of the Performance Demonstration requirements within the 1989 edition of ASME Section XI, Appendix VIII, representatives from all US nuclear utilities formed the Performance Demonstration Initiative (PDI). The PDI recognized the potential benefits that Appendix VIII offered the nuclear industry and initiated a proactive approach to implement the requirements. In doing so it was expected that performance demonstration of ultrasonic examination procedures would allow for improvement in the efficiency and credibility of inservice inspection to be realized. Explicit within the performance demonstration requirements of Appendix VIII is the need for a Performance Demonstration Administrator, a difficult requirement to fulfill. Not only must the administrator exhibit the attributes of understanding the demonstration requirements, but also have solid technical knowledge, integrity and be able to interface with the industry at all levels, from operations to regulatory. For the nuclear industry, the EPRI NDE Center is an obvious choice to fulfill this position. This paper provides a brief background of the PDI, a nuclear industry-wide initiative to implement the performance demonstration requirements of Appendix VIII. Even though the consensus approach adopted by the PDI is discussed, the paper's primary objective is to provide examples of the lessons learned by the Center through the specific requirements of Appendix VIII

  11. Relationships between plasma insulin-like growth factor-1 and insulin concentrations in multiparous dairy cows with cytological endometritis.

    Science.gov (United States)

    Valdmann, Merle; Kurykin, Jevgeni; Kaart, Tanel; Mällo, Gret-Kristel; Waldmann, Andres

    2018-04-21

    Cytological endometritis (CYTO) is a uterine inflammation characterised by the percentage of polymorphonuclear neutrophils in endometrial cytology. This observational study evaluated the association of blood plasma insulin-like growth factor-1 (IGF-1) and insulin concentrations at -2 weeks prepartum, +1 week and +3 weeks postpartum with the development of CYTO in 119 multiparous Holstein cows. Overall CYTO prevalence was 30.3 per cent. Multivariable logistic regression model revealed the odds of developing CYTO were 3.54 times (P=0.018) greater in cows with week -2 prepartum IGF-1 concentrations less than 74.6 ng/ml and 4.41 times (P=0.004) higher in cows with week +1 postpartum IGF-1 concentrations less than 13.2 ng/ml than the odds of this health outcome in cows with IGF-1 concentrations at least 74.6 and13.2 ng/ml, respectively. Additionally, cows with body condition score (BCS) up to 2.75 at week -2 prepartum and cows experiencing calving-related disorders and/or ill health had higher risk for CYTO compared with cows with BCS=3.50-3.75 (OR=6.8, P=0.049) and cows without health complications (OR=3.1, P=0.030). Insulin was not a significant predictor for CYTO in the model. Our findings provide further evidence that reduced dairy cow fertility associated with low plasma concentrations of IGF-1 is in part mediated through the inflammatory status of the uterus. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. A comparative study of metabolism and concentration factors of Fe, Cu, Zn, Mn, Co and Mg in Carcinus maenas and Cancer irroratus ovaries during ovogenesis

    International Nuclear Information System (INIS)

    Martin, J.-L.M.

    1975-01-01

    Fe, Cu, Zn, Mn, Co, and Mg were analysed in the ovary of Carcinus maenas and Cancer irroratus during ovogenesis. In both ovaries, the relatives rates, expressed as parts per millions as a ratio of wet and dry weight, are the following: Mg>Zn>Fe>Cu>Mn>Co, while in the hemolymph of Cancer irroratus these relative rates are the following: Mg>Cu>Zn>Fe>Mn>Co. Compared to concentrations of these metals in sea water, Mg expected, all metals in the ovary of Cancer irroratus have a concentration factor upper than 1. Compared to the concentration of metals in the hemolymph is, for Fe, Mn, and Co, the concentration factor upper than 1, and for Cu, Zn and Mg, the concentration factor lower than 1. A study of correlations was done between the concentrations of metals considered in pairs, and between the concentrations of metals and the parameters: water content and gonad index [fr

  13. Investigation of Primary Factors Affecting the Variation of Modeled Oak Pollen Concentrations: A Case Study for Southeast Texas in 2010

    Science.gov (United States)

    Jeon, Wonbae; Choi, Yunsoo; Roy, Anirban; Pan, Shuai; Price, Daniel; Hwang, Mi-Kyoung; Kim, Kyu Rang; Oh, Inbo

    2018-02-01

    Oak pollen concentrations over the Houston-Galveston-Brazoria (HGB) area in southeastern Texas were modeled and evaluated against in-situ data. We modified the Community Multi-scale Air Quality (CMAQ) model to include oak pollen emission, dispersion, and deposition. The Oak Pollen Emission Model (OPEM) calculated gridded oak pollen emissions, which are based on a parameterized equation considering a plant-specific factor ( C e ), surface characteristics, and meteorology. The simulation period was chosen to be February 21 to April 30 in the spring of 2010, when the observed monthly mean oak pollen concentrations were the highest in six years (2009-2014). The results indicated C e and meteorology played an important role in the calculation of oak pollen emissions. While C e was critical in determining the magnitude of oak pollen emissions, meteorology determined their variability. In particular, the contribution of the meteorology to the variation in oak pollen emissions increased with the oak pollen emission rate. The evaluation results using in-situ surface data revealed that the model underestimated pollen concentrations and was unable to accurately reproduce the peak pollen episodes. The model error was likely due to uncertainty in climatology-based C e used for the estimation of oak pollen emissions and inaccuracy in the wind fields from the Weather Research and Forecast (WRF) model.

  14. Dietary diversity score is associated with cardiovascular risk factors and serum adiponectin concentrations in patients with metabolic syndrome.

    Science.gov (United States)

    Farhangi, Mahdieh Abbasalizad; Jahangiry, Leila

    2018-04-17

    Metabolic syndrome is associated with cardio-metabolic risk factors and lipid abnormalities. Previous studies evaluated the dietary habits and nutrient intakes among patients with metabolic syndrome; however the association between metabolic risk factors and adiponectin with dietary diversity score (DDS) in patients with metabolic syndrome has not been evaluated yet. Therefore the aim of the current study was to evaluate these relationships among patients with metabolic syndrome. One hundred sixty patients with metabolic syndrome were recruited in the study. The anthropometric parameters including weight, height, waist circumference and hip circumference were measured. Serum adiponectin concentration was measured by enzyme- linked immunosorbent assay method (ELISA). Lipid profile and fasting serum glucose concentrations (FSG) were also measured with enzymatic colorimetric methods. Blood pressure was also measured and DDS was calculated using the data obtained from food frequency questionnaire (FFQ). Subjects in lower DDS categorizes had significantly lower energy and fiber intake; whereas mean protein intake of subjects in the highest quartile was significantly higher than second quartile. Higher prevalence of obesity was also observed in the top quartiles (P metabolic syndrome components among patients in lower DDS quartiles was significantly higher (P metabolic syndrome. However, for further confirming the findings, more studies are warranted.

