Numerical Modelling of Industrial Induction

Induction heating is a physical process extensively used in the metallurgical industry for different applications involving metal melting. The main components of an induction heating system are an induction coil connected to a power-supply providing an alternating electric current and a conductive workpiece to be heated, placed inside the coil. The alternating current traversing the coil generates eddy currents in the workpiece and by means of ohmic losses the workpiece is heate

Exercise redox biology from health to performance

In order to support the energy demand during physical exercise, temporary acute responses occur in our organism to meet the homeostatic challenge imposed by the working muscles. As a result of the accumulation of exercise bouts the organism adapts. Exercise adaptations refer to the long-term changes that occur in our body as a consequence of training. The molecular bases of skeletal muscle adaptations to exercise such as mitochondrial biogenesis, hypertrophy, angiogenesis, and cytoprotection, are mediated by signaling events regulating transcriptional and translational processes and the activity of proteins involved in the maintenance of homeostasi

Key Issues In Inhibitor Management In Patients With Haemophilia

[No abstract available]12SUPPL.1s319s329Bray, G.L., Gomperts, E.D., Courter, S., A multicenter study of recombinant factor VIII (recombinate): Safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A. The recombinate study group (1994) Blood, 83, pp. 2428-2435Lusher, J.M., Arkin, S., Abildgaard, C.F., Schwartz, R.S., Recombinant factor VIII for the treatment of previously untreated patients with hemophilia A. Safety, efficacy, and development of inhibitors. Kogenate previously untreated patient study group (1993) N Engl J Med, 328, pp. 453-459Hay, C.R., Baglin, T.P., Collins, P.W., The diagnosis and management of factor VIII and IX inhibitors: A guideline from the UK Haemophilia Centre Doctors' Organization (UKHCDO) (2000) Br J Haematol, 111, pp. 78-90Lawrence, J.S., Johnson, J.B., The presence of a circulating anticoagulant in a male member of a hemophiliac family (1941) Trans Am Clin Climatol Assoc, 57, pp. 223-231Konkle, B.A., Ebbesen, L.S., Erhardtsen, E., Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors (2007) J Thromb Haemost, 5, pp. 1904-1913Leissinger, C., Gringeri, A., Antmen, B., Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors (2011) N Engl J Med, 365, pp. 1684-1692Gouw, S.C., Van Den Berg, H.M., Oldenburg, J., F8 gene mutation type and inhibitor development in patients with severe hemophilia A: Systematic review and meta-analysis (2012) Blood, 119, pp. 2922-2934Gouw, S.C., Van Der Bom, J.G., Auerswald, G., Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: The CANAL cohort study (2007) Blood, 109, pp. 4693-4697Iorio, A., Halimeh, S., Holzhauer, S., Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: A systematic review (2010) J Thromb Haemost, 8, pp. 1256-1265Wight, J., Paisley, S., The epidemiology of inhibitors in haemophilia A: A systematic review (2003) Haemophilia, 9, pp. 418-435Hay, C.R., The epidemiology of factor VIII inhibitors (2006) Haemophilia, 12 (SUPPL. 6), pp. 23-28. , discussion 8-9Astermark, J., Basic aspects of inhibitors to factors VIII and IX and the influence of non-genetic risk factors (2006) Haemophilia, 12 (SUPPL. 6), pp. 8-13Hay, C.R., Palmer, B., Chalmers, E., Incidence of factor VIII inhibitors throughout life in severe hemophilia A in the United Kingdom (2011) Blood, 117, pp. 6367-6370Wacey, A.I., Kemball-Cook, G., Kazazian, H.H., The haemophilia A mutation search test and resource site, home page of the factor VIII mutation database: HAMSTeRS (1996) Nucleic Acids Res, 24, pp. 100-102Green, P.M., Montandon, A.J., Ljung, R., Haemophilia B mutations in a complete Swedish population sample: A test of new strategy for the genetic counselling of diseases with high mutational heterogeneity (1991) Br J Haematol, 78, pp. 390-397Viel, K.R., Ameri, A., Abshire, T.C., Inhibitors of factor VIII in black patients with hemophilia (2009) N Engl J Med, 360, pp. 1618-1627Viel, K.R., Machiah, D.K., Warren, D.M., A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels (2007) Blood, 109, pp. 3713-3724Santos, A., Annichino-Bizzacchi, J.M., Ozelo, M.C., Inhibitors of factor VIII in hemophilia (2009) N Engl J Med, 361, pp. 309-310. , author reply 10Oldenburg, J., Pavlova, A., (2006) Genetic risk factors for inhibitors to factors VIII and IX.Haemophilia, 12 (SUPPL. 