Browsing by Author "Quiroga, Teresa"

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    Association of lipoprotein-associated phospholipase activity A2 with cardiovascular risk factors
    (2013) Acevedo B., Mónica; Varleta, Paola; Krämer Karmy, Verónica; Quiroga, Teresa; Prieto, Carolina; Parada, Jacqueline; Adasme, Marcela; Briones, Luisa; Navarrete, Carlos Arturo
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    Comparison of Lipoprotein-Associated Phospholipase A2 and High Sensitive C-Reactive Protein as Determinants of Metabolic Syndrome in Subjects without Coronary Heart Disease: In Search of the Best Predictor
    (HINDAWI LTD, 2015) Acevedo, Monica; Varleta, Paola; Kramer, Veronica; Valentino, Giovanna; Quiroga, Teresa; Prieto, Carolina; Parada, Jacqueline; Adasme, Marcela; Briones, Luisa; Navarrete, Carlos
    High sensitivity C-reactive protein (hsCRP) is a marker of metabolic syndrome (MS) and cardiovascular (CV) disease. Lipoproteinassociated phospholipase A2 (Lp-PLA2) also predicts CV disease. There are no reports comparing these markers as predictors of MS. Methods. Cross-sectional study comparing Lp-PLA2 and hsCRP as predictors of MS in asymptomatic subjects was carried out; 152 subjects without known atherosclerosis participated. Data were collected on demographics, cardiovascular risk factors, anthropometric and biochemical measurements, and hsCRP and Lp-PLA2 activity levels. A logistic regression analysis was performed with each biomarker and receiver operating characteristic (ROC) curves were constructed for MS. Results. Mean age was 46 +/- 11 years, and 38% of the subjects had MS. Mean Lp-PLA2 activity was 185 +/- 48 nmol/mL/min, and mean hsCRP was 2.1 +/- 2.2mg/L. Subjects with MS had significantly higher levels of Lp-PLA2 (P = 0.03) and hsCRP (P < 0.0001) than those without MS. ROC curves showed that both markers predictedMS. Conclusion. Lp-PLA2 and hsCRP are elevated in subjects withMS. Both biomarkers were independent and significant predictors for MS, emphasizing the role of inflammation in MS. Further research is necessary to determine if inflammation predicts a higher risk for CV events in MS subjects.
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    High prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls
    (FERRATA STORTI FOUNDATION, 2007) Quiroga, Teresa; Goycoolea, Manuela; Panes, Olga; Aranda, Eduardo; Martinez, Carlos; Belmont, Sabine; Munoz, Blanca; Zuniga, Pamela; Pereira, Jaime; Mezzano, Diego
    Background and Objectives
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    Human platelets synthesize and express functional tissue factor
    (AMER SOC HEMATOLOGY, 2007) Panes, Olga; Matus, Valeria; Saez, Claudia G.; Quiroga, Teresa; Pereira, Jaime; Mezzano, Diego
    The source and significance of bloodborne tissue factor (TF) are controversial. TF mRNA, protein, and TF-dependent procoagulant activity (PCA) have been detected in human platelets, but direct evidence of TF synthesis is missing. Nonstimulated monocyte-free platelets from most patients expressed TF mRNA, which was enhanced or induced in all of them after platelet activation. Immunoprecipitation assays revealed TF protein (mainly of a molecular weight [Mr] of approximately 47 kDa, with other bands of approximately 35 and approximately 60 kDa) in nonstimulated platelet membranes, which also increased after activation. This enhancement was concomitant with TF translocation to the plasma membrane, as demonstrated by immunofluorescence-confocal microscopy and biotinylation of membrane proteins. Platelet PCA, assessed by factor Xa (FXa) generation, was induced after activation and was inhibited by 48% and 76% with anti-TF and anti-FVIIa, respectively, but not by intrinsic pathway inhibitors. Platelets incorporated [35S]-methionine into TF proteins with Mr of approximately 47 kDa, approximately 35 kDa, and approximately 60 kDa, more intensely after activation. Puromycin but not actinomycin D or DRB (5,6-dichloro-1 -beta-D-ribofuranosylbenzimidazole)inhibited TIF neosynthesis. Thus, human platelets not only assemble the clotting reactions on their membrane, but also supply their own TIF for thrombin generation in a timely and spatially circumscribed process. These observations simplify, unify, and provide a more coherent formulation of the current cellbased model of hemostasis.