  15. Attached, unattached fraction of progeny concentrations and equilibrium factor for dose assessments from {sup 222}Rn and {sup 220}Rn

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Parminder; Saini, Komal; Bajwa, Bikramjit Singh [Guru Nanak Dev University, Department of Physics, Amritsar, Punjab (India); Mishra, Rosaline; Sahoo, Bijay Kumar [Bhabha Atomic Research Centre, Radiological Physics and Advisory Division, Mumbai (India)

    2016-08-15

    In this study, measurements of indoor radon ({sup 222}Rn), thoron ({sup 220}Rn) and their equilibrium equivalent concentration (EEC) were carried out in 96 dwellings from 22 different villages situated in Hamirpur district, Himachal Pradesh, India, by using LR-115 type II-based pinhole twin cup dosimeters and deposition-based progeny sensors (DRPS/DTPS). The annual average indoor {sup 222}Rn and {sup 220}Rn concentrations observed in these dwellings were 63.82 and 89.59 Bq/m{sup 3}, respectively, while the average EEC (attached + unattached) for {sup 222}Rn and {sup 220}Rn was 29.28 and 2.74 Bq/m{sup 3}. For {sup 222}Rn (f{sub Rn}) and {sup 220}Rn (f{sub Tn}), the average values of unattached fraction were 0.11 and 0.09, respectively. The equilibrium factors for radon (F{sub Rn}) and thoron (F{sub Tn}) varied from 0.12 to 0.77 with an average of 0.50, and from 0.01 to 0.34 with an average of 0.05, respectively. The annual inhalation dose due to mouth and nasal breathing was calculated using dose conversion factors and unattached fractions. The indoor annual effective doses for {sup 222}Rn (AEDR) and {sup 220}Rn (AEDT) were found to be 1.92 and 0.83 mSv a{sup -1}, respectively. The values of {sup 222}Rn/{sup 220}Rn concentrations and annual effective doses obtained in the present study are within the safe limits as recommended by the International Commission on Radiological Protection for indoor dwelling exposure conditions. (orig.)

  16. Concentration factors for 226Ra in the mullet (Mugilidae) species Mugil cephalus from the South Adriatic Sea

    International Nuclear Information System (INIS)

    Ivanka Antovic; Antovic, N.M.

    2011-01-01

    226 Ra activity concentration in the mullet (Mugilidae) species Mugil cephalus whole individuals, and some organs (gills, gastrointestinal system, fins, muscle and bones), was measured by the γ-coincidence spectrometer PRIPYAT-2M. 226 Ra transfer parameters [concentration factors (CFs)] from seawater, sediment and mud with detritus to fish tissues, and annual intake by humans consuming this fish species, have been estimated. Minimum detected radium activity concentration in whole M. cephalus individuals was found to be 0.89 ± 0.42 to 3.09 ± 0.41 Bq kg-1, with arithmetic mean of 1.65 ± 0.39 Bq kg -1 . An average concentration in muscles is found to be 2.28 ± 0.84 Bq kg -1 , in gills - 5.02 ± 1.85 Bq kg -1 , in gastrointestinal system - 12.88 ± 1.71 Bq kg -1 , and in bones - 14.72 ± 3.75 Bq kg -1 . No one fins showed radium activity above minimum detectable one. Annual intake of 226 Ra by human consumers of this fish species is estimated to provide an effective dose of 0.006 mSv year -1 . CFs for 226 Ra indicating transfer from seawater to whole individuals ranged from 8.9 to 30.9, and those indicating transfer from the sediment and mud with detritus - from 0.11 to 0.39 and from 0.08 to 0.3, respectively. The seawater to bones CFs varied from 97.9 to 197.3, to gastrointestinal system - from 59 to 178.8, to gills - from 22.5 to 68.3, to muscles - from 17 to 30.8. (author)

  17. Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium

    Science.gov (United States)

    Ryan, Zachary C.; Ketha, Hemamalini; McNulty, Melissa S.; McGee-Lawrence, Meghan; Craig, Theodore A.; Grande, Joseph P.; Westendorf, Jennifer J.; Singh, Ravinder J.; Kumar, Rajiv

    2013-01-01

    Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost−/−) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion. PMID:23530237

  18. Potential Predictors of Plasma Fibroblast Growth Factor 23 Concentrations: Cross-Sectional Analysis in the EPIC-Germany Study.

    Directory of Open Access Journals (Sweden)

    Romina di Giuseppe

    Full Text Available Increased fibroblast growth factor 23 (FGF23, a bone-derived hormone involved in the regulation of phosphate and vitamin D metabolism, has been related to the development of cardiovascular disease (CVD in chronic kidney disease patients and in the general population. However, what determines higher FGF23 levels is still unclear. Also, little is known about the influence of diet on FGF23. The aim of this study was therefore to identify demographic, clinical and dietary correlates of high FGF23 concentrations in the general population.We performed a cross-sectional analysis within a randomly selected subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Germany comprising 2134 middle-aged men and women. The Human FGF23 (C-Terminal ELISA kit was used to measure FGF23 in citrate plasma. Dietary data were obtained at baseline via validated food frequency questionnaires including up to 148 food items.Multivariable adjusted logistic regression showed that men had a 66% lower and smokers a 64% higher probability of having higher FGF23 (≥ 90 RU/mL levels compared, respectively, with women and nonsmokers. Each doubling in parathyroid hormone, creatinine, and C-reactive protein was related to higher FGF23. Among the dietary factors, each doubling in calcium and total energy intake was related, respectively, to a 1.75 and to a 4.41 fold increased probability of having higher FGF23. Finally, each doubling in the intake of iron was related to an 82% lower probability of having higher FGF23 levels. Results did not substantially change after exclusion of participants with lower kidney function.In middle-aged men and women traditional and non-traditional CVD risk factors were related to higher FGF23 concentrations. These findings may contribute to the understanding of the potential mechanisms linking increased FGF23 to increased CVD risk.