6), pp. 15-22Goodeve, A.C., Peake, I.R., The molecular basis of hemophilia A: Genotype-phenotype relationships and inhibitor development (2003) Semin Thromb Hemost, 29, pp. 23-30Jacquemin, M., Vantomme, V., Buhot, C., CD4+ T-cell clones specific for wild-type factor VIII: A molecular mechanism responsible for a higher incidence of inhibitor formation in mild/moderate hemophilia A (2003) Blood, 101, pp. 1351-1358Kane, W.H., Davie, E.W., Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin (1986) Proc Natl Acad Sci USA, 83, pp. 6800-6804Lacroix-Desmazes, S., Repesse, Y., Kaveri, S.V., Dasgupta, S., The role of VWF in the immunogenicity of FVIII (2008) Thromb Res, 122 (SUPPL. 2), pp. S3-6Rivard, G.E., Lillicrap, D., Poon, M.C., Can activated recombinant factor VII be used to postpone the exposure of infants to factor VIII until after 2 years of age? (2005) Haemophilia, 11, pp. 335-339Hermans, C., De Moerloose, P., Fischer, K., Management of acute haemarthrosis in haemophilia A without inhibitors: Literature review, European survey and recommendations (2011) Haemophilia, 17, pp. 383-392Kurnik, K., Bidlingmaier, C., Engl, W., New early prophylaxis regimen that avoids immunological danger signals can reduce FVIII inhibitor development (2010) Haemophilia, 16, pp. 256-262Gouw, S.C., Van Den Berg, H.M., Fischer, K., Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: The RODIN study (2013) BloodKreuz, W., Ettingshausen, C.E., Zyschka, A., Inhibitor development in previously untreated patients with hemophilia A: A prospective long-term follow-up comparing plasmaderived and recombinant products (2002) Semin Thromb Hemost, 28, pp. 285-290Santagostino, E., Mannucci, P.M., Bianchi Bonomi, A., Guidelines on replacement therapy for haemophilia and inherited coagulation disorders in Italy (2000) Haemophilia, 6, pp. 1-10Rezende, S.M., Pinheiro, K., Caram, C., Registry of inherited coagulopathies in Brazil: First report (2009) Haemophilia, 15, pp. 142-149Manco-Johnson, M.J., Abshire, T.C., Shapiro, A.D., Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia (2007) N Engl J Med, 357, pp. 535-544Kruse-Jarres, R., Inhibitors: Our greatest challenge.Can we minimize the incidence? (2013) Haemophilia, 19 (SUPPL. 1), pp. 2-7Lobet, S., Detrembleur, C., Francq, B., Hermans, C., Natural progression of blood-induced joint damage in patients with haemophilia: Clinical relevance and reproducibility of threedimensional gait analysis (2010) Haemophilia, 16, pp. 813-821Leissinger, C.A., Prevention of bleeds in hemophilia patients with inhibitors: Emerging data and clinical direction (2004) Am J Hematol, 77, pp. 187-193Gringeri, A., Mantovani, L.G., Scalone, L., Cost of care and quality of life for patients with hemophilia complicated by inhibitors: The COCIS Study Group (2003) Blood, 102, pp. 2358-2363Fischer, K., Van Der Bom, J.G., Molho, P., Prophylactic versus on-demand treatment strategies for severe haemophilia: A comparison of costs and long-term outcome (2002) Haemophilia, 8, pp. 745-752Morfini, M., Haya, S., Tagariello, G., European study on orthopaedic status of haemophilia patients with inhibitors (2007) Haemophilia, 13, pp. 606-612Soucie, J.M., Cianfrini, C., Janco, R.L., Joint range-of-motion limitations among young males with hemophilia: Prevalence and risk factors (2004) Blood, 103, pp. 2467-2473Hay, C.R., Dimichele, D.M., The principal results of the International Immune Tolerance Study: A randomized dose comparison (2012) Blood, 119, pp. 1335-1344Astermark, J., Donfield, S.M., Dimichele, D.M., A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: The FEIBA NovoSeven Comparative (FENOC) Study (2007) Blood, 109, pp. 546-551Sorensen, B., Dargaud, Y., Kenet, G., On-demand treatment of bleeds in haemophilia patients with inhibitors: Strategies for securing and maintaining predictable efficacy with recombinant activated factor VII (2012) Haemophilia, 18, pp. 255-262Kenet, G., Martinowitz, U., Single-dose recombinant activated factor VII therapy in hemophilia patients with inhibitors (2008) Semin Hematol, 45, pp. S38-41Treur, M.J., McCracken, F., Heeg, B., Efficacy of recombinant activated factor VII vs. Activated prothrombin complex concentrate for patients suffering from haemophilia complicated with inhibitors: A Bayesian meta-regression (2009) Haemophilia, 15, pp. 420-436Knight, C., Dano, A.M., Kennedy-Martin, T., Systematic