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    Influence of the F12-4 C > T polymorphism on hemostatic tests
    (LIPPINCOTT WILLIAMS & WILKINS, 2010) Corral, Javier; Anton, Ana I.; Quiroga, Teresa; Gonzalez Conejero, Rocio; Pereira, Jaime; Roldan, Vanessa; Vicente, Vicente; Mezzano, Diego
    The common F12 - 4 C>T polymorphism significantly regulates plasma levels of FXII, the first element of the intrinsic pathway of coagulation. Due to the robust effects that this pathway has on blood coagulation in vitro, the objective of our study was to evaluate the influence of this polymorphism on different hemostatic tests. We studied 46 hemostatic parameters in 566 participants: 280 patients with mucocutaneous bleeding and 286 controls. The F12 - 4T allele, associated with reduced levels of FXII (P<0.001), also significantly delayed the activated partial thromboplastin time (aPTT) expressed as aPTTr (ratio sample plasma/normal pooled plasma). Thus, both patients and controls carrying the T allele had higher aPTTr than C/C homozygous individuals (P<0.001). Interestingly, 92% of healthy controls who had prolonged aPTTr carried the F12 - 4T allele. Moreover, individuals with the F12 - 4T allele also had less thrombin generation (assessed by endogenous thrombin potential, thrombin peak and time to achieve the peak of thrombin) using a test with low tissue factor concentration and explicit contact phase activation. Finally, both patients and controls carrying the F12 - 4T allele also displayed significantly lower FIXc and FVIIc levels than C/C individuals (P<0.01). For all associations except for FVIIc, a gene-dosage effect was observed, and homozygous TT individuals had the farthest values. Our study reveals a significant effect of the F12 - 4 C>T polymorphism on hemostatic tests widely used in routine clinical practice. Blood Coagul Fibrinolysis 21: 632-639 (c) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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    Is my patient a bleeder? A diagnostic framework for mild bleeding disorders
    (AMER SOC HEMATOLOGY, 2012) Quiroga, Teresa; Mezzano, Diego
    Congenital mild bleeding disorders (MBDs) are very prevalent and are the source of frequent diagnostic problems. Most MBDs are categorized as disorders of primary hemostasis (ie, type 1 VWD and platelet function disorders), but mild or moderate deficiencies of clotting factors and some rare hyperfibrinolytic disorders are also included. These patients have abnormal bleeding from the skin and mucous membranes, menorrhagia, and disproportionate hemorrhages after trauma, invasive procedures, and surgery. This review addresses the main problems that physicians and hemostasis laboratories confront with the diagnosis of these patients, including: discerning normal/appropriate from pathological bleeding, the role and yield of screening tests, the lack of distinctive bleeding pattern among the different diseases, the inherent difficulties in the diagnosis of type 1 VWD and the most common platelet functional disorders, improvements in assays to measure platelet aggregation and secretion, and the evidence that most of the patients with MBDs end up without a definite diagnosis after exhaustive and repeated laboratory testing. Much research is needed to determine the pathogenesis of bleeding in MBD patients. Better standardization of current laboratory assays, progress in the knowledge of fibrinolytic mechanisms and their laboratory evaluation, and new understanding of the factors contributing to platelet-vessel wall interaction, along with the corresponding development of laboratory tools, should improve our capacity to diagnose a greater proportion of patients with MBDs.
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    Laboratory Assessment of Familial, Nonthrombocytopenic Bleeding: A Definitive Not Possible Mucocutaneous Diagnosis Is Often Not Possible
    (THIEME MEDICAL PUBL INC, 2008) Pereira, Jaime; Quiroga, Teresa; Mezzano, Diego
    Patients with inherited mucocutaneous bleeding (MCB) pose frequent and significant diagnostic challenges. Bleeding symptoms are frequent among the otherwise healthy population, and the clinical distinction between normal subjects and patients with genuine bleeding disorders is complex. Screening or global laboratory assays are nonspecific and have low sensitivity to detect mild bleeding disorders. Moreover, there are inherent difficulties in diagnosing von Willebrand disease and platelet function defects, the best-characterized and most frequent disorders of primary hemostasis. On the other hand, some patients with moderate to severe clotting factor deficiencies and those with increased fibrinolysis usually present with MCB. Finally, in a significant proportion of patients, the definitive diagnosis is not possible even after an extensive laboratory workup. This article reviews the clinical and laboratory approach to the diagnosis of patients presenting with MCB, the limitations of the available methodologies to evaluate the clinical significance of bleeding, and the diagnostic yield of global and specific hemostasis tests used to investigate these patients.