  19. Spectrophotometric determination of hydrogen peroxide with osmium(VIII) and m-carboxyphenylfluorone.

    Science.gov (United States)

    Hoshino, Mitsuru; Kamino, Shinichiro; Doi, Mitsunobu; Takada, Shingo; Mitani, Shota; Yanagihara, Rika; Asano, Mamiko; Yamaguchi, Takako; Fujita, Yoshikazu

    2014-01-03

    Spectrophotometric determination of hydrogen peroxide was accomplished with osmium(VIII) and m-carboxyphenylfluorone (MCPF) in the presence of cetyltrimethylammonium chloride (CTAC). In the determination of hydrogen peroxide based on the fading of the color of osmium(VIII)-MCPF complex, Beer's law was obeyed in the range 20-406 ng mL(-1), with an effective molar absorption coefficient (at 580 nm) of 5.21×10(4) L mol(-1) cm(-1) and a relative standard deviation of 0.33% (n=6). Further, we performed the characterization of MCPF and obtained the crystal structure. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Lacerations to Zones VIII and IX: It Is Not Just a Tendon Injury

    Directory of Open Access Journals (Sweden)

    Charla R. Fischer

    2011-01-01

    Full Text Available Extensor tendon injuries are widely believed to be straightforward problems that are relatively simple to manage. However, these injuries can be complex and demand a thorough understanding of anatomy to achieve the best functional outcomes. When lacerations occur in the forearm as in Zones VIII and IX injury, the repair of the extensor tendon and muscle, and posterior interosseous nerve (PIN is often challenging. A review of the literature shows little guidance and attention for these injuries. We present four patients with injuries to Zones VIII and IX as well as a review of surgical technique, postoperative rehabilitation, and pearls that may be of benefit to those managing these injuries.

  1. Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in women and girls with hereditary factor X deficiency.

    Science.gov (United States)

    Kulkarni, R; James, A H; Norton, M; Shapiro, A

    2018-05-01

    Essentials Plasma-derived factor X concentrate (pdFX) is used to treat hereditary factor X deficiency. pdFX pharmacokinetics, safety and efficacy were assessed in factor X-deficient women/girls. Treatment success rate was 98%; only 6 adverse events in 2 subjects were possibly pdFX related. On-demand pdFX 25 IU kg -1 was effective and safe in women/girls with factor X deficiency. Background A high-purity, plasma-derived factor X concentrate (pdFX) has been approved for the treatment of hereditary FX deficiency, an autosomal recessive disorder. Objective To perform post hoc assessments of pdFX pharmacokinetics, safety and efficacy in women and girls with hereditary FX deficiency. Patients/Methods Subjects aged ≥ 12 years with moderate/severe FX deficiency (plasma FX activity of girls (aged 14-58 years [median, 25.5 years]) received 267 pdFX infusions. Mean monthly infusions per subject were higher among women and girls (2.48) than among men and boys (1.62). In women and girls, 132 assessable bleeding episodes (61 heavy menstrual bleeds, 47 joint bleeds, 15 muscle bleeds, and nine other bleeds) were treated with pdFX, with a 98% treatment success rate versus 100% in men and boys. Mean pdFX incremental recovery was similar in the two groups (2.05 IU dL -1 versus 1.91 IU dL -1 per IU kg -1 ), as was the mean half-life (29.3 h versus 29.5 h). Of 142 adverse events in women and girls, headache was the most common (12 events in six subjects). Six events (two infusion-site erythema, two fatigue, one back pain, one infusion-site pain) in two subjects were considered to be possibly pdFX-related. Following the trial, pdFX was used to successfully maintain hemostasis in two subjects undergoing obstetric delivery. Conclusions pdFX was well tolerated and effective in women and girls with FX deficiency. Although women and girls had different bleeding symptoms and sites than men and boys, their pdFX pharmacokinetic profile was comparable. © 2018 The Authors. Journal of

  2. Identification of key factors affecting the water pollutant concentration in the sluice-controlled river reaches of the Shaying River in China via statistical analysis methods.

    Science.gov (United States)

    Dou, Ming; Zhang, Yan; Zuo, Qiting; Mi, Qingbin

    2015-08-01

    The construction of sluices creates a strong disturbance in water environmental factors within a river. The change in water pollutant concentrations of sluice-controlled river reaches (SCRRs) is more complex than that of natural river segments. To determine the key factors affecting water pollutant concentration changes in SCRRs, river reaches near the Huaidian Sluice in the Shaying River of China were selected as a case study, and water quality monitoring experiments based on different regulating modes were implemented in 2009 and 2010. To identify the key factors affecting the change rates for the chemical oxygen demand of permanganate (CODMn) and ammonia nitrogen (NH3-N) concentrations in the SCRRs of the Huaidian Sluice, partial correlation analysis, principal component analysis and principal factor analysis were used. The results indicate four factors, i.e., the inflow quantity from upper reaches, opening size of sluice gates, water pollutant concentration from upper reaches, and turbidity before the sluice, which are the common key factors for the CODMn and NH3-N concentration change rates. Moreover, the dissolved oxygen before a sluice is a key factor for the permanganate concentration from CODMn change rate, and the water depth before a sluice is a key factor for the NH3-N concentration change rate. Multiple linear regressions between the water pollutant concentration change rate and key factors were established via multiple linear regression analyses, and the quantitative relationship between the CODMn and NH3-N concentration change rates and key affecting factors was analyzed. Finally, the mechanism of action for the key factors affecting the water pollutant concentration changes was analyzed. The results reveal that the inflow quantity from upper reaches, opening size of sluice gates, permanganate concentration from CODMn from upper reaches and dissolved oxygen before the sluice have a negative influence and the turbidity before the sluice has a positive

  3. Concentration- and time-dependent response of human gingival fibroblasts to fibroblast growth factor 2 immobilized on titanium dental implants

    Directory of Open Access Journals (Sweden)

    Ma Q

    2012-04-01

    Full Text Available Qianli Ma1*, Wei Wang1*, Paul K Chu2, Shenglin Mei1,2, Kun Ji3, Lei Jin4, Yumei Zhang11Department of Prosthetic Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China; 2Department of Physics and Materials Science, City University of Hong Kong, Kowloon, Hong Kong, People's Republic of China; 3Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China; 4Stomatology Department, Jinling Hospital, School of Medicine, Southern Medical University, Nanjing, People's Republic of China*These authors contributed equally to this workBackground: Titanium (Ti implants are widely used clinically, but peri-implantitis remains one of the most common and serious complications. Healthy integration between gingival tissue and the implant surface is critical to long-term success in dental implant therapy. The objective of this study was to investigate how different concentrations of immobilized fibroblast growth factor 2 (FGF2 on the titania nanotubular surface influence the response of human gingival fibroblasts (HGFs.Methods: Pure Ti metal was anodized at 20 V to form a vertically organized titanium dioxide nanotube array on which three concentrations of FGF2 (250 ng/mL, 500 ng/mL, or 1000 ng/mL were immobilized by repeated lyophilization. Surface topography was observed and FGF2 elution was detected using enzyme-linked immunosorbent assay. The bioactivity changes of dissolvable immobilized FGF2 were measured by methyl-thiazolyl-tetrazolium assay. Behavior of HGFs was evaluated using adhesion and methyl-thiazolyl-tetrazolium bromide assays.Results: The FGF2 remained for several days on the modified surface on which HGFs were cultured. Over 90% of the dissolvable immobilized FGF2 had been eluted by Day 9, whereas the FGF2 activity was found to diminish gradually from Day 1 to Day 9. The titania nanotubular surface with an optimal preparing

  4. Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF).