review of efficacy of rFVIIa and aPCC treatment for hemophilia patients with inhibitors (2009) Adv Ther, 26, pp. 68-88Valentino, L.A., The benefits of prophylactic treatment with APCC in patients with haemophilia and high-titre inhibitors: A retrospective case series (2009) Haemophilia, 15, pp. 733-742Teitel, J., Berntorp, E., Dolan, G., A consensus statement on clinical trials of bypassing agent prophylaxis in inhibitor patients (2011) Haemophilia, 17, pp. 516-521Young, G., Auerswald, G., Jimenez-Yuste, V., When should prophylaxis therapy in inhibitor patients be considered? (2011) Haemophilia, 17, pp. e849-e857Dimichele, D., Negrier, C., A retrospective postlicensure survey of FEIBA efficacy and safety (2006) Haemophilia, 12, pp. 352-362Valentino, L.A., Assessing the benefits of FEIBA prophylaxis in haemophilia patients with inhibitors (2010) Haemophilia, 16, pp. 263-271Brackmann, H.H., Schwaab, R., Effenberger, W., Hemophilia treatment. Side effects during immune tolerance induction (2000) Haematologica, 85, pp. 75-77Young, G., McDaniel, M., Nugent, D.J., Prophylactic recombinant factor VIIa in haemophilia patients with inhibitors (2005) Haemophilia, 11, pp. 203-207Morfini, M., Auerswald, G., Kobelt, R.A., Prophylactic treatment of haemophilia patients with inhibitors: Clinical experience with recombinant factor VIIa in European Haemophilia Centres (2007) Haemophilia, 13, pp. 502-507Jimenez-Yuste, V., Alvarez, M.T., Martin-Salces, M., Prophylaxis in 10 patients with severe haemophilia A and inhibitor: Different approaches for different clinical situations (2009) Haemophilia, 15, pp. 203-209Young, G., Auerswald, G., Jimenez-Yuste, V., PRO-PACT: Retrospective observational study on the prophylactic use of recombinant factor VIIa in hemophilia patients with inhibitors (2012) Thromb ResGupta, S., Siddiqi, A.E., Soucie, J.M., The effect of secondary prophylaxis versus episodic treatment on the range of motion of target joints in patients with haemophilia (2013) Br J Haematol, 161, pp. 424-433Carcao, M., Lambert, T., Prophylaxis in haemophilia with inhibitors: Update from international experience (2010) Haemophilia, 16 (SUPPL. 2), pp. 16-23Dimichele, D.M., Hoots, W.K., Pipe, S.W., International workshop on immune tolerance induction: Consensus recommendations (2007) Haemophilia, 13 (SUPPL. 1), pp. 1-22Lenk, H., The German Registry of immune tolerance treatment in hemophilia-1999 update (2000) Haematologica, 85, pp. 45-47Brackmann, H.H., Oldenburg, J., Schwaab, R., Immune tolerance for the treatment of factor VIII inhibitors-twenty years' 'bonn protocol' (1996) Vox Sang, 70 (SUPPL. 1), pp. 30-35Oldenburg, J., Schwaab, R., Brackmann, H.H., Induction of immune tolerance in haemophilia A inhibitor patients by the 'Bonn Protocol': Predictive parameter for therapy duration and outcome (1999) Vox Sang, 77 (SUPPL. 1), pp. 49-54Mauser-Bunschoten, E.P., Nieuwenhuis, H.K., Roosendaal, G., Van Den Berg, H.M., Low-dose immune tolerance induction in hemophilia A patients with inhibitors (1995) Blood, 86, pp. 983-988Indications and recommended doses for treating patients with factor VIII inhibitors in hemophilia A (2008) Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives. Executive Committee of the German Medical Association on the Recommendation of the Scientific Advisory Board, p. 91. , German Medical AssociationCoppola, A., Margaglione, M., Santagostino, E., Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance induction of hemophilia A patients with highresponding inhibitors (2009) J Thromb Haemost, 7, pp. 1809-1815Freiburghaus, C., Berntorp, E., Ekman, M., Immunoadsorption for removal of inhibitors: Update on treatments in Malmo-Lund between 1980 and 1995 (1998) Haemophilia, 4, pp. 16-20Auerswald, G., Spranger, T., Brackmann, H.H., The role of plasmaderived factor VIII/von Willebrand factor concentrates in the treatment of hemophilia A patients (2003) Haematologica, 88, pp. EREP05Dimichele, D., The North American Immune Tolerance Registry: Contributions to the thirty-year experience with immune tolerance therapy (2009) Haemophilia, 15, pp. 320-328Mariani, G., Ghirardini, A., Bellocco, R., Immune tolerance in hemophilia-principal results from the International Registry. Report of the factor VIII and IX Subcommittee (1994) Thromb Haemost, 72, pp. 155-158Mariani, G., Kroner, B., Immune tolerance in hemophilia with factor VIII inhibitors: Predictors of success (2001) Haematologica, 86, pp. 