Papers by Abraham Majluf-cruz
Cerebrovascular Diseases, 2010
Gaceta Medica De Mexico, Jun 29, 2013
Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición
The human immunodeficiency virus (HIV) infection is becoming more complex. Hemostatic abnormaliti... more The human immunodeficiency virus (HIV) infection is becoming more complex. Hemostatic abnormalities occur frequently in the patient with HIV. HIV-related thrombocytopenia (Tr-HIV) is the most common hemostatic disorder with a high morbidity and affects patients from every risk group independently of age, sex, or stage of infection. Two mechanisms are responsible for the Tr-HIV: bone marrow failure and immunological disorders, namely, circulating immune complex deposited on the platelet membrane and the production of autoantibodies directed against platelets. The treatment of choice is zidovudine; other available options are not as effective as zidovudine. In addition, there are some abnormalities in the fluid phase of the coagulation cascade which can produce bleeding or thrombosis in the HIV patient. The most common are a prolonged partially activated thromboplastin time test, the production of a lupic anticoagulant and anticardiolipin antibodies, and several abnormalities in the n...
PubMed, May 25, 2012
Venous thromboembolism (VTE) is a worldwide public health problem, with an annual incidence of 1-... more Venous thromboembolism (VTE) is a worldwide public health problem, with an annual incidence of 1-2 cases/1,000 individuals in the general population and a 1-5% associated mortality. Orthopedic surgery is a major surgical risk factor for VTE, but the problem is more important for patients with hip and knee joint replacement, multiple traumatisms, severe damage to the spine, or large fractures. Thromboprophylaxis is defined as the strategy and actions necessary to diminish the risk of VTE in high-risk orthopedic surgery. Antithrombotics may prevent VTE. At the end of this paper, we describe a proposal of thromboprophylaxis actions for patients requiring high-risk orthopedic surgery, based on the opinion of specialists in Orthopedics and Traumatology who work with high-risk orthopedic surgery patients. A search for evidence about this kind of surgery was performed and a 100-item inquiring instrument was done in order to know the opinions of the participants. Then, recommendations and considerations were built. In conclusion, this document reviews the problem of VTE in high-risk orthopedic surgery patients and describes the position of the Colegio Mexicano de Ortopedia y Traumatología related to VTE prevention in this setting.
Scientific Reports
The cell surface serine protease Transmembrane Protease 2 (TMPRSS2) is required to cleave the spi... more The cell surface serine protease Transmembrane Protease 2 (TMPRSS2) is required to cleave the spike protein of SARS-CoV-2 for viral entry into cells. We determined whether negatively-charged heparin enhanced TMPRSS2 inhibition by alpha-1-antitrypsin (AAT). TMPRSS2 activity was determined in HEK293T cells overexpressing TMPRSS2. We quantified infection of primary human airway epithelial cells (hAEc) with human coronavirus 229E (HCoV-229E) by immunostaining for the nucleocapsid protein and by the plaque assay. Detailed molecular modeling was undertaken with the heparin–TMPRSS2–AAT ternary complex. Enoxaparin enhanced AAT inhibition of both TMPRSS2 activity and infection of hAEc with HCoV-229E. Underlying these findings, detailed molecular modeling revealed that: (i) the reactive center loop of AAT adopts an inhibitory-competent conformation compared with the crystal structure of TMPRSS2 bound to an exogenous (nafamostat) or endogenous (HAI-2) TMPRSS2 inhibitor and (ii) negatively-char...