    Science.gov (United States)

    Masuki, Hideo; Okudera, Toshimitsu; Watanebe, Taisuke; Suzuki, Masashi; Nishiyama, Kazuhiko; Okudera, Hajime; Nakata, Koh; Uematsu, Kohya; Su, Chen-Yao; Kawase, Tomoyuki

    2016-12-01

    The development of platelet-rich fibrin (PRF) drastically simplified the preparation procedure of platelet-concentrated biomaterials, such as platelet-rich plasma (PRP), and facilitated their clinical application. PRF's clinical effectiveness has often been demonstrated in pre-clinical and clinical studies; however, it is still controversial whether growth factors are significantly concentrated in PRF preparations to facilitate wound healing and tissue regeneration. To address this matter, we performed a comparative study of growth factor contents in PRP and its derivatives, such as advanced PRF (A-PRF) and concentrated growth factors (CGF). PRP and its derivatives were prepared from the same peripheral blood samples collected from healthy donors. A-PRF and CGF preparations were homogenized and centrifuged to produce extracts. Platelet and white blood cell counts in A-PRF and CGF preparations were determined by subtracting those counts in red blood cell fractions, supernatant acellular serum fractions, and A-PRF/CGF exudate fractions from those counts of whole blood samples. Concentrations of growth factors (TGF-β1, PDGF-BB, VEGF) and pro-inflammatory cytokines (IL-1β, IL-6) were determined using ELISA kits. Compared to PRP preparations, both A-PRF and CGF extracts contained compatible or higher levels of platelets and platelet-derived growth factors. In a cell proliferation assay, both A-PRF and CGF extracts significantly stimulated the proliferation of human periosteal cells without significant reduction at higher doses. These data clearly demonstrate that both A-PRF and CGF preparations contain significant amounts of growth factors capable of stimulating periosteal cell proliferation, suggesting that A-PRF and CGF preparations function not only as a scaffolding material but also as a reservoir to deliver certain growth factors at the site of application.

  5. Glucose concentrations modulate brain-derived neurotrophic factor responsiveness of neurones in the paraventricular nucleus of the hypothalamus.

    Science.gov (United States)

    McIsaac, W; Ferguson, A V

    2017-04-01

    The hypothalamic paraventricular nucleus (PVN) is critical for normal energy balance and has been shown to contain high levels of both brain-derived neurotrophic factor (BDNF) and tropomyosin-receptor kinase B mRNA. Microinjections of BDNF into the PVN increase energy expenditure, suggesting that BDNF plays an important role in energy homeostasis through direct actions in this nucleus. The present study aimed to examine the postsynaptic effects of BDNF on the membrane potential of PVN neurones, and also to determine whether extracellular glucose concentrations modulated these effects. We used hypothalamic PVN slices from male Sprague-Dawley rats to perform whole cell current-clamp recordings from PVN neurones. BDNF was bath applied at a concentration of 2 nmol L -1 and the effects on membrane potential determined. BDNF caused depolarisations in 54% of neurones (n=25; mean±SEM, 8.9±1.2 mV) and hyperpolarisations in 23% (n=11; -6.7±1.4 mV), whereas the remaining cells were unaffected. These effects were maintained in the presence of tetrodotoxin (n=9; 56% depolarised, 22% hyperpolarised, 22% nonresponders), or the GABA a antagonist bicuculline (n=12; 42% depolarised, 17% hyperpolarised, 41% nonresponders), supporting the conclusion that these effects on membrane potential were postsynaptic. Current-clamp recordings from PVN neurones next examined the effects of BDNF on these neurones at varying extracellular glucose concentrations. Larger proportions of PVN neurones hyperpolarised in response to BDNF as the glucose concentrations decreased [10 mmol L -1 glucose 23% (n=11) of neurones hyperpolarised, whereas, at 0.2 mmol L -1 glucose, 71% showed hyperpolarising effects (n=12)]. Our findings reveal that BDNF has direct GABA A independent effects on PVN neurones, which are modulated by local glucose concentrations. The latter observation further emphasises the critical importance of using physiologically relevant conditions in an investigation of the central

  6. Implementation of a more physiological plasma rich in growth factor (PRGF) protocol: Anticoagulant removal and reduction in activator concentration.

    Science.gov (United States)

    Anitua, Eduardo; Prado, Roberto; Troya, María; Zalduendo, Mar; de la Fuente, María; Pino, Ander; Muruzabal, Francisco; Orive, Gorka

    2016-07-01

    Plasma rich in growth factors (PRGF) is a biological therapy that uses patient's own growth factors for promoting tissue regeneration. Given the current European regulatory framework in which anticoagulant solution in blood extraction tubes could be considered as a medicinal product, a new PRGF protocol has been developed. The actual protocol (PRGF-A) and the new one (PRGF-B) have been performed and compared under Good Laboratory Practices. PRGF-A protocol uses extraction tubes with 0.9 mL of trisodium citrate as anticoagulant and 50 μL of calcium chloride/mL PRGF to activate it. The PRGF-B reduces the amount of sodium citrate and calcium chloride to 0.4 mL and to 20 μL, respectively. Basic hematological parameters, platelet function, the scaffold obtaining process, growth factors content, and the biological effect were compared between both PRGF obtaining protocols. PRGF-B protocol led to a statistically significant higher enrichment and recovery of platelets regarding to the PRGF-A. Hypotonic stress response by platelets was significantly better in the new protocol. A statistically significant decrease in the basal platelet activation status of PRGF-B compared to PRGF-A was also observed. The duration of the lag phase in the platelet aggregation assay was statistically lower for the PRGF-B protocol. Both the clotting and the clot retraction time were significantly reduced in the B protocol. A higher growth factor concentration was detected in the plasma obtained using the PRGF-B protocol. The new PRGF obtaining protocol, with a reduction in the amount of anticoagulant and activator, has even improved the actual one.

