TPEN selectively eliminates lymphoblastic B cells from bone marrow pediatric acute lymphoblastic leukemia patients.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N', N'-tetrakis(2-pyridylmethyl)-ethylenediamine) is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cell lines. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), ex vivo. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n = 3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells (CD34 + /CD19 +) but no other cell populations in BM (CD34 + /CD19-; CD34-/CD19 + ; CD34-/CD19-) independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.

Uso práctico de inhibidores de bomba de protones / Practical use of proton pump inhibitors / Uso prático de inibidores da bomba de prótons

Los inhibidores de la bomba de protones (IBP) se encuentran entre los medicamentos más utilizados en el mundo por su bajo costo, extensa prescripción y efectividad. Sin embargo, su uso a largo plazo no es inocuo y aún hay vacíos en el conocimiento del empleo adecuado de estos medicamentos. Por lo tanto, en esta revisión se expone, además de sus propiedades generales, sus verdaderas indicaciones, el uso recomendado a largo plazo y las estrategias para lograr la deprescripción, con el fin de evitar el uso indiscriminado.

Proton pump inhibitors (PPIs) are among the most widely used drugs in the world, due to their low cost, extensive prescription and effectiveness. However, its long-term use is not safe and there are still certain gaps in the knowledge of the proper use of these drugs. Therefore, this review aims to expose their general properties as well as their true indications, the appropriate long-term use and strategies to achieve adequate deprescription of these drugs, seeking to avoid indiscriminate use.

Os inibidores da bomba de prótons (IBP) se encontram entre os medicamentos mais utilizados no mundo pelo seu baixo custo, extensa prescrição e efetividade. Embora, seu uso a longo prazo não é inócuo e ainda há vazios no conhecimento do uso adequado destes medicamentos. Por tanto, nesta revisão se expõe, além das suas propriedades gerais, suas verdadeiras indicações, o uso recomendado ao longo prazo e as estratégias para conseguir a deprescrição, com o fim de evitar o uso indiscriminado.

Tumor carcinoide de estómago: presentación de dos casos

Se presentan los hallazgos clínicos, endoscópicos e histológicos de dos casos de tumor carcinoide gástrico. Endoscópicamente se encontró en ambos casos, lesión levantada única del tipo Yamada II-III. Las biopsias obtenidas inicialmente mediante pinza convencional fallaron para establecer el diagnóstico, el cual se obtuvo mediante toma de biopsias en profundidad y biopsia en ojal. Los hallazgos de anatomía patológica se interpretaron como tumor típico carcinoide de tipo A, localizado en la submucosa. En ninguno de los dos casos se presentó síndrome carcinoide típico o atípico; las determinaciones de 5-HIAA y serotonina fueron normales. Ambos casos presentaban pérdida de sangre por tracto gastrintestinal proveniente de ulceración en el pólipo gástrico. En ambos pacientes se hizo resección gástrica segmentaria