Brain Injury, 2021
ABSTRACT Background: Patients in intensive care units with traumatic brain injuries (TBI) frequen... more ABSTRACT Background: Patients in intensive care units with traumatic brain injuries (TBI) frequently present acid-base abnormalities and coagulability disorders, which complicate their condition. Objective: To identify protonation through in silico simulations of molecules involved in the process of coagulation in standard laboratory tests. Materials and methods: Ten patients with TBI were selected from the intensive care unit in addition to ten “healthy control subjects”, and another nine patients as “disease control subjects”; the latter being a comparative group, corresponding to subjects with diabetes mellitus 2 (DM2). Fibrinogen, FVII, FVIII, FIX, FX, and D-dimer in the presence of acidification were evaluated in 20 healthy subjects in order to compare clinical results with molecular dynamics (MD), and to explain proton interactions and coagulation molecules. Results: The TBI group presented a slight, non-significant increase in D-dimer; but this was not present in “disease control subjects”. Levels of fibrinogen, FVII, FIX, FX, and D-dimer were affected in the presence of acidification. We observed that various specific residues of coagulation factors “trap” ions. Conclusion: Protonation of tissue factor and factor VIIa may favor anticoagulant mechanisms, and protonation does not affect ligand binding sites of GPIIb/IIIa (PAC1) suggesting other causes for the low affinity to PAC1.
Gaceta Medica De Mexico, 2015
espanolEl diagnostico de la EvW es complejo, pues requiere diversas pruebas para su escrutinio y ... more espanolEl diagnostico de la EvW es complejo, pues requiere diversas pruebas para su escrutinio y confirmacion, como el analisis de multimeros del factor de von Willebrand (FvW), considerado el estandar de oro para la subtipificacion de la EvW, aunque solo discrimina el subtipo 2A; las variantes 2B, 2M y 2N requieren pruebas complementarias para su confirmacion definitiva, incluido el diagnostico genetico. Es importante considerar el hemotipo de los pacientes para el diagnostico de EvW, particularmente en Mexico, con poblacion predominante de grupo sanguineo O que presenta una disminucion del 20-25% del FvW plasmatico y mayor tendencia hemorragica. EnglishThe diagnosis of von Willebrand disease (vWD) is complex and requires several screening and confirmation tests, such as the analysis of vWF multimers, which is considered the gold standard for vWD subtyping; however, it only discriminates 2A subtype while the 2B, 2M, and 2N subtypes require additional tests and even genetic testing ...
Gaceta Medica De Mexico, 2016
Background: The treatment of hemophilia generates a disproportionally large economic impact relat... more Background: The treatment of hemophilia generates a disproportionally large economic impact relative to its prevalence. Objective: To determine the economic impact of hemophilia A and B in Mexico in 2011 from the perspective of public health institutions. Methods: Hemophilia was epidemiologically characterized in Mexico during the year of interest, direct costs (diagnosis, monitoring or follow-up, care of bleeding events, and consumption of hemostatic factors), as well as absenteeism associated with illness (indirect costs) were estimated. Records, surveys and official data were supplemented by expert opinion to assess costs. Results: The investment in hemostatic factors is the primary source of cost: 68.6 and 74.3% of total investment in hemophilia A and B, respectively. Sensitivity analysis showed that the most decisive variable is the cost of acquisition of hemostatic factors, including bypass agents. The second most important source of cost is the attention to bleeding events, b...
Gaceta de M�xico, 2021
Introduction: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous t... more Introduction: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous thromboembolic disease; however, numerous factors affect their pharmacology. Objective: To evaluate the quality of VKA anticoagulation at three different time periods in Mexico. Methods: Prospective study, nested in patient cohorts at three different clinical scenarios between 2013 and 2019. Outpatients with indication for treatment with VKAs for at least 12 months were included. Patients were managed according to the criteria of the treating physician. Results: Patient general characteristics were similar between groups, except for the VKA indication. The results of 4,148 patients and 38,548 INR assessments were analyzed. The times in therapeutic range during the three phases of the study and pooled data were significantly higher for the anticoagulation clinic. Only the number of patient visits was significantly associated with the results, unlike age, gender, and type of VKA. Conclusions: VKAs are widely used, but it is difficult for therapeutic goals to be achieved, especially in non-specialized clinical services. Creation of anticoagulation clinics is an urgent need for the Mexican health system.