  7. Derivation of Elastic Stress Concentration Factor Equations for Debris Fretting Flaws in Pressure Tubes of Pressurized Heavy Water Reactors

    International Nuclear Information System (INIS)

    Kim, Jong Sung; Oh, Young Jin

    2014-01-01

    If volumetric flaws such as bearing pad fretting flaws and debris fretting flaws are detected in the pressure tubes of pressurized heavy water reactors during in-service inspection, the initiation of fatigue cracks and delayed hydrogen cracking from the detected volumetric flaws shall be assessed by using elastic stress concentration factors in accordance with CSA N285.8-05. The CSA N285.8-05 presents only an approximate formula based on linear elastic fracture mechanics for the debris fretting flaw. In this study, an engineering formula considering the geometric characteristics of the debris fretting flaw in detail was derived using two-dimensional finite element analysis and Kinectrics, Inc.'s engineering procedure with slight modifications. Comparing the application results obtained using the derived formula with the three-dimensional finite element analysis results, it is found that the results obtained using the derived formula agree well with the results of the finite element analysis

  8. Circulating ghrelin, leptin, and soluble leptin receptor concentrations and cardiometabolic risk factors in a community-based sample.

    Science.gov (United States)

    Ingelsson, Erik; Larson, Martin G; Yin, Xiaoyan; Wang, Thomas J; Meigs, James B; Lipinska, Izabella; Benjamin, Emelia J; Keaney, John F; Vasan, Ramachandran S

    2008-08-01

    The conjoint effects and relative importance of ghrelin, leptin, and soluble leptin receptor (sOB-R), adipokines involved in appetite control and energy expenditure in mediating cardiometabolic risk, is unknown. The objective of the study was to study the cross-sectional relations of these adipokines to cardiometabolic risk factors in a community-based sample. We measured circulating ghrelin, leptin, and sOB-R in 362 participants (mean age 45 yr; 54% women) of the Framingham Third Generation Cohort. Body mass index, waist circumference (WC), blood pressure, lipid measures, fasting glucose, smoking, and metabolic syndrome (MetS) were measured. Ghrelin and leptin concentrations were significantly higher in women (P risk.

  9. Acute hyperinsulinemia is followed by increased serum concentrations of fibroblast growth factor 23 in type 2 diabetes patients

    DEFF Research Database (Denmark)

    Winther, Kristian; Nybo, Mads; Vind, Birgitte

    2012-01-01

    Background. Phosphate homeostasis is connected to glucose metabolism and is influenced by insulin, but the role of fibroblast growth factor 23 (FGF23) is unknown in this relation. Therefore, the levels of FGF23 and phosphate were investigated during a euglycemic-hyperinsulinemic clamp in healthy...... and type 2 diabetic individuals. Methods. The study population consisted of ten type 2 diabetic patients, ten weight-matched glucose-tolerant obese subjects, and ten healthy lean subjects. All subjects underwent a 4-h euglycemic-hyperinsulinemic clamp using physiological hyperinsulinemia (40 mU/min per m(2...... the groups. Conclusions. Physiological hyperinsulinemia is under euglycemic conditions followed by a significant increase in serum FGF23 concentrations in diabetic individuals, which correlated with change in insulin level. The interplay between insulin effects and FGF23 may be important...

  10. Long-term glucocorticoid concentrations as a risk factor for childhood obesity and adverse body-fat distribution.

    Science.gov (United States)

    Noppe, G; van den Akker, E L T; de Rijke, Y B; Koper, J W; Jaddoe, V W; van Rossum, E F C

    2016-10-01

    Childhood obesity is an important risk factor for premature development of the metabolic syndrome (MetS) at adulthood. There is need for understanding of the mechanisms underlying the MetS and obesity. Patients with Cushing's disease suffer from similar metabolic complications, leading to the hypothesis that inter-individual cortisol variation may contribute to the onset of obesity. In addition, glucocorticoid receptor (GR)-gene polymorphisms resulting in differential glucocorticoid (GC) sensitivity, have been associated with an adverse metabolic profile. To study associations of GC levels in scalp hair, as a marker of long-term systemic GC concentrations, and genetically determined GC sensitivity with obesity and body-fat distribution in children. We performed a cross-sectional study of cortisol and cortisone concentrations over a 3-month period, measured by LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in hair of 3019 6-year-old children participating in the Generation R study. Genotyping of GR-gene polymorphisms was performed. Of all children, 4.3% was obese and 13.4% overweight. Cortisol was significantly associated with risk of obesity (odd ratio (OR): 9.4 (3.3-26.9)) and overweight (OR: 1.4 (1.0-2.0)). Cortisone was associated with risk of obesity (OR: 1.9 (1.0-3.5)). Cortisol and cortisone were significantly positively associated with body mass index, fat mass (FM) index and android/gynecoid FM ratio. GR polymorphisms were not associated with adiposity parameters. Long-term cortisol concentrations are strongly associated with an increased risk of childhood obesity and adverse body-fat distribution. Future research may reveal whether these are causal relations and may be a target for therapy.

  11. 137Cs Inter-Plant Concentration Ratios Provide a Predictive Tool for Coral Atolls with Distinct Benefits Over Transfer Factors

    Energy Technology Data Exchange (ETDEWEB)

    Robison, W L; Hamilton, T F; Bogen, K; Corado, C L; Kehl, S R

    2007-07-17

    Inter-plant concentration ratios (IPCR), [Bq g{sup -1} {sup 137}Cs in coral atoll tree food-crops/Bq g{sup -1} {sup 137}Cs in leaves of native plant species whose roots share a common soil volume], can replace transfer factors (TF) to predict {sup 137}Cs concentration in tree food-crops in a contaminated area with an aged source term. The IPCR strategy has significant benefits relative to TF strategy for such purposes in the atoll ecosystem. IPCR strategy applied to specific assessments takes advantage of the fact tree roots naturally integrate 137Cs over large volumes of soil. Root absorption of {sup 137}Cs replaces large-scale, expensive soil sampling schemes to reduce variability in {sup 137}Cs concentration due to inhomogeneous radionuclide distribution. IPCR [drinking-coconut meat (DCM)/Scaevola (SCA) and Tournefortia (TOU) leaves (native trees growing on all atoll islands)] are log normally distributed (LND) with geometric standard deviation (GSD) = 1.85. TF for DCM from Enewetak, Eneu, Rongelap and Bikini Atolls are LND with GSD's of 3.5, 3.0, 2.7, and 2.1, respectively. TF GSD for Rongelap copra coconut meat is 2.5. IPCR of Pandanus fruit to SCA and TOU leaves are LND with GSD = 1.7 while TF GSD is 2.1. Because IPCR variability is much lower than TF variability, relative sampling error of an IPCR field sample mean is up 6- to 10-fold lower than that of a TF sample mean if sample sizes are small (10 to 20). Other IPCR advantages are that plant leaf samples are collected and processed in far less time with much less effort and cost than soil samples.