1186-1193Franchini, M., Mannucci, P.M., Inhibitors of propagation of coagulation (factors VIII, IX and XI): A review of current therapeutic practice (2011) Br J Clin Pharmacol, 72, pp. 553-562Greninger, D.A., Saint-Remy, J.M., Jacquemin, M., The use of factor VIII/von Willebrand factor concentrate for immune tolerance induction in haemophilia A patients with high-titre inhibitors: Association of clinical outcome with inhibitor epitope profile (2008) Haemophilia, 14, pp. 295-302Gringeri, A., Musso, R., Mazzucconi, M.G., Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response (2007) Haemophilia, 13, pp. 373-379Kurth, M.A., Dimichele, D., Sexauer, C., Immune tolerance therapy utilizing factor VIII/von Willebrand factor concentrate in haemophilia A patients with high titre factor VIII inhibitors (2008) Haemophilia, 14, pp. 50-55Astermark, J., Morado, M., Rocino, A., Current European practice in immune tolerance induction therapy in patients with haemophilia and inhibitors (2006) Haemophilia, 12, pp. 363-371Garvey, B., Rituximab in the treatment of autoimmune haematological disorders (2008) Br J Haematol, 141, pp. 149-169Franchini, M., Mengoli, C., Lippi, G., Immune tolerance with rituximab in congenital haemophilia with inhibitors: A systematic literature review based on individual patients' analysis (2008) Haemophilia, 14, pp. 903-912Sorensen, B., Johansen, P., Christiansen, K., Whole blood coagulation thrombelastographic profiles employing minimal tissue factor activation (2003) J Thromb Haemost, 1, pp. 551-558De Paula, E.V., Kavakli, K., Mahlangu, J., Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors: A randomized controlled trial (2012) J Thromb Haemost, 10, pp. 81-89Holmberg, H.L., Lauritzen, B., Tranholm, M., Ezban, M., Faster onset of effect and greater efficacy of NN1731 compared with rFVIIa, aPCC and FVIII in tail bleeding in hemophilic mice (2009) J Thromb Haemost, 7, pp. 1517-1522Moss, J., Scharling, B., Ezban, M., Moller Sorensen, T., Evaluation of the safety and pharmacokinetics of a fast-acting recombinant FVIIa analogue, NN1731, in healthy male subjects (2009) J Thromb Haemost, 7, pp. 299-305Sorensen, B., Persson, E., Ingerslev, J., Factor VIIa analogue (V158D/E296V/M298Q-FVIIa) normalises clot formation in whole blood from patients with severe haemophilia A (2007) Br J Haematol, 137, pp. 158-165Allen, G.A., Persson, E., Campbell, R.A., A variant of recombinant factor VIIa with enhanced procoagulant and antifibrinolytic activities in an in vitro model of hemophilia (2007) Arterioscler Thromb Vasc Biol, 27, pp. 683-689Mahlangu, J.N., Coetzee, M.J., Laffan, M., Phase I, randomized, double-blind, placebo-controlled, single-dose escalation study of the rFVIIa variant BAY 86-6150 in hemophilia (2012) J Thromb Haemost, 10, pp. 773-780Karpf, D.M., Sorensen, B.B., Hermit, M.B., Prolonged halflife of glycoPEGylated rFVIIa variants compared to native rFVIIa (2011) Thromb Res, 128, pp. 191-195Sen, P., Ghosh, S., Ezban, M., Effect of glycoPEGylation on factor VIIa binding and internalization (2010) Haemophilia, 16, pp. 339-348Toschi, V., OBI-1, porcine recombinant factor VIII for the potential treatment of patients with congenital hemophilia A and alloantibodies against human Factor VIII (2010) Curr Opin Mol Ther, 12, pp. 617-625Parker, E.T., Craddock, H.N., Barrow, R.T., Lollar, P., Comparative immunogenicity of recombinant B domain-deleted porcine factor VIII and Hyate: C in hemophilia A mice presensitized to human factor VIII (2004) J Thromb Haemost, 2, pp. 605-611Kempton, C.L., Abshire, T.C., Deveras, R.A., Pharmacokinetics and safety of OBI-1, a recombinant B domain-deleted porcine factor VIII, in subjects with haemophilia A (2012) Haemophilia, 18, pp. 798-804Abshire, T.C., Brackmann, H.H., Scharrer, I., Sucrose formulated recombinant human antihemophilic factor VIII is safe and efficacious for treatment of hemophilia A in home therapy-International Kogenate-FS Study Group (2000) Thromb Haemost, 83, pp. 811-816Tarantino, M.D., Collins, P.W., Hay, C.R., Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: Pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A (2004) Haemophilia, 10, pp. 428-437Young, G., Cooper, D.L., Gut, R.Z., Dosing and effectiveness of recombinant activated factor VII (rFVIIA) in congenital haemophilia with inhibitors by bleed type and location: The experience of the Haemophilia and Thrombosis Research Society (HTRS) Registry (2004-2008) (2012) Haemophilia, 18, pp. 990-99

