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Endothelial colony-forming cells (ECFCs) contribute to postnatal vasculogenesis. In venous thromboembolic disease (VTD), they are functionally abnormal and produce high concentrations of TNF-α.To analyze the TNF-α signaling pathway and its relationship with the expression of cell-cycle regulators.Mononuclear cells (MNCs) were collected from the peripheral blood of 20 healthy human volunteers (controls) and 30 patients with VTD matched by age (20-50 years) and sex to obtain ECFCs. We analyzed the relative quantification of the gene transcripts of TNF, NFkB1, PLAU, HMOX1, GSS, eNOS, CDKN1A, and CDKN1B through quantitative RT-PCR (qRT-PCR assays). Identification of NF-κB and activated targets of each pathway: NF-κB (Ser536); IκBα (Ser32/Ser36); p38 (Thr180/Tyr182) JNK (Thr183/Tyr185), p53 and cell-cycle regulators: p16, p18, p21, p27, p57, Cyclin D, Cyclin E, Cyclin A, Cyclin B, CDK2, CDK4; cell-cycle status was determined by KI-67 and 7-AAD. Cells were analyzed with flow cytometry and the FlowJo vX software.In ECFCs from VTD patients, TNF-α receptor and NFkB were overexpressed and hyper-phosphorylated; eNOS and HMOX1 were down-regulated; cell-cycle regulators (p53, p18, p21) were elevated. In addition, the cell cycle was locked in the G2 phase.Our results strongly suggest that these molecular alterations in the pathway of TNF-α and cell cycle regulation induce endothelial dysfunction, reduced proliferation potential and vascular regeneration, and consequently, the occurrence of new thrombotic events.

Background and Aims Rituximab is effective in the treatment of B-cell lymphoid malignances and some autoimmune diseases. Most patients receiving the first infusion of rituximab experience symptoms that decrease with subsequent infusions. It is assumed that the first dose of rituximab should be infused slowly during a 6-h period and during 4-h periods subsequently. The aim of the study was to evaluate the frequency and severity of adverse reactions to rituximab in patients with non-Hodgkin's lymphoma. Methods This was an intensive pharmacovigilance prospective, observational, open labeled, multicenter cohort study conducted in 12 hospitals. Adults requiring treatment with rituximab (375 mg/m 2 body surface area) alone or with chemotherapy were included. Adverse reactions were graded according to the National Cancer Institute scale, whereas causality was established using the Naranjo algorithm. Infusions were classified as fast (0–90 min) and slow (>91 min). Fast infusions were used to analyze the associated adverse reactions. Results We included 550 adult patients. Total infusion episodes were 1,749 and 52 adverse reactions were reported in 22 patients (4%). Thirty-one of 52 adverse reactions occurred during the first infusion. The risk of adverse reactions was lower with the fast infusions (10/52 adverse reactions [19.23%]). All adverse effects were mild. Twenty-three adverse effects were possibly related to rituximab. Conclusions Rituximab can be infused at a fast rate without an increase in adverse reactions. Peri-infusional adverse reactions are similar to those described for other populations but the incidence rate is lower. Rituximab has a favorable safety profile in patients with non-Hodgkin's lymphoma.

The C677T polymorphism of 5,10 methylenetetrahydrofolate reductase (MTHFR) gene has been associated with hypertension and coronary artery disease in several populations worldwide, but results are still controversial. The aim of this study was to examine the possible association of C677T polymorphism with ST-elevation myocardial infarction (STEMI) in young Mexican subjects.In a case-control study, 167 unrelated patientsor = 45 years of age with diagnosis of STEMI who were admitted to a cardiovascular intense care unit and 167 unrelated controls subjects matched by age and gender were recruited from January 2006 and June 2009. The C677T polymorphism was determined in all participants by a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP).There was no significant difference in the genotype distribution between groups (p = 0.69) or allele frequency (p = 0.40). There were independent factors for STEMI: smoking (OR 4.9, 95% CI 3.0-8.1, p = 0.001), hypertension (OR 1.8, 95% CI 1.0-3.3, p = 0.03), family history of atherothrombotic disease (OR 2.3, 95% CI 2.0-4.6, p = 0.02), and dyslipidemia (OR 3.2, 95% CI 1.8-5.6, p0.001). Diabetes mellitus did not represent an independent risk factor for STEMI (OR 1.2, 95% CI 0.2-2.2, p = 0.82).The TT genotype from the C677T of 5,10 MTHFR gene is not an independent risk factor for STEMI in the Mexican population. However, more studies are needed to determine the possible "protective effect" of the C677T polymorphism in our population.

The clinical suspicion of hereditary spherocytosis (HS) must be confirmed at the clinical laboratory. The osmotic fragility test (OFT) and the autohemolysis test (AHT) are the worldwide accepted assays to establish a definite diagnosis of HS; however, they have some disadvantages. We describe herein our experience with the cryohemolysis test (CHT) as a tool to confirm the HS diagnosis. We included four groups of subjects, namely, patients with clinical HS, patients with mechanical heart valve prosthesis, malignant hematological diseases and healthy blood donors. CHT was carried out in all the groups, while OFT and AHT only in the HS patients and healthy individuals. OFT and AHT were performed according to previously described techniques. CHT was performed using red blood cells incubated in a hypertonic solution, preheated for 10 min and then transferred to an ice bath for an additional 10 min. The resulting cryohemolysis was determined measuring the free hemoglobin in the sample. There were no differences among the groups in terms of general characteristics. All HS suspicious patients had a positive OFT and AHT. CHT was positive in all patients from the HS group but in none of the subjects from the control groups (p0.001). We found that CHT is a faster and easier-to-perform assay compared with OFT and AHT. Moreover, using CHT, the zone between normal and abnormal results is wider than OFT or AHT. We propose 0.7 to 11% hemolysis as reference values for CHT.