  12. 137Cs inter-plant concentration ratios provide a predictive tool for coral atolls with distinct benefits over transfer factors

    International Nuclear Information System (INIS)

    Robison, William L.; Hamilton, Terry F.; Bogen, Kenneth T.; Conrado, Cynthia L.; Kehl, Steven R.

    2008-01-01

    Inter-plant concentration ratios (IPCR) [Bq g -1137 Cs in coral atoll tree food crops/Bq g -1137 Cs in leaves of native plant species whose roots share a common soil volume] can replace transfer factors (TF) to predict 137 Cs concentration in tree food crops in a contaminated area with an aged source term. The IPCR strategy has significant benefits relative to TF strategy for such purposes in the atoll ecosystem. IPCR strategy applied to specific assessments takes advantage of the fact that tree roots naturally integrate 137 Cs over large volumes of soil. Root absorption of 137 Cs replaces large-scale, expensive soil sampling schemes to reduce variability in 137 Cs concentration due to inhomogeneous radionuclide distribution. IPCR [drinking-coconut meat (DCM)/Scaevola (SCA) and Tournefortia (TOU) leaves (native trees growing on all atoll islands)] are log-normally distributed (LND) with geometric standard deviation (GSD) = 1.85. TF for DCM from Enewetak, Eneu, Rongelap and Bikini Atolls are LND with GSDs of 3.5, 3.0, 2.7, and 2.1, respectively. TF GSD for Rongelap copra coconut meat is 2.5. IPCR of Pandanus fruit to SCA and TOU leaves are LND with GSD = 1.7 while TF GSD is 2.1. Because IPCR variability is much lower than TF variability, relative sampling error of an IPCR field sample mean is up 6- to 10-fold lower than that of a TF sample mean if sample sizes are small (10-20). Other IPCR advantages are that plant leaf samples are collected and processed in far less time with much less effort and cost than soil samples

  13. Factors influencing the formation of histaminol, hydroxytyrosol, tyrosol, and tryptophol in wine: Temperature, alcoholic degree, and amino acids concentration.

    Science.gov (United States)

    Bordiga, M; Lorenzo, C; Pardo, F; Salinas, M R; Travaglia, F; Arlorio, M; Coïsson, J D; Garde-Cerdán, T

    2016-04-15

    The validation of a HPLC-PDA-MS/MS chromatographic method for the quali/quantitative characterization of histaminol, hydroxytyrosol, tyrosol, and tryptophol in wine has been described and discussed. Four standards showed a good linearity with high correlation coefficient values (over 0.9989) and LOD and LOQ were 0.001-0.015 mg/L and 0.004-0.045 mg/L, respectively. Furthermore, this study reported how factors such as temperature, alcoholic degree, and amino acids concentration are able to influence the formation of these four alcohols in Monastrell wines. The quantification values of these alcohols has been detected both at the half and end of alcoholic fermentation, and at the end of malolactic fermentation. In relation to interactions between factors, several significant variations emerged (p ⩽ 0.001). The impact of amino acids supplementation in Monastrell must it has been demonstrated, mainly in regards to histaminol and tryptophol. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Living in a physical world VIII. Gravity and life in water

    Indian Academy of Sciences (India)

    2006-07-31

    Jul 31, 2006 ... Home; Journals; Journal of Biosciences; Volume 31; Issue 3. Living in a physical world VIII. Gravity and life in water. Steven Vogel. Series Volume 31 Issue 3 September 2006 pp 309-322. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/jbsc/031/03/0309-0322 ...

  15. Visualizing the Life and Legacy of Henry VIII: Guiding Students with Eight Types of Graphic Organizers

    Science.gov (United States)

    Gallavan, Nancy P.; Kottler, Ellen

    2010-01-01

    Delving into the life and legacy of Henry VIII is both complex and captivating. People seem compelled to learn more abut his critical contributions and controversial conduct that range from the significant to the scandalous. Reflecting on the history of the world would be incomplete without investigating the events and escapades associated with…

  16. Quark matter coupled to domain walls in Bianchi types II, VIII and IX ...

    Indian Academy of Sciences (India)

    In this study of Bianchi types II, VIII and IX Universes, quark matter coupled to domain walls in the ... The self-bound state appears to be at ρ ... The observations suggest that the Hubble expansion of the Universe ... Taking motivation from.

  17. Glioneuronal Heterotopia Presenting As a Cerebellopontine angle Tumor of the cranial Nerve VIII, Case Report.

    Science.gov (United States)

    Peris-Celda, M; Giannini, C; Diehn, F E; Eckel, L J; Neff, B A; Van Gompel, J J

    2018-04-03

    Vestibular schwannomas and meningiomas account for the great majority of lesions arising in the cerebellopontine angle (CPA). In this report, we present a case of glioneuronal heterotopia, also known as glioneuronal hamartoma, arising from the VIII cranial nerve, which is an extremely uncommon lesion. Important radiologic and surgical aspects are reviewed, which may help in early recognition and intraoperative decision making when these lesions are encountered. A healthy 29-year-old female presented with intermittent right facial numbness. Magnetic resonance imaging (MRI) showed an incidental minimally enhancing cerebellopontine angle lesion on the right VII-VIII cranial nerve complex. The patient declined serial observation and opted for operative intervention for resection. Intraoperatively, the lesion resembled neural tissue and was continuous with the VIII cranial nerve. Pathological analysis demonstrated mature glioneuronal tissue consistent with hamartomatous brain tissue. The patient maintained normal hearing and facial nerve function after surgery. Radiologic, surgical and pathological characteristics are described. Ectopic glioneuronal tissue of the VIII cranial nerve is a rare non-neoplastic lesion, and should be considered in the differential diagnosis of unusual appearing intracanalicular and cerebellopontine angle lesions. The congenital and benign nature of this entity makes observation a valid option for these cases, although they are so infrequent that they are often presumptively managed as vestibular schwannomas. Attempts to radically resect these lesions may result in higher rates of hearing loss or facial palsy due to their continuity with the cranial nerves. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Synthesization of the Ar VIII 3s-3p beam-foil decay curve

    International Nuclear Information System (INIS)

    Lindgaard, A.; Veje, E.

    1981-01-01

    The beam-foil decay curve for the 3s-3p transition in Ar VIII has been simulated from experimentally determined relative initial level populations and transition probabilities calculated in the numerical Coulomb approximation. Good agreement is observed between simulated and measured decay curves. A discussion of the simulation is given. (Auth.)

  19. Quark matter coupled to domain walls in Bianchi types II, VIII and IX ...

    Indian Academy of Sciences (India)

    In this study of Bianchi types II, VIII and IX Universes, quark matter coupled to domain walls in the context of general relativity are explored. To obtain deterministic solution of the Einstein's field equations, various techniques are adopted. The features of the obtained solution are discussed.