Breast treatments with Axxent equipment.Comparison with Mammosite for skin, lung and heart dose

Poster Session [EP-1314] Purpose or Objective We have treated 250 patients at our center from May 2015 to September 2017 for breast cancer with Axxent (Xoft Inc.) intraoperativ e radiotherapy (IORT) following the inclusion parameters of the TARGIT study, in this work we compare the doses in the skin of the first 150 patients treated with the 50 kVp source with the skin doses they would have received using the Mammosite kit using an Ir192 source. Material and Methods To the 250 patients treated in our center after removing the tumor, the appropriate balloon size is chosen to cover the tumor area with a dose of 20 Gy on the ball oon surface, the sizes used range fro m 30-65 cm3, after which it is verified that the distance to skin from the 3 closest points of the balloon i s less than 10 mm and then the treatment is carried out with an average duration of 10.3 minutes being the volumes of 30 and 35 cm3 the most used due to the inclusion criteria of the procedure. Treatment plans are previously per formed in a Brachyvision treatment planning system (TPS) (Varian Inc.) for each of the possible volumes. In tur n, another plan is calculated with the Mammosite applicator and Ir192 source, from which the skin dose of each control point is estimated, compared to our results. We present also the cases of acute dermatitis seen for these first 150 patients in a time less than 6 months after the surgical act and irradiation. Results The differences in maximum skin dose for bot h types of treatment are 8.1 ± 1.2 Gy for the case of Mammosite and 5.7 ± 1.5 Gy for patients treated with electronic source, due to the difference in the depht dos e percentage of both types of treatment (Image 1). This, in turn, explains the very few cases of acute dermatitis at 6 months (8 cases of grade 2 and 2 cases of grade 3) (Image 2) with no recurrence to date.We also show the mean and maximum doses (expressed as percentage of prescribed dose) for the left lung and heart in cases of left breast tumor for the volumes of 30 and 35 cm3, which are the most common volumes in our hospital (70% of cases): LEFT LUNG (Left Breast tratment) AXXENT MAMMOSITE Maximun Dose (%PD) 20.4% 29.9% Mean Dose (%PD) 1.0% 3.9% HEART (Left Breast tratment) AXXENT MAMMOSITE Maximun Dose (%PD) 4.1% 10.4% Mean Dose (%PD) 0.8% 3.3% Conclusion It is concluded that the IORT treatments performed with the Axxent equipment with electronic source are a good alternative to those performed with Ir192 and our 250 patients treated to date to the good results presented by other centers are joined.In additi on to the low skin toxicity, there is no recurrence in patients treated so far, which makes us very optimistic about the results