End-stage renal disease (ESRD) patients have an elevated risk of cardiovascular (CV) complication... more End-stage renal disease (ESRD) patients have an elevated risk of cardiovascular (CV) complications including acute myocardial infarction (AMI); endothelial dysfunction and accumulation of uremic toxins have been associated with such CV-events. To explore which molecular pathways are involved in this CV-complication and the effects of the uremic serum on gene expression, an endothelial dysfunction model was studied through microarrays and pathway analysis. mRNA was isolated of human coronary arterial endothelial cells (HCAEC) primary cultures supplemented with 20% uremic serum from two groups of patients, USI: ESRD-patients; UCI: ESRD-AMI-patients. Affymetrix GeneChip® microarray and the LIMMA-package (Linear Models for Microarray Data) of the Bioconductor sofware17 was implemented to identify relevant DEGs between the two groups of uremic patients. Protein-protein interaction networks and pathway analysis were made to analyze the interaction and expression tendency of differentially...
Gaceta de M�xico, Jan 29, 2019
Royal Society Open Science, 2020
Royal Society Open Science, 2020
Atherothrombosis is the cornerstone of cardiovascular diseases and the primary cause of death wor... more Atherothrombosis is the cornerstone of cardiovascular diseases and the primary cause of death worldwide. Genetic contribution to disturbances in lipid metabolism, coagulation, inflammation and oxidative stress increase the susceptibility to its development and progression. Given its multifactorial nature, the multiloci studies have been proposed as potential predictors of susceptibility. A cross-sectional study was conducted to explore the contribution of nine genes involved in oxidative stress, inflammatory and thrombotic processes in 204 subjects with atherothrombosis matched by age and gender with a healthy group (n= 204). To evaluate the possibility of spurious associations owing to the Mexican population genetic heterogeneity as well as its ancestral origins, 300 unrelated mestizo individuals and 329 Native Americans were also included.ALOX5,LPA,MMP9andTPOgene polymorphisms, as well as their multiallelic combinations, were twice to four times more frequent in those individuals ...
Gaceta Médica de México, 2019
Gaceta Médica de México, 2018
Objetivo: Examinar la contribución de los polimorfismos G20210A, G1691A y G10976A en los factores... more Objetivo: Examinar la contribución de los polimorfismos G20210A, G1691A y G10976A en los factores de coagulación FII, FV y FVII respectivamente; Glu298Asp y C677T en la óxido nítrico sintasa endotelial y 5,10 metilentetrahidrofolato reductasa, en población joven mexicana con infarto cerebral (IC). Método: Se incluyeron 224 pacientes ≤ 45 años de edad con diagnóstico de IC y 224 controles pareados por edad y sexo, de 2006 a 2014. Los polimorfismos fueron determinados por la técnica de reacción en cadena de la polimerasa-polimorfismos de longitud de fragmentos de restricción. Resultados: Identificamos una diferencia significativa en la distribución genotípica de los polimorfismos Glu298Asp (p = 0.001) y C677T (p = 0.01) entre el grupo de pacientes con IC y el control. La distribución genotípica de los polimorfismos FII G20210A, FV G1691A y FVII G10976A fue similar entre ambos grupos. Se identificaron como factores independientes de IC los polimorfismos Glu298Asp y C677T, el tabaquismo, la hipertensión y el antecedente de familiar de enfermedad trombótica. Conclusiones: Los polimorfismos Glu298Asp y C677T, pero no FII G20210A, FV G1691A y FVII G10976A, se asociaron con IC. Nuestros resultados sugieren que la disfunción endotelial en interacción sinérgica con otros factores de riesgo, como tabaquismo e hipertensión, contribuye al IC en individuos jóvenes.