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    Low serum sphingolipids in children with attention deficit-hyperactivity disorder
    (2015) Henríquez Henríquez, Marcela Patricia; Solari, Sandra; Quiroga, Teresa; Kim, Benjamin I.; Deckelbaum, Richard J.; Worgall, Tilla S.
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    Mutations in sphingolipid metabolism genes are associated with ADHD
    (2020) Henriquez-Henriquez, Marcela; Acosta, Maria T.; Martinez, Ariel F.; Velez, Jorge, I; Lopera, Francisco; Pineda, David; Palacio, Juan D.; Quiroga, Teresa; Worgall, Tilla S.; Deckelbaum, Richard J.; Mastronardi, Claudio; Molina, Brooke S. G.; Arcos-Burgos, Mauricio; Muenke, Maximilian
    Attention deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder in children, with genetic factors accounting for 75-80% of the phenotypic variance. Recent studies have suggested that ADHD patients might present with atypical central myelination that can persist into adulthood. Given the essential role of sphingolipids in myelin formation and maintenance, we explored genetic variation in sphingolipid metabolism genes for association with ADHD risk. Whole-exome genotyping was performed in three independent cohorts from disparate regions of the world, for a total of 1520 genotyped subjects. Cohort 1 (MTA (Multimodal Treatment study of children with ADHD) sample, 371 subjects) was analyzed as the discovery cohort, while cohorts 2 (Paisa sample, 298 subjects) and 3 (US sample, 851 subjects) were used for replication. A set of 58 genes was manually curated based on their roles in sphingolipid metabolism. A targeted exploration for association between ADHD and 137 markers encoding for common and rare potentially functional allelic variants in this set of genes was performed in the screening cohort. Single- and multi-locus additive, dominant and recessive linear mixed-effect models were used. During discovery, we found statistically significant associations between ADHD and variants in eight genes (GALC,CERS6,SMPD1,SMPDL3B,CERS2,FADS3,ELOVL5, andCERK). Successful local replication for associations with variants inGALC,SMPD1, andCERS6was demonstrated in both replication cohorts. Variants rs35785620, rs143078230, rs398607, and rs1805078, associated with ADHD in the discovery or replication cohorts, correspond to missense mutations with predicted deleterious effects. Expression quantitative trait loci analysis revealed an association between rs398607 and increasedGALCexpression in the cerebellum.
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    Normal plasma insulin and HOMA values among chilean children and adolescents
    (SOC MEDICA SANTIAGO, 2011) Barja, Salesa; Arnaiz, Pilar; Dominguez, Angelica; Villarroel, Luis; Cassis, Berta; Castillo, Oscar; Salomo, Gianina; Farias, Marcelo; Goycoolea, Manuela; Quiroga, Teresa; Mardones, Francisco
    Background: Plasma insulin and HOMA (homeostasis model assessment) index, used to determine insulin resistance, do not have local standard values for children and adolescents in Chile. Aim: To establish the normal reference intervals for insulin and HOMA in children and adolescents aged 10-15 years, according to sex and puberal maturation. Material and Methods: A cross-sectional study of 2,153 children and adolescents from Puente Alto County was performed, during 2009 and 2010. Anthropoinetry and self-report of puberal maturation were assessed. Fasting glucose (hexoquinase) and insulin blood levels (chemiluminiscence), were determined and HOMA index was calculated. Percentile distributions of these variables were calculated. Results: The reference group included only subjects with normal body mass index and fasting blood glucose (n = 1,192). Girls had higher insulin and HOMA values than boys (12.5 +/- 6.0 and 9.1 +/- 4.9 mu U/mL (p <0.01) and 2.7 +/- 1.4 and 2.1 +/- 1,1 (p <0.01), respectively). Subjects with Tanner land II puberal stages had lower insulin and HOMA mean values than subjects with Tanner III and IV (9.0 +/- 4.3 and 12.5 +/- 6.2 mu U/ml (p < 0.01) and 2.0 +/- 1 and 2.8 +/- 1.4 (p <0.01), respectively). Conclusions: The 90th percentile of insulin and HOMA distributions according to sex and maturation, was selected as the upper cut-off point to identify individuals with insulin resistance. HOMA cutoff point for Tanner I and II boys was 3.2, for Tanner land II girls was 4.1, for Tanner III and IV boys was 4.2 and for Tanner III and IV girls was 5.0. (Rev Med Chile 2011; 139: 1435-1443).