BMP type II receptor as a therapeutic target in pulmonary arterial hypertension

Cancer Signaling networks and Molecular Therapeutic

Woolliness assessment in peaches (Cv. Springcrest) by sensory and instrumental means.

Mealiness is a negative attribute of sensory texture, characterised by the lack of juiciness without variation of total water content in the tissues. In peaches, mealiness is also known as "woolliness" and "leatheriness". This internal disorder is characterised by the lack of juiciness and flavour. In peaches, it is associated with interna browning near the stone and the incapacity of ripening although there is externa ripe appearance. Woolliness is associated with inadequate cold storage and is considered as a physiological disorder that appears in stone fruits when an unbalanced pectolitic enzyme activity during storage occurs (Kailasapathy and Melton, 1992). Many attempts have been carried out to identify and measure mealiness and woolliness in fruits. The texture of a food product is composed by a wide spectrum of sensory attributes. Consumer defines the texture integrating simultaneously all the sensory attributes. However, an instrument assesses one or several parameters related to a fraction of the texture spectrum (Kramer, 1973). The complexity of sensory analysis by means of trained panels to assess the quality of some producing processes, supports the attempt to estimate texture characteristics by instrumental means. Some studies have been carried out comparing sensory and instrumental methods to assess mealiness and woolliness. The current study is centered on analysis and evaluation of woolliness in peaches and is part of the European project FAIR CT95 0302 "Mealiness in fruits: consumer perception and means for detection". The main objective of this study was to develop procedures to detect woolly peaches by sensory and by instrumental means, as well as to compare both measuring procedures

Alterations in biomarkers of cardiovascular disease (CVD) in active acromegaly

Objectives: In acromegalic patients, cardiovascular and metabolic comorbidities contribute to enhance mortality. Available data on the lipoprotein profile of these patients are controversial. Our aim was to characterize the lipoprotein profile and emergent biomarkers of cardiovascular disease in active acromegalic patients in comparison with sex- and age-matched healthy controls. Patients: Eighteen patients with active acromegaly and 18 controls were studied. Measurements: Glucose levels, hormonal status, lipoprotein profile and C reactive protein (CRP) were evaluated by standardized methods. Cholesteryl ester transfer protein (CETP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured by radiometric techniques, endothelin-1 and vascular cell adhesion molecule (VCAM)-1 by enzyme-linked immunosorbent assay, and leucocytes CD18, CD49d and CD54 by flow cytometry. Results: After adjusting for body mass index (BMI), acromegalic patients presented a more atherogenic lipoprotein profile, consisting of higher levels of triglycerides and apolipoprotein B and alterations in the ratios which estimate insulin resistance and atherogenic risk. CETP activity was significantly increased in acromegalic patients as compared to controls (168 ± 17 vs. 141 ± 30% per ml h, respectively; P < 0.05). Endothelin-1 levels evidenced an increase in the patients' group (0.9 ± 0.2 vs. 0.7 ± 0.2 ng/l, respectively; P < 0.01) and showed positive and significant correlations with GH, IGF-1 and IGFBP-3 (r = 0.45, 0.42 and 0.44, respectively; P < 0.01 for all of them; with BMI as a fixed variable). Lymphocytes from acromegalic patients showed increased CD49d content (282 ± 59 vs. 246 ± 48 arbitrary units, respectively; P < 0.05). Conclusions: Taken together, the alterations described seem to contribute to constituting a state of higher propensity for the development of atherosclerotic cardiovascular disease, which adds to the presence of specific cardiomyopathy.Fil: Boero, Laura Estela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Manavela, M.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Gomez Rosso, Leonardo Adrián. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Insua, C.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Berardi, V.. No especifíca;Fil: Fornari, M.C.. No especifíca;Fil: Brites, Fernando Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Opipramol inhibits lipolysis in human adipocytes without altering glucose uptake and differently from antipsychotic and antidepressant drugs with adverse effects on body weight control