PLOS ONE, 2017
Background Venous thromboembolic disease (VTD) is a public health problem. We recently reported t... more Background Venous thromboembolic disease (VTD) is a public health problem. We recently reported that endothelial colony-forming cells (ECFCs) derived from endothelial cells (EC) (ECFC-ECs) from patients with VTD have a dysfunctional state. For this study, we proposed that a dysfunctional status of these cells generates a reduction of its proliferative ability, which is also associated with senescence and reactive oxygen species (ROS). Methods and results Human mononuclear cells (MNCs) were obtained from peripheral blood from 40 healthy human volunteers (controls) and 50 patients with VTD matched by age (20−50 years) and sex to obtain ECFCs. We assayed their proliferative ability with plasma of patients and controls and supernatants of cultures from ECFC-ECs, senescence-associated β-galactosidase (SA-β-gal), ROS, and expression of ephrin-B2/Eph-B4 receptor. Compared with cells from controls, cells from VTD patients showed an 8-fold increase of ECFCs that emerged 1 week earlier, reduced proliferation at long term (39%) and, in passages 4 and 10, a highly senescent rate (30±1.05% vs. 91.3±15.07%, respectively) with an increase of ROS and impaired expression of ephrin-B2/Eph-4 genes. Proliferation potential of cells from VTD patients was reduced in endothelial medium [1.4±0.22 doubling population (DP)], control plasma (1.18±0.31 DP), or plasma from VTD patients (1.65±0.27 DP).
BioMed Research International, 2017
Background. Metabolic and genetic factors induce plasminogen activator inhibitor type-1 (PAI-1) o... more Background. Metabolic and genetic factors induce plasminogen activator inhibitor type-1 (PAI-1) overexpression; higher PAI-1 levels decrease fibrinolysis and promote atherothrombosis.Aim. To assess PAI-1 antigen levels among subjects with type 2 diabetes mellitus (T2DM) plus Metabolic Syndrome (MetS) before clinical manifestations of atherothrombosis and the contribution of metabolic factors and 4G/5G polymorphism of PAI-1 gene on the variability of PAI-1.Methods. We conducted an observational, cross-sectional assay in a hospital in Mexico City from May 2010 to September 2011. MetS was defined by the International Diabetes Federation criteria. PAI-1 levels and 4G/5G polymorphism were determined by ELISA and PCR-RFLP analysis.Results. We enrolled 215 subjects with T2DM plus MetS and 307 controls. Subjects with T2DM plus MetS had higher PAI-1 levels than the reference group (58.4 ± 21 versus 49.9 ± 16 ng/mL,p=0.026). A model with components of MetS explained only 12% of variability on...
Revista De Investigacion Clinica, 2011
Mujer de 28 años de edad sin antecedentes de importancia en el séptimo mes del primer embarazo, s... more Mujer de 28 años de edad sin antecedentes de importancia en el séptimo mes del primer embarazo, sufrió herpes gestacional asociado a tendencia hemorrágica grave que forzó la realización de una operación cesárea en la semana 32 de gestación. En el ev Inv ón C a ti
Cirugia Y Cirujanos, 2014
Background: Acute myocardial infarction is the first cause of morbidity and mortality in the worl... more Background: Acute myocardial infarction is the first cause of morbidity and mortality in the world, resulting in the combination of genetic and environmental factors. It has been postulated that the R353Q polymorphism of the coagulation FVII gene represents a protective factor for acute myocardial infarction, whereas the N700S polymorphism in the thrombospondin-1 gene is associated with an increased risk for acute myocardial infarction; however, the results are still contradicted. The objective of the study was to examine the possible association of the FVII R353Q and N700S polymorphism and acute myocardial infarction in Mexican patients with acute myocardial infarction younger than 45 years old. Methods: Case-control study that included 252 patients who were diagnosed with acute myocardial infarction and 252 apparently healthy, age-and gender-matched individuals without a history of coronary artery disease. R353Q and N700S polymorphisms were determined in all participants by PCR-RFLP. Results: There was no statistical significant difference in genotype distribution (p = 0.06) between the acute myocardial infarction and control groups. Also, there was a similar genotype distribution of N700S polymorphism between stroke and control groups (p = 0.50). Hypertension, diabetes mellitus, family history of coronary disease and dyslipidemia represented independent risk factors for acute myocardial infarction. Conclusions: Polymorphisms R353Q and N700S do not represent a protective or risk factor for acute myocardial infarction in young Mexican individuals.
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Papers by Abraham Majluf-cruz