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    Novel loci involved in platelet function and platelet count identified by a genome-wide study performed in children
    (FERRATA STORTI FOUNDATION, 2011) Guerrero, Jose A.; Rivera, Jose; Quiroga, Teresa; Martinez Perez, Angel; Isabel Anton, Ana; Martinez, Constantino; Panes, Olga; Vicente, Vicente; Mezzano, Diego; Soria, Jose Manuel; Corral, Javier
    Background
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    Prevalence of Advanced Liver Fibrosis and Nonalcoholic Steato-hepatitis Diagnosed by Noninvasive Methods in Chilean Type 2 Diabetic Patients
    (2014) Gallego, Consuelo; Valderas, Juan P.; Uribe, Sergio; Tejos, Cristian; Serrano, Cristobal; Huete, Alvaro; Barrera, Francisco; Liberona, Jessica; Labbe, Pilar; Quiroga, Teresa; Irarrazabal, Pablo; Arrese, Marco
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    Procarboxypeptidase U (TAFI) and the Thr325Ile proCPU polymorphism in patients with hereditary mucocutaneous hemorrhages
    (ELSEVIER, 2009) Matus, Valeria; Willemse, Johan; Quiroga, Teresa; Goycoolea, Manuela; Aranda, Eduardo; Panes, Olga; Pereira, Jaime; Hendriks, Dirk; Mezzano, Diego
    Background: Patients with hereditary mucocutaneous bleeding are difficult to diagnose and many of them fulfill the category of bleeders of unknown cause (BUC). The pathogenic role of hyperfibrinolysis has received little attention, despite the successful use of antifibrinolytic drugs in treating many of these patients. Theoretically, decreased plasma procarboxypeptidase U (proCPU) levels or lower carboxypeptidase U (CPU) stability would result in higher fibrinolytic activity and bleeding tendency.
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    Study of 18 functional hemostatic polymorphisms in mucocutaneous bleeding disorders
    (2010) Anton, Ana I.; Gonzalez-Conejero, Rocio; Roldan, Vanessa; Quiroga, Teresa; Sanchez-Vega, Beatriz; Corral, Javier; Vicente, Vicente; Mezzano, Diego
    Hereditary disorders of primary hemostasis, characterized by mucocutaneous bleeding (MCB), are highly prevalent in children. Few cases are clearly monogenic, but the overwhelming majority are classified as mild bleeding disorders, with wide clinical and laboratory heterogeneity suggestive of complex polygenic diseases. In this framework, and by homology with venous thrombosis, some functional polymorphisms affecting the hemostatic system should be considered. We evaluated the role of 18 common hemostatic polymorphisms on the occurrence and severity of MCB in a case-control study including 269 patients and 286 matched controls consecutively recruited. FV Leiden was associated with milder bleeding severity, assessed by a standardized bleeding score (p=0.013). Multivariate analysis revealed that three additional polymorphisms protected against MCB (F13 Leu34, OR=0.66; 95% CI, 0.47-0.94; p=0.024; VKORC1 1173T, OR=0.59; 95% CI, 0.40-0.87; p=0.009; and non-O blood group alleles, OR=0.59; 95% CI, 0.41-0.86; p=0.006). When combined, these polymorphisms showed an additive protection (OR=0.24; 95% CI, 0.11-0.52), supporting the polygenic nature of MCB. Our data suggest that some common polymorphisms affecting hemostasis-related genes could protect from bleeding.