Treatment with several antipsychotic drugs exhibits a tendency to induce weight gain and diabetic complications. The proposed mechanisms by which the atypical antipsychotic drug olanzapine increases body weight include central dysregulations leading to hyperphagia and direct peripheral impairment of fat cell lipolysis. Several investigations have reproduced in vitro direct actions of antipsychotics on rodent adipocytes, cultured preadipocytes, or human adipose tissue-derived stem cells. However, to our knowledge, no such direct action has been described in human mature adipocytes. The aim of the present study was to compare in human adipocytes the putative direct alterations of lipolysis by antipsychotics (haloperidol, olanzapine, ziprazidone, risperidone), antidepressants (pargyline, phenelzine), or anxiolytics (opipramol). Lipolytic responses to the tested drugs, and to recognized lipolytic (e.g., isoprenaline) or antilipolytic agents (e.g., insulin) were determined, together with glucose transport and amine oxidase activities in abdominal subcutaneous adipocytes from individuals undergoing plastic surgery. None of the tested drugs were lipolytic. Surprisingly, only opipramol exhibited substantial antilipolytic properties in the micromolar to millimolar range. An opipramol antilipolytic effect was evident against isoprenaline-, forskolin-, or atrial natriuretic peptide-stimulated lipolysis. Opipramol did not impair insulin activation of glucose transport but inhibited monoamine oxidase (MAO) activity to the same extent as antidepressants recognized as MAO inhibitors (pargyline, harmine, or phenelzine), whereas antipsychotics were inefficient. Considering its unique properties, opipramol, which is not associated with weight gain in treated patients, is a good candidate for drug repurposing because it limits exaggerated lipolysis, prevents hydrogen peroxide release by amine oxidases in adipocytes, and is thereby of potential use to limit lipotoxicity and oxidative stress, two deleterious complications of diabetes and obesity

Skeletal maturation in relation to ethnic background in children of school age: The Generation R Study

Ethnicity is a well-established determinant of pediatric maturity, but the underlying genetic and environmental contributions to these ethnic differences are poorly comprehended. We aimed to evaluate the influence of ethnicity on skeletal age (SA), an assessment of pediatric maturation widely used in clinical settings. We included children from the Generation R Study, a multiethnic population-based pregnancy cohort, assessed at a mean age of 9.78 (±0.33) years. SA was evaluated by a trained observer on hand DXA scans using the Greulich and Pyle method. Ethnic background was defined as geographic ancestry (questionnaire-based assessment) (N = 5325) and genetic ancestry (based on admixture analysis) (N = 3413). Associations between the ethnic background and SA were investigated separately in boys and girls, using linear regression models adjusted for age, height and BMI. Based on geographic ancestry, 84% of the children were classified as European, 6% as Asian and 10% as African. Children of European background had on average younger SA than those of Asian or African descent. Asian boys had 0.46 (95% CI 0.26–0.66, p-value < 0.0001) and African boys 0.36 years (95% CI 0.20–0.53, p-value < 0.0001) older SA as compared to European boys. Similarly, Asian girls showed 0.64 (95% CI 0.51–0.77, p-value < 0.0001) and African girls 0.38 years (95% CI 0.27–0.48, p-value < 0.0001) older SA as compared to European girls. A similar pattern was observed in the analysis with genetically-defined ancestry. Furthermore, an increase in the proportion of Asian or African component was associated with older SA in both boys (log[Non-European/European]proportion = 0.10, 95% CI 0.06–0.13, p-value < 0.0001) and girls (log[Non-European/European]proportion = 0.06, 95% CI 0.04–0.08, p-value < 0.0001). In summary, children of Asian and African backgrounds have on average older SA as compared to children of European descent, partially explained by a genetic com