  20. Chaos in long-term behavior of some Bianchi-type VIII models

    Energy Technology Data Exchange (ETDEWEB)

    Halpern, P

    1987-01-01

    The long-term behavior of Bianchi-type VIII models with three different types of stress-energy tensors are examined and compared. The vacuum model, a matter-filled model, and a model with an electromagnetic field are considered. In each case the existence of chaotic behavior and transitions to chaotic behavior are discussed.

  1. Absorption signatures of warm-hot gas at low redshift : Ne VIII

    NARCIS (Netherlands)

    Tepper-García, T

    2013-01-01

    At z {lt} 1 a large fraction of the baryons is thought to reside in diffuse gas that has been shock-heated to high temperatures (10$^{5}$-10$^{6}$ K). Absorption by the 770.41, 780.32 å doublet of Ne VIII in quasar spectra represents a unique tool to study this elusive warm-hot phase. We have

  2. Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Perez-Cornago, Aurora; Appleby, Paul N.; Tipper, Sarah; Key, Timothy J.; Allen, Naomi E.; Nieters, Alexandra; Vermeulen, Roel; Roulland, Sandrine; Casabonne, Delphine; Kaaks, Rudolf; Fortner, Renee T.; Boeing, Heiner; Trichopoulou, Antonia; La Vecchia, Carlo; Klinaki, Eleni; Hansen, Louise; Tjønneland, Anne; Bonnet, Fabrice; Fagherazzi, Guy; Boutron-Ruault, Marie Christine; Pala, Valeria; Masala, Giovanna; Sacerdote, Carlotta; Peeters, Petra H.; Bueno-de-Mesquita, H. Bas; Weiderpass, Elisabete; Dorronsoro, Miren; Quirós, J. Ramón; Barricarte, Aurelio; Gavrila, Diana; Agudo, Antonio; Borgquist, Signe; Rosendahl, Ann H.; Melin, Beatrice; Wareham, Nick; Khaw, Kay Tee; Gunter, Marc; Riboli, Elio; Vineis, Paolo; Travis, Ruth C.

    2017-01-01

    Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested

  3. RELATIONSHIP OF INTEREST, LEARNING MOTIVATION AND ATTITUDE WITH RESULTS LEARNING CLASS VIII SMP STATE 13 MAKASSAR

    Directory of Open Access Journals (Sweden)

    Putri Athirah Azis

    2016-12-01

    Full Text Available The study aims at examining (1 the correlation of learning interest towards learning result of grade students, (2 the correlation of learning motivation towards learning result of grade students, (3 the correlation of students attitude towards learning result, (4 the correlationof interest, learning motivation, and attitude collaboratively towards learning result. The study is an ex post facto. The population of the study was grade VIII at SMPN 13 Makassar. Samples were 105 students taken by employing random sampling technique. Data were collected through questionnaire and documentation. Data were analyzed using regression test. The result of study reveal that (1 there is significant correlation (p<0,01 of interest towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,718 and its effectiveness contribution (R2 is 51,5%, (2 there is significant correlation (p<0,01 of motivation towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,775 and its effectiveness contribution (R2 is 60,1%, (3 there is significant correlation (p<0,01 of attitude towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,737 and its effectiveness contribution (R2 is 54,4%, (4 there is significant correlation (p<0,01 of interest, motivation and attitude collaboratively towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,861 and its effectiveness contribution (R2 is 74,1%,

  4. VIII Olimpíada Brasileira de Astronomia e Astronáutica

    Science.gov (United States)

    Garcia Canalle, João Batista; Villas da Rocha, Jaime Fernando; Wuensche de Souza, Carlos Alexandre; Pereira Ortiz, Roberto; Aguilera, Nuricel Villalonga; Padilha, Maria De Fátima Catta Preta; Pessoa Filho, José Bezerra; Soares Rodrigues, Ivette Maria

    2007-07-01

    Neste trabalho apresentamos as motivações pelas quais organizamos, em conjunto, pela primeira vez, a Olimpíada Brasileira de Astronomia incluindo a Astronáutica, em colaboração com a Agência Espacial Brasileira. Esta ampliação contribuiu para atrair ainda mais alunos, professores, escolas e patrocinadores para participarem desta Olimpíada. Em 2005 participaram da VIII Olimpíada Brasileira de Astronomia e Astronáutica (VIII OBA) 187.726 alunos distribuídos por 3.229 escolas, pertencentes a todos os estados brasileiros, incluindo o Distrito Federal. O crescimento em número de alunos participantes foi 52,4% maior do que em 2004. Em abril de 2005 organizamos, em Itapecerica da Serra, SP, um curso para os 50 alunos previamente selecionados e participantes da VII OBA e ao final selecionamos, dentre eles, uma equipe de 5 alunos, os quais representaram o Brasil na X Olimpíada Internacional de Astronomia, na China, em outubro de 2005. Ganhamos, pela primeira vez, uma medalha de ouro naquele evento. Em Agosto de 2005, organizamos a VIII Escola de Agosto para 50 alunos e respectivos professores, em Águas de Lindóia, SP, juntamente com a XXXI reunião anual da Sociedade Astronômica Brasileira (SAB). Em novembro de 2005 realizamos a I Jornada Espacial, em São José dos Campos, com 22 alunos e 22 professores selecionados dentre os participantes que melhores resultados obtiveram nas questões de Astronáutica da VIII OBA. Neste trabalho detalhamos os resultados da VIII OBA bem como as ações subseqüentes.

  5. Quantitative Analysis of Major Factors Affecting Black Carbon Transport and Concentrations in the Unique Atmospheric Structures of Urban Environment

    Science.gov (United States)

    Liang, Marissa Shuang

    Black carbon (BC) from vehicular emission in transportation is a principal component of particulate matters ≤ 2.5 mum (PM2.5). PM2.5 and other diesel emission pollutants (e.g., NOx) are regulated by the Clean Air Act (CAA) according to the National Ambient Air Quality standards (NAAQS). This doctoral dissertation details a study on transport behaviors of black carbon and PM2.5 from transportation routes, their relations with the atmospheric structure of an urban formation, and their relations with the use of biodiesel fuels. The results have implications to near-road risk assessment and to the development of sustainable transportation solutions in urban centers. The first part of study quantified near-roadside black carbon transport as a function of particulate matter (PM) size and composition, as well as microclimatic variables (temperature and wind fields) at the interstate highway I-75 in northern Cincinnati, Ohio. Among variables examined, wind speed and direction significantly affect the roadside transport of black carbon and hence its effective emission factor. Observed non-Gaussian dispersion occurred during low wind and for wind directions at acute angles or upwind to the receptors, mostly occurring in the morning hours. Meandering of air pollutant mass under thermal inversion is likely the driving force. In contrary, Gaussian distribution predominated in daytime of strong downwinds. The roles of urban atmospheric structure, wind fields, and the urban heat island (UHI) effects were further examined on pollutant dispersion and transport. Spatiotemporal variations of traffic flow, atmospheric structure, ambient temperature and PM2.5 concentration data from 14 EPA-certified NAAQS monitoring stations, were analyzed in relation to land-use in the Cincinnati metropolitan area. The results show a decade-long UHI effects with higher interior temperature than that in exurban, and a prominent nocturnal thermal inversion frequent in urban boundary layer. The

  6. Relating Magnetic Parameters to Heavy Metal Concentrations and Environmental Factors at Formosa Mine Superfund Site, Douglas County, OR

    Science.gov (United States)

    Upton, T. L.

    2016-12-01

    Advances in the field of environmental magnetism have led to exciting new applications for this field. Magnetic minerals are ubiquitous in the environment and tend to have an affinity for heavy metals. Hence, it has been demonstrated that magnetic properties are often significantly related to concentrations of heavy metals and other pollutants. As a result, magnetic techniques have been used as proxy for determining hot spots of several types of pollution produced from a diversity of anthropogenic sources. Magnetic measurements are non-destructive and relatively inexpensive compared to geochemical analyses. The utility of environmental magnetic methods varies widely depending on biological, chemical and physical processes that create and transform soils and sediments. Applications in the direction of mapping heavy metals have been studied and shown to be quite useful in countries such as China and India but to date, little research has been done in the US. As such, there is need to expand the scope of research to a wider range of soil types and land uses, especially within the US. This study investigates the application of environmental magnetic techniques to mapping of heavy metal concentrations at the Formosa Mine Superfund Site, an abandoned mine about 25 miles southwest of Roseburg, OR. The soils and sediment at this site are derived from pyrite-rich bedrock which is weak in terms of magnetic susceptibility. Using hotspot analysis, correlation and cluster analyses, interactions between metals and magnetic parameters are investigated in relation to environmental factors such as proximity to seeps and adits. Preliminary results suggest significant correlation of magnetic susceptibility with certain heavy metals, signifying that magnetic methods may be useful in mapping heavy metal hotspots at this site. Further analysis examines the relation of various land use differences in magnetic signatures obtained throughout the Cow Creek watershed.

  7. Chloride concentrations, loads, and yields in four watersheds along Interstate 95, southeastern Connecticut, 2008-11: factors that affect peak chloride concentrations during winter storms

    Science.gov (United States)

    Brown, Craig J.; Mullaney, John R.; Morrison, Jonathan; Martin, Joseph W.; Trombley, Thomas J.

    2015-07-01

    Chloride (Cl-) concentrations and loads and other water chemistry characteristics were assessed to evaluate potential effects of road-deicer applications on streamwater quality in four watersheds along Interstate 95 (I–95) in southeastern Connecticut from November 1, 2008, through September 30, 2011. Streamflow and water quality were studied in the Four Mile River, Oil Mill Brook, Stony Brook, and Jordan Brook watersheds, where developed land ranged from 9 to 32 percent. Water-quality samples were collected and specific conductance was measured continuously at paired water-quality monitoring sites, upstream and downstream from I–95. Specific conductance values were related to Cl- concentrations to assist in determining the effects of road-deicing operations on the levels of Cl-in the streams. Streamflow and water-quality data were compared with weather data and with the timing, amount, and composition of deicers applied to State highways. Grab samples were collected during winter stormwater-runoff events, such as winter storms or periods of rain or warm temperatures in which melting takes place. Grab samples were also collected periodically during the spring and summer and during base-flow conditions.

  8. Quantitative relations between chemical oxygen demand concentration and its influence factors in the sluice-controlled river reaches of Shaying River, China.

    Science.gov (United States)

    Dou, Ming; Li, Guiqiu; Li, Congying

    2015-01-01

    Recent research on the effects of dam and sluice construction on the water environment has attracted extensive attention from academia and governments alike. Because the operation of sluices greatly alters environmental factors such as water flow and sediment load, the water quality in sluice-controlled river reaches (SCRRs) undergoes complex changes compared with those in normal reaches. This work used river reaches near the Huaidian Sluice in Shaying River of China as a case study to analyse the effects of sluice operation on water quality evolution in SCRRs. The most influential factors affecting the rate of change in chemical oxygen demand (COD) concentration in SCRRs were identified through water quality monitoring experiments performed under various modes of sluice operation and by applying a statistical method 'partial correlation analysis'. Then, a hydrodynamic model incorporating sluice operation and a water quality transport and transform model incorporating the release of endogenous loads were developed. Using these two models, the processes of temporal and spatial change of COD concentrations in the SCRRs were simulated under various scenarios designed to represent the dominant factors of influence. Finally, the simulation results were used to develop empirical relationships between the rate of change in COD concentrations and the dominant factors of influence. The results reveal that three factors, i.e., water inflow concentration, gate opening size, and gate opening number, are the dominant factors of influence, and there are logarithmic relationships between the rate of change in COD concentration in the SCRRs and these factors.

  9. Risk factors of methane hydrate resource development in the concentrated zones distributed in the eastern Nankai Trough

    Science.gov (United States)

    Yamamoto, K.; Nagakubo, S.

    2009-04-01

    Some environmental and safety concerns on the offshore methane hydrate development have been raised, but the ground of such allegations are sometime not fully reasonable. The risks of methane hydrate resource development to environment and safety should be discussed upon methane hydrate occurrences condition, the production methods, and the designs of production system, under comprehensively scientific manners. In the Phase 1 of the Methane Hydrate Exploitation Program in Japan (FY2001-2008), the Research Consortium for Methane Hydrate Resources in Japan (MH21 Research Consortium) found methane hydrate concentrated zones in the eastern Nankai Trough that are potential prospects for resource development. The concentrated zones are consisted of turbidite-derived sandy sediments and hydrate crystals in pore spaces of sand grains (pore-filling type structure). The MH21 Research Consortium proposed the depressurization method as prime technique due to its efficiency of gas production in such concentrated zones, and has tried to develop conceptual designs of production systems based on the information of existing devices and facilities. Under the condition and circumstances described above, the authors tried to extract and evaluate some risk factors concerning methane hydrate development using depressurization in the area. Leakage of methane gas, that is less harmful substance to ecosystem than heavier hydrocarbons, from production system can be one possible risk. However, in the case of gas production through wellbore, even if catastrophic damages happen in the subsea production system during gas production, the leakages do not continue b